Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants

Spittle AJ, Orton J, Doyle LW, Boyd R

 

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables and Graphs

Dates

Date edited: 14/03/2007
Date of last substantive update: 01/12/2006
Date of last minor update: 20/01/2007
Date next stage expected 01/01/2009
Protocol first published: Issue 4, 2005
Review first published: Issue 2, 2007

Contact reviewer

Ms Alicia Spittle
Physiotherapist/Senior Clinician
Murdoch Children's Research Institute
c/o Royal Children's Hospital
2nd Floor, Flemington Road
Parkville
Melbourne AUSTRALIA
3052
Telephone 1: 03 9345 4830
Facsimile: 03 9345 4840
E-mail: alicia.spittle@rch.org.au

Contribution of reviewers

Alicia Spittle and Jane Orton wrote the protocol. Alicia Spittle and Jane Orton searched the literature, reviewed all possible trials for inclusion, extracted details of the studies' methods and results, entered the data into RevMan, wrote the initial synthesis of the results, and contributed to all versions of the review. Ros Boyd extracted details of the results and contributed to all versions of the review. Lex Doyle contributed to the synthesis of the results, and to all versions of the review.

Internal sources of support

Murdoch Childrens Research Institute, AUSTRALIA

External sources of support

NHMRC - Grant 284512, AUSTRALIA
NHMRC Public Health Scholarship, AUSTRALIA
Allens Arthur Robinsons Grant, AUSTRALIA

What's new

Dates

Date review re-formatted: / /
Date new studies sought but none found: / /
Date new studies found but not yet included/excluded: / /
Date new studies found and included/excluded: / /
Date reviewers' conclusions section amended: / /
Date comment/criticism added: / /
Date response to comment/criticisms added: / /

Text of review

Synopsis


Preterm infants (babies born before 37 weeks) are at risk of development problems, including problems with cognitive and motor development. Cognitive development refers to thinking and learning ability and motor development refers to the way infants move, such as sitting, crawling and walking. Early developmental interventions aim to reduce cognitive and/ or motor problems; however, the benefits of these programs are not clear. A review of trials suggests early developmental intervention programs post discharge from hospital for preterm infants are effective at improving cognitive development in the short to medium term (up to preschool age). There is limited evidence that early developmental interventions improve motor outcome or long term cognitive outcome (up to school age). The early developmental intervention programs in this review had to commence within the first 12 months of life, focus on the parent-infant relationship and/or infant development and, although they could commence while the baby was still in hospital, they had to have a component that was delivered post-discharge from hospital. The early developmental intervention programs included in this review are different in content, frequency of intervention and focus of intervention. The variability in the intervention programs limits the conclusions that can be made about the effectiveness of early developmental interventions.

Abstract



Background


Infants born preterm are at increased risk of developing cognitive and motor impairments compared with infants born at term. Early developmental interventions have been used in the clinical setting with the aim of improving the overall functional outcome for these infants. However, the benefit of these programs remains unclear.

Objectives


To review the effectiveness of early developmental intervention post-discharge from hospital for preterm (< 37 weeks) infants on motor or cognitive development.

Search strategy


The Cochrane Neonatal Review group search strategy was used to identify randomised and quasi-randomised controlled trials of early developmental interventions post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE Advanced, CINAHL, PsychINFO and EMBASE (1966 through February 2006).

Selection criteria


Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programs that commenced within the first 12 months of life for infants born at < 37 weeks with no major congenital abnormalities. Intervention could commence as an inpatient; however, a post discharge component was necessary to be included in this review. The outcome measures were not pre-specified other than that they had to assess cognitive and/or motor ability. The rates of intellectual impairment, cerebral palsy and development co-ordination disorder were also documented.

Data collection & analysis


Data were extracted and entered by two independent review authors. Cognitive and motor outcomes were pooled in three age groups - infant (0 to 2 years), preschool (3 to < 5 years) or school age (5 to 17 years). Meta-analysis was carried out using RevMan 4.2 to determine the effects of early developmental intervention in the short (0 to 2 years), medium (3 to < 5 years) and long term (5 to 17 years). Subgroup analysis was carried out in relation to; gestational age, birthweight, brain injury, commencement of intervention, focus of intervention and study quality.

Main results


Sixteen studies met the inclusion criteria (2379 randomised patients). Six of these studies were RCTs and had strong methodological quality. There was variability with regard to the focus and intensity of the intervention, and in length of follow-up. Meta-analysis concluded that intervention improved cognitive outcomes at infant age (developmental quotient [DQ]: standard mean difference [SMD] 0.46 SD; 95% CI 0.36 0.57; P < 0.0001), and at preschool age (intelligence quotient [IQ]; SMD 0.46 SD; 95%CI 0.33, 0.59; P < 0.0001). However, this effect was not sustained at school age (IQ; SMD 0.02 SD; 95% CI -0.10, 0.14; P = 0.71). There was significant heterogeneity between studies for cognitive outcomes at infant and school ages. There was little evidence of an effect of early intervention on motor outcomes in the short, medium or long-term, but there were only two studies reporting outcomes beyond 2 years.

Reviewers' conclusions


Early intervention programs for preterm infants have a positive influence on cognitive outcomes in the short to medium term. However, there was significant heterogeneity between the interventions included in this review. Further research is needed to determine which early developmental interventions are the most effective at improving cognitive and motor outcomes, and on the longer-term effects of these programs. Cost-effectiveness and access to services should also be evaluated since they are important factors when considering implementation of an early developmental intervention program for a preterm infant.

Background


Infants born preterm or low birth weight are at increased risk of developing motor, cognitive and behavioural impairments compared with infants born at term (Doyle 2004; Pedersen 2000; Bhutta 2002). Despite improving rates of survival for extremely low birth weight infants over the past two decades, the rate of disabilities has remained relatively constant, with up to 50% of these infants later exhibiting developmental disabilities such as motor, cognitive or behavioural impairments (Bhutta 2002; Doyle 2004) . Five to fifteen percent will have cerebral palsy (Tin 1997; Vohr 2005).

These neurosensory impairments are complex and often subtle, and may affect various aspects of the child's development. At school age, children born preterm experience problems across most educational domains. They tend to have difficulties learning, particularly in applying mathematical concepts (Anderson 2003). Attentional problems and hyperactivity are commonly reported in children born prematurely (Horwood 1998). These can substantially affect academic achievement and social integration (Hoy 1992; Botting 1998; Sommerfelt 1996). Minor motor impairments, which are now classified as Developmental Coordination Disorder (DSM-IV), have also been found to be more prevalent in very low birth weight infants (Polatajko 1995; Holsti 2002; Marlow 1989). These motor problems persist into adolescence and can affect school performance and self esteem (Powls 1995). In adulthood, very low birthweight infants continue to exhibit higher rates of neurosensory impairments, with lower academic scores and a lower high school graduation rate compared with adults born at normal birth weights (Hack 2002).

The learning, behaviour and motor impairments in preterm children can be associated with medical risk factors [e.g. birth weight, gestational age, periventricular leukomalacia (PVL), intraventricular haemorrhage (IVH), respiratory distress syndrome and necrotising enterocolitis]; however, they account for only a portion of the variance associated with these long-term outcomes (Vohr 2000). Non-medical factors such as social class, parental education, parenting style, parental mental health, family structure, family functioning and the home environment are also associated with developmental outcome of children born preterm (Laucht 1997; Hogan 2000).

Early developmental interventions have been used in the clinical setting with the aim of improving the overall functional outcome for these infants. Due to the complex biological, medical and environmental elements that contribute to development, early intervention may encompass many different components, and services may be provided by a variety of disciplines (Berger 1998). Early intervention for preterm infants may focus on different aspects of early development, depending on the outcomes that are being targeted.

Developmental care is an intervention that focuses on environment and the infant, and is designed to minimize the stress of the infant in the neonatal intensive care environment [NICU] (Als 1997; Symington 2003). Several systematic reviews have shown variable short term benefits of developmental care, such as reduced oxygen dependency and improved neurodevelopmental outcomes up to 12 months; however, benefits were not sustained at two years (Jacobs 2002; Symington 2003).

Early intervention programs that focus on development post-discharge from the hospital and into the community setting may have a greater impact on long term morbidity as they are able to focus more on family factors and the home environment. Interventions that are aimed at enhancing the parent-infant relationship focus on sensitising the parents to infant cues and teach appropriate and timely responses to the infant's needs. There is evidence that early high quality parent-infant interactions positively influence cognitive and social development in children (Melnyk 2001). There are several types of interventions such as physical therapy and infant stimulation programs that focus on infant development. Physical therapy programs aim to optimise motor development and are often based upon the principles of neuro-developmental therapy (NDT), which aims to modify sensory input and/ or abnormal movement patterns to improve motor outcome through active and/or passive techniques (Brown 2001; Blauw-Hospers 2005). Systematic reviews of the effect of NDT for children with neurological dysfunction have been inconclusive. A review by Brown 2001 showed NDT to be of benefit in six out of 15 studies. A review by Ottenbacher 1986 showed a small treatment effect on motor outcome compared with the comparison group. Infant stimulation programs may involve multisensory stimulation such as auditory, visual, vestibular and tactile stimulation. This type of intervention is usually carried out by health professionals or parents under the guidance of health professionals.

For the purpose of this review, early developmental intervention is considered to be a program beginning within the first year of life, with or without an inpatient hospital component, where the aim is to enhance infant development. The interventions have been grouped into interventions that focus on the parent-infant relationship, the infant's development, or both. While some interventions may specifically target motor or cognitive development, there is a strong relationship between these areas. For example, by influencing motor function, cognitive outcome may also be improved as it allows the infant more opportunity to interact with their environment (Thelen 1996; Becker 1999). The intervention may be seen as a prevention or treatment program. When intervention is begun at this early age in infants at high risk of neurodevelopmental problems, it is usually a prevention program. However, during the course of an intervention if a specific dysfunction becomes apparent this dysfunction would become the focus and be treated accordingly.

Objectives


PRIMARY OBJECTIVE
To determine the effect of early developmental intervention programs post hospital discharge on cognitive and motor development compared with standard medical follow-up of preterm infants at infant (0 - 2 years), preschool (3 - < 5 years) and school ages (5 - 17 years).

SECONDARY OBJECTIVES
To perform subgroup analysis to determine:

SUBGROUPS
Population subgroups:

Intervention subgroups:


Criteria for considering studies for this review



Types of studies


All trials using random or quasi-random allocation that met the inclusion criteria for types of participant, interventions and outcome were included.

Types of participants


Preterm infants of less than 37 weeks' gestational age (according to best obstetric estimate at the time of delivery).

Types of interventions


Early developmental intervention programs that aimed to improve cognitive or motor outcome were included. Enrollment in the early intervention programs could occur while the infant was an inpatient during the primary hospitalisation or post-hospital discharge. Intervention had to begin within the first 12 months post-term age and could occur at home, hospital or community centre. Intervention must have been carried out by a health professional, such as a physical therapist, doctor, psychologist or nurse. Types of interventions could include: physical therapy, occupational therapy, psychology, neuro-developmental therapy, parent-infant relationship enhancement, infant stimulation, infant development, developmental care and early intervention (education). These interventions could focus on the parent-infant relationship, infant development, or both.

Types of outcome measures


The following includes some of the possible outcome measures that were used to assess cognitive and motor development.

Cognitive outcome
Continuous

Categorical
Rate of intellectual impairment defined as the number of children scoring more than 2 standard deviations below the mean of the relevant IQ test.

Motor outcome

Continuous

Categorical


Search strategy for identification of studies


The review used the search strategy for the Cochrane Neonatal Review Group. See: Cochrane Neonatal Group, Search strategy for specialised register in The Cochrane Library. A comprehensive search was undertaken by the review authors including Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE Advanced (1966 - February 2006), CINAHL (1982 - February 2006), PsychINFO (1966 - February 2006) and EMBASE (1988 - February 2006). The review authors cross referenced relevant literature including identified trials and existing review articles.

The following search strategy was used:
1. infant-premature OR infant-low birth weight
2. AND early intervention (education) OR developmental care OR physical therapy OR occupational therapy OR psychology OR parent-infant relationship OR rehabilitation OR exercise OR neurodevelopmental therapy OR infant stimulation
3. AND child development OR infant development OR cognition OR intellectual disability OR developmental disabilities OR psychomotor performance OR psychomotor disorders OR cerebral palsy OR developmental coordination disorder OR movement disorders OR motor skill disorders
4. NOT drug therapy OR genetics OR chest physiotherapy OR cardiac

Studies that are reported in English or a language for which a translator was available were included.

Methods of the review


(i) Inclusion/Exclusion
The standard methods of the Cochrane Neonatal Review Group (CNRG) were used; however, studies where allocation concealment was not used were also included. Eligibility of studies for inclusion were assessed independently by two of the authors who are working in the fields of early intervention and neonatology (AS, JO). The initial search yield was reviewed based upon title and abstract and studies that did not meet the inclusion criteria were excluded. The review authors then evaluated the full text of the remaining articles that appeared to meet the inclusion criteria.

(ii) Methodological quality
Methodological quality of the included trials was evaluated using the CNRG methodological scheme where each article was assessed for selection (blinding of randomisation), performance (blinding of intervention), attrition (completeness of follow up) and detection (blinding of outcome measures). When data were entered into RevMan 4.2 software, allocation concealment was classified as adequate (A), unclear (B), inadequate (C), or was not used (D), as another criterion to assess validity. Additional information was requested from the authors of trials to clarify methodology and obtain missing data (in order to perform analyses on intention-to-treat basis), when necessary. Methodological quality ratings were conducted independently by three review authors (AS, JO, RB).

The PEDro (Physiotherapy Evidence Database) Scale adapted from the Delphi Scale was also used to assess quality of the included trials (Verhagen 1998). A point is given for each of the following (maximum score = 11): specification of eligibility criteria, random allocation, allocation concealment, prognostic similarity at baseline, subject blinding, therapist blinding, assessor blinding, greater than 85% follow up of one key outcome, intention to treat analysis, between group statistical comparison of at least one key outcome and reporting of point estimates and measures of variability of at least one key outcome. Sensitivity analysis was conducted using the higher quality studies which had to be randomised trials, and to score at least 7 out of 11 on the PEDro Scale.

(iii) Quantitative analysis
RevMan 4.2 software was used to conduct the data management and analysis. Data were independently entered by two review authors. Standard methods of CNRG were used to synthesise the data. For data analysis "intervention group" refers to infants who were involved in early developmental intervention programs and "follow-up" group refers to infants who had standard medical follow-up. Standard follow-up varied between studies, as different hospitals/ institutions had different standard follow up procedures. For individual trials, where possible, mean values for treatment and control groups (and 95% confidence intervals) were reported for continuous variables. For the meta-analysis of continuous outcomes, standardised mean differences (SMD) were calculated since there were a variety of outcome measures (with different standard deviations) that measure the same outcome. For example, cognitive outcome at infant age can be measured by Bayley MDI or Griffiths GCI. For dichotomous outcomes, the relative risk and risk difference (and 95% confidence intervals) were reported for treatment and follow up groups. Number needed to treat (NNT) was calculated if the risk difference was statistically significant. Cognitive and motor outcome data were pooled into three age groups - infant age (0 - 2 years), preschool age (3 - < 5 years) or school age (5 - 17 years). If studies reported data at more than one time point within an age group, data from the latest assessment was used. For example, if a study reported cognitive outcome at 12 and 24 months, then only the 24 month data were used. Pooled effects for treatment effects were calculated across the trials using a fixed effect model when more than one trial assessed treatment effect on the same outcome in similar populations and used similar outcome measures. Heterogeneity was evaluated using the I2 statistic. The possible reasons for heterogeneity were explored by scrutinising the studies and, where appropriate, performing sub-group analyses.

Description of studies



Sixteen randomised or quasi-randomised controlled trials of early developmental interventions post hospital discharge were identified. The search strategy initially retrieved 1,092 references of which 1034 publications were excluded based upon the title and abstract. The remaining 58 publications required more detailed examination by the two independent review authors. Twenty publications were excluded from the review as they did not fit all the inclusion criteria (see Table Characteristics of Excluded Studies).

Of the 38 publications that met the inclusion criteria there were only 16 individual trials, since most studies had published several papers related to cognitive and motor outcomes at different ages. The following is a description of each of these 16 studies.

