Department of Economics and Business Economics

Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies

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Maternal and infant outcomes associated with lithium use in pregnancy : an international collaborative meta-analysis of six cohort studies. / Munk-Olsen, Trine; Liu, Xiaoqin; Viktorin, Alexander; Brown, Hilary K; Di Florio, Arianna; D'Onofrio, Brian M; Gomes, Tara; Howard, Louise M; Khalifeh, Hind; Krohn, Holly; Larsson, Henrik; Lichtenstein, Paul; Taylor, Clare L; Van Kamp, Inge; Wesseloo, Richard; Meltzer-Brody, Samantha; Vigod, Simone N; Bergink, Veerle.

In: The Lancet Psychiatry, Vol. 5, No. 8, 2018, p. 644-652.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Munk-Olsen, T, Liu, X, Viktorin, A, Brown, HK, Di Florio, A, D'Onofrio, BM, Gomes, T, Howard, LM, Khalifeh, H, Krohn, H, Larsson, H, Lichtenstein, P, Taylor, CL, Van Kamp, I, Wesseloo, R, Meltzer-Brody, S, Vigod, SN & Bergink, V 2018, 'Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies', The Lancet Psychiatry, vol. 5, no. 8, pp. 644-652. https://doi.org/10.1016/S2215-0366(18)30180-9

APA

CBE

Munk-Olsen T, Liu X, Viktorin A, Brown HK, Di Florio A, D'Onofrio BM, Gomes T, Howard LM, Khalifeh H, Krohn H, Larsson H, Lichtenstein P, Taylor CL, Van Kamp I, Wesseloo R, Meltzer-Brody S, Vigod SN, Bergink V. 2018. Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies. The Lancet Psychiatry. 5(8):644-652. https://doi.org/10.1016/S2215-0366(18)30180-9

MLA

Vancouver

Author

Munk-Olsen, Trine ; Liu, Xiaoqin ; Viktorin, Alexander ; Brown, Hilary K ; Di Florio, Arianna ; D'Onofrio, Brian M ; Gomes, Tara ; Howard, Louise M ; Khalifeh, Hind ; Krohn, Holly ; Larsson, Henrik ; Lichtenstein, Paul ; Taylor, Clare L ; Van Kamp, Inge ; Wesseloo, Richard ; Meltzer-Brody, Samantha ; Vigod, Simone N ; Bergink, Veerle. / Maternal and infant outcomes associated with lithium use in pregnancy : an international collaborative meta-analysis of six cohort studies. In: The Lancet Psychiatry. 2018 ; Vol. 5, No. 8. pp. 644-652.

