Antidepressant use during pregnancy and the risk of attention‐deficit/hyperactivity disorder in the children: a meta‐analysis of cohort studies

Hy, Jiang; Ct, Peng; X, Zhang; Ruan, Bing

doi:10.1111/1471-0528.15059

Cited by 20 publications

(24 citation statements)

References 37 publications

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“…odds, hazard, or relative risk ratios) ranging from approximately 1.0–2.5 (Table ; Andalib et al., ; Brown, Hussain‐Shamsy, Lunsky, Dennis, & Vigod, ; Kaplan, Keskin‐Arslan, Acar, & Sozmen, ; Kaplan, Keskin‐Arslan, Acar, & Sozmen, ; Kobayashi, Matsuyama, Takeuchi, & Ito, ; Man et al., ; Mezzacappa et al., ; Morales et al., ; Zhou, Li, Ou, & Li, ).The meta‐analyses on ADHD have generally reported pooled point estimates (i.e. odds or relative risk ratios) of about 1.5 (Table ; Jiang, Peng, Zhang, & Ruan, ; Man et al., ; Morales et al., ).…”

Section: Observational Studiesmentioning

confidence: 99%

“…Four meta‐analyses, which included overlapping studies, found statistically significant associations between antidepressant use before pregnancy and ASD (Table ; Kaplan, Keskin‐Arslan, Acar, et al., ; Mezzacappa et al., ; Morales et al., ; Zhou et al., ), and three meta‐analyses also including overlapping studies found statistically significant associations between antidepressant use before pregnancy and ADHD (Table ; Jiang et al., ; Man et al., ; Morales et al., ; Table includes results from individual studies). These associations were of similar magnitude as associations reported for use during pregnancy.…”

Section: Observational Studiesmentioning

confidence: 99%

“…Three individual sibling‐comparison studies have examined associations between prenatal antidepressant exposure and ADHD (Table ; Laugesen, Olsen, Telén Andersen, Frøslev, & Toft Sørensen, ; Man et al., ; Sujan et al., ). Three meta‐analyses have been conducted and they each included all three of these sibling‐comparison studies (Table ; Jiang et al., ; Man et al., ; Morales et al., ). All three meta‐analyses and all three individual studies found adjusted point estimates at or below 1.0 for associations with ADHD.…”

Section: Observational Studiesmentioning

confidence: 99%

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Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems – a critical review and recommendations for future research

Sujan

Öberg

Quinn

et al. 2018

Child Psychology Psychiatry

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Children of women treated with antidepressants during pregnancy are more likely to develop neurodevelopmental problems than are unexposed children. Associations between prenatal antidepressant exposure and neurodevelopmental problems could reflect a causal effect or could be partially or fully explained by other factors that differ between exposed and unexposed offspring, including having mothers with conditions requiring antidepressant treatment (e.g. depression), environmental risk factors, and/or genetic risk factors shared across disorders. This translational review aims to provide a brief overview of findings from rodent experiments and critically evaluate observational studies in humans to assess the extent to which associations between prenatal antidepressant exposure and neurodevelopmental problems are due to causal mechanisms versus other influences. We focus our review on two important neurodevelopmental outcomesautism spectrum disorder (ASD) and attention-deficit/ hyperactivity disorder (ADHD). In general, rodent studies have reported adverse effects of perinatal antidepressant exposure on neurodevelopment. Between-species differences raise questions about the generalizability of these findings to humans. Indeed, converging evidence from studies using multiple designs and approaches suggest that observed associations between prenatal antidepressant exposure and neurodevelopmental problems in humans are largely due to confounding factors. We also provide specific recommendations for future research. Animal research should explicitly evaluate the impact of timing of exposure and dosage of medications, as well as better map outcome measures in rodents to human neurodevelopmental problems. Observational studies should investigate specific confounding factors, specific antidepressant drugs and classes, the potential impact of timing of exposure, and a wider range of other potential offspring outcomes. The findings summarized in this review may help women and their doctors make informed decisions about antidepressant use during pregnancy by providing reassurance that use of these medications during pregnancy is unlikely to substantially increase the risk of ASD and ADHD.

