Epidemiology studies on effects of lithium salts in pregnancy are confounded by the inability to control for other potentially teratogenic factors.

INTRODUCTION: In bipolar women who took lithium during pregnancy, several epidemiology studies have reported small increases in a rare fetal cardiac defect termed Ebstein's anomaly. METHODS: Behavioral, environmental, and lifestyle-associated risk factors associated with bipolar disorder and health insurance status were determined from an Internet search. The search was conducted from October 1, 2023, through October 14, 2023. The search terms employed included the following: bipolar, bipolar disorder, mood disorders, pregnancy, congenital heart defects, Ebstein's anomaly, diabetes, hypertension, Medicaid, Medicaid patients, alcohol use, cigarette smoking, marijuana, cocaine, methamphetamine, narcotics, nutrition, diet, obesity, body mass index, environment, environmental exposures, poverty, socioeconomic status, divorce, unemployment, and income. No quotes, special fields, truncations, etc., were used in the searches. No filters of any kind were used in the searches. RESULTS: Women who remain on lithium in the United States throughout their pregnancy are likely to be experiencing mania symptoms and/or suicidal ideation refractory to other drugs. Pregnant women administered the highest doses of lithium salts would be expected to have been insufficiently responsive to lower doses. Any small increases in the retrospectively determined risk of fetal cardiac anomalies in bipolar women taking lithium salts cannot be disentangled from potential developmental effects resulting from very high rates of cigarette smoking, poor diet, alcohol abuse, ingestion of illegal drugs like cocaine or opioids, marijuana smoking, obesity, and poverty. CONCLUSIONS: The small risks in fetal cardiac abnormalities reported in the epidemiology literature do not establish a causal association for lithium salts and Ebstein's anomaly.

When lithium hurts: a look at Ebstein anomaly.

Ebstein anomaly (EA) is a congenital defect of the tricuspid valve (TV) and the right ventricle (RV) in which the attachments of the septal and posterior valve leaflets are apically displaced. The latter creates 3 morphologic components inside the right heart, namely the right atrium proper, the atrialized RV, and the functional RV. This rare anomaly accounts for <1.5% of all congenital heart diseases. The current opinion among authors is that it is a genetically heterogeneous condition caused by failure of delamination of the TV leaflets from the underlying myocardium and the interventricular septum. Its characteristic electrocardiographic findings include tall, broad, right atrial P waves, prolonged PR intervals, and deep Q waves in the right precordial leads. Echocardiography is currently the best technique for diagnosing this anomaly, although cardiac magnetic resonance imaging is also gaining traction as an alternative modality. The management strategies for EA correlate with the age of the patient, severity of the heart disease, and/or associated cardiac abnormalities. TV repair, rather than valve replacement, is preferred because of its favorable long-term prognosis. Nevertheless, a large, randomized study is still needed to compare the different valve repair techniques used in patients with EA.

[Lithium and bipolar disorder--a renaissance?]. / Lithium und bipolare Erkrankung--eine Renaissance?

OBJECTIVE: Overview and discussion regarding the use and relevance of lithium as an therapeutic agent for bipolar disorder in general, with a special focus on pregnancy, suicidality and possible side-effects. METHOD: Literature was handsearched and by searches of medline with special interest in recent results and comparative studies. RESULTS: Lithium is still of high importance in the treatment of bipolar disorder. It is unmatched regarding decades of clinical experience and scientific evidence. It has a proven efficacy in every spectrum of bipolar illness, with less profound data regarding acute bipolar depression. Especially long term treatment of bipolar patients with lithium shows clear clinical benefits i.e.: importance of a continuous setting, gain of mood stabilizing effect over time, no loss of efficacy, reduced morbidity and mortality. DISCUSSION: Lithium should be regarded as a first line treatment for bipolar disorder.

Anomalía de Ebstein y exposición al litio en el embarazo / Ebstein’s anomaly and lithium exposure during pregnancy

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A reevaluation of risk of in utero exposure to lithium.

OBJECTIVE: To reevaluate the risk associated with in utero exposure to lithium. DATA SOURCES AND STUDY SELECTION: Data were obtained from all published studies, in multiple languages, referenced in MEDLINE, Toxline, and the Lithium Information Center databases. Unpublished studies were not included. The search terms were lithium, pregnancy, teratogen, abnormalities (drug induced), Ebstein's anomaly, and adverse effects. DATA EXTRACTION AND SYNTHESIS: In the 1970s a very strong association was suggested between maternal lithium treatment during pregnancy and Ebstein's anomaly of the heart in the offspring. The relative risk for Ebstein's anomaly among such children was estimated to be 400 on the basis of data collected from a registry of voluntarily submitted cases. More recent controlled epidemiologic studies have consistently shown a lower risk. No women who took lithium during pregnancy were found among four case-control studies of Ebstein's anomaly involving 25, 34, 59, and 89 affected children, respectively. In two cohort studies, risk ratios of 3.0 (95% confidence interval [CI], 1.2 to 7.7) and 1.5 (95% CI, 0.4 to 6.8) for all congenital anomalies have been observed. The risk ratios for cardiac malformations in these studies were 7.7 (95% CI, 1.5 to 41.2) and 1.2 (95% CI, 0.1 to 18.3), respectively. CONCLUSION: While initial information regarding the teratogenic risk of lithium treatment was derived from biased retrospective reports, more recent epidemiologic data indicate that the teratogenic risk of first-trimester lithium exposure is lower than previously suggested. The clinical management of women with bipolar disorder who have childbearing potential should be modified with this revised risk estimate.

[Ebstein's anomaly of the tricuspid valve following prenatal exposure to lithium]. / Anomalie van Ebstein van de tricuspidalisklep na expositie aan lithium voor de geboorte.

An 18-year-old man visited the outpatient cardiology clinic because of a cardiac murmur found at a medical examination for military service. An Ebstein's anomaly was diagnosed, with tricuspid valve insufficiency. Exposure to lithium in utero was established. Literature reports indicate an association between exposure to lithium in utero and cardiac anomalies, notably Ebstein's anomaly.

Lithium and Ebstein's anomaly.

The article deals with Ebstein's anomaly, lithium and their relationship. Some studies suggest that lithium might be involved as a teratogen increasing the incidence of Ebstein's anomaly in the offspring of female patients with manio-depressive psychosis and lithium-administered during pregnancy. The second part of the article contains data on the incidence of Ebstein's anomaly in the Czech Socialist Republic between 1960 and 1985. The results indicate a steady rise in the incidence of this congenital malformation over the above period of time.

Lithium efficacy and adverse effects.

The primary use of lithium is as maintenance treatment of bipolar disorders to prevent relapse. Although it effectively treats acute mania, lithium must often be used in conjunction with neuroleptics. Once-daily lithium therapy may help avoid some side effects and long-term renal damage. Neurotoxicity can be a problem for a small number of sensitive patients when neuroleptics and lithium are combined. Whenever possible, lithium should be avoided in the first trimester of pregnancy because of its potential for inducing cardiovascular abnormalities in the fetus.

Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography.

Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. Cross-sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium-induced cardiac malformations.

Cardiovascular malformations with lithium use during pregnancy.

The 143 cases of lithium use during pregnancy collected by the Register of Lithium Babies show that infants exposed to lithium appear to have a higher than expected ratio of cardiovascular anomalies to all anomalies and may have an increased risk of congenital heart disease. The authors believe that these findings justify a conservative policy on the use of lithium with fertile and pregnant women.