APIP 1998 conducted a multicenter randomised controlled trial comparing two interventions with standard follow-up. All eligible infants (n = 309) born over a two and one-half year period were randomised to one of the three groups at seven to 10 days after birth (Portage = 111, Parent advisor = 99, Follow-up = 99). Consent to participate in the study was obtained post-randomisation to evaluate the acceptability and impact of intervention in population terms. This resulted in the families of 284 infants consenting to participate in the study out of the 309 infants randomly assigned to the 3 groups (Portage = 97, Parent advisor = 90, Standard follow-up = 97). The families of infants who did not consent to the intervention were invited to participate in outcome assessments and outcome data at two years (but not at five years) and results are reported on an intention to treat basis. Both intervention groups were enrolled in a program directed by research nurses at home upon discharge from hospital until two years. Visits were weekly for the first two months, then one to two per month for the next 12 months and then one per month until two years of corrected age. The frequency of visits was tailored to suit the family. The Portage program is a home visiting educational service for children with additional support needs and their families. It takes place in the child's own home and aims to equip parents with the skills and confidence they will need to help their child. Portage offers practical help and ideas to encourage a child's interests and make learning fun for the entire family. The primary focus of the Portage group was the developmental progress of the child, although parental support was provided as part of the delivery. A second intervention group was used to control for the parent support given with the Portage group. The parent support group received supportive counseling for parents but no advice on the infant's development. Details of the care for the standard follow-up group are not given. At two years cognitive development was assessed using the Griffiths GCI, and at five years with the BAS. Motor outcome was assessed at five years with the Movement-ABC. A cut off equivalent to the upper quartile of the term reference group scores was used to defined motor impairment. Rates of cerebral palsy were also reported at five years. All outcomes were measured by a blinded assessor. Data from the two intervention groups were combined and compared with the standard follow-up group for all analyses except for the subgroup analysis of "Focus of Intervention".

Bao 1999 conducted a multicenter quasi-randomised controlled trial of an intervention package that focused on the infants' development compared with standard follow-up. Parents of infants in the intervention group (n = 52) were taught to carry out the program, implemented by a doctor, from term equivalent age to two years of age. The program aimed to enhance motor, cognitive and speech development, and to improve social behaviour. The program involved checking the development of the infant and then instructing the parents how to carry out a home program until the next examination. The home program included exercise, suggestion of toys, books and pictorials appropriate to the child's age. The visits were one per month for the first year and one every two months for the second year. Parent education classes were also reported to occur "sometimes". Details of the care for the standard follow-up group (n = 51) are not given. Cognitive and motor outcomes were measured at 18 and 24 months using the BSID MDI-II and PDI-II by a blinded assessor.

Barrera 1986 conducted a multicenter randomised controlled trial comparing two types of intervention programs with standard follow-up. Eighty preterm infants were randomly assigned to one of three groups: parent-infant intervention (n = 22), developmental intervention (n = 16) or a standard follow-up (n = 21) group. There were 21 infants who did not complete the study for a variety of reasons (e.g. death of infant, family moved). The number of infants in each group is reported only for the infants who completed the program. The parent-infant intervention aimed to improve the quality of the interaction between the parent and the child by enhancing the parents' observational skills and teaching them to be mutually responsive to their infant. The developmental program aimed to improve the infants' cognition, communication, gross and fine motor development, socio-emotional skills and self help skills. Parents worked with therapists to plan and implement developmental activities. Both interventions were implemented by one of four therapists with training in speech pathology, occupational therapy or early childhood education. Sessions were weekly for 3-4 months, bi-weekly for the next six months, and then monthly for three months. The mean number of home visits was 23 (range 12 - 28). The standard follow-up group received home visits for assessment purposes only. During these visits the examiner answered any questions parents had related to their child's development, reading material or community resources. Cognitive and motor outcomes were obtained at four, eight, twelve and sixteen months using BSID MDI-and PDI-I. At 4.5 - 5 years the child's cognitive development was assessed using McCarthy Scales of Children's Abilities - GCI. All outcome assessors were blinded to the child's group allocation. Data from the two intervention groups were combined and compared with the standard follow-up group for all relevant analyses.

Cameron 2005 conducted a single centre randomised controlled trial to investigate the effects of a physiotherapy early intervention program compared with standard follow-up. The intervention group (n = 34) received a physiotherapy program which aimed to improve motor outcome by promoting symmetry, muscle balance and movement using postural support and facilitation techniques. The intervention began while the infant was an inpatient with daily (weekdays) sessions from birth to discharge. It was then provided on a needs-orientated basis post-discharge up to four months. This included advice on play activities to encourage the infant's development based upon the infant's progress. The standard follow-up group (n = 38) received no physiotherapy or placebo interventions. Motor development was assessed at four months using the AIMS, and rates of CP were reported at 18 months by assessors blinded to the child's group allocation.

Field 1980 carried out a randomised controlled study to assess the effects of combined risks of being born preterm to a teenage mother and to evaluate the effects of an intervention program. The study was comprised of 60 preterm infants with teenage mothers who were randomly assigned to intervention (n = 30) or standard follow-up (n = 30). Teenage mothers were < 19 years, had an average of 10 years of education and were unmarried but living with a parent. The intervention consisted of home visits made by a two person team; a trained interventionist and a female student. The aim was to educate the mother regarding developmental milestones and child rearing practices, to teach the mother age-appropriate stimulation to facilitate cognitive and social interaction, communication skills and to facilitate mother-infant relationships. Some tasks were based on the infant assessments. Intervention was targeted at the at-risk mother even when the infant was cared for by grandparents during the day. Home activities were prescribed and adherence to the program monitored. The intervention began post-discharge and was biweekly for four months, and then once a month for the next four months (up to eight months). Details of the care for the standard follow-up group are not given. Cognitive and motor outcomes were measured at 8 months with the BSID MDI-I and PDI-I by an assessor blinded to group allocation.

Goodman 1985 conducted a quasi-randomised controlled trial to investigate the effects of early neurodevelopmental therapy compared with standard follow up. The 107 infants were assessed as being "normal" or "at-risk" on the basis of a neurodevelopmental score and were then alternatively assigned to intervention or control groups. Prior to beginning the study the authors stated that their intention was to study 40 infants in the intervention and follow-up groups. To allow for attrition they enrolled 107 infants into the study at three months. However, the formal study ceased when there were 40 infants in each category who were followed for 12 months. Therefore, data is only presented for 80 of the 107 infants enrolled in the study. The intervention group (n = 40) received monthly outpatient neurodevelopmental therapy (NDT) at the hospital by a physiotherapist for 12 months. Duration of the treatment was at least 45 minutes, during which time parents were also shown exercises for use at home, where the parents were expected to carry out the program on a daily basis. Infants in both treatment and standard follow-up group (n = 40) were seen at the hospital's follow up clinic, which was staffed by neonatologists, physiotherapists, speech and hearing therapists, ophthalmologists, public health nurses and social workers, at six weeks, three, six, nine and 12 months' corrected age. In addition to the scheduled visits infants in either group could also attend when clinically indicated. At 12 months and six years of age motor and cognitive development was assessed using the Griffiths GCI and locomotor subscales by a blinded assessor.

The study by I.H.D.P. 1990 is the largest multi-centre trial that investigated the effects of early intervention compared with standard follow-up. To minimize the cost of the study, one-third of subjects were randomly assigned to intervention (n = 377) and two-thirds were randomised to standard follow-up (n = 608). The intervention program began post-discharge from the neonatal nursery and continued until 36 months corrected age. The intervention was provided by educational professionals. The intervention group had home visits, attended at a child development centre, and attended parent group meetings. The home visits were weekly for the first year and biweekly for the second and third years. The home visits emphasised cognitive, linguistic and social development via a program of games for the parent to use with the child and aimed to help parents manage self identified problems. Children in the intervention group attended child development centres 5 days per week, from 12 to 36 months corrected age. Teachers at the centre continued with the above curriculum, taking into account the child's needs and developmental levels. Parent group meetings were held bi-monthly from 12 months, and provided information on child rearing, health and safety and other parental concerns. The standard follow up group received medical, developmental and social assessments, with referral to other services as indicated. The compliance with the program was variable. The mean number of home visits in the first year = 34.0 (SD 10.2, range 0 - 51); second year = 17.4 (SD 7.2, range 0 - 29) and third year = 15.4 (SD 7.4, range 0 -26). The mean attendance at child centres for the 2nd year = 132.5 (SD 76.2, range 0-235) and 3rd year = 134.9 (SD 78.5, range 0-241. The mean number of attendances at parent meetings in the 2nd year = 2.1 (SD 1.9, range 0 - 7) and third year =1.6 (SD 1.7, range 0-6). Cognitive outcome was measured at 12 and 24 months with the BSID-MDI-I, at three years with the Stanford-Binet Intelligence Scale, at five years with the WPPSI, and at 8 years with the WISC-III. Motor outcome was assessed at 12 and 24 months with the BSID-PDI-I. Not all this data is published and missing data was requested from the authors. All outcome assessors were blinded to the child's group allocation.

Lekskulchai 2001 conducted a randomised controlled trial to evaluate the effect of a physiotherapy motor developmental program in improving motor performance for preterm infants. The 84 infants were classified as at risk of developmental delay using the TIMP assessment. The motor developmental program (n = 43) began at 40 weeks postmenstrual age, with a further three visits at one, two and three months corrected age. A physiotherapist instructed the primary care-giver in how to perform three activities with the infant during each session, which were to be carried out at home. Prior to the next visit, the principal researcher evaluated the previous month's program with the care-giver through an interview and demonstration of the activities by the care-giver. The standard follow up group (n = 41) were assessed (using the TIMP) by a research assistant at one, two, three and four months, and were able to discuss any concerns with the principal researcher. Motor outcome was assessed by a physiotherapist blinded to group allocation at one, two, three and four months' corrected age using the TIMP.

Melnyk 2001 carried out a quasi-randomised pilot project comparing the "creating opportunities for parent empowerment" (COPE) program with a placebo intervention. The intervention program was carried out in blocks (related to date of admission) so that there was no contamination of the comparison group by staff and parents in the treatment group. The COPE program (n = 26) was a four phase program and consisted of audio-taped, written information and work books on infant behaviour and parental roles. The first three sessions occurred two to four days after admission to hospital and the last session occurred approximately one week after discharge. The comparison program (n = 29) was delivered at the same four time points and involved audio-taped and written information about hospital services, routine discharge information and education about immunizations. Cognitive outcome was measured using the BSID-MDI-II at three and six months by an assessor blinded to infant group allocation.

Nelson 2001 conducted a randomised controlled study to investigate the effects of an infant stimulation program compared with standard follow-up. Infants were randomly assigned to an intervention group (n = 21) or standard follow-up group (n = 16) at 33 weeks of age and were eligible to commence the intervention program after this point. The intervention group received a multi-sensory stimulation program including auditory, tactile, visual and vestibular stimuli in response to infant behavioural and physiological cues. The intervention was provided by a research assistant in the hospital twice daily, five days per week until discharge. Mothers were taught the intervention, which they continued to administer at home until the infants reached 2 months' corrected age. The standard follow-up group and the intervention group received a baseline of care in the nursery designed to optimise development, reduce stress, and facilitate both sleep cycles and motor development. All infants also received a home program of physical therapy intervention. Cognitive and motor outcomes were assessed at 12 months using the Bayley MDI-II and PDI-II.

The Mother Infant Transaction Program (MITP), also known as the Vermont Intervention Program by Nurcombe 1984, was a randomised controlled trial comparing the MITP with standard medical follow up. The intervention group (n = 38) received a program designed to enhance mother-infant interaction and infant development by teaching mothers to be more sensitive and responsive to the baby's physiological, behavioural and social cues. Intervention consisted of a total of 11 sessions delivered by a trained neonatal intensive care nurse. Seven sessions were conducted in hospital prior to discharge and four at home during the first three months following discharge. The initial seven inpatient sessions focused on educating to the mother (and father if available) with regard to the infant's motor system, state regulation, social interaction, daily care and preparing for home. The information given at these sessions was then consolidated in the first session post-discharge. The remaining three sessions at home involved discussion regarding mutual enjoyment through play and understanding of temperamental patterns. Details of the care for the standard follow-up group (n = 40) are not reported. There was a significant difference in the SES between the intervention and standard follow-up groups despite randomisation. The authors reported data that has been adjusted to account for differences in SES. Cognitive and motor outcome was measured at six, 12 and 24 months using the BSID MDI-I and PDI-I. At three and four years cognitive development was assessed using the McCarthy Scale of Children's Abilities. At seven and nine years cognitive development was assessed using the Kaufman Assessment Battery for Children. All outcome assessors were blinded to the child's group allocation.

Ohgi 2004 conducted a randomised controlled trial to determine the effect of an early intervention program on preterm infants with a high risk of cerebral palsy compared with standard follow up. The intervention group (n = 12) received a behavioural-based intervention combined with developmental support designed to enhance the infant's development and parent-infant relationship. The intervention began in the NICU and lasted until six months corrected age. There were two components to the program. The first was designed to facilitate mother-infant interaction and involved three to four, 30 minute sessions, at 36 - 40 weeks' postmenstrual age, prior to discharge. The second component was focused on advising mothers on how to handle their infant according to the infant's abilities and developmental needs. The second component was taught to parents during visits at the hospital. After discharge the intervention group had weekly or biweekly outpatient sessions for 40 - 60 minutes. The standard follow-up group (n = 12) had the same care as the treatment group with respect to attendance at clinics and referral to developmental services if the infants developed signs of neurological dysfunction or developmental delay. Motor and cognitive outcomes were assessed at six months with the BSID MDI-I and PDI-I by an assessor blind to the infant's group allocation.

Piper 1986 conducted a randomised controlled trial to assess the effects of early physiotherapy intervention compared with conventional follow up for infants at risk of neurological sequelae. The infants included in the study consisted of two groups - the first were born weighing < 1,500 g and the second were infants with birth asphyxia, seizures or central nervous system (CNS) dysfunction. The preterm intervention group (n = 56) received a 12 month physiotherapy program from 40 weeks postmenstrual age. The outpatient treatment program taught parents specific handling techniques, positioning and stimulation techniques based on neurodevelopmental principles and patterns of movements. All treatment sessions involved individualised treatment, demonstration and parent instruction. For the first three months infants were seen weekly by the same physiotherapist for one hour. For the remaining nine months the infants were seen every two weeks. Individualised written treatment programs were provided to the parent in a notebook and parents were instructed to incorporate handling, positioning and specific exercise routines into activities of daily living. Parents were requested to record in a notebook on a daily basis whether or not they had carried out activities and any specific problems. The standard follow-up group (n = 59) attended the same neonatal follow-up programs as the intervention group and could be referred to physiotherapy at any time if desired by their paediatrician. Cognitive and motor outcome was measured at 12 months using the Wolanski Gross Motor Evaluation, the Milani-Comparetti Motor Development Screening Test and Griffith Mental Developmental Scales and loco-motor subscale. All outcome assessors were blinded to the child's group allocation.

Resnick 1988 conducted a quasi-randomised controlled trial designed to evaluate a program of hospital and home-based intervention compared with standard follow-up. Infants in the treatment group (n = 21) had an early childhood development specialist deliver two developmental interventions per day while the infant was in NICU. These interventions involved a stimulation program (auditory, visual, vestibular and tactile) and passive movements. After discharge, a nurse visited the home weekly until term corrected age. From term age until 12 months corrected age an early childhood developmental specialist visited the infant and caregiver twice monthly for one - one and half hour sessions. The post-discharge program focused on language enrichment, social skills, cognitive development, parenting activities and muscular development. The standard follow-up group (n = 20) received a full range of services, including social services, physiotherapy and occupational therapy depending on the baby's condition. Outcome assessments were made at six and 12 months of age using the BSID MDI-I and PDI-I.

