Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infants
Ibrahim M, Sinn J, McGuire W
Cover sheet
Title
Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infantsReviewers
Ibrahim M, Sinn J, McGuire WDates
Date edited: 20/02/2006
Date of last substantive update: 14/02/2006
Date of last minor update: / /
Date next stage expected 30/11/2007
Protocol first published: Issue 2, 2005
Review first published: Issue 2, 2006
Contact reviewer
Dr Mohammed DH Ibrahim
Consultant Paediatrician
Department of Paediatrics
Victoria Hospital
Hayfield Road
Kirkcaldy
Fife UK
KY2 5AH
Telephone 1: 44 1592 643355
E-mail: Mohammed@doctors.org.ukContribution of reviewers
Mohammed
Ibrahim, John Sinn, and William McGuire developed the protocol jointly. Mohammed
Ibrahim and William McGuire undertook the electronic and hand searches, screened
the title and abstract of all studies identified, and the full text of the
report identified as of potential relevance. Mohammed Ibrahim and William
McGuire independently assessed the methodological quality of the included
trial, extracted the relevant information and data, and completed the final
review.
Internal sources of support
ANU Medical School, AUSTRALIA
External sources of support
NoneWhat'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
There is currently insufficient evidence to suggest that supplementing the diet of preterm infants with iodine is beneficial.
Iodine
is essential for the production of thyroid hormones. Thyroid hormones are
important for brain development in newborn infants. Preterm infants often
have low levels of iodine and of thyroid hormones in the first few weeks
after birth. This may in part be due to a lack of iodine in their diet. We
found only one trial that assessed the effect of giving preterm babies extra
iodine. This study did not find any evidence that providing extra iodine
increased the level of thyroid hormones. The trial did not assess the effect
of providing extra iodine on brain development. Further trials are needed.Abstract
Background
Parenteral
nutrition solutions, formula milks, and human breast milk contain insufficient
iodine to meet recommended intakes for preterm infants. Iodine deficiency
may exacerbate transient hypothyroxinaemia in preterm infants and this may
be associated with adverse respiratory or neurological outcomes.Objectives
To
assess the evidence from randomised controlled trials that dietary supplementation
with iodine reduces mortality and morbidity in preterm infants. Search strategy
We
used the standard search strategy of the Cochrane Neonatal Review Group.
This included searches of the Cochrane Central Register of Controlled Trials
(CENTRAL, The Cochrane Library, Issue 4, 2005), MEDLINE (1966 - November
2005), EMBASE (1980 - November 2005), CINAHL (1982 - November 2005), conference
proceedings, and previous reviews.Selection criteria
Randomised or
quasi-randomised controlled trials that compared a policy of supplementing
enteral or parenteral feeds with iodine (more than 30 micrograms per kilogram
per day) versus placebo or no supplementation in preterm infants.Data collection & analysis
The
standard methods of the Cochrane Neonatal Review Group, with separate evaluation
of trial quality and data extraction by two reviewers, and synthesis of data
using relative risk, risk difference and weighted mean difference. The primary
outcomes for this review were neonatal mortality, death before hospital discharge,
and longer term neurodevelopmental outcomes including severe neurodevelopmental
disability.Main results
We found only one randomised controlled trial
(N = 121) that fulfilled the review eligibility criteria (Rogahn 2000). The
participants were infants born before 33 weeks' gestation (but most were
of birth weight greater than 1000 grams). The primary aim of this trial was
to assess the effect of iodine supplementation on thyroid function. The investigators
did not detect any statistically significant effects on the plasma levels
of thyroxine (free and total), triiodothyronine, or thyrotrophin in preterm
infants (measured up to 40 weeks' post-conceptional age). Only one infant
died and the trial was therefore underpowered to detect an effect on mortality.
