Lithium and Pregnancy--I, Report from the Register of Lithium Babies

Abstract

SummaryWe have collected information about 118 children born to mothers who were given lithium treatment during the first trimester of pregnancy. The data show that the risk of teratogenic effects is lower than one might have expected from some of the studies carried out on rats and mice; they do not answer the question of whether or not lithium is teratogenic in man. The data were collected retrospectively and therefore overestimate rather than underestimate the risk of teratogenicity. Introduction It has been known for many years that lithium (lithium salts, lithium ions) added to the medium surrounding eggs of sea urchins, snails, and other lower organisms may interfere with morphogenesis so that monsters are produced (Herbst, 1893;Schou, 1957

Lithium Use in Pregnancy and the Risk of Cardiac Malformations

“…1 Results from this registry-based study were interpreted as supporting a risk of Ebstein’s anomaly that was increased by a factor of 400 among infants exposed in utero to lithium, 3 despite substantial methodologic limitations, including the lack of a control group and a possible over-representation of cases owing to retrospective enrollment. 4 Since then, anecdotal reports 10–14 and small studies have been published with inconclusive results (Table S1 in the Supplementary Appendix).…”

“…In the early 1970s, results from the International Register of Lithium Babies evaluating infants born to mothers who were treated with lithium early in pregnancy 1,2 suggested a risk of Ebstein’s anomaly, a right ventricular outflow tract obstruction defect, that was increased by a factor of 400 (on the basis of two cases associated with lithium exposure) and a risk of overall cardiac defects that was increased by a factor of 5. 3 By 1979, the final report included data on 225 infants born to lithium-exposed women; 18 infants had congenital cardiac defects (8%), including 6 with Ebstein’s anomaly (3%).…”

“…Several small case–control studies failed to show an association between lithium and Ebstein’s anomaly, 15–19 overall cardiac defects, 20 or any congenital malformations. 21 In two uncontrolled cohort studies of lithium-exposed pregnancies, no cardiac malformations were detected in the 82 newborns examined 22,23 ; another uncontrolled study showed four mild cardiac defects in 79 exposed infants.…”

The pharmacology of bipolar disorder during pregnancy and breastfeeding

“…The teratogenic and toxic effects of lithium, including cardiac malformations, have long been known [18][19][20][21][22][23][24][25][26]. Lithium use in pregnancy has been associated in open, multi-centred studies with an increased risk of cardiac malformations of Ebstein type [18,24], and in case reports with atrial flutter in a neonate [27], toxicity to the fetal thyroid [28] and goitre [21], nephrogenic diabetes insipidus in a neonate [29,30], and gross functional lesions of the cardiovascular, renal and neuromuscular systems with no structural abnormalities in a neonate [31]. There is some evidence to suggest an association between transplacental lithium exposure and premature birth, macrosomia and increased perinatal mortality [32].…”

“…Schou et al identified the adverse safety issues with lithium and pregnancy 30 years ago in three papers [18,38,39], but concluded that the risks were not sufficient to contraindicate the use of lithium during pregnancy. They also believed that the risks associated with breastfeeding were small but that bottle-feeding was advisable.…”