Rice 1979 conducted the first randomised controlled trial of infant stimulation for preterm infants compared with standard follow-up. The intervention group (n = 15) received a tactile-kinaesthetic stimulation program administered by their mothers that aimed at enhancing the parent-infant relationship and give infants appropriate levels of stimulation. The program consisted of a stroking treatment for 15 minutes; then the infant was rocked and cuddled for another five minutes. The mother was taught to deliver the intervention by a nurse, four times a day for a period of 30 days beginning the day the infant was discharged from hospital. The standard follow-up group (n = 15) received normal discharge information and was visited regularly (number of visits not reported by authors) by the researcher and by other public health nurses in order to provide social reinforcement for appropriate mothering behaviour. Cognitive and motor development was assessed at four months by an assessor blinded to group allocation using the BSID MDI-I and PDI-I.

Yigit 2002 carried out a randomised controlled trial investigating the effects of early physiotherapy intervention compared with standard follow-up for low-risk preterm infants. The authors do not report how many infants were initially randomised to each group; however, they do report that 39 infants were dropped from the study within the first 12 months due to lack of participation. This resulted in 80 infants in the physiotherapy intervention group and 80 infants in the standard follow-up group at 12 months. The infants were registered for the study prior to hospital discharge; however, it is unclear when the study began. The physiotherapy intervention was based upon the principles of infant stimulation and neurodevelopmental therapy. It is reported that infants attended an early intervention program and were also given a home program; however, no further details of either program are given. It is reported that all study infants were seen by the same physiotherapist once a month for the first nine months, then once every three months until 18 - 24 months old. However, it is unclear whether the physiotherapist provided intervention or assessments at these sessions. No further details of the care for the standard follow up group are reported. Motor outcomes were assessed throughout the intervention based on reflexes and motor milestones and the rates of CP were reported. It is not clear whether assessors were blinded to the infant's group allocation.

TYPES OF STUDIES

Twelve of the 16 included studies were randomised controlled trials (Rice 1979; Field 1980; Nurcombe 1984; Piper 1986; Barrera 1986; I.H.D.P. 1990; APIP 1998; Lekskulchai 2001; Nelson 2001; Yigit 2002; Ohgi 2004;Cameron 2005), and four were quasi-randomised controlled trials of early developmental programs (Goodman 1985; Resnick 1988; Bao 1999; Melnyk 2001). The randomisation methods for five of the studies was not clear (Rice 1979; Field 1980; Barrera 1986;Nelson 2001; Yigit 2002). For a summary of the included studies see the table 'Characteristics of Included Studies'.

TYPES OF PARTICIPANTS

All studies included infants who were born preterm. Piper 1986 also included infants who were at high risk of developmental problems due to birth asphyxia. The inclusion criteria for the majority of studies were preterm infants born at < 37 weeks of gestation or born weighing < 2500 g (Rice 1979; Field 1980; Nurcombe 1984; Barrera 1986; I.H.D.P. 1990; Bao 1999; Lekskulchai 2001; Melnyk 2001; Nelson 2001). Four studies included infants born at GA <34 weeks' or born weighing < 1800 g (Goodman 1985; Resnick 1988; Piper 1986; Yigit 2002) and two studies included infants born at GA < 33 weeks (APIP 1998; Cameron 2005). Two studies included only infants born preterm with cerebral injuries (Nelson 2001; Ohgi 2004).

TYPES OF INTERVENTION

The aim of intervention programs varied between the studies with the majority of programs aiming to improve both cognitive and motor outcomes (Rice 1979; Field 1980; Nurcombe 1984; Piper 1986; Barrera 1986; Resnick 1988; I.H.D.P. 1990; APIP 1998; Bao 1999; Nelson 2001). The main aim of the five studies that involved physical therapy was to improve motor outcomes in the intervention group (Cameron 2005; Goodman 1985; Lekskulchai 2001; Piper 1986; Yigit 2002). Melnyk 2001 aimed to improve only cognitive outcomes in the intervention group.

Each study was classified according to the main focus of the intervention program, with possible classifications being "parent-infant relationship", "infant development" or "infant development and parent-infant relationship". Enhancing the parent-infant relationship and infant development were the focus of 4 studies (Nurcombe 1984; Resnick 1988; I.H.D.P. 1990; Nelson 2001). Infant development alone was the focus of seven studies (Rice 1979; Goodman 1985; Piper 1986; Bao 1999; Lekskulchai 2001; Yigit 2002; Cameron 2005). One study focused on enhancing the parent-infant relationship alone (Melnyk 2001). Two studies had two intervention groups and a control group. Barrera 1986 had one group that received a parent-infant focused intervention and the other received an infant development focused intervention, while APIP 1998 had one group that received an infant development intervention and one group that received "parent support". An additional classification of "parent support" was added in for this study.

Although the focus of the intervention programs was to improve cognitive and/or motor outcomes, the theoretical constructs and components of the intervention programs varied greatly. The programs were implemented by doctors (Bao 1999), physiotherapists (Piper 1986; Goodman 1985; Lekskulchai 2001; Yigit 2002; Cameron 2005), nurses (Rice 1979; Nurcombe 1984; Resnick 1988; APIP 1998), intervention therapists (Nurcombe 1984), education professionals (I.H.D.P. 1990; Resnick 1988) or occupational therapists and speech pathologists (Barrera 1986). The theoretical constructs of intervention programs included teaching parents about infant development and milestones (Barrera 1986; Resnick 1988;I.H.D.P. 1990; Bao 1999; Ohgi 2004; Cameron 2005), understanding behavioural cues (Nurcombe 1984; Barrera 1986; Bao 1999; Melnyk 2001; Ohgi 2004; Cameron 2005), infant stimulation (Rice 1979; Field 1980; Nurcombe 1984; Nelson 2001), physical therapy (Goodman 1985; Piper 1986; Lekskulchai 2001; Nelson 2001; Yigit 2002; Cameron 2005), early educational intervention (I.H.D.P. 1990; Bao 1999), and the enhancement of the parent-infant relationship ( Field 1980; Nurcombe 1984; Resnick 1988; I.H.D.P. 1990; Melnyk 2001; Ohgi 2004).

The frequency and duration of the intervention programs ranged from four sessions over approximately one month (Melnyk 2001), to weekly sessions for 12 months, followed by bi-weekly sessions for a further two years (IHDP 1990). The majority of the interventions began post-discharge from hospital (Rice 1979; Field 1980; Goodman 1985; Barrera 1986; Piper 1986; I.H.D.P. 1990;APIP 1998; Bao 1999; Lekskulchai 2001; Yigit 2002), while four studies began when the infant was still an inpatient (Nurcombe 1984; Resnick 1988;Ohgi 2004, Cameron 2005).

TYPES OF OUTCOME MEASURES

Thirteen studies reported on cognitive outcome.
- At infant age (0 - 2 years) seven studies reported cognitive outcome using the BSID-MDI I (Rice 1979; Field 1980; Nurcombe 1984; Barrera 1986; Resnick 1988; I.H.D.P. 1990; Bao 1999), three with the BSID-MDI II (Melnyk 2001; Nelson 2001; Ohgi 2004) and three with Griffiths Development Mental Development Scale (Goodman 1985; Piper 1986; APIP 1998).
- At preschool age (3 - <5 years) three studies reported cognitive outcome using either the Stanford-Binet Intelligence Scale (IHDP 1990) or McCarthy Scales of Children's Abilities (Barrera 1986; Nurcombe 1984).
- At school age (5 - 17 years) four studies reported cognitive outcome using either the WPPSI and WISC-III (IHDP 1990), Kaufman Assessment Battery for Children - Mental Processing Composite (Nurcombe 1984), Griffiths Mental Development Scale (Goodman 1985), and the British Ability Scale (APIP 1998).
- No studies reported the incidence of intellectual impairment.

Fifteen studies reported on motor outcomes using a wide variety of outcome measures at different ages.
- At infant age 13 studies reported motor outcomes using standardised measurement tools including the BSID-PDI-I (Rice 1979; Field 1980; Nurcombe 1984; Barrera 1986; Resnick 1988; I.H.D.P. 1990; Bao 1999 ), BSID-PDI-II (Nelson 2001; Ohgi 2004), Griffiths Locomotor Subscale (Goodman 1985; Piper 1986), Test of Infant Motor Performance (Lekskulchai 2001) and Alberta Infant Motor Scale (Cameron 2005). An additional study (Yigit 2002) reported on the age of acquisition of motor skills such as sitting and crawling.
- No studies reported on motor outcomes at preschool age.
- At school age two studies reported motor outcome using either the Movement ABC (APIP 1998) or the Griffiths Locomotor subscale (Goodman 1985).
- The rate of cerebral palsy was reported by four studies (Goodman 1985; APIP 1998; Yigit 2002; Cameron 2005).
- No studies reported on the rate of developmental co-ordination disorder, however, one study did report on the number of children classified as having a motor impairment (APIP 1998).


Methodological quality of included studies



CONCEALMENT OF ALLOCATION
Of the 16 studies, seven had adequate concealment of allocation (I.H.D.P. 1990; APIP 1998; Lekskulchai 2001; Nurcombe 1984; Ohgi 2004; Piper 1986; Cameron 2005), five studies did not clearly state randomisation methods (Rice 1979; Field 1980; Barrera 1986; Nelson 2001; Yigit 2002) and the remaining studies did not use adequate methods of allocation concealment (Goodman 1985; Resnick 1988; Bao 1999; Melnyk 2001).

BLINDING OF INTERVENTION
Melnyk 2001 was the only study that had a comparison treatment group and, therefore, the only study that may have blinded the participants to the intervention. APIP 1998 had two intervention groups, one that received a developmental intervention and one that received parent support only, to control for the parent support component of an intervention that occurs with any family contact. Barrera 1986 also had two intervention groups; however, this was a comparison of two types of intervention. All other studies involved comparison of the intervention program with standard follow up and, therefore, families were not blinded to the intervention. No studies report masking of the therapists delivering the interventions. Masking of the therapists delivering the interventions is often not feasible unless there is a program similar to the one in the study by Melnyk 2001, where the content of the intervention is delivered through audio-tape and written material.

COMPLETENESS OF FOLLOW UP
The completeness of follow up varied greatly both within and between studies. Eight studies had greater than 85% follow up at one time point (Field 1980;Nurcombe 1984;Piper 1986; I.H.D.P. 1990; APIP 1998; Bao 1999; Lekskulchai 2001; Ohgi 2004). It was difficult to assess the completeness of follow up of some studies since the initial number of subjects participating in the trials was not clearly stated (Rice 1979; Piper 1986; Barrera 1986; Resnick 1988). Studies that began in the NICU had a greater potential for lower follow up rates, since the survival of infants was not always as apparent as when infants were recruited post-hospital discharge. For example, Cameron 2005 began the intervention program in hospital and had only 83% follow up at four months of age, as 7% (five infants) of infants in the study died prior to the first outcome assessment at four months. Goodman 1985 stopped their study after there were 20 infants in four subgroups who had completed the study, despite enrolling 107 infants.

BLINDING OF OUTCOME MEASURES
All studies had at least one blinded outcome measure except for Yigit 2002, where it is unclear whether the assessors were blinded to the subjects' intervention status.

FURTHER QUALITY ASSESSMENT
Seven studies were considered to be of higher quality, scoring at least seven out of 11 using the PEDro scale of methodological quality (Nurcombe 1984; I.H.D.P. 1990; APIP 1998; Lekskulchai 2001; Melnyk 2001; Ohgi 2004; Cameron 2005). All of these studies, except for the study by Melnyk 2001, were randomised trials and, therefore, considered as the higher quality studies in the sensitivity analysis. The highest quality studies were the trials by IHDP 1990 and APIP 1998, which scored 9/11 on the PEDro scale, followed by Lekskulchai 2001; Nurcombe 1984 and Ohgi 2004 which scored 8/11, followed by Melnyk 2001 and Cameron 2005 which scored 7/11. All studies specified their inclusion criteria except for Bao 1999 who only indicated that infants were born at less than 37 weeks GA. All studies had similar prognostic characteristics of intervention and controls at baseline related to perinatal factors such as gestational age; however, some studies reported differences in socio-demographic variables (Nurcombe 1984; APIP 1998). Intention to treat analysis was only specified in the studies by IHDP 1990; APIP 1998 and Melnyk 2001. Piper 1986 and Barrera 1986 did not report point estimates and measures of variability for the preterm infants in their respective studies for cognitive or motor outcomes and, therefore, these studies could not be included in the meta-analysis.

Results


This review found 16 quasi-randomised or randomised controlled trials involving 2408 infants. The primary objective was to determine the effect of early developmental intervention programs post hospital discharge for preterm infants on cognitive and motor development compared with standard medical follow-up at infant (0 - 2 years), preschool (3 - <5 years) and school ages (5 - 17 years).

EARLY DEVELOPMENTAL INTERVENTION VS. STANDARD FOLLOW UP (All studies) (COMPARISON 01)

Cognitive outcome at infant age (Outcome 01.01):
Eight studies reported sufficient data on cognitive outcome to be pooled for meta-analysis. Infants who received early developmental intervention (n = 670) scored a standardized mean DQ of 0.46 SD (95% CI 0.36; 0.57; P < 0.001) higher than infants who received standard follow up (n = 774). Of the 8 studies, only three studies (I.H.D.P. 1990; Bao 1999; Melnyk 2001) showed a statistical significance in favour of the treatment group, while the other studies showed a non-statistical difference in favour of the intervention group (Nurcombe 1984; Goodman 1985; APIP 1998; Nelson 2001; Ohgi 2004). There was significant heterogeneity between the studies (I2 = 63.4%) that reflects the diversity in the early intervention programs but limits the conclusions of these results. An additional four studies did not provide adequate data for meta-analysis. Two of these studies reported a significant difference in favour of the intervention group (Rice 1979; Field 1980) and two found no difference (Barrera 1986; Piper 1986). Rice 1979 reported a significant difference ( P < 0.05) in favour of the intervention group (n = 15) at four months of age compared with the control group (N = 15) on the BSID-I; however, means and standard deviations were not reported. Field 1980 reported the intervention group (n = 27) scored a mean of nine DQ points higher than the control group (n = 25) on the BSID-I at eight months; however, standard deviations were not reported (P < 0.001).

Cognitive outcome at preschool age (Outcome 01.02):
Three studies reported cognitive outcome and these data were pooled for meta-analysis. At preschool age, children who received early developmental intervention as infants (n = 403) had a standardized mean IQ of 0.46 SD (95% CI 0.33, 0.59; P < 0.001) higher than children who received standard follow up (n = 603). Two studies reported a significant difference favouring the intervention group (Nurcombe 1984; I.H.D.P. 1990) and the other study found no difference between groups (Barrera 1986).

Cognitive outcome at school age (Outcome 01.03):
Three studies reported sufficient data for meta analysis (Nurcombe 1984; I.H.D.P. 1990; APIP 1998). At school age, children who received early developmental intervention (n = 484) did not score significantly higher than the children who received standard follow up (n = 627) on IQ measures (IQ; SMD 0.02 SD; 95% CI -0.10, 0.14; P = 0.71). Of the three studies, only Nurcombe 1984 reported a significant difference in favour of the intervention group, however, this study had a small sample size (n = 55). There was significant heterogeneity (I2 = 84.1%) between the studies that limits the conclusions that can be made from these results. Goodman 1985 also reported that there was no difference between intervention and standard follow-up groups when cognitive outcome was measured on the Griffiths GCI.

Motor outcome at infant age (Outcome 01.04):
Six studies provided sufficient data for meta analysis with the Bayley PDI and one with the Griffiths Locomotor Subscale. There was no difference in motor outcome for infants who received early developmental intervention (n = 477) compared with infants who received standard follow up (n = 672), (DQ: SMD 0.05 SD; CI 95% -0.06, 0.17; P = 0.37). None of the six studies found a significant difference between intervention and standard follow-up (Nurcombe 1984; Goodman 1985; I.H.D.P. 1990; Bao 1999; Nelson 2001; Ohgi 2004). An additional seven studies reported motor outcomes; however, these studies were not appropriate for use in meta-analysis (due to type of assessment tool or missing data). Of these studies, Lekskulchai 2001 was the only study that reported a significant difference in favour the intervention group (P < 0.001) using the Test of Infant Motor Performance at four months of age. The remaining six studies found no difference at infant age.

Motor outcome at preschool age (Outcome 01.05):
No studies reported motor outcomes at preschool age.