The trial did not assess the effect of the intervention on neurodevelopmental
morbidity. There was not a statistically significant difference in the incidence
of chronic lung disease. Reviewers' conclusions
There are insufficient
data at present to determine whether providing preterm infants with supplemental
iodine (to match fetal accretion rates) prevents morbidity and mortality
in preterm infants. Future randomised controlled trials of iodine supplementation
should focus on extremely preterm and extremely low birth weight infants,
the group at greatest risk of transient hypothyroxinaemia. These trials should
aim to assess the effect of iodine supplementation on clinically important
outcomes including respiratory morbidity and longer term neurodevelopment.Background
Transient
hypothyroxinaemia, a temporary postnatal reduction in serum levels of thyroxine
and triiodothyronine with normal levels of thyroid stimulating hormone, is
well described in preterm infants (Rooman 1996).
The incidence, and degree and duration, of hypothyroxinaemia is inversely
related to birth weight and gestational age and positively correlated with
illness severity (particularly the severity of respiratory distress syndrome).
The incidence of transient hypothyroxinaemia, defined as plasma thyroxine
levels below 40 micrograms per litre, ranges from 40% in infants born at
23 weeks' gestation to 10% in infants born at 28 weeks' gestation (Reuss 1996).
There
is concern that transient hypothyroxinaemia may harm brain development. Observational
studies have suggested a link between hypothyroxinaemia and poor neurodevelopmental
outcomes including low intelligence and cerebral palsy (Meijer 1992; Reuss 1996; Lucas 1996; Den Ouden 1996).
It is unclear whether transient hypothyroxinaemia is causally related to
adverse neurodevelopmental outcomes or is a consequence of extreme prematurity
or severe illness in preterm infants.
Studies in animal models have
suggested that thyroid hormones may act synergistically with corticosteroids
to accelerate surfactant production and reduce the severity of respiratory
distress syndrome in preterm infants (Liggins 1988).
However, meta-analyses of randomised controlled trials of antenatal administration
of thyrotropin releasing hormone did not show any improvement in outcomes
for preterm infants. In fact, antenatal exposure to thyrotrophin releasing
hormone is associated with a higher risk of infants needing mechanical ventilation
(Crowther 2004). Similarly, the Cochrane review
of trials of thyroid hormones administered shortly after birth to very preterm
infants did not find any evidence of effect on mortality or neurodevelopment,
or on the severity of respiratory distress syndrome or the incidence of chronic
lung disease (Osborn 2001). However, the small
number of infants included in trials in that review limited the power of
the meta-analyses to detect clinically important differences in outcomes.
The aetiology of transient hypothyroxinaemia is multifactorial. As
well as the contribution of non-thyroidal illness and immaturity of the hypothalamic-pituitary-thyroid
axis, it is speculated that iodine deficiency may contribute to transient
hypothyroxinaemia (Ares 1997). The neonatal thyroid
gland stores low levels of iodine and is very sensitive to iodine deficiency.
Nutrient balance studies in healthy preterm infants indicate that daily iodine
intakes of at least 30 micrograms per kilogram are needed to maintain a positive
iodine balance (Ares 1997). An international consensus
statement recommends daily iodine intakes of 30 to 60 micrograms per kilogram
for healthy growing formula fed preterm infants (Tsang 1993).
The
breast milk of mothers of preterm infants contains about 100 to 150 micrograms
of iodine per litre (depending on the dietary iodine intake of the mother).
The iodine content of formula milks ranges from 20 to 170 micrograms per
litre (Ares 1994; Seibold-Weiger 1999; Semba 2001).
Neither commercially available breast-milk fortifiers nor mineral and vitamin
supplements contain iodine. Enterally fed preterm infants therefore may not
achieve the recommended intake of iodine, especially during the first weeks
of postnatal life when feed volumes are still being advanced (Ares 1997).