Bibtex

@article{21b62e3a6a9546178cf3e711d0104ef2,
title = "Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies",
abstract = "BACKGROUND: Concerns about teratogenicity and maternal and offspring complications restrict the use of lithium during pregnancy for the treatment of mood disorders. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity, and congenital malformations.METHODS: In this meta-analysis, primary data from pregnant women and their children from six international cohorts based in the community (Denmark, Sweden, and Ontario, Canada) and in clinics (the Netherlands, UK, and USA) were analysed. Pregnancies were eligible for analysis if the pregnancy resulted in a liveborn singleton between 1997 and 2015, if health-related information was available for both mother and infant, and if the mother had a mood disorder (bipolar disorder or major depressive disorder) or if she had been given lithium during pregnancy (at least two dispensations of lithium during pregnancy that were dispensed any time from 1 month before conception until the delivery, or a single lithium dispensation during pregnancy when there was at least one other lithium dispensation within 6 months before or after this date). Pregnancies during which the mother had been prescribed known teratogenic drugs were excluded. Pregnancies were grouped into a lithium-exposed group and a mood disorder reference group. The main outcome measures were pregnancy complications, delivery outcomes, neonatal readmission to hospital within 28 days of birth, and congenital malformations (major malformations and major cardiac malformations). Analyses were done at each site by use of a shared protocol. Adjusted odds ratios (aORs) and 95{\%} CIs were calculated by use of logistic regression models, and site-specific prevalence rates and ORs were pooled by use of random-effects meta-analytical models.FINDINGS: 22   124 eligible pregnancies were identified across the six cohorts, of which 727 pregnancies were eligible for inclusion in the lithium-exposed group (557 [77{\%}] from register-based cohorts and 170 [23{\%}] from clinical cohorts). Lithium exposure was not associated with any of the predefined pregnancy complications or delivery outcomes. An increased risk for neonatal readmission within 28 days of birth was seen in the lithium-exposed group compared with the reference group (pooled prevalence 27·5{\%} [95{\%} CI 15·8-39·1] vs 14·3{\%} [10·4-18·2]; pooled aOR 1·62, 95{\%} CI 1·12-2·33). Lithium exposure during the first trimester was associated with an increased risk of major malformations (pooled prevalence 7·4{\%} [95{\%} CI 4·0-10·7] vs 4·3{\%} [3·7-4·8]; pooled aOR 1·71, 95{\%} CI 1·07-2·72) but for major cardiac malformations the difference was not significant (2·1{\%} [0·5-3·7] vs 1·6{\%} [1·0-2·1]; pooled aOR 1·54, 95{\%} CI 0·64-3·70).INTERPRETATION: Considering both the effect sizes and the precision of the estimates in this meta-analysis, treatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy-in particular those associated with use of lithium during the first trimester-against its effectiveness at reducing relapse.FUNDING: None.",
author = "Trine Munk-Olsen and Xiaoqin Liu and Alexander Viktorin and Brown, {Hilary K} and {Di Florio}, Arianna and D'Onofrio, {Brian M} and Tara Gomes and Howard, {Louise M} and Hind Khalifeh and Holly Krohn and Henrik Larsson and Paul Lichtenstein and Taylor, {Clare L} and {Van Kamp}, Inge and Richard Wesseloo and Samantha Meltzer-Brody and Vigod, {Simone N} and Veerle Bergink",
note = "Copyright {\circledC} 2018 Elsevier Ltd. All rights reserved.",
year = "2018",
doi = "10.1016/S2215-0366(18)30180-9",
language = "English",
volume = "5",
pages = "644--652",
journal = "The Lancet Psychiatry",
issn = "2215-0366",
publisher = "TheLancet Publishing Group",
number = "8",

}

RIS

TY - JOUR

T1 - Maternal and infant outcomes associated with lithium use in pregnancy

T2 - an international collaborative meta-analysis of six cohort studies

AU - Munk-Olsen, Trine

AU - Liu, Xiaoqin

AU - Viktorin, Alexander

AU - Brown, Hilary K

AU - Di Florio, Arianna

AU - D'Onofrio, Brian M

AU - Gomes, Tara

AU - Howard, Louise M

AU - Khalifeh, Hind

AU - Krohn, Holly

AU - Larsson, Henrik

AU - Lichtenstein, Paul

AU - Taylor, Clare L

AU - Van Kamp, Inge

AU - Wesseloo, Richard

AU - Meltzer-Brody, Samantha

AU - Vigod, Simone N

AU - Bergink, Veerle

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018

Y1 - 2018

N2 - BACKGROUND: Concerns about teratogenicity and maternal and offspring complications restrict the use of lithium during pregnancy for the treatment of mood disorders. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity, and congenital malformations.METHODS: In this meta-analysis, primary data from pregnant women and their children from six international cohorts based in the community (Denmark, Sweden, and Ontario, Canada) and in clinics (the Netherlands, UK, and USA) were analysed. Pregnancies were eligible for analysis if the pregnancy resulted in a liveborn singleton between 1997 and 2015, if health-related information was available for both mother and infant, and if the mother had a mood disorder (bipolar disorder or major depressive disorder) or if she had been given lithium during pregnancy (at least two dispensations of lithium during pregnancy that were dispensed any time from 1 month before conception until the delivery, or a single lithium dispensation during pregnancy when there was at least one other lithium dispensation within 6 months before or after this date). Pregnancies during which the mother had been prescribed known teratogenic drugs were excluded. Pregnancies were grouped into a lithium-exposed group and a mood disorder reference group. The main outcome measures were pregnancy complications, delivery outcomes, neonatal readmission to hospital within 28 days of birth, and congenital malformations (major malformations and major cardiac malformations). Analyses were done at each site by use of a shared protocol. Adjusted odds ratios (aORs) and 95% CIs were calculated by use of logistic regression models, and site-specific prevalence rates and ORs were pooled by use of random-effects meta-analytical models.FINDINGS: 22   124 eligible pregnancies were identified across the six cohorts, of which 727 pregnancies were eligible for inclusion in the lithium-exposed group (557 [77%] from register-based cohorts and 170 [23%] from clinical cohorts). Lithium exposure was not associated with any of the predefined pregnancy complications or delivery outcomes. An increased risk for neonatal readmission within 28 days of birth was seen in the lithium-exposed group compared with the reference group (pooled prevalence 27·5% [95% CI 15·8-39·1] vs 14·3% [10·4-18·2]; pooled aOR 1·62, 95% CI 1·12-2·33). Lithium exposure during the first trimester was associated with an increased risk of major malformations (pooled prevalence 7·4% [95% CI 4·0-10·7] vs 4·3% [3·7-4·8]; pooled aOR 1·71, 95% CI 1·07-2·72) but for major cardiac malformations the difference was not significant (2·1% [0·5-3·7] vs 1·6% [1·0-2·1]; pooled aOR 1·54, 95% CI 0·64-3·70).INTERPRETATION: Considering both the effect sizes and the precision of the estimates in this meta-analysis, treatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy-in particular those associated with use of lithium during the first trimester-against its effectiveness at reducing relapse.FUNDING: None.