Motor outcome at school age (continuous variables) (Outcome 01.06):
Goodman 1985 was the only study to report motor outcomes using the Griffith locomotor scale at six years of age and there was no difference in motor outcomes for children who received early intervention (SMD: -0.34; 95%CI -0.91,0.23; P = 0.25).

Motor outcome at school age (dichotomous variables) (Outcome 01.07):
APIP 1998 reported the number of children with motor impairments at five years using the Movement ABC. A cut off equivalent to the upper quartile of the term reference group scores was used to define motor impairment. There was no difference in motor outcome for children who received early intervention (typical RR 1.04; 95%CI 0.78, 1.38; P=0.79).

Rate of cerebral palsy (Outcome 01.08):
Four studies reported rates of cerebral palsy (Goodman 1985; APIP 1998; Yigit 2002; Cameron 2005). There was no difference in the relative risk of cerebral palsy between intervention and standard follow-up (typical RR 0.95; 95% CI 0.57, 1.58; P = 0.84).

SUBGROUP ANALYSIS: GESTATIONAL AGE (COMPARISON 02)

Cognitive outcome at infant age (Outcome 02.01):
The majority of studies used infants born at a wide range of gestational ages and did not report outcomes related to subgroups of gestational age. The only study that investigated the impact of GA on the effect of early developmental intervention was the study by APIP 1998. They reported that infants born at GA<28 (DQ; SMD 0.39; 95%CI -0.06, 0.84; P = 0.09) benefited more from the intervention program than infants born at GA > 28 weeks at infant age (DQ; SMD 0.09; 95%CI -0.25, 0.43; P = 0.60); however, the effect for both subgroups was not statistically significant.

Cognitive outcome at preschool age:
No studies reported outcomes in relation to gestational age.

Cognitive outcome at school age:
No studies reported outcomes in relation to gestational age.

Motor outcome at infant age:
No studies reported outcomes in relation to gestational age.

Motor outcome at preschool age:
No studies reported outcomes in relation to gestational age.

Motor outcome at school age (continuous variables):
No studies reported outcomes in relation to gestational age.

Motor outcome at school age (dichotomous variables):
No studies reported outcomes in relation to gestational age.

Rate of cerebral palsy:
No studies reported outcomes in relation to gestational age.

SUBGROUP ANALYSIS: BIRTHWEIGHT (COMPARISON 03)

Cognitive outcome at infant age (Outcome 03.01):

Three studies investigated the impact of birthweight on the effect of early developmental interventions. However, only one of these studies (Barrera 1986) used the birthweight subgroups of LBW (1500 - 2499 g), VLBW (1000 - 1499 g) and ELBW (< 1000 g). Barrera 1986 carried out subgroup analysis of heavier infants (1500 - 1999 g) and lighter infants (< 1500 g) and reported that infants born at LBW in both intervention groups had significant therapeutic gains compared with the higher birth weight infants at infant age. However, they did not report means and standard deviations. I.H.D.P. 1990 analysed the results of a higher weight subgroup (BW > 2000 g) and a lower weight subgroup (BW < 2000 g) and reported that infants born at higher birth weights benefited more from the intervention program. The heavier infants who received intervention (n = 125) scored 0.75 of a SD (95% CI 0.52, 0.98; P < 0.001) higher than heavier infants who had standard follow up (n = 197), whereas there was no difference in outcome between infants born at lighter birthweights (n = 218) who received intervention or standard follow up (n = 355). This data could not be added to the meta-analysis because the weight categories were different. APIP 1998 reported data for infants born at higher birth weights (> 1250 g) and lighter birth weights (< 1250 g). They found that the lighter birthweight infants who were in the "portage group" (n = 22) scored 5.3 DQ points (95% CI 0.2, 10.2; P < 0.05) higher than infants in the control group (n = 29), whereas there was no difference between infants in the heavier subgroup who had intervention or standard follow up at 12 months. There is conflicting evidence about benefits of early developmental interventions according to birthweight.

Cognitive outcome at preschool age (Outcome 03.02):
The study by I.H.D.P. 1990 was the only study to report outcomes according to birthweight at preschool age. At preschool age the higher birth weight infants who received intervention scored 0.70 of a SD (95% CI 0.47, 0.93: p < 0.001) higher than infants who had standard follow up. Lighter weight infants who received intervention scored 0.33 of a SD (95% CI 0.16, 0.50; P < 0.001) higher than infants who received standard follow-up.

Cognitive outcome at school age:
I.H.D.P. 1990 at school age report that the higher birth weight infants who received intervention were reported to score 4.4 IQ points than heavier infants that received standard follow up, however, there was no difference for the lighter weight group (standard deviations were not reported). At 5 years APIP 1998 did not find any difference between intervention and control groups related to birth weight. There is conflicting evidence about benefits of early developmental interventions according to birthweight.

Motor outcome at infant age:
I.H.D.P. 1990 reported no difference in motor outcome between intervention and control groups who were born at heavier (> 2000 g) or lighter (< 2000 g) weights at infant age. Barrera 1986 also reported no difference in motor outcome between intervention and control groups born at heavier (1500 - 1999 g) or lighter (< 1500 g) weights at infant age.

Motor outcome at preschool age:
No studies reported motor outcomes in relation to birthweight.

Motor outcome at school age (continuous variables):
No studies reported motor outcomes in relation to birthweight.

Motor outcome at school age (dichotomous variables):
No studies reported outcomes in relation to birth weight.

Rate of cerebral palsy:
No studies reported outcomes in relation to birth weight.

SUBGROUP ANALYSIS: BRAIN INJURY (COMPARISON 04)

Cognitive outcome at infant age (Outcome 04.01):
Most of the included studies did not report separate results for infants who had PVL or IVH. Two studies only included infants who were at risk of adverse neurological outcomes due to periventricular leukomalacia and/ or intraventricular haemorrhage (Nelson 2001; Ohgi 2004). These two studies did not demonstrate a significant difference in cognitive outcome of the intervention and control groups at infant age (DQ; SMD 0.5; 95%CI -0.12, 1.13; P = 0.11). The only study that reported the cognitive outcome for infants in the intervention and control groups who had abnormal ultrasound results compared with those with normal ultrasound results was the study by APIP 1998. They reported that infants who were at risk of adverse neurological outcome had a significant benefit from early developmental intervention, whereas those infants who were not at-risk did not show any cognitive benefits from the intervention program.

Cognitive outcome at preschool age:
No studies reported cognitive outcome in relation to brain injury.

Cognitive outcome at school age:
APIP 1998 was the only study that reported outcomes in relation to normal and abnormal ultrasound findings and reported that there was no difference between groups at school age.

Motor outcome at infant age (Outcome 04.02):
The studies by Ohgi 2004 and Nelson 2001 included infants who were at risk of adverse neurological outcomes due to PVL and/ or IVH and did not demonstrate a significant difference between intervention and follow-up groups (DQ; SMD 0.47; 95% CI -0.15, 1.10; P = 0.14). The standard follow-up groups in both of these studies had access to physiotherapy services as required.

Motor outcome at preschool age:
No studies reported motor outcome in relation to brain injury.

Motor outcome at school age (continuous variables):
No studies reported motor outcome in relation to brain injury.

Motor outcome at school age (dichotomous variables):
No studies reported outcomes in relation to brain injury.

Rate of cerebral palsy:
No studies reported outcomes in relation to brain injury.

SUBGROUP ANALYSIS: COMMENCEMENT OF INTERVENTION PROGRAM (INPATIENT VS. POST HOSPITAL DISCHARGE) (Comparison 05)

Cognitive outcome at infant age (Outcome 05.01):
Of the eight studies that reported sufficient data for meta-analysis, four began when the infants were in the NICU (Nurcombe 1984; Melnyk 2001; Nelson 2001; Ohgi 2004) and four began post-hospital discharge (Goodman 1985; I.H.D.P. 1990; APIP 1998; Bao 1999). The programs that began while the infants were inpatients had a significant impact on cognitive outcome at infant age (DQ; SMD 0.55; 95%CI 0.22, 0.89; P = 0.001), as did the programs that commenced post hospital discharge (DQ; SMD 0.45; 95%CI 0.34, 0.57, P < 0.001) compared with standard follow-up. Interventions that commenced in the NICU were statistically homogenous (I2 = 0%), whereas there was significant heterogeneity between the interventions that commenced post hospital discharge (I2 = 83.6%). Interventions that commenced while the infant was in-hospital were more similar in focus of and intensity of intervention, whereas the only interventions to have a significant effect post discharge were the studies by I.H.D.P. 1990 and Bao 1999. The IHDP study had much larger subject numbers and was greater in intensity than any other program.

Cognitive outcome at preschool age (Comparison 05.02):
There was only one study that began in the NICU (Nurcombe 1984) and it reported a significant effect in favour of the intervention group (IQ; SMD 0.79; 95%CI 0.23, 1.35; p = 0.006). Of the two studies that began post-discharge, Barrera 1986 reported no difference between groups, whereas I.H.D.P. 1990 reported a significant difference in favour of the intervention group (IQ: SMD 0.44; 95%CI 0.31, 0.57; p < 0.0001). Due to the much larger sample size of the study by I.H.D.P. 1990 (n = 908) compared to the study by Barrera 1986 (n = 45) there was an overall effect in favour of the intervention group; however, there is significant heterogeneity (I2 = 58%) that limits the conclusions of these results.

Cognitive outcome at school age (Outcome 05.03):
The study by Nurcombe 1984 is the only study that began in the NICU and reported school age outcomes. This study reported that school age children who had intervention that began as an inpatient had a significantly higher IQ scores than those infants who received standard follow up (IQ; SMD 1.02; 95% CI 0.45, 1.59, P < 0.001). The two studies that began post-hospital discharge did not demonstrate a difference between outcomes. The sample of size of the study in which interventions began in the NICU (n = 55) is much smaller than the sample size of the studies where interventions that began post-hospital discharge (n = 1056).

Motor outcome at infant age (Outcome 05.04)
Of the studies that provided sufficient data for meta-analysis, three began when the infants were in the NICU (Nurcombe 1984; Nelson 2001; Ohgi 2004) and three began post- hospital discharge (Goodman 1985; I.H.D.P. 1990; Bao 1999). The programs that began post-hospital discharge had a slightly greater impact on motor outcome at infant age (DQ; SMD 0.06; -0.06, 0.19; P = 0.32) than the programs that began while the infants were in the NICU (DQ; SMD -0.03; 95%CI -0.39, 0.33, P = 0.88); however, neither group showed a significant effect.

Motor outcome at preschool age (outcome 05.05):
No studies reported motor outcome at preschool age.

Motor outcome at school age (continuous variables) (Outcome 05.06):
The study by Goodman 1985 began post-hospital discharge and did not show any difference between groups.

Motor outcome at school age (dichotomous variables) (Outcome 05.07):
The study by APIP 1998 was the only study to report rates of motor impairment and there was no difference between groups.

Rate of cerebral palsy (Outcome 05.08):
The study by Cameron 2005 was the only study to begin in the NICU and report rates of CP and there was no difference between groups. The three studies by Goodman 1985; APIP 1998 and Yigit 2002 began post-hospital discharge and also found no difference in rates of CP between groups.

SUBGROUP ANALYSIS: FOCUS OF INTERVENTION (PARENT-INFANT RELATIONSHIP VS. INFANT DEVELOPMENT VS. COMBINATION) (COMPARISON 06)

Cognitive outcome at infant age (Outcome 06.01):
The primary focus of one study was on the parent-infant relationship (Melnyk 2001). Infants who received early intervention that focused on the parent- infant relationship alone scored a standardised mean DQ of 0.73 SD (95%CI 0.11, 1.36, P = 0.02) higher than infants who received standard follow up. Three studies primarily focused on the infants development (Goodman 1985; APIP 1998; Bao 1999). Of these three studies, only one study reported a significant difference in favour of the intervention group (Bao 1999), while the other two studies reported a trend in favour of the treatment group. Overall, infants who received intervention that focused on infant development scored a standardised mean DQ of 0.39 SD (95%CI 0.17, 0.61; P < 0.001) higher than infants who received standard follow up. However, there was significant heterogeneity (I2 = 87.2) between these studies that reflects the diversity in early intervention programs that focus on the infants development. There were four studies that focused on both the parent-infant relationship and infant development (Nurcombe 1984; I.H.D.P. 1990; Nelson 2001; Ohgi 2004). The I.H.D.P. 1990 was the only study to report a significant difference in favour of the intervention group, whereas the other studies reported a trend in favour of the treatment group. Overall, infants who received intervention that focused on both parent-infant relationship and infant development scored a standardized mean DQ of 0.51 SD (95%CI 0.38, 0.64; P < 0.001) higher than infants who received standard follow up at infant age. The study by APIP 1998 investigated the effect of parent support or infant development (with parent support) compared to standard follow-up and reported no difference between groups.

Cognitive outcome at preschool age (Outcome 06.02):
At preschool age there were two studies (Nurcombe 1984; I.H.D.P. 1990) that focused on both the parent-infant relationship and infant development together and one study (Barrera 1986) that had two intervention groups. In the study by Barrera 1986, one treatment group focused on infant development and the other intervention group focused on parent-infant relationship. Only the pooled results of the two different intervention groups were reported by Barrera 1986 and, therefore, were not included. Infants who received intervention that focused on both parent-infant relationship and infant development scored a standardized mean IQ of 0.48 SD (95%CI 0.35, 0.61; P < 0.001) higher than infants who received standard follow up at preschool age.

Cognitive outcome at school age (Outcome 06.03):
At school age there were two studies that had focused on parent-infant relationship and infant development (Nurcombe 1984; I.H.D.P. 1990) and one study that had two intervention groups (APIP 1998). The two studies that focused on both the parent-infant relationship and infant development had different results, with the study by I.H.D.P. 1990 showing no effect and the study by Nurcombe 1984 showing a significant different in favour of the intervention group. There is significant heterogeneity (I2 = 96%) due to the difference in sample size and outcomes of these studies. Overall there was no significant difference at school age in the cognitive development of children who received any of the four types of early intervention programs compared with children who received standard follow up as infants.

Motor outcome at infant age (Outcome 06.04):
Studies that reported on motor outcome at infant age either focused on both parent-infant relationship and infant development (Nurcombe 1984;I.H.D.P. 1990; Nelson 2001; Ohgi 2004) or on the infants' development alone (Goodman 1985; Bao 1999). Programs that focused on infant development had a slightly greater impact on motor outcome at infant age (DQ: SMD 0.26 SD; 95%CI -0.05, 0.58; P = 0.1) than those that focused on the parent-infant relationship and infant development together (DQ: SMD 0.02 SD; 95%CI -0.11, 0.15, P = 0.76); however, the effect of both groups was not significant.

Motor outcome at preschool age:
No studies reported on motor outcome at preschool age.

Motor outcome at school age (continuous variables) (Outcome 06.05):
The study by Goodman 1985 focused on infant development and there was no significant difference between groups.

Motor outcome at school age (dichotomous variables):
The study by APIP 1998 focused on infant development and reported no difference between groups.

Rate of cerebral palsy (Outcome 06.06):
The four studies that reported rates of CP focused on infant development and reported no difference between groups (Goodman 1985; APIP 1998;Yigit 2002; Cameron 2005).

SUBGROUP ANALYSIS: QUALITY OF STUDIES (HIGHER vs LOWER) (COMPARISON 07)

Cognitive outcome at infant age (Outcome 07.01):
Four of the studies included in meta-analysis were of high quality (Nurcombe 1984; I.H.D.P. 1990; APIP 1998; Ohgi 2004) and reported a significant treatment effect supporting the intervention group (IQ; SMD 0.44 SD; 95% CI 0.32, 0.56; P < 0.001). There was less heterogeneity between the higher quality studies, than when all studies were included in the meta-analysis.

Cognitive outcome at preschool age (Outcome 07.02):
At preschool age two (Nurcombe 1984; I.H.D.P. 1990) of the three studies were high quality; again, a significant treatment effect supporting the intervention group was demonstrated (IQ; SMD 0.48 SD; 95%CI 0.35, 0.61; P < 0.001).

Cognitive outcome at school age (Outcome 07.03):
At school age the studies were all of high quality and, therefore, no subgroup analysis was necessary.