Preterm
infants who are predominantly parenterally-fed are at even greater risk of
negative iodine balance. Most commercially available parenteral nutrition
solutions contain less iodine than breast or formula milk (even though gastrointestinal
absorption of iodine is high). The American Society for Clinical Nutrition
has recommended daily parenteral iodine intakes of about one microgram per
kilogram. This conservative recommendation was influenced by an assumption
that most parenterally fed preterm infants will also absorb iodine transcutaneously
from topical iodinated antiseptic solutions. However, the use of iodinated
antiseptics for preterm infants has decreased due to concern that excessive
transcutaneous iodine intake (100 micrograms per day or more) causes early
acquired neonatal hypothyroidism (Smerdely 1989).
Evidence exists that parentally fed very preterm infants who have not been
exposed to other sources of iodine achieve daily iodine intakes of about
1 to 3 micrograms per kilogram and are in negative iodine balance during
the first week of postnatal life (Ibrahim 2003).
Given
the potential for negative iodine balance to cause hypothyroxinaemia and
consequently adverse neurological and respiratory outcomes, especially in
parentally fed or sick preterm infants, and despite the lack of evidence
that exogenous thyroid hormone supplementation is beneficial, we have reviewed
the available evidence concerning iodine supplementation for preventing morbidity
and mortality in preterm infants.Objectives
To determine whether
dietary supplementation with iodine affects mortality and morbidity in preterm
infants. We planned to examine the evidence of effect of enteral and parenteral
iodine supplementation in separate comparisons.
Sub group analyses:
1. Very low birth weight (less than 1.5 kilograms) or very preterm (born before 32 weeks' gestation) infants
2. Extremely low birth weight (less than 1 kilogram) or extremely preterm (born before 28 weeks' gestation) infantsCriteria for considering studies for this review
Types of studies
Controlled trials using random or quasi-random patient allocation. Types of participants
Preterm infants (less than 37 weeks completed gestation).Types of interventions
Supplementation
with iodine compared with placebo or no supplementation. Iodine supplementation
will be defined as aiming to provide more than 30 micrograms per kilogram
of iodine per day. Enteral supplementation may be achieved either by:
1. Adding iodine to breast or formula milk, or
2. Feeding with formula milk that is already iodine enriched.
Similarly, parenteral supplementation may be achieved either by:
1. Adding iodine to the nutrient solution in the ward or pharmacy, or
2. Feeding with a pre-prepared iodine enriched solution.
The
comparison groups should have received the same nutrient input (and other
treatments) apart from the level of iodine input. Analysis should be as intention-to-treat.Types of outcome measures
Primary:
1. Neonatal mortality and mortality prior to hospital discharge.
2.
Neurodevelopmental outcomes at greater than, or equal to, 12 months of age
(corrected for preterm birth) measured using validated assessment tools such
as Bayley Scales of Infant Development.
3. Severe neurodevelopmental disability
defined as any one or combination of the following: non-ambulant cerebral
palsy, developmental delay (developmental quotient less than 70), auditory
and visual impairment. We planned to analyse each component individually
as well as part of the composite outcome.
4 Cognitive and educational
outcomes at aged more than five years old: Intelligence quotient and/or indices
of educational achievement measured using a validated assessment tool (including
school examination results).
Secondary:
1. Measures of
the severity of respiratory distress syndrome: for example, duration of mechanical
ventilation (days), incidence of air leaks, incidence of chronic lung disease
(supplemental oxygen requirement at 36 weeks' post-conceptional age).
2.
Biochemical measures of thyroid function and iodine status such as plasma
levels of thyroxine (free and total), triiodothyronine, or thyrotrophin.Search strategy for identification of studies
We
used the standard search strategy of the Cochrane Neonatal Review Group,
including electronic searches of the Cochrane Central Register of Controlled
Trials (CENTRAL, The Cochrane Library, Issue 4, 2005), MEDLINE (1966 - November
2005), CINAHL (1982 - November 2005), and EMBASE (1980 - November 2005).