AB - BACKGROUND: Concerns about teratogenicity and maternal and offspring complications restrict the use of lithium during pregnancy for the treatment of mood disorders. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity, and congenital malformations.METHODS: In this meta-analysis, primary data from pregnant women and their children from six international cohorts based in the community (Denmark, Sweden, and Ontario, Canada) and in clinics (the Netherlands, UK, and USA) were analysed. Pregnancies were eligible for analysis if the pregnancy resulted in a liveborn singleton between 1997 and 2015, if health-related information was available for both mother and infant, and if the mother had a mood disorder (bipolar disorder or major depressive disorder) or if she had been given lithium during pregnancy (at least two dispensations of lithium during pregnancy that were dispensed any time from 1 month before conception until the delivery, or a single lithium dispensation during pregnancy when there was at least one other lithium dispensation within 6 months before or after this date). Pregnancies during which the mother had been prescribed known teratogenic drugs were excluded. Pregnancies were grouped into a lithium-exposed group and a mood disorder reference group. The main outcome measures were pregnancy complications, delivery outcomes, neonatal readmission to hospital within 28 days of birth, and congenital malformations (major malformations and major cardiac malformations). Analyses were done at each site by use of a shared protocol. Adjusted odds ratios (aORs) and 95% CIs were calculated by use of logistic regression models, and site-specific prevalence rates and ORs were pooled by use of random-effects meta-analytical models.FINDINGS: 22   124 eligible pregnancies were identified across the six cohorts, of which 727 pregnancies were eligible for inclusion in the lithium-exposed group (557 [77%] from register-based cohorts and 170 [23%] from clinical cohorts). Lithium exposure was not associated with any of the predefined pregnancy complications or delivery outcomes. An increased risk for neonatal readmission within 28 days of birth was seen in the lithium-exposed group compared with the reference group (pooled prevalence 27·5% [95% CI 15·8-39·1] vs 14·3% [10·4-18·2]; pooled aOR 1·62, 95% CI 1·12-2·33). Lithium exposure during the first trimester was associated with an increased risk of major malformations (pooled prevalence 7·4% [95% CI 4·0-10·7] vs 4·3% [3·7-4·8]; pooled aOR 1·71, 95% CI 1·07-2·72) but for major cardiac malformations the difference was not significant (2·1% [0·5-3·7] vs 1·6% [1·0-2·1]; pooled aOR 1·54, 95% CI 0·64-3·70).INTERPRETATION: Considering both the effect sizes and the precision of the estimates in this meta-analysis, treatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy-in particular those associated with use of lithium during the first trimester-against its effectiveness at reducing relapse.FUNDING: None.

U2 - 10.1016/S2215-0366(18)30180-9

DO - 10.1016/S2215-0366(18)30180-9

M3 - Journal article

C2 - 29929874

VL - 5

SP - 644

EP - 652

JO - The Lancet Psychiatry

JF - The Lancet Psychiatry

SN - 2215-0366

IS - 8

ER -