Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy.
OBJECTIVE
Lithium has been used during pregnancy for more than four decades, but quantification of fetal lithium exposure and clinical correlations of such exposure are limited. The study objectives were to 1) quantify the rate of lithium placental passage, 2) assess any association between plasma concentration of lithium at delivery and adverse perinatal events, and 3) determine whether lithium concentrations can be reduced by briefly suspending therapy proximate to delivery.


METHODS
Maternal blood and umbilical cord blood were obtained at delivery for assay of lithium concentrations, and obstetrical outcome data were collected prospectively for 10 participants. These data were combined with results from MEDLINE and PsycINFO searches that identified 32 cases in which maternal lithium was administered throughout delivery. Statistical analysis of the pooled data was conducted.


RESULTS
The ratio of lithium concentrations in umbilical cord blood to maternal blood (mean=1.05, SD=0.13) was uniform across a wide range of maternal concentrations (0.2-2.6 meq/liter). Significantly lower Apgar scores, longer hospital stays, and higher rates of CNS and neuromuscular complications were observed in infants with higher lithium concentrations (>0.64 meq/liter) at delivery. Withholding lithium therapy for 24-48 hours before delivery resulted in a 0.28 meq/liter reduction in maternal lithium concentration.


CONCLUSIONS
Lithium completely equilibrates across the placenta. Higher lithium concentrations at delivery are associated with more perinatal complications, and lithium concentrations can be reduced by brief suspension of therapy proximate to delivery. Treatment guidelines are proposed to improve neonatal well-being when lithium use is indicated in late pregnancy.
Newport
D Jeffrey
DJ
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. jeff.newport@emory.edu
Viguera
Adele C
AC
Beach
Aquila J
AJ
Ritchie
James C
JC
Cohen
Lee S
LS
Stowe
Zachary N
ZN
D001034:Apgar Score; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn / Q000097:blood; D008094:Lithium / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D036801:Parturition / Q000187:drug effects / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D011446:Prospective Studies
D008094:Lithium