The search strategy used the following text words and MeSH terms: Infant-Newborn;
Infant-Low Birth Weight; Infant-Premature; infan$; neonat$; newborn; premature;
low birth weight; LBW; Infant-Nutrition; enteral nutrition; milk; infant
food; parenteral nutrition; TPN; iodine; iodide; Thyroid Hormones; Thyroxine;
Triiodothyronine; hypothyroxin$. We limited the search outputs with the relevant
filters for clinical trials. We did not apply any language restriction.
We
examined references in previous reviews and in studies identified as potentially
relevant. We hand searched the abstracts presented at the annual scientific
meetings of the Society for Pediatric Research, the European Society for
Pediatric Research, the North American Society of Pediatric Gastroenterology
and Nutrition, and the European Society of Paediatric Gastroenterology, Hepatology
and Nutrition (from 1980 - 2004). Unpublished studies and studies published
only as abstracts were eligible for inclusion if assessment of study quality
was possible and if other criteria for inclusion were fulfilled. We planned
to contact authors of studies published as abstracts for further information.Methods of the review
1.
Mohammed Ibrahim (MI) screened the title and abstract of all studies identified
by the above search strategy and obtained the full articles for all potentially
relevant trials. MI and William McGuire (WM) re-assessed independently the
full text of these reports using an eligibility form based on the pre-specified
inclusion criteria. We excluded studies that did not meet all of the inclusion
criteria. The reviewers resolve any disagreements by discussion until consensus
was achieved.
2. MI and WM used the criteria and standard methods
of the Cochrane Neonatal Review Group to assess independently the methodological
quality of the included trial in terms of allocation concealment, blinding
of parents or carers and assessors to intervention, and completeness of assessment
in all randomised individuals.
3. MI and WM used a data collection
form to aid extraction of relevant information and data from the included
study. Each reviewer extracted the data separately, compared data, and resolved
differences by discussion
4. We have presented outcomes for categorical
data as relative risk, risk difference, and number needed to treat, with
respective 95% confidence intervals. For continuous data, we planned to use
the weighted mean difference with 95% confidence interval.
5. We
planned estimate the treatment effects of individual trials and examine heterogeneity
between trial results by inspecting the forest plots and quantifying the
impact of heterogeneity in any meta-analysis using a measure of the degree
of inconsistency in the studies' results (I- squared statistic). If we detected
statistical heterogeneity, we planned to explore the possible causes (for
example, differences in study quality, participants, intervention regimens,
or outcome assessments) using post hoc sub group analyses. We planned to
use a fixed effects model for meta-analyses. Description of studies
We identified only one study that fulfilled the review inclusion criteria (Rogahn 2000).
We did not identify any studies that appeared eligible, but did not meet
all inclusion criteria following systematic appraisal.
The investigators randomly allocated 121 infants born before 33 weeks' gestation to receive either:
1. iodine-supplemented "preterm" formula milk (iodine concentration 272 micrograms per litre), or
2. the same formula without iodine supplementation (iodine concentration 68 micrograms per litre).
This
strategy was designed to provide an iodine intake of 40 - 50 micrograms/kg/day
in the intervention group versus 12 - 16 micrograms/kg/day in the control
group. Infants were allocated to receive the trial formula milks until they
reached 40 weeks' post conceptional age. Infants may have received parenteral
nutrition prior to receiving formula milk. This is unlikely to have contained
iodine (but this is not stated explicitly in the trial report). Similarly,
it is not clear from the published report whether infants may have been exposed
to iodine in skin disinfecting solutions.
The primary outcome was
the plasma level of thyroid hormones. Short term clinical outcome data were
also reported. Neurodevelopment and cognitive function were not assessed
but longer term follow up of the trial cohorts may examine these outcomes.
The formula milk was supplied on demand either as the sole feed or in addition
to maternal breast milk. Infants who were enrolled in the study but who received
sufficient maternal breast milk such that they never received any of the
trial formula were still included in the primary intention-to-treat analyses.
