Prenatal exposure to antidepressants or antipsychotics and the risk of seizure in children

Wang, Zixuan; Chan, Adrienne; Ho, Phoebe W.H.; Wong, Kirstie H.T.W.; Brauer, Ruth; Besag, Frank; Ip, Patrick; Howard, Louise M.; Lau, Wallis C.Y.; Taxis, Katja; Wei, Li; Wong, Ian C K; Man, Kenneth K C

doi:10.1002/wps.20948

Cited by 7 publications

(6 citation statements)

References 8 publications

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“…In a second study by Wang et al [ 82 ], the authors examined the risk of seizure in offspring with prenatal antidepressant exposure using data for children born between 2001 and 2015 from the Hong Kong Clinical Data Analysis and Reporting System. At least 1 year of follow-up data were available for each child.…”

Section: Resultsmentioning

confidence: 99%

“…Esen et al noted that the possible influence of residual biases could not be discounted. Ar cles a er removal of duplicates N = 1,389 Iden fica n (an depressant OR "serotonin reuptake inhibitor" OR "norepinephrine reuptake inhibitor" OR SSRI OR SNRI OR SRI OR tricyclic) AND (pregnan* OR prenatal OR antenatal OR "in utero" OR intrauterine OR gesta n*) AND (au sm OR au s c OR ASD OR "a en n deficit" OR ADHD OR ina en * OR hyperac v* OR preterm OR s birth OR "intrauterine death" OR "spontaneous abor n" OR "birth weight" OR "gesta nal age" OR cognit* OR IQ OR intell* OR speech OR language OR Apger OR "autonomous adapta n" OR "autonomous regula n" OR motor OR neuromuscular OR "neonatal intensive care" OR epilepsy OR seizure OR behav* OR psych* OR emo n* OR conduct OR opposi on* OR ODD OR "pulmonary hypertension" OR "body mass" OR BMI OR asthma OR cancer OR "cardiac defect" OR "cardiac abnormalit*" OR "congenital malforma n" OR "neonatal withdrawal syndrome" OR "neonatal abs nence syndrome") Search Terms In a second study by Wang et al [82], the authors examined the risk of seizure in offspring with prenatal antidepressant exposure using data for children born between 2001 and 2015 from the Hong Kong Clinical Data Analysis and Reporting System. At least 1 year of follow-up data were available for each child.…”

Section: Recent Studiesmentioning

confidence: 99%

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Should Antidepressants be Avoided in Pregnancy?

Besag

Vasey²

2022

Drug Saf

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Many (> 40%) women discontinue antidepressants during pregnancy because of concerns about effects on the foetus, based on information from inadequately-controlled studies. The sibling-control study design provides the best control for confounding factors, notably maternal depression. The purpose of this review was to investigate the evidence from sibling-control analyses for adverse outcomes in offspring associated with antidepressant exposure during pregnancy. Fourteen sibling-control studies were identified through searches of PubMed and Embase. Outcomes included preterm birth, small for gestational age, neonatal size, birth defects, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), behavioural problems, neurodevelopmental deficits, and scholastic attainment. For the majority of these outcomes, no statistically significant associations were found when comparing exposed and unexposed siblings. Single studies reported associations with preterm birth, reduced gestational age, ADHD, anxiety at 36 months, and lower mathematics test scores, which persisted in the sibling-control analyses. However, differences were small and possibly not clinically significant. Moreover, effects of residual confounding could not be excluded. These findings provide evidence that many of the previously reported associations between prenatal antidepressant exposure and adverse outcomes in offspring are no longer statistically significant when exposed offspring are compared with unexposed siblings. The few statistically significant differences in sibling-control analyses were generally small with doubtful clinical significance. Decisions on antidepressant treatment during pregnancy should be made individually, based on evidence from properly controlled studies, not on misleading information based on studies that have not controlled adequately for confounding factors.

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Section: Resultsmentioning

confidence: 99%

Section: Recent Studiesmentioning

confidence: 99%

Should Antidepressants be Avoided in Pregnancy?