Motor outcome at infant age (Outcome 07.04):
Three studies were of high quality (Nurcombe 1984; I.H.D.P. 1990; Ohgi 2004) and reported no significant difference between groups (SMD 0.01 SD; -0.12, 0.14, p = 0.87).

Motor outcome at preschool age:
No studies reported motor outcomes.

Motor outcome at school age (continuous) (Outcome 07.05):
There were no high quality studies that reported motor outcomes.

Motor outcome at school age (dichotomous) (Outcome 07.06):
APIP 1998 was the only high quality study to report rates of motor impairment and there was no difference between groups.

Rate of cerebral palsy (Outcome 07.07):
APIP 1998 and Cameron 2005 were the only two high quality studies to report rates of cerebral palsy and found no difference between groups.

Discussion


The primary goal of this current review was to determine the effect of early developmental intervention programs post-discharge from hospital for preterm infants on cognitive and motor development compared with standard medical follow-up at infant (0 - 2 years), preschool (3 - < 5 years) and school age (5 - 17 years). There were 16 randomised or quasi randomised controlled trials of early developmental interventions for preterm infants included in the review; however, not all studies provided sufficient data to be included in the meta-analysis. Meta-analysis demonstrated a treatment effect for early intervention on cognitive outcomes at infant and preschool age of approximately half a standard deviation on standardised cognitive tests. The size of the effect is considered to be of clinical significance. Meta analysis indicates that intervention did not have a significant effect on motor outcome up to two years of age, or in the two studies that reported on longer-term motor outcomes.

There has been considerable debate as to how best to reduce or prevent long term impairments and improve the cognitive and motor outcomes for children born preterm. To our knowledge, this is the first reported meta-analysis of early developmental interventions post-discharge from hospital for preterm infants. Blauw-Hospers 2005 recently published a systematic review investigating the effects of early intervention on motor outcomes for all infants at risk, or with developmental motor disorders. They defined early intervention as "multidisciplinary services provided to children from birth to five years of age to promote child health and well-being, enhance emerging competencies, minimize developmental delays, existing or emerging disabilities, prevent functional deterioration, and promote adaptive parenting and overall family functioning". They reported that NIDCAP, an inpatient program using interventions that focus on specific motor training such as treadmill training or general development programs that aim to increase the child's exploration, have a positive effect on motor outcome for high risk infants. Blauw-Hospers 2005 systematic review was broader than this review since it included all early intervention programs that began from birth to 18 months for all infants at risk for, or with developmental motor disorders and, therefore, it was not appropriate for meta-analysis to be performed. They did not include preterm infants at "low risk" of developmental motor disorders and, therefore, many of the studies included in this review are not included by Blauw-Hospers 2005. The inclusion criteria for early developmental interventions programs in this review was very specific in an attempt to limit the variability in intervention programs. As Blauw-Hospers 2005 reported in their systematic review, the term "early intervention" can be understood in two-ways, intervention that occurs early in life, or intervention that occurs early in the expression of the condition. We have only included intervention programs that began early in life, within the first 12 months when the brain is highly plastic (Hadders-Algra 2001). These intervention programs are more likely to be prevention programs since specific problems that require "treatment" are less likely to be apparent.

There are a number of limitations of this review and in the performance of meta-analysis with studies on early developmental intervention. The programs of early developmental intervention that the "treatment groups" received in this review varied in theoretical content, environmental context, intensity and duration of follow up. This resulted in significant levels of heterogeneity when pooling cognitive outcomes and, therefore, limits the conclusions that can be drawn from these results. Subgroup analysis was useful to investigate areas of variation between the trials. The majority of included studies recruited infants in the 1980s when the mean gestational age at entry was older than studies conducted in the 1990s. Advances in perinatal care mean that medical interventions received by infants may not be the same across studies, and pooling results across eras may result in comparing different groups of infants with respect to outcomes. However, rates of neurosensory morbidity have remained relatively constant over the past two decades, compared with rates of mortality that have decreased (Doyle 2004). To account for the difference in gestational age and birthweights of infants across studies, subgroup analysis was planned for both of these factors. The majority of studies did not report the outcomes according to gestational age or birthweight and, therefore, subgroup analysis was limited. I.H.D.P. 1990 reported that infants who were born between 2000 - 2500 g had a greater response to intervention. The studies by Barrera 1986 and APIP 1998 found the opposite response, with infants born at very low birth weights having a greater cognitive response at infant age. No studies reported a difference in motor outcome between intervention and control groups related to gestational age or birthweight. The presence of brain injury is also important to consider when assessing the effect of intervention for preterm infants. Only two studies included infants with periventricular leukomalacia or intraventricular haemorrhage and these studies reported no difference in cognitive and motor outcome between intervention and control groups (Nelson 2001; Ohgi 2004). The standard follow-up group in both of these studies received physiotherapy as required, which may have affected the motor outcomes of these infants. The study by APIP 1998 reported that infants with abnormal cranial ultrasound findings had a positive cognitive response to intervention, whereas there was no difference in outcome between the infants who had intervention or standard follow up with normal cranial ultrasound. The other studies did not report whether they excluded infants with abnormal imaging, PVL or IVH and, therefore, could not be included in the subgroup analysis.

Other perinatal variables such as socio-economic status (SES) are also important to consider when comparing different studies. The studies by Rice 1979 and Field 1980 only included infants who were born to mothers of low SES. Both of the studies by APIP 1998 and Nurcombe 1984 had significant differences in SES between groups despite randomisation. The control group in the study by APIP 1998 had a higher percentage of mothers who were educated beyond 16 years of age, were in non-manual occupations and had use of a car compared with the intervention groups. All three of these variables were independently associated with Griffiths quotients and may explain part of the variance in outcome. Using a regression model to account for the SES differences between groups, the authors report an improvement in IQ scores of both the portage and parent advisor groups compared with the standard follow up group. The study by Nurcombe 1984 reported that results were adjusted to account for the difference in SES between groups. The studies by Field 1980 and Rice 1979 included only families of low SES, which limits the generalisability of the results to the general population.

Two types of subgroup analyses were performed in relation to the types of intervention programs. The first subgroup analysis compared interventions that were begun while the infant was still in hospital with those that were begun post-hospital discharge. Both types of programs had a significant effect on cognitive outcome at infant and preschool age. At school age, the only study to demonstrate a difference in favour of the intervention group began as an inpatient; however, this study (Nurcombe 1984) had small subject numbers and low follow-up rates. The interventions that began when the infants were inpatients were homogenous, since they all focused on the parent-infant relationship and enhancing the parents' abilities to read and respond appropriately to their infants' behavioural cues. There was significant heterogeneity between the interventions that occurred post-hospital discharge, which can be explained by the variety of intervention programs. Interventions that began post-hospital discharge had a greater impact on motor outcome in infants; however, the effect was not significant. The second subgroup analysis related to the focus of the intervention program being the parent-infant relationship, infant development or both. Interventions that had a component that focused on the parent-infant relationship had a greater impact on cognitive outcome at infant and preschool ages than interventions that focused on infant development or parent support alone. Although interventions that focused on infant development alone had a greater impact on motor development, the effect was not significant and the studies were of lower quality.

This review has compared early developmental interventions with standard follow-up; however, details of standard follow-up were not always reported. Many of the studies that reported details of follow-up reported that infants and families still had access to developmental services such as physiotherapy and social services. Although there is limited evidence for some of these services (Wang 2006), it may be unethical to prevent access to them. The services received by the standard follow-up group may improve their outcomes and, therefore, a treatment effect may be more difficult to detect. For example, the standard follow-up group in five studies (Goodman 1985; Piper 1986; Resnick 1988; Nelson 2001; Ohgi 2004) received physiotherapy in accordance with the institutions' policies, which may have influenced the motor outcomes of the standard follow-up group. Contamination of the control and intervention groups with additional treatments or other therapies is also problematic, as families of preterm infants may seek additional treatments for their child who is perceived to be "at risk" of developmental difficulties. None of the studies reported the "dosage" of other interventions received by the standard follow-up group or performed analysis in relation to services accessed by the follow-up group.

The amount of intervention received by infants and families in the treatment groups varied greatly between studies (from 4 - 336 sessions) and within studies. The relationship between intervention dosage and compliance with the intervention is important. Compliance may be estimated by attendance at designated visits or by therapists' recordings of the impressions of compliance. The study by I.H.D.P. 1990 reported that higher levels of participation were related to better outcomes on the MDI and IQ scores at 24 and 36 months. In the study by Cameron 2005, a better motor outcome was reported at four months for the families with good compliance. However, subjective measurement of compliance by the study investigators may be biased and should be monitored independently.

There was a wide variety of measurement tools used in the studies, restricting the ability to pool data. There were fewer measurement tools utilized for assessing cognitive development than those used for assessing motor development, which made it possible to pool cognitive data for meta-analysis at different ages. The effect of early intervention on motor development could only be subjected to meta-analysis at infant age using the BSID-PDI or the Griffiths locomotor subscale and there was no treatment effect of intervention with either assessment. The BSID-PDI and Griffiths are broad measures of motor development and do not specifically evaluate minor motor problems, which are common in preterm infants. It is possible that these studies either have no effect on motor outcome or the measures were not sensitive enough to detect the effects of intervention on motor problems. Other motor measurement tools that assess movement quality and motor performance in more detail such as the AIMS, TIMP and Movement ABC were used by individual studies; however, it was not appropriate to pool these data for meta-analysis. The diversity of motor assessment tools and the lack of data at older ages limits the ability to compare results between studies. For example, the studies that relate to physical therapy all had different outcome measures. The meta-analysis of the long term effects of early developmental interventions on motor and cognitive outcome was limited not only by the small number of studies, but the low rates of follow up of these studies. The study by Nurcombe 1984 is the only study to report a treatment effect at school age; however, it is a relatively small study (n = 78) with only 71% children assessed at 9 years. The age of assessment of cognitive and motor outcomes may also be important. Interestingly, only five of the 11 studies that reported on cognitive outcome up to one year showed a significant effect favouring the intervention group. However, at two years, two studies that had previously shown no difference at 12 months between treatment and control groups did have a significant effect favouring the intervention group. This may reflect the reliability and validity of the outcome measures at one year compared with two years, or that the effect of intervention is more apparent at two years.

The meta-analysis in this review has examined motor and cognitive outcomes using standardised assessments. In the past five years there has been a shift in how disability is measured. Instead of measuring disability using a medical framework, disability is measured using functional outcome, activity limitations and participation restrictions as part of a social and environmental framework (Simeonsson 2003). The World Health Organization now uses the International Classification of Functioning, Disability and Health rather than the old model of International Classification of Impairments, Disabilities and Handicaps (WHO 2001). It is possible that early intervention may not be able to change the physical outcome of a motor disorder, such as cerebral palsy; however, it may change how affected individuals function and participate in society. Intervention may affect motor outcome in a functional way. For example, the infant may be able to play outside on uneven surfaces, whereas without intervention the child may be restricted to indoor activities. Outcome measures such as the BSID-PDI and the Griffiths locomotor subscale measure global motor development in a controlled environment. The controlled environment where these assessments occur is often a quiet room set up for the infant or child to perform at their best. The skill level achieved in this setting may not be achievable in another setting, so it is important that their skills are assessed out of the testing situation and in their own specific environments. This review has only included traditional outcome measures of motor and cognitive outcome; however, as functional measures become more widely used it will be important to include these.

The methodological quality of the included studies was variable with only six of the 16 studies considered to be of high quality, that is being an RCT with a PEDro score greater than seven. Sensitivity analysis was performed to assess the effect of study quality on cognitive and motor outcomes. When only the higher quality studies were included in the meta-analysis there was still an intervention effect on cognitive outcome at infant and preschool age. There are some limitations to conducting intervention trials of developmental interventions. It is not feasible to mask the person implementing the intervention or the recipient of the intervention (in this case the mother and baby) unless a comparison group providing an alternative intervention is used instead of a control group. Only one study had a comparison treatment instead of a non-treatment control group (Melnyk 2001); however, this was not a randomised trial. When interventions are delivered, whether they focus on infant development or the parent-infant relationship, there is a component of parental support that may affect outcome. The study by APIP 1998 was the only study to control for parent support by having the three groups, one that received an infant development program, one that received parent support only, and a control group. The methodology quality assessments used in this review did not take sample size into account. Sample size is important when assessing the outcomes of individual programs since some studies may not have had enough power to demonstrate a difference between groups. The study by I.H.D.P. 1990 was by far the largest, with 985 infants included, followed by the study by APIP 1998 with 308 infants. The significant results of the I.H.D.P. 1990 and the large sample size influenced the overall results of the meta-analysis. The study by I.H.D.P. 1990 is very different from the other early developmental programs in frequency and duration of intervention, and this should be considered when interpreting the results of this review.

This systematic review has not investigated which aspects of early developmental interventions affect outcome more such as whether it is the optimal duration of intervention, the best age to begin the intervention, the optimal frequency, or the focus of intervention. Further research is needed to determine the components of intervention that are most effective based on cost and benefits. The I.H.D.P. 1990 was estimated to cost US$15,146 per year per child. The investigators suggest this value could be reduced to US$8806 if the centres were located in the community and teacher-child ratios were decreased. However, this is still a costly intervention compared with the study by Nurcombe 1984, which had better long term outcomes and would cost less to implement since there were only 11 sessions over four months compared with the intensive program over three years received by infants in the intervention group of the I.H.D.P. 1990 study.

Reviewers' conclusions



Implications for practice


Meta-analysis demonstrated that early developmental interventions post-hospital discharge for preterm infants have a significant impact on cognitive development at infant and preschool age. However, there is currently little evidence of an effect of early developmental interventions post-hospital discharge on motor development at infant age. At school age there have only been three studies that investigated the long term effects of intervention on cognitive outcome and two that investigated the effect on motor outcome, none of which demonstrated any substantial difference in long term outcomes. Interventions that focus on the parent-infant relationship, along with infant development, have the greatest impact on cognitive development in the short to medium term. The heterogeneity between early developmental intervention programs in regard to content, focus and intensity limit the conclusions that can be drawn from this review.

Implications for research


Further high quality randomised controlled trials are needed to identify the effective components of successful early development interventions for preterm infants. Greater selectivity of high risk populations may identify those infants who may benefit most from intervention. Targeting intervention to address the needs of the infant and family more specifically may reduce costs and increase effectiveness. Further research is also required on the effects of intervention programs on motor outcomes since only limited conclusions can be drawn from this review. There is a need for more high quality randomised controlled trials of intervention with long term follow up studies focusing on both motor and cognitive outcomes for preterm infants. Measurement tools need to be sensitive enough to detect change in motor performance and to identify minor neurological problems. This review has not investigated the effects on behaviour, parental outcomes (such as depression and anxiety), function, activity levels or participation, which may also be influenced by early developmental intervention programs.

Acknowledgements


Professor Jenny Keating, School of Primary Health Care, Monash University for her support and guidance at the commencement of this review.
Dr Klebenov for 12 and 24 month motor data from the IHDP.
Dr Ohgi for clarifying follow-up rates of participants.

Potential conflict of interest


All authors involved in this review are currently involved in a randomised controlled trial of intervention with preterm infants.