Methodological quality of included studies
The methodological quality
of the included study was good. The random sequence was derived from a random
number table and allocation was concealed with sealed opaque envelopes. The
intervention and control formula milks were identical in appearance and the
iodine levels were not known to parents, carers, or outcome assessors. Complete
biochemical outcome data up to 40 weeks' post-menstrual age were available
for 114 (of 121) infants. Biochemical data were not available for six infants
withdrawn from study post-randomisation (reasons not stated) and for one
infant who died during the study period. The primary analyses were by intention-to-treat.Results
Enteral iodine supplementation: One eligible trial (Rogahn 2000).
1.
Mortality: Only one infant died during the study period. The infant was randomised
to the control group but only received breast milk (personal communication
Steven Ryan): Relative risk 0.33 (95% confidence interval 0.01 to 7.89);
risk difference -0.02 (-0.06 to 0.03).
2. Neurodevelopmental and cognitive outcomes: not assessed.
3.
Respiratory outcomes: The trial did not detect any statistically significant
difference in the duration of mechanical ventilation or of treatment with
supplemental oxygen. These data were reported as median (range) but without
standard deviations and therefore relative risks and risk differences could
not be calculated.
16 of 61 surviving infants in the intervention
group developed chronic lung disease (supplemental oxygen requirement at
36 weeks' post-conceptional age) versus 24 of 59 surviving infants in the
control group: Relative risk 0.64 (95% confidence interval 0.38 to 1.09);
risk difference -0.14 (-0.31 to 0.02). Because death prior to hospital discharge
and the development of chronic lung disease (supplemental oxygen requirement
at 36 weeks' post-conceptional age) are competing outcomes, we aggregated
these as a composite outcome "chronic lung disease or prior death". This
outcome did not differ significantly between the groups: Relative risk 0.63
(95% confidence interval 0.38 to 1.06); risk difference -0.15 (-0.32 to 0.01).
4. Measures of thyroid function: The study did not detect any statistically
significant differences in the plasma levels of thyroid hormones (thyroxine,
triiodothyronine, free thyroxine, thyrotrophin) measured at 30, 35, and 40
weeks' post-conceptional age:
1. Total plasma thyroxine:
(i) mean difference at 30 weeks' post conception 3.0 (95% confidence interval -9.2 to 15.2) nmol/L.
(ii) mean difference at 35 weeks' post conception 0.0 (95% confidence interval -10.3 to 10.3) nmol/L.
(iii) mean difference at 40 weeks' post conception -2.0 (95% confidence interval -12.0 to 8.0) nmol/L.
2. Total plasma triiodothyronine:
(i) mean difference at 30 weeks' post conception 0.02 (95% confidence interval -0.16 to 0.20) nmol/L.
(ii) mean difference at 35 weeks' post conception 0.01 (95% confidence interval -0.14 to 0.16) nmol/L.
(iii) mean difference at 40 weeks' post conception 0.11 (95% confidence interval -0.07 to 0.29) nmol/L.
3. Free thyroxine:
(i) mean difference at 30 weeks' post conception -1.10 (95% confidence interval -4.05 to 1.85) pmol/L.
(ii) mean difference at 35 weeks' post conception -1.10 (95% confidence interval -3.48 to 1.28) pmol/L.
(iii) mean difference at 40 weeks' post conception -0.40 (95% confidence interval -1.67 to 0.87) pmol/L.
4. Thyrotrophin:
(i) mean difference at 30 weeks' post conception -0.30 (95% confidence interval -0.79 to 0.19) mU/L.
(ii) mean difference at 35 weeks' post conception -0.20 (95% confidence interval -0.69 to 0.29) mU/L.
(iii) mean difference at 40 weeks' post conception 0.08 (95% confidence interval -0.28 to 0.44) mU/L.
The
data presented in the report did not allow birth weight and gestational age
subgroup analyses to be undertaken. We will contact the trial authors to
determine if these subgroup data are available for inclusion in a future
update.