Besag

Vasey²

2022

Drug Saf

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“…Diagnosis records in CDARS were coded using ICD-9-CM [International Classification of Diseases, Ninth Revision, Clinical Modification] codes instead of ICD-10 codes. Nevertheless, data validation has demonstrated high coding accuracy in CDARS [19][20][21] which has been used for various pharmacoepidemiological studies [22][23][24], including studies on prenatal psychotropic use [25] and neurodevelopmental disorders [26][27][28][29]. Study protocol was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (approval number: UW20-051).…”

Section: Data Source and Study Designmentioning

confidence: 99%

Maternal Benzodiazepines and Z-Drugs Use during Pregnancy and Adverse Birth and Neurodevelopmental Outcomes in Offspring: A Population-Based Cohort Study

Chan¹,

Gao²,

Howard³

et al. 2023

Psychother Psychosom

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Introduction: The use of benzodiazepines and/or z-drugs in women of childbearing age has increased. Objective: The aim of the study was to evaluate whether gestational benzodiazepine and/or z-drug exposure is associated with adverse birth and neurodevelopmental outcomes. Methods: A population-based cohort including mother-child pairs from 2001 to 2018 in Hong Kong was analysed to compare gestationally exposed and nonexposed children on the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) through logistic/Cox proportional hazards regression with a 95% confidence interval (CI). Sibling-matched analyses and negative control analyses were applied. Results: When comparing gestationally exposed with gestationally nonexposed children, the weighted odds ratio (wOR) was 1.10 (95% CI = 0.97–1.25) for preterm birth and 1.03 (95% CI = 0.76–1.39) for small for gestational age, while the weighted hazard ratio (wHR) was 1.40 (95% CI = 1.13–1.73) for ASD and 1.15 (95% CI = 0.94–1.40) for ADHD. Sibling-matched analyses showed no association between gestationally exposed children and their gestationally nonexposed siblings for all outcomes (preterm birth: wOR = 0.84, 95% CI = 0.66–1.06; small for gestational age: wOR = 1.02, 95% CI = 0.50–2.09; ASD: wHR = 1.10, 95% CI = 0.70–1.72; ADHD: wHR = 1.04, 95% CI = 0.57–1.90). Similarly, no significant differences were observed when comparing children whose mothers took benzodiazepines and/or z-drugs during pregnancy to children whose mothers took benzodiazepines and/or z-drugs before but not during pregnancy for all outcomes. Conclusions: The findings do not support a causal relationship between gestational benzodiazepines and/or z-drugs exposure and preterm birth, small for gestational age, ASD, or ADHD. Clinicians and pregnant women should carefully balance the known risks of benzodiazepines and/or z-drugs use against those of untreated anxiety and sleep problems.

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“…CDARS contains electronic medical records of over 7.5 million Hong Kong residents, including their demographics, diagnosis, and prescription records. The database has been used for various high-quality epidemiological studies [22][23][24][25], including studies that examined the safety of prenatal medication use on birth/neurodevelopmental complications [26][27][28].…”

Section: Data Source and Study Designmentioning

confidence: 99%

“…CDARS contains hospital diagnoses from specialists, so the positive predictive value of the neurodevelopmental outcomes is high. The database has previously been used to study ADHD and ASD in children and has been accepted to be a valid database [26][27][28][29][30].…”

Section: Main Outcomes and Follow-upmentioning

confidence: 99%

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study

Cheung

Man

et al. 2022

BMC Med

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Background The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. Methods This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. Results Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. Conclusions There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy.

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Prenatal exposure to antidepressants or antipsychotics and the risk of seizure in children

Cited by 7 publications

References 8 publications

Should Antidepressants be Avoided in Pregnancy?

Should Antidepressants be Avoided in Pregnancy?

Maternal Benzodiazepines and Z-Drugs Use during Pregnancy and Adverse Birth and Neurodevelopmental Outcomes in Offspring: A Population-Based Cohort Study

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study

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