The grades of evidence (I-III) and levels of recommendations (A-C) are defined at the end of "Major Recommendations."
The following recommendations and conclusions are based on good and consistent scientific evidence (Level A):
- Lithium exposure in pregnancy may be associated with a small increase in congenital cardiac malformations, with a risk ratio of 1.2 to 7.7.
- Valproate exposure in pregnancy is associated with an increased risk of fetal anomalies, including neural tube defects, fetal valproate syndrome, and long term adverse neurocognitive effects. It should be avoided in pregnancy, if possible, especially during the first trimester.
- Carbamazepine exposure in pregnancy is associated with fetal carbamazepine syndrome. It should be avoided in pregnancy, if possible, especially during the first trimester.
- Maternal benzodiazepine use shortly before delivery is associated with floppy infant syndrome.
The following recommendations and conclusions are based on limited or inconsistent scientific evidence (Level B):
- Paroxetine use in pregnant women and women planning pregnancy should be avoided, if possible. Fetal echocardiography should be considered for women who are exposed to paroxetine in early pregnancy.
- Prenatal benzodiazepine exposure increased the risk of oral cleft, although the absolute risk increased by 0.01%.
- Lamotrigine is a potential maintenance therapy option for pregnant women with bipolar disorder because of its protective effects against bipolar depression, general tolerability, and a growing reproductive safety profile relative to alternative mood stabilizers.
- Maternal psychiatric illness, if inadequately treated or untreated, may result in poor compliance with prenatal care, inadequate nutrition, exposure to additional medication or herbal remedies, increased alcohol and tobacco use, deficits in mother–infant bonding, and disruptions within the family environment.
The following recommendations and conclusions are based primarily on consensus and expert opinion (Level C):
- Whenever possible, multidisciplinary management involving the patient's obstetrician, mental health clinician, primary health care provider, and pediatrician is recommended to facilitate care.
- Use of a single medication at a higher dose is favored over the use of multiple medications for the treatment of psychiatric illness during pregnancy.
- The physiologic alterations of pregnancy may affect the absorption, distribution, metabolism, and elimination of lithium, and close monitoring of lithium levels during pregnancy and postpartum is recommended.
- For women who breastfeed, measuring serum levels in the neonate is not recommended.
- Treatment with all selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors or both during pregnancy should be individualized.
- Fetal assessment with fetal echocardiogram should be considered in pregnant women exposed to lithium in the first trimester.
Grades of Evidence
I Evidence obtained from at least one properly designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled trials without randomization.
II-2 Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.
II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.
III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Levels of Recommendations
Level A - Recommendations are based on good and consistent scientific evidence.
Level B - Recommendations are based on limited or inconsistent scientific evidence.
Level C - Recommendations are based primarily on consensus and expert opinion.