—(Medscape-- Nov. 29, 2005) — There is a strong correlation between infant levels and maternal levels of lithium at the time of delivery, according to the results of a study published in the November issue of the American Journal of Psychiatry. The investigators provide guidelines for managing peripartum lithium.

"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," write D. Jeffrey Newport, M.D., M.S., M.Div., from Emory University School of Medicine, and colleagues. "The literature includes numerous reports of neonatal complications in association with lithium treatment during late pregnancy, including cardiac dysfunction, diabetes insipidus, hypothyroidism, low muscle tone, lethargy, hepatic abnormalities, and respiratory difficulties."

The objectives of this study were to quantify the rate of lithium placental passage, to determine any association between plasma concentration of lithium at delivery and adverse perinatal events, and to determine whether lithium concentrations can be reduced by briefly suspending therapy proximate to delivery.

In 10 women, lithium was assayed in maternal blood and umbilical cord blood at delivery, and obstetrical outcome data were collected prospectively. These data were pooled with those from 32 cases in which maternal lithium was administered throughout delivery, identified from MEDLINE and PsycINFO searches.

Across a wide range of maternal concentrations (0.2 - 2.6 mEq/L), the ratio of lithium concentrations in umbilical cord blood to maternal blood was uniform (mean, 1.05 ± 0.13). Infants with higher lithium concentrations (>0.64 mEq/L) at delivery had significantly lower Apgar scores, longer hospital stays, and higher rates of central nervous system (CNS) and neuromuscular complications. Withholding lithium therapy for 24 to 48 hours before delivery reduced maternal lithium concentrations by 0.28 mEq per L.

"Lithium completely equilibrates across the placenta," the authors write. "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."

To improve neonatal well-being when lithium use is indicated in late pregnancy, the authors propose the following guidelines:

• Maintain a target lithium concentration at the minimum effective level (sometimes lower than the ideal cited of 0.8 to 1.0 mEq/L).
• Periodically monitor lithium concentrations during pregnancy, especially during late gestation when marked changes in glomerular filtration rate can alter lithium clearance.
• During pregnancy, avoid treatments that increase the potential for lithium toxicity, but if such measures are needed, more frequent lithium monitoring and dose reduction are indicated.
• When pregnancy is complicated by preeclampsia, polyhydramnios, or other conditions predisposing the mother or her child to lithium toxicity, lower the maternal lithium dose. Oligohydramnios or other abnormality in amniotic fluid volume could also increase the likelihood of lithium-associated fetal nephrotoxicity.
• Suspend lithium treatment 24 to 48 hours before a scheduled cesarean section or induction or at the onset of labor in the event of spontaneous delivery.
• Check the maternal lithium concentration when the mother presents to the hospital for delivery.
• Administer oral and/or intravenous fluids throughout labor and delivery, and check maternal lithium concentration if there are clinical signs of toxicity.
• As soon as the mother is medically stabilized after delivery, reinstitute lithium therapy at the preconception dose, because the maternal glomerular filtration rate rapidly returns to pregravid levels after delivery.
Study limitations include the small number of participants, limited statistical power to elucidate the association between clinical outcome and lithium concentration, limited generalizability of the results because of a homogeneous population, and inclusion of case data from earlier reports, some of which were incomplete.

"Given the considerable morbidity of untreated bipolar disorder and the significant risk of perinatal relapse in the absence of continued pharmacotherapy, prolonged discontinuation of treatment is seldom a viable option," the authors write. "Despite documented concerns about effects of lithium in reproduction, this medication remains the preferred alternative during gestation for many women with bipolar disorder. When lithium is used during late pregnancy, infant and maternal well-being can be maximized by maintaining maternal concentrations at the minimal effective level, suspending lithium therapy 24 - 48 hours before delivery to reduce neonatal concentrations further, and avoiding inadvertent or iatrogenic lithium toxicity during gestation."

The National Institutes of Health have disclosed that it supported this study.

Am J Psych. 2005; 162:2162-2170 “Lithium Placental Passage and Obstetrical Outcome: Implications for Clinical Management During Late Pregnancy.” Authors: Newport, D.J., Viguera, A.C., Beach A.J., Ritchie J.C., Cohen L.S. and Stowe Z.N. Newport is a NARSAD 2003 Young Investigator. Viguera received NARSAD Young Investigator Awards in 1999 and 2002. Cohen has had two NARSAD Awards: a Young Investigator Award in 1993 and an Independent Investigator Award in 1998.

Reprinted with permission from Medscape Medical News 2005. The original url for the article is: http://www.medscape.com/viewarticle/518041 © 2005, Medscape. This article was originally certified for CME credit on Medscape. Return to the original link to obtain CME credit. Please be advised that Medscape requires registration to view articles.