Parenteral iodine supplementation: No eligible trials found.Discussion
The
single trial that we have identified did not find any evidence that enteral
iodine supplementation affected thyroid hormone levels or clinical outcomes
in preterm infants. However, the infants who participated in this trial did
not belong to the population most likely to be affected by iodine and thyroid
hormone deficiency. Most of the infants were in the 1000 to 1500 grams birth
weight range and were clinically stable. Only 17 of the 121 participants
were of birth weight less than 1000 grams. Observational data suggest that
transient hypothyroxinaemia is most strongly associated with adverse respiratory
and neurological outcomes in extremely low birth weight or extremely preterm
infants (Reuss 1996; Rooman 1996).
Secondly, the intervention (iodine-supplemented formula milk) was started
when the infants had established enteral feeding, usually two weeks after
birth. In extremely preterm infants, iodine balance is negative and transient
hypothyroxinaemia is established in the first one to two weeks after birth.
Some of the participating infants received all or part of their intake as
breast milk which has a higher iodine concentration than standard formula
milk. Including these infants in the intention to treat analysis may have
reduced the difference in the average amounts of iodine that each group actually
received. Participating infants may also have received parenteral nutrition.
However, this is not likely to have contained iodine. It is not clear whether
infants may have been exposed to iodine containing antiseptics. If so, this
may also have contributed to reducing the difference in actual iodine intake
between the groups. We will attempt to clarify these issues with the trial
investigators.
An alternative option to iodine supplementation for
infants at risk of transient hypothyroxinaemia is treatment with thyroid
hormones. The available data from randomised controlled trials of post-natal
thyroid hormone supplementation have not provided any evidence that this
intervention prevents morbidity or mortality in very preterm infants (Osborn 2001).
However, in one trial post hoc subgroup analyses suggest that thyroxine replacement
might prevent neurodevelopmental morbidity in extremely preterm infants (van Wassenaer 1997).
The Cochrane review concluded that further trials in this population may
be warranted. It is not clear whether direct thyroid hormone supplementation
has any advantages over iodine supplementation. Theoretically, since iodine
supplementation is metabolically "upstream" of thyroid hormone replacement,
it is likely to result in more physiologically appropriate tissue levels
of thyroxine and triiodothyronine than direct supplementation with thyroid
hormones (Ares 1997). However, there is also the
theoretical disadvantage that over-treatment with iodine can cause transient
hypothyroidism in preterm neonates who are exquisitely sensitive to the anti-thyroid
effects of iodine excess (Smerdely 1989).Reviewers' conclusions
Implications for practice
The
data are insufficient at present to determine whether iodine supplementation
prevents mortality and morbidity in preterm infants. Implications for research
There
is a need for a large pragmatic randomised controlled trial to determine
if iodine supplementation, started within a few days after birth, prevents
morbidity and mortality in preterm infants. Trials should focus on extremely
preterm and/or extremely low birth weight infants, the group at greatest
risk of transient hypothyroxinaemia, and should aim to assess the effect
of iodine supplementation on clinically important outcomes including respiratory
morbidity and long term neurodevelopment. We are aware of one such trial
that is currently in the development stage: see http://www.euthyroid.org/.
Acknowledgements
We thank Vijay Shingde for helpful discussions and input during the early stages of development of the protocol.Potential conflict of interest
NoneCharacteristics of included studies
Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
Rogahn 2000 | Blinding of randomisation: yes. Blinding of intervention: yes. Complete follow-up: yes. Blinding of outcome measurement: yes. | 121 infants < 33 weeks' gestation at birth, clinically
stable and receiving all their nutrition enterally by 2 weeks after birth
(if more than or equal to 28 weeks' gestation at birth) or by 31 weeks after
conception (if less than 28 weeks' gestation). 17 of the 121 participants were of birth weight less than 1000 grams. | Treatment (N=61): Iodine supplemented "preterm" formula milk: iodine concentration 272 micrograms/L. Control
(N=60): Same milk without iodine supplementation: iodine concentration 68
micrograms/L. These milks were identical in appearance. Allocated formula continued until infants reached 40 weeks' postmenstrual age. | 1.
