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Lithium Use in Pregnancy and the Risk of Cardiac Malformations.

Abstract There has been concern that exposure to lithium early in pregnancy may be associated with a marked increase in the risk of Ebstein's anomaly (a right ventricular outflow tract obstruction defect) in infants and overall congenital cardiac defects, but data are conflicting and limited.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title the new england journal of medicine
Publication Year Start




PMID- 28591541
OWN - NLM
STAT- MEDLINE
DA  - 20170607
DCOM- 20170620
LR  - 20170620
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 376
IP  - 23
DP  - 2017 Jun 08
TI  - Lithium Use in Pregnancy and the Risk of Cardiac Malformations.
PG  - 2245-2254
LID - 10.1056/NEJMoa1612222 [doi]
AB  - BACKGROUND: There has been concern that exposure to lithium early in pregnancy
      may be associated with a marked increase in the risk of Ebstein's anomaly (a
      right ventricular outflow tract obstruction defect) in infants and overall
      congenital cardiac defects, but data are conflicting and limited. METHODS: We
      conducted a cohort study involving 1,325,563 pregnancies in women who were
      enrolled in Medicaid and who delivered a live-born infant between 2000 and 2010. 
      We examined the risk of cardiac malformations among infants exposed to lithium
      during the first trimester as compared with unexposed infants and, in secondary
      analyses, with infants exposed to another commonly used mood stabilizer,
      lamotrigine. Risk ratios and 95% confidence intervals were estimated with control
      for psychiatric and medical conditions, medications, and other potential
      confounders. RESULTS: Cardiac malformations were present in 16 of the 663 infants
      exposed to lithium (2.41%), 15,251 of the 1,322,955 nonexposed infants (1.15%),
      and 27 of the 1945 infants exposed to lamotrigine (1.39%). The adjusted risk
      ratio for cardiac malformations among infants exposed to lithium as compared with
      unexposed infants was 1.65 (95% confidence interval [CI], 1.02 to 2.68). The risk
      ratio was 1.11 (95% CI, 0.46 to 2.64) for a daily dose of 600 mg or less, 1.60
      (95% CI, 0.67 to 3.80) for 601 to 900 mg, and 3.22 (95% CI, 1.47 to 7.02) for
      more than 900 mg. The prevalence of right ventricular outflow tract obstruction
      defects was 0.60% among lithium-exposed infants versus 0.18% among unexposed
      infants (adjusted risk ratio, 2.66; 95% CI, 1.00 to 7.06). Results were similar
      when lamotrigine-exposed infants were used as the reference group. CONCLUSIONS:
      Maternal use of lithium during the first trimester was associated with an
      increased risk of cardiac malformations, including Ebstein's anomaly; the
      magnitude of this effect was smaller than had been previously postulated. (Funded
      by the National Institute of Mental Health.).
FAU - Patorno, Elisabetta
AU  - Patorno E
AD  - From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
      Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of
      Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women's
      Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H.
      Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women's Mental
      Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) - all
      in Boston.
FAU - Huybrechts, Krista F
AU  - Huybrechts KF
AD  - From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
      Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of
      Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women's
      Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H.
      Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women's Mental
      Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) - all
      in Boston.
FAU - Bateman, Brian T
AU  - Bateman BT
AD  - From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
      Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of
      Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women's
      Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H.
      Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women's Mental
      Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) - all
      in Boston.
FAU - Cohen, Jacqueline M
AU  - Cohen JM
AD  - From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
      Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of
      Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women's
      Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H.
      Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women's Mental
      Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) - all
      in Boston.
FAU - Desai, Rishi J
AU  - Desai RJ
AD  - From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
      Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of
      Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women's
      Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H.
      Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women's Mental
      Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) - all
      in Boston.
FAU - Mogun, Helen
AU  - Mogun H
AD  - From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
      Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of
      Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women's
      Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H.
      Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women's Mental
      Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) - all
      in Boston.
FAU - Cohen, Lee S
AU  - Cohen LS
AD  - From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
      Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of
      Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women's
      Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H.
      Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women's Mental
      Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) - all
      in Boston.
FAU - Hernandez-Diaz, Sonia
AU  - Hernandez-Diaz S
AD  - From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
      Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of
      Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women's
      Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H.
      Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women's Mental
      Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) - all
      in Boston.
LA  - eng
GR  - R01 MH100216/MH/NIMH NIH HHS/United States
GR  - K01 MH099141/MH/NIMH NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Anticonvulsants)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Antimanic Agents)
RN  - 0 (Lithium Compounds)
RN  - 0 (Triazines)
RN  - U3H27498KS (lamotrigine)
SB  - AIM
SB  - IM
MH  - Adult
MH  - Anticonvulsants/adverse effects/therapeutic use
MH  - Antidepressive Agents/*adverse effects/therapeutic use
MH  - Antimanic Agents/adverse effects/therapeutic use
MH  - Bipolar Disorder/*drug therapy
MH  - Cohort Studies
MH  - Female
MH  - Heart Defects, Congenital/*chemically induced/epidemiology
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Lithium Compounds/*adverse effects/therapeutic use
MH  - Pregnancy
MH  - Pregnancy Complications/*drug therapy
MH  - Pregnancy Trimester, First
MH  - Prevalence
MH  - Triazines/adverse effects/therapeutic use
MH  - Young Adult
EDAT- 2017/06/08 06:00
MHDA- 2017/06/21 06:00
CRDT- 2017/06/08 06:00
AID - 10.1056/NEJMoa1612222 [doi]
PST - ppublish
SO  - N Engl J Med. 2017 Jun 8;376(23):2245-2254. doi: 10.1056/NEJMoa1612222.

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