But increase in risk of neonatal readmission, major malformations There was no link between lithium use in pregnancy and certain pregnancy complications or adverse delivery outcomes, though there was a higher risk of hospital readmission and congenital malformations, a meta-analysis found. An examination of six international cohorts found that pregnant women who took lithium were not associated with increased pregnancy complications (including pre-eclampsia, diabetes during pregnancy, fetal distress, post-partum hemorrhage) or labor and delivery outcomes (including cesarean section, preterm birth, low birthweight or small-for-gestational-age infants), reported Trine Munk-Olsen, PhD, of Aarhus University in Denmark, and colleagues. However, there was an increased risk of major congenital malformations associated with lithium use in the first trimester, as well as increased risk of neonatal readmissions linked to lithium, the authors wrote in The Lancet Psychiatry. They noted that for women with bipolar disorder, treatment with lithium can "reduce the risk of relapse during both pregnancy and post-partum," according to previous research published in the American Journal of Psychiatry. But concerns about teratogenicity and the potential for renal or thyroid problems or preterm birth restrict its use, they said. The authors also cited congenital anomalies due to teratogenicity as a potential concern of lithium use in the first trimester. Human studies echoed the earlier findings of animal studies, which found risk of malformations, preterm birth and other pregnancy and neonatal complications -- though they noted that these findings are "not consistent across all studies," and the results may have been complicated by either lack of statistical power, recall bias or other confounding variables. Researchers examined six international cohorts from Denmark, Sweden, Ontario, Canada, the Netherlands, the U.K. and the U.S. Participants were eligible if health-related information was available for both mother and infant, and if mother had a mood disorder or she had been given lithium during pregnancy. Outcomes included pregnancy complications (during pregnancy or within 42 days after delivery), labor and delivery outcomes identified in the hospital, neonatal hospital readmission within 28 days of birth and congenital malformations in the infant. Overall, there were 22,124 eligible pregnancies, 727 of which were classified as being exposed to lithium. Compared with the reference group, women in the lithium-exposed group were more likely to be older, nulliparous and to have filled a prescription for a psychotropic drug other than lithium during pregnancy. Prevalence of neonatal readmission to the hospital within 28 days of birth was higher among the lithium-exposed group compared to the reference group (27.5% versus 4.3%, respectively, pooled adjusted OR 1.62, 95% CI 1.12 to 2.33). There was also a higher prevalence of major malformations for infants in the lithium-exposed group (7.2% versus 4.3% in the reference group). The authors also noted that 654 out of the 727 lithium-exposed infants had exposure during the first trimester (7.4% in lithium group versus 4.3% in reference group, pooled aOR 1.71, 95% CI 1.71, 95% CI 1.07 to 2.72). "Given the well-documented effectiveness of lithium in reducing relapse in the perinatal period, some important clinical considerations are either to continue lithium in a lower dose during the first trimester or to restart lithium after the first trimester or immediately postpartum," co-author Veerle Bergink, MD, of the Icahn School of Medicine at Mount Sinai in New York City said in a statement. However, there was no increased risk of major cardiac malformations in the lithium-exposed group compared with the reference group, the authors said. Moreover, while there was a higher risk of congenital malformations linked to lithium use in the first trimester of pregnancy, the authors stated that their results, along with those in an earlier study, suggest "the absolute risk of malformations is much smaller than those reported in earlier studies." Limitations to the data included that only pregnancies resulting in a liveborn infant were included, that the sample lacked statistical power to study rare events (specifically, there were only 16 cases of major cardiac malformations in infants with lithium exposure in the first trimester) and that residual confounding cannot be ruled out, due to the observational nature of the research. Source