Nutrition and growth: volume of milk ingested (infants were demand fed),
weekly change in weight, leg length, and head circumference during trial
period. 2. Respiratory outcomes: days ventilated, days requiring supplemental oxygen therapy, incidence of chronic lung disease. 3. Incidence of severe intraventricular haemorrhage and of cystic periventricular leucomalacia. 4. Duration of hospital admission (days to discharge). | Study sites: Neonatal units in the Mersey Region, UK. | A |
References to studies
References to included studies
Rogahn 2000 {published data only}Rogahn
J, Ryan S, Wells J, Fraser B, Squire C, Wild N, et al. Randomised trial of
iodine intake and thyroid status in preterm infants. Archives of Disease
in Childhood Fetal and Neonatal Edition 2000;83:F86-90.
* indicates the primary reference for the study
Other references
Additional references
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Ares 1997
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S, Escobar-Morreale HF, Quero J, Duran S, Presas MJ, Herruzo R, Morreale
de Escobar G. Neonatal hypothyroxinemia: effects of iodine intake and premature
birth. Journal of Clinical Endocrinology and Metabolism 1997;82:1704-12.
Bremer 1987
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HJ, Brooke OG, Orzalesi M. Nutrition and feeding of preterm infants. Committee
on Nutrition of the Preterm Infant, European Society of Paediatric Gastroenterology
and Nutrition (ESPGAN). Acta Paediatrica Scandinavica 1987;336:S1-14.
Crowther 2004
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CA, Alfirevic Z, Haslam RR. Thyrotropin-releasing hormone added to corticosteroids
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Ibrahim 2003
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Liggins 1988
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GC, Schellenberg JC, Manzai M, Kitterman JA, Lee CC. Synergism of cortisol
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WJ, Verloove-Vanhorick SP, Brand R, van den Brande JL. Transient hypothyroxinaemia
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Osborn 2001
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N, Pinto-Martin JA, Lorenz JM, Susser M. The relation of transient hypothyroxinemia
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Semba RD, Delange F. Iodine in human milk: perspectives for infant health. Nutrition Reviews 2001;59:269-78.
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Wassenaer AG, Kok JH, de Vijlder JJ, Briet JM, Smit BJ, Tamminga P, et al.
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Comparisons and data
01 Enteral iodine supplementation versus control
01.01 Death before hospital discharge
01.02 Chronic lung disease in surviving infants (supplemental oxygen requirement at 36 weeks' post-conceptional age)
01.03 Chronic lung disease or prior death
01.04 Total plasma thyroxine (nmol/L) at 30 weeks' post-conception
01.05 Total plasma thyroxine (nmol/L) at 35 weeks' post-conception
01.06 Total plasma tryroxine (nmol/L) at 40 weeks' post-conception
01.07 Total plasma triiodothyronine (nmol/L) at 30 weeks' post-conception
01.08 Total plasma triiodothyronine (nmol/L) at 35 weeks' post-conception
01.09 Total plasma triiodothyronine (nmol/L) at 40 weeks' post-conception