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Section: Observational Studiesmentioning

confidence: 99%

Section: Observational Studiesmentioning

confidence: 99%

Section: Observational Studiesmentioning

confidence: 99%

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Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems – a critical review and recommendations for future research

Sujan

Öberg

Quinn

et al. 2018

Child Psychology Psychiatry

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“…None of the meta‐analyses included data on TCAs. The number of meta‐analyses evaluating individual neonatal outcomes was as follows: autism spectrum disorders, 10 15‐24 ; ADHD, 4 21,23,31,32 ; preterm birth, 4 25‐28 ; persistent pulmonary hypertension, 3 14,33,34 ; low birth weight, 2 25,29 ; and spontaneous abortion, 2 28,30 …”

Section: Resultsmentioning

confidence: 99%

“…All meta‐analyses found that first‐trimester exposure was significantly associated with the risk of ADHD (OR/RR/HR for any antidepressant, 1.37‐1.39; HR/OR for SSRIs, 1.52‐1.75). The increased risk of ADHD in children of women using any antidepressant during the second trimester 31 or second/third trimester 32 was reported in 1 meta‐analysis.…”

Section: Resultsmentioning

confidence: 99%

Neonatal and Childhood Outcomes in Offspring of Pregnant Women Using Antidepressant Medications: A Critical Review of Current Meta‐Analyses

Uğuz

2020

The Journal of Clinical Pharma

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This article reviewed the results of 21 recent meta‐analyses examining the relationship between maternal use of antidepressants during pregnancy and negative outcomes in newborns and children. PubMed was searched for meta‐analyses published in English between January 1, 2011, and November 30, 2019, by using combinations of the keywords pregnancy, antidepressants, review, meta‐analysis, selective serotonin reuptake inhibitors, selective serotonin‐norepinephrine reuptake inhibitors, tricyclic antidepressants, neonatal outcomes, autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, infant, newborn, children, and offspring. The present review included a total of 21 relevant meta‐analyses that met the inclusion criteria. Most of the meta‐analyses reported that compared to non‐users, the risks of preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, autism spectrum disorders, and ADHD in offspring of antidepressant users were significantly higher. Some meta‐analyses also noted that the elevated risks were no longer statistically significant when pregnant women with psychiatric diagnoses treated with an antidepressant were compared with control patients who remained untreated. Although this review of current meta‐analyses suggests a moderately increased risk of neonatal and childhood outcomes assessed with maternal use of antidepressants, it is difficult to ascertain whether these outcomes are independent of underlying maternal psychiatric disorders.

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Making Decisions About Antidepressant Treatment in Pregnancy

Brown

Vigod

2021

JAMA

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Depression is a common complication of pregnancy and is estimated to affect 9.2% of pregnant women in highincome countries, according to a 2017 meta-analysis. 1 Prenatal depression is associated with negative outcomes, including elevated risk of postpartum depression and chronic mental illness in women, preterm birth and other perinatal complications, and child developmental, social, and behavioral problems. 2 As such, treatment of depression in pregnancy is a priority for affected women, their children, and their families. Psychotherapies may be effective to treat depression of mild and moderate severity; however, antidepressants may be required to effectively treat more severe depression or when therapy does not lead to remission. 3 Therefore, the short-term and longterm outcomes of fetal exposure to antidepressant medications must be considered.In this issue of JAMA, Christensen et al 4 present a population-based cohort study that evaluated the association between maternal antidepressant prescriptions filled during pregnancy and standardized language and mathematics test scores of Danish school-aged children assessed at ages 7 to 17 years. Among 575 369 children, 10 198 (1.8%) were born to mothers who filled an antidepressant prescription during pregnancy. After controlling for several key confounders, no statistically significant association was found between maternal prescription fills for antidepressant medication (assumed to represent in utero antidepressant exposure) and child standardized language scores (on a 100-point scale, mean score among children with maternal antidepressant prescription fills, 53.4; mean score among children without maternal antidepressant prescription fills, 56.6; adjusted difference, −0.1 [95% CI, −0.6 to 0.3]). 4 A small statistically significant absolute difference was found for standardized mathematics scores among children with maternal antidepressant prescriptions fills, compared with children without maternal antidepressant prescription fills (mean scores, 52.1 vs 57.4, respectively; adjusted difference, −2.2 [95% CI, −2.7 to −1.6]). 4 The authors suggest that the small difference in mathematics scores "unlikely represents a clinically relevant" finding and recommend that any concerns about the small absolute differences in standardized mathematics scores should be weighed against the clinical benefits of treating maternal depression in pregnancy. 4 A substantial amount of research has focused on antidepressants in pregnancy, especially in the last decade. [5][6][7] Randomized clinical trials on the use of antidepressants in pregnancy cannot be conducted because of ethical consider-

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Antidepressant use during pregnancy and the risk of attention‐deficit/hyperactivity disorder in the children: a meta‐analysis of cohort studies

Abstract: Antidepressant use during pregnancy may be not associated with ADHD in the offspring.

Cited by 20 publications

References 37 publications

Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems – a critical review and recommendations for future research

Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems – a critical review and recommendations for future research

Neonatal and Childhood Outcomes in Offspring of Pregnant Women Using Antidepressant Medications: A Critical Review of Current Meta‐Analyses

Making Decisions About Antidepressant Treatment in Pregnancy

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