Neonatal Feeding Trajectories in Mothers With Bipolar Disorder Taking Lithium: Pharmacokinetic Data

Abstract

Purpose: Women who take lithium during pregnancy and continue after delivery may choose to breastfeed, formula feed, or mix these options. The aim of the study was to evaluate the neonatal lithium serum concentrations based on these three feeding trajectories.Methods: We followed 24 women with bipolar disorder treated with lithium monotherapy during late pregnancy and postpartum (8 per trajectory). Lithium serum concentrations were determined by an AVL 9180 electrolyte analyser with a 0.10 mEq/L detection limit and a 0.20 mEq/L limit of quantification (LoQ).Results: There was complete lithium placental passage at delivery, with a mean ratio of lithium concentration in the umbilical cord to maternal serum of 1.12 ± 0.17. The median times to LoQ were 6–8, 7–8, and 53–60 days for formula, mixed, and exclusive breastfeeding respectively. The generalized log-rank testing indicated that the median times to LoQ differ according to feeding trajectory (p = 0.037). According to the multivariate analysis-adjusted lithium serum concentrations at birth, times to LoQ are, on average, longer under exclusive breastfeeding (formula, p = 0.015; mixed, p = 0.012). No lithium accumulation was observed in infants under either exclusive or mixed breastfeeding. During the lactation follow-up, there was no acute growth or developmental delays in any neonate or infant. Indeed, lithium concentrations in the three trajectories declined in all cases. However, the time needed to reach the LoQ was much longer for those breastfeeding exclusively.Conclusions: In breastfeed infant no sustained accumulation of lithium and no adverse effects on development or growth were observed.

Early Postnatal Outcome and Care after in Utero Exposure to Lithium: A Single Center Analysis of a Belgian Tertiary University Hospital

“…The available information was based on a small and heterogeneous number of case reports or case series, and the quality of the studies included was all less than optimal [ 44 ]. In 2021, it was documented that the median times for lithium serum concentration to reach a limit of quantification of 0.20 mEq/L in full-term neonates of mothers with lithium monotherapy, and receiving formula, mixed (formula/breastfeeding), or exclusive breastfeeding were 6–8, 7–8, and 53–60 days respectively [ 45 ]. Very recently, Heinonen et al (2022) considered lithium during breastfeeding safe in selected cases, and under strict follow-up [ 46 ].…”

“…As derived from Figure 4 , sampling after day 1 mainly occurred on days 3–4. Imaz et al recommend sampling at birth, after 2 days (i.e., 48 h) and 1 week postpartum for all neonatal feeding trajectories, and additionally at 1 and 2 months in case of exclusive breastfeeding during maternal lithium use [ 44 , 45 ]. In addition, if neonatal lithemia is <0.2 mmol/L, an additional measurement is only recommended in case of symptoms [ 45 ].…”

“…Imaz et al recommend sampling at birth, after 2 days (i.e., 48 h) and 1 week postpartum for all neonatal feeding trajectories, and additionally at 1 and 2 months in case of exclusive breastfeeding during maternal lithium use [ 44 , 45 ]. In addition, if neonatal lithemia is <0.2 mmol/L, an additional measurement is only recommended in case of symptoms [ 45 ]. Since our median neonatal lithium TDM only fell below 0.20 mmol/L from day 5 ( Figure 4 ), we suggest follow-up at least until this moment, coinciding with the clinical observation period of 5 days.…”

Lithium in breast milk transiently affects the renal electrolytic balance of infants

“…With regards to the risks, clinical data are limited 51,52 ; some case series are reassuring 53 while other studies report cases of hypotonia 18 and hypothyroidism, 17 which can have long-term consequences on cognitive and neuro development of the child. Our study in rats suggests that lithium use during breastfeeding could lead to abnormal renal function which warrants further study in humans.…”

Postpartum psychosis: A proposed treatment algorithm

“…Some evidence suggests that lithium may not be an absolute contraindication in breastfeeding, particularly in lithium monotherapy in infants over 2 months of age (Hermann et al, 2019;LactMed, 2022;Newmark et al, 2019;Uguz and Sharma, 2016). Infant serum lithium concentrations were compared among different feeding strategies (exclusive breastfeeding, formula feeding, and combination breast and formula feeding; n = 8 participants in each group) in a recent study of women with bipolar disorder taking lithium and their infants (Imaz et al, 2021). There were no adverse infant effects reported in this study in the first 2 months postpartum.…”