Introduction

Lithium is an effective mood stabilizer and is widely used as a first-line treatment for bipolar disorder in the perinatal period. Several guidelines have provided clinical advice on dosing strategy ( dose reduction versus stop lithium) in the peripartum period to minimize the risk of neonatal complications. An association has been observed between high neonatal lithium concentrations (> 0.64 mEq/L) and lower 1-min Apgar scores, longer hospital stays, and central nervous system and neuromuscular complications.

Objectives

To quantify the rate of lithium placental passage at delivery.

To assess any association between plasma concentration of lithium at delivery and neonatal outcome.

Methods

In this retrospective observational cohort study, we included women treated with llithium at least in late pregnancy. Maternal (MB) and umbilical cord (UC) lithium blood level measurement were collected at delivery. Lithium serum concentrations were determined by means of an AVL 9180 electrolyte analyzer. The limit of quantification (LoQ) was 0.20 mEq/L and detection limit was 0.10 mEq/L.

From the medical records, we extracted information on neonatal outcomes (preterm birth, birth weight, Apgar scores, pH-values, and admision to NICU) and complications categoriced by organ system: respiratory, circulatory, hematological, gastro-intestinal, metabolic, neurological, and immune system (infections).

Results

Umbilical cord and maternal lithium blood levels were strongly correlated: mean (SD) range UC/MR ratio 1.15 (0.24).

Umbilical cord lithium levels ranged between 0.20 to 1.42 mEq/L.

We observed no associations between umbilical cord lithium blood levels at delivery and neonatal outcomes.

Conclusions

In our study, newborns tolerated well a wide range of lithemias, between 0.20 and 1.42 mEq/L.

Introduction

Clozapine is a second-generation antipsychotic agent approved for treatment-resistant schizophrenia and risk reduction of recurrent suicidal behavior in schizophrenia and schizoaffective disorder. Given the known negative consequences of relapse of severe mental disorders for both mother and infant, the maintenance of clozapine during pregnancy is recommended.¹ Studies of pregnancy regarding to clozapine have demonstrated a heterogenous range of neonatal and infant complications.²

Objectives

To evaluate neonatal and infants outcomes of clozapine exposure in pregnancy.

Methods

We report three cases of infants exposed to clozapine politherapy throughout pregnancy. The dose range for all women on clozapine was 200-600 mg/day. Infants were evaluated between 4-6 months of chronological age with the Bayley-III infant development scale (BSID-III)³ and with the Alarme Détresse Bébé Scale (ADBB)⁴ for the detection of early-signs of withdrawal.

Results

Women remained stable during pregnancy but presented obesity and gestational diabetes. Clozapine Newborn were born to term by caesarean section due to breech presentation (N=2) or instrumental delivery due to loss of fetal well-being (N=1). They presented normal weight (3500-3800 gr). Two presented Apgar_min1-5 9/10 and one Apgar_min1-5 6/8 which showed lethargy and low alertness during the first weeks of life. All showed normal capacity for sociability, reciprocity and development of language and communication. However, one baby had scores in the low normal zone for cognition and another for motor skills.

Conclusions

The infant’s risks of clozapine exposure during pregnancy should be discussed with women and weighed against those associated with other treatments and/or with untreated severe mental illness.

Introduction

Women who take lithium during pregnancy and continue after delivery may opt to breastfeed, formula feed, or mix these options.

Objectives

To evaluate the neonatal lithium plasma concentrations and nursing infant outcomes based on these three feeding trajectories.

Methods

We followed 24 women with bipolar disorder on 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

The mean ratio of lithium concentration in the umbilical cord to maternal serum being 1.12 (0.17). We used the Turnbull estimator for interval-censored data to estimate the probability that the LoQ was reached as a function of time. The median times to LoQ was 6–8, 7–8, and 53–60 days for formula, mixed, and breastfeeding, respectively. Generalised log-rank testing indicated that the median times to LoQ differed by feeding trajectory (p = 0.037). Multivariate analysis confirmed that the differences remained after adjusting for serum lithium concentrations at birth (formula, p = 0.015; mixed, p = 0.012). We did not found any acute observable growth or developmental delays in any of the neonates/infants.

Conclusions

Lithium did not accumulate in the infant under either exclusive or mixed-breastfeeding. Lithium concentrations declined in all trayectories. The time needed to reach the LoQ was much longer for those breastfeeding exclusively. Lithium transfer via breastmilk is much less than via the placenta. We did not found any acute observable growth or developmental delays in any infant during follow-up.