01.10 Free thyroxine (pmol/L) at 30 weeks' post-conception
01.11 Free thyroxine (pmol/L) at 35 weeks' post-conception
01.12 Free thyroxine (pmol/L) at 40 weeks' post-conception
01.13 Thyrotrophin (mU/L) at 30 weeks' post-conception
01.14 Thyrotrophin (mU/L) at 35 weeks' post-conception
01.15 Thyrotrophin (mU/L) at 40 weeks' post-conception
Comparison or outcome | Studies | Participants | Statistical method | Effect size |
---|
01 Enteral iodine supplementation versus control |
01 Death before hospital discharge | 1 | 121 | RR (fixed), 95% CI | 0.33 [0.01, 7.89] |
02 Chronic lung disease in surviving infants (supplemental oxygen requirement at 36 weeks' post-conceptional a | 1 | 120 | RR (fixed), 95% CI | 0.64 [0.38, 1.09] |
03 Chronic lung disease or prior death | 1 | 121 | RR (fixed), 95% CI | 0.63 [0.38, 1.06] |
04 Total plasma thyroxine (nmol/L) at 30 weeks' post-conception | 1 | 119 | WMD (fixed), 95% CI | 3.00 [-9.23, 15.23] |
05 Total plasma thyroxine (nmol/L) at 35 weeks' post-conception | 1 | 110 | WMD (fixed), 95% CI | 0.00 [-10.34, 10.34] |
06 Total plasma tryroxine (nmol/L) at 40 weeks' post-conception | 1 | 113 | WMD (fixed), 95% CI | -2.00 [-11.96, 7.96] |
07 Total plasma triiodothyronine (nmol/L) at 30 weeks' post-conception | 1 | 115 | WMD (fixed), 95% CI | 0.02 [-0.16, 0.20] |
08 Total plasma triiodothyronine (nmol/L) at 35 weeks' post-conception | 1 | 109 | WMD (fixed), 95% CI | 0.01 [-0.14, 0.16] |
09 Total plasma triiodothyronine (nmol/L) at 40 weeks' post-conception | 1 | 110 | WMD (fixed), 95% CI | 0.11 [-0.07, 0.29] |
10 Free thyroxine (pmol/L) at 30 weeks' post-conception | 1 | 95 | WMD (fixed), 95% CI | -1.10 [-4.05, 1.85] |
11 Free thyroxine (pmol/L) at 35 weeks' post-conception | 1 | 100 | WMD (fixed), 95% CI | -1.10 [-3.48, 1.28] |
12 Free thyroxine (pmol/L) at 40 weeks' post-conception | 1 | 107 | WMD (fixed), 95% CI | -0.40 [-1.67, 0.87] |
13 Thyrotrophin (mU/L) at 30 weeks' post-conception | 1 | 117 | WMD (fixed), 95% CI | -0.30 [-0.79, 0.19] |
14 Thyrotrophin (mU/L) at 35 weeks' post-conception | 1 | 108 | WMD (fixed), 95% CI | -0.20 [-0.69, 0.29] |
15 Thyrotrophin (mU/L) at 40 weeks' post-conception | 1 | 111 | WMD (fixed), 95% CI | 0.08 [-0.28, 0.44] |
Notes
Published notes
Contact details for co-reviewers
Dr William McGuire
Associate Professor of Neonatology
Department of Paediatrics and Child Health
Australian National University Medical School
Canberra Hospital Campus
Canberra
ACT 2606 AUSTRALIA
Telephone 1: +61 2 62442222
Facsimile: +61 2 62443112
E-mail: william.mcguire@act.gov.au
Secondary address:
Tayside Institute of Child Health
Ninewells Hospital and Medical School
Dundee
Scotland UK
DD6 8DL
Telephone: 0044 1382 633942
Facsimile: 0044 1382 632597Dr John KH Sinn
Staff Specialist
Neonatal Unit
Westmead Hospital
Hawkesbury Road
Westmead
New South Wales AUSTRALIA
2145
Telephone 1: 612 9845 8748
Facsimile: 02 9845 7490
E-mail: johnsinn@westgate.wh.usyd.edu.au
The review is published as a Cochrane review in The
Cochrane Library, Issue 2, 2006 (see http://www.thecochranelibrary.com for
information). Cochrane reviews are regularly updated as new evidence emerges
and in response to comments and criticisms, and The Cochrane Library should
be consulted for the most recent version of the Review.
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