Characteristics of included studies

StudyMethodsParticipantsInterventionsOutcomesNotesAllocation concealment
APIP 1998Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: yes at 12 months* (86%)
Concealment of allocation: yes (opaque envelopes)
309 infants
Inclusion criteria: GA <33 weeks
Exclusion criteria: English not first language and did not live within the study area
Characteristics: mean GA for the 2 treatment groups (Portage and Parent Advisor) and standard follow-up group was 31, 30 and 31 weeks respectively		Two intervention programs were used, "Portage" and "Parent advisor" to control for the support aspect of Portage.
Portage group (n=111): infant development and parent support
Parent advisor group (n=99): parent support
For data analysis the Portage and parent advisor groups were included together as the intervention group.
Standard follow-up group (n=99): details of standard follow up for the control group are not reported		COGNITIVE:
- Infant age: Griffiths GCI (24 months)
- Preschool age: none
- School age: British Ability Scales 2nd Edition (5 years)

MOTOR
- Infant age: incidence of cerebral palsy
- Preschool age: none
- School age: Movement ABC (5 years)

The control group had a higher percentage of mothers who were educated beyond 16 years of age, were in non-manual occupations and had the use of a car compared with both intervention groups.A
Bao 1999Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: unclear as it is not stated if there were any infants who withdrew from the study
Concealment of allocation: the methods used to randomise the infants are not stated and therefore allocation concealment is unclear		103 infants
Inclusion criteria: GA 28-37 weeks
Exclusion criteria: not reported
Characteristics: mean GA for the intervention and standard follow-up groups was 33.9 (SD 1.8) weeks and 34.2 (2.1) respectively
Intervention group (n=52): infant development
Standard follow-up group (n=51): details are not described
COGNITIVE
-Infant age: BSID-MDI-I (18 and 24 months)

MOTOR
-Infant age: BSID-PDI-I (18 and 24 months)

C
Barrera 1986Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: no at 4,8,12 and 16 months (73%) and 5 years (56%)
Concealment of allocation: unclear (infants were block randomised according to sex, birth weight, socio-economic status and pre-/ post-natal complications, however, it is unclear what measures were taken to ensure concealment of allocation)		80 infants
Inclusion criteria: BW <2000 g or GA </= 37 weeks and discharged home from hospital with a good prognosis for survival
Exclusion criteria: life threatening illnesses or did not live within the study area
Characteristics: The mean GA for all groups was 33 weeks
Two intervention programs were compared to standard follow-up.
Parent-infant intervention (n=22*): parent-infant relationship
Developmental programme (n=16*): infant development
For data analysis the two parent-infant and developmental groups were included together as the intervention group.
Standard follow-up (n=21*): home visits for assessment purposes only. During these visits the examiner answered any questions parents had related to their child's development, reading material or community resources.		COGNITIVE
- Infant age: BSID-MDI-I (4, 8, 12 and 16 months)
- Preschool age: McCarthy Scales of Children's Abilities - general cognitive index (4.5-5 years)

MOTOR
- Infant age: BSID-PDI-I (4, 8, 12 and 16 months)

*Twenty-one infants did not complete the study. The number of infants in each group listed is for infants who completed the 1-year program, as the number of infants randomised to each group at the beginning of the study is not stated. It is reported that there was no differences in reasons for withdrawing from the study between groups.B
Cameron 2005Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: no at 4 months (83%)
Concealment of allocation: adequate (toss of coin)		72 infants
Inclusion criteria: BW <1500 g and GA<32 weeks
Exclusion criteria: required oxygen at 4 months corrected age, severe hydrocephalus requiring a shunt, demonstrated signs of drug withdrawal or with history of social problems
Characteristics: mean GA for the treatment and standard follow-up groups was 28.7 (SD = 2.4) and 29.6 (SD = 2.0) respectively		Intervention group (n=34): infant development
Standard follow-up group (n = 38): no physiotherapy intervention or other placebo intervention was given
COGNITIVE
- none

MOTOR
-Infant age: Alberta Infant Motor Scale (4 months) and incidence of cerebral palsy (18 months)

A
Field 1980Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: yes at 8 months (85.5%)
Concealment of allocation: unclear		60 infants
Inclusion criteria: BW <2500 g and GA<37. All infants were born to African American teenage mothers with low socio-demographic status.
Exclusion criteria: serious neonatal complications that would require long periods of intensive care and early separation
Characteristics: mean GA of the intervention and standard follow-up groups was 35.5 and 35.3 weeks respectively		Intervention group (n=30): infant development and parent-infant relationship
Standard follow up (n=30): no details on standard follow up are given		COGNITIVE
- Infant age: BSID-I MDI (8 months)

MOTOR
- Infant age: BSID-I PDI (8 months)

B
Goodman 1985Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: no at 12 months (75%) and 6 years (61%)
Concealment of allocation: inadequate (infants were alternatively allocated to treatment or control groups)		107 infants*
Inclusion criteria: BW <1700 g or GA <34 weeks.
Exclusion criteria: infants who were considered as neurologically impaired were excluded from the study as they were all given intervention.
Characteristics: mean GA of the intervention and standard follow-up groups was 30.9 (SD =1.9) and 31 (SD = 1.8) respectively		Intervention group (n=40): infant development
Standard follow up group (n=40): infants in both groups (intervention and standard follow-up) attended a follow up clinic at 6 weeks, 3, 6, 9 and 12 months' corrected age. This clinic was staffed by a neonatologist, physiotherapists, speech and hearing therapist, ophthalmologists, public health nurses and social workers. It is not clear how much "intervention" was provided to infants in the control group during these visits.		COGNITIVE
- Infant age: Griffiths Mental Development Scale (12 months)
- School age: Griffiths Mental Development Scale 2 (6 years)

MOTOR
- Infant age: the Griffiths Developmental Quotient (locomotor sub scale) (12 months)
- School age: the Griffiths Development Quotient (locomotor sub scale), neurological examination to assess the incidence of cerebral palsy and clumsiness/ co-ordination problems (6 years)

* Prior to commencing study the authors stated that intention was to study 40 infants in each group. To allow for attrition, 107 infants were enrolled in to the study at 3 months. However, the formal study ceased when 80 infants were followed up to 3 months.C
I.H.D.P. 1990Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: yes at 12 months (90%), 24 month (89%), 36 month (93%) and 8 years (89%), however, not at 5 years (82%)
Concealment of allocation: adequate (adaptive randomisation method)		985 infants
Inclusion criteria: BW =/<2500 g or GA < 37 weeks
Exclusion criteria: congenital abnormalities, genetic disorders still hospitalised or too sick to participate in the program at term
Characteristics: mean GA for the intervention and standard follow-up groups was 33 weeks		Intervention group (n=377): infant development and parent-infant relationship
Standard follow-up group (n=608): both groups received medical, developmental and social assessments, with referral to other services as indicated
COGNITIVE
- Infant age: BSID-I MDI (12 and 24 months)
- Preschool age: Stanford-Binet Intelligence Scale (36 months)
- School age: WPPSI (5 years) and WISC-III (8 years)

MOTOR
- Infant age: BSID-I PDI (12 and 24 months)

Additional data (means and SD for 12 and 24 months for MDI and PDI) were obtained from authors for meta-analysis.
A
Lekskulchai 2001Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: yes at 1, 2, 3 and 4 months (86%)
Concealment of allocation: adequate (intervention or control slip was taken blindly from a container)
84 infants
Inclusion criteria: BW GA<37 weeks considered to be "at-risk" of adverse neurological sequelae assessed with the TIMP at 40 weeks post conceptional age.
Exclusion criteria: congenital abnormalities, genetic disorders, surgery or developed serious illness including hydrocephalus and periventricular haemorrhage (grade III) were excluded prior to randomisation.
Characteristics: mean GA for the intervention and standard follow-up group was 31.9 (SD=2.4) and 32.3 (SD=2.2) weeks respectively		Intervention group (n=43): infant development
Standard follow-up (n=41): all families (intervention and standard follow-up) were assessed (using the TIMP) by a research assistant 1, 2, 3 and 4 months and were able to discuss any concerns with principal researcher.		COGNITIVE
- None

MOTOR
- Infant age: Test of Infant Motor Performance (1, 2, 3 and 4 months)

Unable to use data in meta-analysis as the outcome measure (TIMP) was not appropriate to pool with other outcome measures.A
Melnyk 2001Blinding of intervention: yes
Blinding of outcome assessments: yes
Completeness of follow-up: no at 3 and 6 months (76%)
Concealment of allocation: inadequate (infants were randomised according to date admitted to hospital)		55 infants
Inclusion criteria: BW <2000 g and GA <34 weeks
Exclusion criteria: perinatal hypoxia or abnormal ultra-sound, with no congenital or chromosomal abnormalities or metabolic disease
Characteristics: mean GA for the intervention group and standard follow-up groups was 31.3 (SD=2.2) and 32.0 (SD=1.6) weeks respectively		Intervention group (n=26): parent-infant relationship
Standard follow-up group (n=29): received a placebo intervention which also consisted of audio-taped and written information in relation to hospital services, routine discharge information and education about immunisations.		COGNITIVE
- Infant age: Bayley Scales of Infant Development-MDI II (3 and 6 months)

MOTOR
- None

This was the only study to have a comparison group who received a placebo intervention.C
Nelson 2001Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: no at 12 months (70%)
Concealment of allocation: unclear		37 infants
Inclusion criteria: BW <1500 g and GA 23-26 weeks (group 1) or born between 23-32 weeks and diagnosed with PVL or grade III IVH (group 2)
Exclusion criteria: not medically stable, required mechanical ventilation or not feeding at the commencement of the study (intervention commenced while the infants were in the NICU), intra-uterine growth restriction, chromosome disorders and necrotizing enterocolitis.
Characteristics: mean GA for the intervention and control groups for group 1 was 25.6 (SD=1.1) and 25.6 (SD=1.5) and for group 2 was 27.2 (SD =2.9) and 27.3 (SD=2.4) weeks respectively.
The intervention group (n=21): infant development and parent-infant relationship
Standard
follow-up (n=16): all infants (intervention and standard follow-up groups) received developmental care as inpatients and a physiotherapy program post hospital discharge.		COGNITIVE
- Infant age: BSID-II MDI (12 months)

MOTOR
- Infant age: BSID-II PDI (12 months)

B
Nurcombe 1984Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: yes at 12 months (95%), however, longer term follow up was not adequate at 24, 36 and 48 months (68%) and at 7 and 9 years (71%).
Concealment of allocation: adequate (infants were randomised by toss of coin, ensuring allocation concealment)		78 infants
Inclusion criteria: BW <2250 g and GA <37 weeks
Exclusion criteria: congenital abnormalities, severe neurological defects, multiple births and single mothers
Characteristics: mean GA for the treatment and standard follow-up groups was 32.3 (SD=2.4) and 31.9 (SD=2.4) weeks respectively. There was a significant difference in the SES of the intervention and standard follow-up groups despite randomisation.		Intervention group (n=38): infant development and parent-infant relationship
Standard follow-up (n=40): no details of the standard follow-up are reported

COGNITIVE
Infant age: BSID-I MDI (6, 12 and 24 months)
Preschool age: McCarthy Scales (3 and 4 years)
School age: Kaufman Assessment Battery for Children (7 and 9 years)

MOTOR
Infant age: BSID-I PDI (6, 12 and 24 months)

Reported data has been adjusted to control for socio-economic status of familiesA
Ohgi 2004Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: yes at 12 months (96%)
Concealment of allocation: yes (method of minimisation)		24 infants
Inclusion criteria: BW <2500 g who were at high-risk of neurological problems due to PVL and/or IVH (as shown by ultrasound)
Exclusion criteria: multiple births, born in another town and returned there
Characteristics: Mean GA for treatment and followup groups were 30.3(SD=3.3) and 30.3(SD=2.7) weeks respectively. There were no significant differences between groups for infant and maternal factors, social factors, distribution of diagnoses and severity of injury.		The intervention group (n=12): infant developmental and parent-infant relationship
Standard follow-up (n=12): all infants in the control and intervention groups attended follow up clinics and were referred to developmental services if infants presented with signs of neurological dysfunction or developmental delay.		COGNITIVE
Infant age: BSID-II MDI (6 months)

MOTOR
Infant age: BSID-II PDI (6 months)

A
Piper 1986Multi centre randomised trial
Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: yes at 12 months* (86%)
Concealment of allocation: yes (opaque envelopes)
134 infants (115 LBW infants)
Inclusion criteria: BW <1500 g (group 1) or birth asphyxia and seizures regardless of GA (group 2).
Characteristics: mean GA for the intervention and control groups was 29.9 (SD=3.8) and 29.3 (SD=3.7) weeks respectively.		Intervention group (n=56): infant development
Standard follow-up (n=59): all infants attended neonatal follow-up programs and infants in the standard follow-up group could be referred to physiotherapy at any time if indicated by their paediatrician. Seven control infants received physical therapy intervention after 6 months of age.		COGNITIVE
-The Griffiths Mental Development Scale (12 months)

MOTOR
-Infant age: The Wolanski Gross Motor Evaluation, The Wilson Reflex Profile, The Milani-Comparetti Motor Development Screening Test, The Griffiths Mental Development Scale (locomotor subscale) (12 months)

*The study involved a group of preterm infants and a group of infants at risk of neurological sequelae. There was adequate follow up of the whole cohort at 12 months with 86% of infants seen, however, the follow up rates of the preterm infant group alone are not stated.
Not used in meta-analysis as standard deviations are not reported and population includes infants who were not born preterm.		A
Resnick 1988Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: unclear as it is not stated whether there was any subjects who exited the study prior to the 12 month assessment
Concealment of allocation: inadequate (infants were randomised according to the last digit of hospital number)
41 infants
Inclusion criteria: BW<1800 g , GA < 37 weeks
Exclusion criteria: not specified
Characteristics: mean GA for the intervention group and control groups was 31.7 (SD=2.9) and 31.0 (SD=2.0) weeks respectively		Intervention group (n=21): infant development and parent-infant relationship
Standard follow-up group (n=20): received access to a full range of social services, physiotherapy and occupational therapy.		COGNITIVE
Infant age: Bayley Scales of Infant Development-I MDI (6 and 12 months)

MOTOR
Infant age: Bayley Scales of Infant Development-I PDI (6 and 12 months)

C
Rice 1979Blinding of intervention: no
Blinding of outcome assessments: yes
Completeness of follow-up: unclear (it is not stated if there was any infants who withdrew from the study)
Concealment of allocation: unclear		30 infants
Inclusion criteria:born at GA <37 weeks between 1974 and 1975 born to mothers of low socioeconomic status.
Exclusion criteria: not specified
Characteristics: mean GA for the intervention and control group is not stated but reported to be similar between control and intervention groups.		Intervention group (n=15): infant development
Standard follow-up (n=15): mothers were given standard discharge information related to caring for their infant. It is reported that mothers were visited regularly by the experimenter and by other public health nurses to provide social reinforcement for appropriate mothering behavior.		COGNITIVE
- Infant age: BSID-I MDI (4 months)

MOTOR
-Infant age: BSID-I PDI (4 months)

B
Yigit 2002Blinding of intervention: no
Blinding of outcome assessments: unclear
Completeness of follow-up: no (83% follow up at 12 months)
Concealment of allocation: unclear		199 infants*
Inclusion criteria: BW <2000 g and GA <34 weeks
Exclusion criteria: perinatal hypoxia or abnormal ultra-sound, with no congenital or chromosomal abnormalities or metabolic disease
The mean GA for the intervention group and standard follow-up groups was 31.3 (SD=2.2) and 32.0 (SD=1.6) weeks respectively.		The intervention group (n=80): infant development
The standard follow-up group (n=80): both groups seen monthly by the same physiotherapist for the first 9 months, then every 3 months until 18-24 months of age. It is unclear whether this was for assessment or intervention.		COGNITIVE
- None

MOTOR
- Infant age only: Non-standardised measures of motor outcome such as age of acquisition of milestones and loss of primitive reflexes (1 month - 18-24 months). Incidence of cerebral palsy

*It is stated that 39 infants dropped out of the study due to lack of participation at 12 months, however, the number of infants initially randomised to intervention and standard follow-up is not reported
Data not able to be used in meta-analysis as it is not standardised.
B

Characteristics of excluded studies

StudyReason for exclusion
Beckwith 1988Intervention: no post-hospital discharge component
Beeghly 1995Population: infants not preterm
Britain 1995Methodology: case studies
Chen 2001Language: published in Chinese
Culp 1989Outcome measures: parent focused only
Girolami 1994Intervention: no post-hospital discharge component
Israel 2003Outcome measures: no results reported
Methodology: unclear
Kanda 2004Methodology: case-control study
Kang 1995Outcome measures: parent-infant interaction only
Kendrick 2000Methodology: literature review only
Kleberg 2000Intervention: no post-hospital discharge component
Kleberg 2002Intervention: no post-hospital discharge component
Matsuishi 1998Methodology: case-control study
Ment 2003Intervention: pharmaceutical (intraventricular haemorrhage (IVH) prevention)
Ross 1984Methodology: case-control study
Sajaniemi 2001Methodology: case-control study
Salokorpi 2002Methodology: case-control study
Scott 1989Methodology: literature review only
Slater 1987Methodology: cohort study
Wasik 1990Population: infants are not preterm

References to studies

References to included studies

APIP 1998 {published data only}

* Avon Premature Infant Project. Randomised trial of parental support for families with very preterm children. Archives of Disease in Childhood Fetal Neonatal Edition 1998;79:F4-11.

