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- Halfdanarson, O, et al.
(författare)
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Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study
- 2022
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Ingår i: Evidence-based mental health. - : BMJ. - 1468-960X .- 1362-0347. ; 25:2, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- Antipsychotics are increasingly used among women of childbearing age and during pregnancy.ObjectiveTo determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders.DesignPopulation-based cohort study, including a sibling analysis.SettingNationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016).Participants4 324 086 children were eligible for inclusion to the study cohort.InterventionAntipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use.Main outcome measuresNon-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors.FindingsAmong 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD.DiscussionOur findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics.Clinical implicationsResults regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.
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- Huybrechts, KF, et al.
(författare)
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Association of In Utero Antipsychotic Medication Exposure With Risk of Congenital Malformations in Nordic Countries and the US
- 2023
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 80:2, s. 156-166
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.ObjectiveTo evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes.Design, Setting, and ParticipantsThis cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022.ExposuresOne or more first-trimester dispensing of any atypical, any typical, and individual antipsychotic drugs.Main Outcomes and MeasuresAny major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization.ResultsA total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions.Conclusions and RelevanceIn this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.
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| 10. |
- Huybrechts, KF, et al.
(författare)
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Association of In Utero Antipsychotic Medication Exposure With Risk of Congenital Malformations in Nordic Countries and the US
- 2023
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 80:2, s. 156-166
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.ObjectiveTo evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes.Design, Setting, and ParticipantsThis cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022.ExposuresOne or more first-trimester dispensing of any atypical, any typical, and individual antipsychotic drugs.Main Outcomes and MeasuresAny major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization.ResultsA total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions.Conclusions and RelevanceIn this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.
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