Johnson S, Ring W, Anderson P, Marlow N. Randomised trial of parental support for families with very preterm children: outcome at 5 years. Archives of Disease in Childhood 2005;90:909-15.

Bao 1999 {published data only}

Bao X, Sun S, Wei S. Early intervention promotes intellectual development of premature infants: a preliminary report. Chinese Medical Journal 1999;112:520-3.

Barrera 1986 {published data only}

* Barrera ME, Cunningham CE, Rosenbaum CE. Low birth weight and home intervention strategies: preterm infants. Journal of Developmental and Behavioural Pediatrics 1986;7:361-6.

Barrera ME, Doucet DA , Kitching KJ. Early home intervention and socio-emotional development of preterm infants. Infant Mental Health Journal 1990;11:142-57.

Barrera ME, Kitching KJ. A 3 year early home intervention follow-up study with low birthweight infants and their parents. Topics in Early Childhood Special Education 1991;10:14-28.

Barrera ME, Rosenbaum PL, Cunningham CE. Early home intervention with low-birth-weight infants and their parents. Child Development 1986;57:20-33.

Cameron 2005 {published data only}

Cameron EC, Maehle V, Reid J. The effects of an early physical therapy intervention for very preterm, very low birth weight infants: a randomized controlled clinical trial. Pediatric Physical Therapy 2005;17:107-19.

Field 1980 {published data only}

Field TM, Widmayer SM, Stringer S, Ignatoff E. Teenage, lower-class, black mothers and their preterm infants: an intervention and developmental follow-up. Child Development 1980;51:426-36.

Goodman 1985 {published data only}

* Goodman M, Rothberg AD, Houston-McMillan JE, Cooper PA, Cartwright JD, van der Velde MA. Effect of early neurodevelopmental therapy in normal and at-risk survivors of neonatal intensive care. Lancet 1985;2:1327-30.

Rothberg AD, Goodman M, Jacklin LA, Cooper PA. Six-year follow-up of early physiotherapy intervention in very low birth weight infants. Pediatrics 1991;88:547-52.

I.H.D.P. 1990 {published and unpublished data}

Berlin LJ, Brooks-Gunn J, McCarton C, McCormick MC. The effectiveness of early intervention: examining risk factors and pathways to enhanced development. Preventive Medicine 1998;27:238-45.

Blair C, Ramey CT, Hardin JM. Early intervention for low birth weight, premature infants: participation and intellectual development. American Journal of Mental Retardation 1995;99:542-54.

Brooks-Gunn J, Klebanov PK, Liaw F, Spiker D. Enhancing the development of low-birthweight, premature infants: changes in cognition and behavior over the first three years. Child Development 1993;64:736-53.

Brooks-Gunn J, Liaw, F, Klebanov PK. Effects of early intervention on cognitive function of low birth weight preterm infants. Journal of Pediatrics 1992;120:350-9.

Brooks-Gunn J, McCarton CM, Casey PH, McCormick MC, Bauer CR, Bernbaum JC et al. Early intervention in low-birth-weight premature infants: Results through age 5 years from the Infant Health and Development Program. JAMA 1994;272:1257-62.

Hollomon HA, Scott KG. Influence of birth weight on educational outcomes at age 9: the Miami site of the Infant Health and Development Program. Journal of Developmental and Behavioral Pediatrics 1998;19:404-10.

Infant Health Development Program. Enhancing the outcomes of low-birth-weight, premature infants. A multisite randomized trial. JAMA 1990;263:3035-42.

McCarton C. Behavioral outcomes in low birth weight infants. Pediatrics 1998;102 (5 suppl E):1293-7.

McCarton CM, Brooks-Gunn J, Wallace IF, Bauer CR, Bennett FC, Bernbaum JC et al. Results at age 8 years of early intervention for low-birth-weight premature infants: the Infant Health and Developmental Program. JAMA 1997;277:126-32.

McCormick MC, McCarton C, Brooks-Gunn J, Belt P, Gross RT. The Infant Health and Development Program: interim summary. Journal of Developmental and Behavioral Pediatrics 1998;19:359-70.

McCormick MC, McCarton C, Tonascia J and Brooks-Gunn J. Early educational intervention for very low birth weight infants: results from the Infant Health and Development Program. Journal of Pediatrics 1993;123:527-33.

Lekskulchai 2001 {published data only}

Lekskulchai R, Cole J. Effect of a developmental program on motor performance in infants born preterm. Australian Journal of Physiotherapy 2001;47:169-76.

Melnyk 2001 {published data only}

Melnyk BM, Alpert-Gillis L, Fischbeck Feinstein N, Fairbanks E, Czarniak-Schultz N et al. Improving cognitive development of low-birth-weight premature infants with the COPE program: a pilot study of the benefit of early NICU intervention with mothers. Research in Nursing and Health 2001;24:373-89.

Nelson 2001 {published data only}

Nelson NM, White-Traut RC, Vasan U, Silvestri J, Comiskey E, Meleedy-Rey P et al. One-year outcome of auditory-tactile-visual-vestibular intervention in the neonatal intensive care unit: effects of severe prematurity and central nervous system injury. Journal of Child Neurology 2001;16:493-8.

Nurcombe 1984 {published data only}

Achenbach RM, Howell CT, Aoki MF, Rauh VA. Nine-year outcome of the Vermont Intervention Program for Low Birth Weight Infants. Pediatrics 1993;91:45-55.

Achenbach TM, Phares V, Howell CT, Rauh VA, Nurcombe B. Seven-year outcome of the Vermont Intervention Program for Low-Birth Weight Infants. Child Development 1990;61:1672-81.

Nurcombe B, Howell DC, Rauh V, Teti DM, Ruoff P, Brennan J. An intervention program for mothers of low-birthweight babies: preliminary results. Journal of the American Academy of Child Psychiatry 1984;23:319-25.

* Rauh VA, Achenbach TM, Nurcombe BH, Howell CT, Teti DM. Minimizing adverse effects of low birthweight: four-year results of an early intervention program. Child Development 1988;59:544-53.

Rauh VA, Nurcombe B, Achenbach T, Howell C. The Mother-Infant Transaction Program: The content and implications of an intervention for the mothers of low-birthweight infants. Clinics in Perinatology 1990;17:31-45.

Ohgi 2004 {published and unpublished data}

Ohgi S, Fukuda M, Akiyama T, Gima H. Effect of an early intervention programme on low birthweight infants with cerebral injuries. Journal of Paediatric and Child Health 2004;40:689-95.

Piper 1986 {published data only}

Piper MC, Kunos VI, Willis DM, Mazer BL, Ramsay M, Silver KM. Early physical therapy effects on the high-risk infant: a randomized controlled trial. Pediatrics 1986;78:216-24.

Resnick 1988 {published data only}

Resnick MB, Armstrong S, Carter RL. Developmental intervention program for high-risk premature infants: effects on development and parent infant interactions. Developmental and Behavioral Pediatrics 1988;9:73-8.

Rice 1979 {published data only}

Rice RD. The effects of the Rice infants sensorimotor stimulation treatment on the development of high risk infants. Birth Defects Original Article Series 1979;15:7-26.

Yigit 2002 {published data only}

Yigit S, Kerem M, Livanelioglu A, Oran O, Erdem G, Mutlu A et al. Early physiotherapy intervention in premature infants. The Turkish Journal of Pediatrics 2002;44:224-9.

References to excluded studies

Beckwith 1988 {published data only}

Beckwith L. Intervention with disadvantaged parents of sick preterm infants. Psychiatry 1988;51:242-7.

Beeghly 1995 {published data only}

Beeghly M, Brazelton TB, Flannery KA, Nugent JK, Barrett DE, Tronick EZ. Specificity of preventative pediatric intervention effects in early infancy. Journal Developmental and Behavioural Pediatrics 1995;16:158-66.

Britain 1995 {published data only}

Britain LA, Holmes GE, Hassanein RS. High-risk children referred to an early-intervention developmental program. Clinical Pediatrics 1995;34:635-41.

Chen 2001 {published data only}

Chen D, Zhang J, Chen Y. Early intervention on intelligent development of premature infant. Chinese Mental Health Journal 2001;15:55-7.

Culp 1989 {published data only}

Culp RE, Culp AM, Harmon RJ. A tool for educating parents about their premature infants. Birth 1989;16:23-6.

Girolami 1994 {published data only}

Girolami JL, Campbell SK. Efficacy of a neuro-developmental treatment program to improve motor control in infants born prematurely. Pediatric Physical Therapy 1994;6:175-84.

Israel 2003 {published data only}

Israel C. The preterm infant parenting study. Midirs Midwifery Digest 2003;13:239-41.

Kanda 2004 {published data only}

Kanda T, Pidcock FS, Hayakawa K, Yamori Y, Shikata Y. Motor outcome differences between two groups of children with spastic diplegia who received different intensities of early onset physiotherapy followed for 5 years. Brain and Development 2004;26:118-26.

Kang 1995 {published data only}

Kang R, Barnard K, Hammond M, Oshio S, Spencer C, Thibodeaux B, Williams J. Preterm infant follow-up project: a multi-site field experiment of hospital and home intervention programs for mothers and preterm infants. Public Health Nursing 1995;12:171-80.

Kendrick 2000 {published data only}

Kendrick D, Elkan R, Hewitt M, Dewey M, Blair M, Robinson J et al. Does home visiting improve parenting and the quality of the home environment? A systematic review and meta analysis. Archives of Disease in Childhood 2000;82:443-51.

Kleberg 2000 {published data only}

Kleberg A, Westrup B and Stjernqvist K. Developmental outcome, child behavior and mother-child interaction at 3 years of age following Newborn Individualized Developmental Care and Intervention Program (NIDCAP) intervention. Early Human Development 2000;60:123-35.

Kleberg 2002 {published data only}

Kleberg A, Westrup B, Stjernqvist K, Lagercrantz H. Indications of improved cognitive development at one year of age among infants born very prematurely who received care based on the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). Early Human Development 2002;68:83-91.

Matsuishi 1998 {published data only}

Matsuishi T, Ishibashi S, Kamiya Y, Shoju J, Yamashita Y, Fukuda S et al. Early intervention for very-low-birth-weight infants. Brain and Development 1998;20:18-21.

Ment 2003 {published data only}

Ment LR, Vohr B, Allan W, Katz KH, Schneider KC, Westerveld M et al. Change in cognitive function over time in very low-birth-weight infants. JAMA 2003;289:705-11.

Ross 1984 {published data only}

Ross GS. Home intervention for premature infants of low-income families. American Journal of Orthopsychiatry 1984;54:263-70.

Sajaniemi 2001 {published data only}

Sajaniemi N, Makela J, Salokorpi T, von Wendt L, Hamalainen T, Hakamies-Blomqvist L. Cognitive performance and attachment patterns at four years of age in extremely low birth weight infants after early intervention. European Child and Adolescent Psychiatry 2001;10:122-9.

Salokorpi 2002 {published data only}

Salokorpi T, Rautio T, Kajantie E, Von Wendt L. Is early occupational therapy in extremely pre-term infants of benefit in the long run? Pediatric Rehabilitation 2002;5:91-8.

Scott 1989 {published data only}

Scott DT, Spiker D. Research on the sequelae of prematurity: early learning, early interventions and later outcomes. Seminars in Perinatology 1989;13:495-505.

Slater 1987 {published data only}

Slater MA, Naqvi M, Andrew L, Haynes K. Neurodevelopment of monitored versus nonmonitored very low birth weight infants: the importance of family influences. Journal of Developmental and Behavioral Pediatrics 1987;8:278-85.

Wasik 1990 {published data only}

Wasik BH, Ramey CT, Bryant DM, Sparling JM. A longitudinal study of two early intervention strategies: project CARE. Child Development 1990;61:1682-96.

* indicates the primary reference for the study

Other references

Additional references

Als 1997

Als H, Gilkerson L. The role of relationship-based developmentally supportive newborn intensive care in strengthening outcome of preterm infants. Seminars in Perinatology 1997;21:178-89.

Anderson 2003

Anderson P, Doyle L; The Victorian Infant Collaborative Study Group. Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990's. JAMA 2003;289:3264-72.

Bayley 1969

Bayley N. Bayley Scales of Infant Development. New York: The Psychological Corporation, 1969.

Bayley 1993

Bayley N. The Bayley Scales of Infant Development. 2nd edition edition. New York: The Psychological Corporation, 1993.

Becker 1999

Becker P, Grunwald PC, Brazy JE. Motor organization in very low birth weight infants during caregiving: effects of a developmental intervention. Developmental and Behavioral Pediatrics 1999;20:344-54.

Berger 1998

Berger S, Holt-Turner I, Cupoli JM, Mass M, Hageman JR. Caring for the graduate from the neonatal intensive care unit. Pediatric Clinics of North America 1998;45:701-12.

Bhutta 2002

Bhutta AT, Cleves MA, Casey PH, Craddock MM, Anand KJ. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002;288:728-37.

Blauw-Hospers 2005

Blauw-Hospers C, Hadders-Algra M. A systematic review of the effects of early intervention on motor development. Developmental Medicine and Child Neurology 2005;47:421-32.

Botting 1998

Botting N, Powls, Cooke RW, Marlow N. Cognitive and educational outcome of very-low-birthweight children in early adolescence. Developmental Medicine and Child Neurology 1998;40:652-60.

Brown 2001

Brown GT, Burns SA. The efficacy of neurodevelopmental treatment in paediatrics: a systematic review. British Journal of Occupational Therapy 2001;64:235-44.

Bruininks 1978

Bruininks RH. Bruininks-Oseretsky Test of Motor Proficiency Examiner's Manual. Circle Pines: American Guidance Service, 1978.

Campbell 1995

Campbell SK, Kolobe TH, Osten ET, Lenke M, Girolami GL. Construct validity of the Test of Infant Motor Performance. Physical Therapy 1995;75:585-96.

Doyle 2004

Doyle LW; The Victorian Infant Collaborative Study Group. Evaluation of neonatal intensive care for extremely low birthweight infants in Victoria over two decades: I. Effectiveness. Pediatrics 2004;113:505-9.

Elliot 1996

Elliot C, Smith P, McCullock K. British Abilities Scales. London: Nelson Publishing Co Ltd, 1996.

Folio 2000

Folio MR, Fewell RR. Peabody Developmental Motor Scales. 2nd edition. Austin: Pro-Education Incorporated, 2000.

Griffiths 1954

Griffiths R. The Abilities of Babies: A Study of Mental Measurement. London: University of London Press, 1954.

Griffiths 1970

Griffiths R. The Abilities of Young Children: A Comprehensive System of Mental Measurement for the First Eight Years. London: Child Development Research Center, 1970.

Hack 2002

Hack M, Flannery DJ, Schluchter M, Cartar L, Borawski E, Klein N. Outcomes in young adults for very-low-birth-weight infants. The New England Journal of Medicine 2002;346:149-57.

Hadders-Algra 2001

Hadders-Algra M. Early brain damage and the development of motor behavior in children: clues for therapeutic intervention? Neural Plasticity 2001;8:31-49.

Henderson 1992

Henderson SE, Sugden DA. Movement Assessment Battery for Children Checklist. The Psychological Corporation, 1992.

Hogan 2000

Hogan DP, Park JM. Family factors and social support in the developmental outcomes of very-low birth weight children. Clinics in Perinatology 2000;27:433-59.

Holsti 2002

Holsti L, Grunau R, Whitfield MF. Developmental coordination disorder in extremely low birth weight children at nine years. Developmental and Behavioral Pediatrics 2002;23:9-15.

Horwood 1998

Horwood LJ, Mogridge N, Darlow BA. Cognitive educational, and behavioural outcomes at 7 to 8 years in a national very low birthweight cohort. Archives of Disease in Childhood Fetal and Neonatal Edition 1998;79:F12-20.

Hoy 1992

Hoy E, Sykes DH, Bill JM, Halliday HL, McClure BG, Reid MM. The social competence of very-low-birth weight children: teacher, peer and self-perceptions. Journal of Abnormal Child Psychology 1992;20:123-50.

Jacobs 2002

Jacobs SE, Sokol J, Ohlsson A. The Newborn Individualized Developmental Care and Assessment Program is not supported by meta-analyses of the data. Journal of Pediatrics 2002;140:699-706.

Kaufman 1983

Kaufman A, Kaufman NL. Kaufman Assessment Battery for Children. Circle Pines: American Guidance Service, 1983.

Laucht 1997

Laucht M, Esser G, Schmidt MH. Developmental outcomes of infants born with biological and psychosocial risks. Journal Child Psychology and Psychiatry 1997;38:843-53.

Marlow 1989

Marlow N, Roberts BL, Cooke RW. Motor skills in extremely low birthweight children at the age of 6 years. Archives of Disease in Childhood 1989;64:839-47.

McCarthy 1972

McCarthy. Manual for McCarthys Scales of Children's Ablities. New York: Psychological Corporation, 1972.

Melnyk 2001

Melnyk BM, Alpert-Gillis L, Feinstein NF, Fairbanks E, Schultz-Czarniak J, Hust D et al. Improving cognitive development of low-birth-weight premature infants with the COPE program: a pilot study of the benefit of early NICU interventions with mothers. Research in Nursing and Health 2001;24:373-89.

Ottenbacher 1986

Ottenbacher KJ, Biocca Z, DeCremer G, Gevelinger M, Jedlovec KB, Johnson MB. Quantitative analysis of the effectiveness of pediatric therapy. Emphasis on the neurodevelopmental treatment approach. Physical Therapy 1986;66:1095-101.

Pedersen 2000

Pedersen SJ, Sommerfelt K, Markestad T. Early motor development of premature infants with birthweight less than 2000 grams. Acta Paediatrica 2000;89:1456-61.

Piper 1994

Piper MC, Darrah J. Motor Assessment of the Developing Infant. Philadelphia: WB Saunders, 1994.

Polatajko 1995

Polatajko H, Fox M, Missiuna C. An international consensus on children with developmental co-ordination disorder. Canadian Journal of Occupational Therapy 1995;62:3-6.

Powls 1995

Powls A, Botting N, Cooke RW, Marlow N. Motor impairment in children 12 to 13 years old with a birthweight less than 1250 g. Archives of Disease in Childhood Fetal and Neonatal Edition 1995;73:F62-6.

Simeonsson 2003

Simeonsson RJ, Leonard M, Lollar D, Bjorck-Akesson E, Hollenweger J, Martinuzzi A. Applying the International Classification of Functioning, Disability and Health to measure childhood disability. Disability and Rehabilitation 2003;25:602-10.

Sommerfelt 1996

Sommerfelt K, Troland K, Ellertsen B, Markestad T. Behavioral problems in low-birthweight preschoolers. Developmental Medicine and Child Neurology 1996;38:927-40.

Symington 2003

Symington A, Pinelli J. Developmental care for promoting development and preventing morbidity in preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 3, 2003.

Terman 1973

Terman LM, Merrill MA. Stanford-Binet Intelligence Scale: Manual for the Third Revision, Form L-M. Boston: Houghton Miffin Company, 1973.

Thelen 1996

Thelen E, Smith L. A Dynamic Systems Approach to the Development of Cognition and Action. Cambridge: MIT Press, 1996.

Tin 1997

Tin W, Wariyar U, Hey E. Changing prognosis for babies of less than 28 weeks' gestation in the north of England between 1983 and 1994. Northern Neonatal Network. British Medical Journal 1997;314:107-11.

Verhagen 1998

Verhagen AP, de Vet H, de Bie RA, Kessels AG, Boers M, Bouter LM et al. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. Journal of Clinical Epidemiology 1998;51:1235-41.

Vohr 2000

Vohr BR, Wright LL, Dusick AM, Mele L, Verter J, Steichen JJ et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993-1994. Pediatrics 2000;105:1216-26.

Vohr 2005

Vohr BR, Wright LL, Poole WK, McDonald SA. Neurodevelopmental outcomes of extremely low birth weight infants <32 weeks' gestation between 1993 and 1998. Pediatrics 2005;116:635-43.

Wang 2006

Wang CJ, McGlynn EA, Brook RH, Leonard CH, Piechuch RE, Hsueh SI, Schuster MA. Quality-of-care indicators for the neurodevelopmental follow-up of very low birth weight children: results of an expert panel process. Pediatrics 2006;117:2080-92.

Wechsler 1989

Wechsler D. Wechsler preschool and primary scale of intelligence - revised. Psych Corp, 1989.

Wechsler 1991

Wechsler D. Manual for Wechsler Intelligence Scale for Children. 3rd edition edition. Texas: The Psychological Corporation, 1991.

WHO 2001

World Health Organization. International Classification of Functioning, Disability and Health. World Health Organization.

Comparisons and data

Comparison or outcome
Studies
Participants
Statistical method
Effect size
01 Early developmental intervention vs standard follow-up (all studies)
01 Cognitive outcome at infant age - DQ (BSID-MDI, Griffiths GCI)
8
1444
SMD (fixed), 95% CI
0.46 [0.36, 0.57]
02 Cognitive outcome at preschool age - IQ (Stanford Binet, McCarthy)
3
1006
SMD (fixed), 95% CI
0.46 [0.33, 0.59]
03 Cognitive outcome at school age - IQ (WISC, Kaufmann)
3
1111
SMD (fixed), 95% CI
0.02 [-0.10, 0.14]
04 Motor outcome at infant age (BSID PDI, Griffiths locomotor)
6
1149
SMD (fixed), 95% CI
0.05 [-0.06, 0.17]
05 Motor outcome at pre-school age
0
0
SMD (fixed), 95% CI
Not estimable
06 Motor outcome at school age (Griffiths locomotor)
1
49
SMD (fixed), 95% CI
-0.34 [-0.91, 0.23]
07 Motor outcome at school age (Low score on Movement-ABC)
1
197
RR (fixed), 95% CI
1.04 [0.78, 1.38]
08 Rate of cerebral palsy
4
586
RR (fixed), 95% CI
0.95 [0.57, 1.58]
02 Early developmental intervention vs standard follow-up (subgroup analysis: gestational age)
01 Cognitive outcome at infant age DQ (BSID- MDI, Griffiths GCI)
SMD (fixed), 95% CI
Subtotals only
03 Early developmental intervention vs standard follow-up (subgroup analysis: birthweight)
01 Cognitive outcome at infant age -DQ (BSID- MDI, Griffiths GCI)
SMD (fixed), 95% CI
Subtotals only
02 Cognitive outcome at pre-school age - IQ(Stanford Binet, McCarthy)
SMD (fixed), 95% CI
Subtotals only
04 Early developmental intervention vs standard follow-up (subgroup analysis: brain injury)
01 Cognitive outcome at infant age - DQ (BSID- MDI, Griffiths GCI)
SMD (fixed), 95% CI
Subtotals only
02 Motor outcome at infant age (BSID PDI, Griffiths locomotor)
SMD (fixed), 95% CI
Subtotals only
05 Early developmental intervention vs standard follow-up (subgroup analysis: commencement of intervention)
01 Cognitive outcome at infant age - DQ (BSID- MDI, Griffiths GCI)
SMD (fixed), 95% CI
Subtotals only
02 Cognitive outcome at pre-school age - IQ (Stanford Binet, McCarthy)
SMD (fixed), 95% CI
Subtotals only
03 Cognitive outcome at school age - IQ (WISC, Kaufmann)
SMD (fixed), 95% CI
Subtotals only
04 Motor outcome at infant age (BSID PDI, Griffiths locomotor)
SMD (fixed), 95% CI
Subtotals only
05 Motor outcome at pre-school age
SMD (fixed), 95% CI
Subtotals only
06 Motor outcome at school age (Griffiths locomotor)
SMD (fixed), 95% CI
Subtotals only
07 Motor outcome at school age (Low score on Movement-ABC)
RR (fixed), 95% CI
Subtotals only
08 Rate of cerebral palsy
RR (fixed), 95% CI
Subtotals only
06 Early developmental intervention vs standard follow-up (subgroup analysis: focus of intervention)
01 Cognitive outcome at infant age - DQ (BSID- MDI, Griffiths GCI)
SMD (fixed), 95% CI
Subtotals only
02 Cognitive outcome at pre-school age - IQ (Stanford Binet, McCarthy)
SMD (fixed), 95% CI
Subtotals only
03 Cognitive outcome at school age - IQ (WISC, Kaufmann)
SMD (fixed), 95% CI
Subtotals only
04 Motor outcome at infant age (BSID PDI, Griffiths locomotor)
SMD (fixed), 95% CI
Subtotals only
05 Motor outcome at school age (Griffiths locomotor)
SMD (fixed), 95% CI
Subtotals only
06 Rate of cerebral palsy
RR (fixed), 95% CI
Subtotals only
07 Early developmental intervention vs standard follow-up (subgroup analysis:quality of studies)
01 Cognitive outcome at infant age (BSID- MDI, Griffiths GCI: DQ)
SMD (fixed), 95% CI
Subtotals only
02 Cognitive outcome at pre-school age (Stanford Binet, McCarthy: IQ)
SMD (fixed), 95% CI
Subtotals only
03 Cognitive outcome at school age (WISC, Kaufmann: IQ)
SMD (fixed), 95% CI
Subtotals only
04 Motor outcome at infant age (BSID PDI, Griffiths locomotor: DQ)
SMD (fixed), 95% CI
Subtotals only
05 Motor outcome at school age (Griffiths locomotor)
SMD (fixed), 95% CI
Subtotals only
06 Motor outcome at school age (Low score on Movement-ABC)
RR (fixed), 95% CI
Subtotals only
07 Rate of cerebral palsy
RR (fixed), 95% CI
Subtotals only

 

01 Early developmental intervention vs standard follow-up (all studies)

01.01 Cognitive outcome at infant age - DQ (BSID-MDI, Griffiths GCI)

01.02 Cognitive outcome at preschool age - IQ (Stanford Binet, McCarthy)

01.03 Cognitive outcome at school age - IQ (WISC, Kaufmann)

01.04 Motor outcome at infant age (BSID PDI, Griffiths locomotor)

01.05 Motor outcome at pre-school age

01.06 Motor outcome at school age (Griffiths locomotor)

01.07 Motor outcome at school age (Low score on Movement-ABC)

01.08 Rate of cerebral palsy

02 Early developmental intervention vs standard follow-up (subgroup analysis: gestational age)

02.01 Cognitive outcome at infant age DQ (BSID- MDI, Griffiths GCI)

02.01.01 Preterm

02.01.02 Very preterm

02.01.03 Extremely preterm

03 Early developmental intervention vs standard follow-up (subgroup analysis: birthweight)

03.01 Cognitive outcome at infant age -DQ (BSID- MDI, Griffiths GCI)

03.01.01 Low birth weight

03.01.02 Very low birth weight

03.01.03 Extremley low birth weight

03.02 Cognitive outcome at pre-school age - IQ(Stanford Binet, McCarthy)

03.02.01 Low birth weight

03.02.02 Very low birth weight

03.02.03 Extremley low birth weight

04 Early developmental intervention vs standard follow-up (subgroup analysis: brain injury)

04.01 Cognitive outcome at infant age - DQ (BSID- MDI, Griffiths GCI)

04.01.01 Absence of PVL/ IVH

04.01.02 Presence of PVL/ IVH

04.02 Motor outcome at infant age (BSID PDI, Griffiths locomotor)

04.02.01 Absence of PVL/ IVH

04.02.02 Presence of PVL/IVH

05 Early developmental intervention vs standard follow-up (subgroup analysis: commencement of intervention)

05.01 Cognitive outcome at infant age - DQ (BSID- MDI, Griffiths GCI)

05.01.01 In-patient

05.01.02 Post hospital discharge

05.02 Cognitive outcome at pre-school age - IQ (Stanford Binet, McCarthy)

05.02.01 In-patient

05.02.02 Post hospital discharge

05.03 Cognitive outcome at school age - IQ (WISC, Kaufmann)

05.03.01 In-patient

05.03.02 Post hospital discharge

05.04 Motor outcome at infant age (BSID PDI, Griffiths locomotor)

05.04.01 In-patient

05.04.02 Post hospital discharge

05.05 Motor outcome at pre-school age

05.05.01 In-patient

05.05.02 Post hospital discharge

05.06 Motor outcome at school age (Griffiths locomotor)

05.06.01 In-patient

05.06.02 Post hospital discharge

05.07 Motor outcome at school age (Low score on Movement-ABC)

05.07.01 In-patient

05.07.02 Post hospital discharge

05.08 Rate of cerebral palsy

05.08.01 In-patient

05.08.02 Post hospital discharge

06 Early developmental intervention vs standard follow-up (subgroup analysis: focus of intervention)

06.01 Cognitive outcome at infant age - DQ (BSID- MDI, Griffiths GCI)

06.01.01 Parent-infant relationship

06.01.02 Infant development

06.01.03 Parent-infant relationship and Infant development

06.02 Cognitive outcome at pre-school age - IQ (Stanford Binet, McCarthy)

06.02.01 Parent-infant relationship

06.02.02 Infant development

06.02.03 Parent-infant relationship and Infant development

06.03 Cognitive outcome at school age - IQ (WISC, Kaufmann)

06.03.01 Parent-infant relationship

06.03.02 Infant development

06.03.03 Parent-infant relationship and Infant development

06.04 Motor outcome at infant age (BSID PDI, Griffiths locomotor)

06.04.01 Parent-infant relationship

06.04.02 Infant development

06.04.03 Parent infant relationship/ infant development

06.05 Motor outcome at school age (Griffiths locomotor)

06.05.01 Parent-infant relationship

06.05.02 Infant development

06.05.03 Parent infant relationship/ infant development

06.06 Rate of cerebral palsy

06.06.01 Parent-infant relationship

06.06.02 Parent-infant relationship and infant development

06.06.03 Infant development

06.06.04 Parent support

07 Early developmental intervention vs standard follow-up (subgroup analysis:quality of studies)

07.01 Cognitive outcome at infant age (BSID- MDI, Griffiths GCI: DQ)

07.01.01 Higher quality studies

07.01.02 Lower quality studies

07.02 Cognitive outcome at pre-school age (Stanford Binet, McCarthy: IQ)

07.02.01 Higher quality studies

07.02.02 Lower quality studies

07.03 Cognitive outcome at school age (WISC, Kaufmann: IQ)

07.03.01 Higher quality studies

07.03.02 Lower quality studies

07.04 Motor outcome at infant age (BSID PDI, Griffiths locomotor: DQ)

07.04.01 Higher quality studies

07.04.02 Lower quality studies

07.05 Motor outcome at school age (Griffiths locomotor)

07.05.01 Higher quality studies

07.05.02 Lower quality studies

07.06 Motor outcome at school age (Low score on Movement-ABC)

07.06.01 High quality studies

07.06.02 Lower quality studies

07.07 Rate of cerebral palsy

07.07.01 High quality studies

07.07.02 Lower quality studies


Contact details for co-reviewers

Ms Roslyn Boyd
Senior Physiotherapist, Neonatal Neurology
Murdoch Children's Research Institute
c/o Royal Children's Hospital
2nd Floor, Flemington Road
Parkville
Melbourne AUSTRALIA
3052
Telephone 1: 03 9345 4830
Facsimile: 03 9345 4840
E-mail: roslyn.boyd@rch.org.au

Prof Lex W Doyle
Professor
Department of Obstetrics and Gynaecology
University of Melbourne
The Royal Women's Hospital
132 Grattan Street
Melbourne
Victoria AUSTRALIA
3053
Telephone 1: 61 3 9344 2151
Facsimile: 61 3 9347 1761
E-mail: lwd@unimelb.edu.au

Ms Jane Orton
Senior Physiotherapist, Neonatal Neurology
Murdoch Children's Research Institute
c/o Royal Children's Hospital
2nd Floor, Flemington Road
Parkville
Melbourne AUSTRALIA
3052
Telephone 1: 03 9345 4830
Facsimile: 03 9345 4840
E-mail: jane.orton@rch.org.au

 
This review is published as a Cochrane review in The Cochrane Library, Issue 2, 2007 (see http://www.thecochranelibrary.com for information). Cochrane reviews are regularly updated as new evidence emerges and in response to feedback. The Cochrane Library should be consulted for the most recent version of the review.