Neonatal Withdrawal Syndrome following Late in utero Exposure to Selective Serotonin Reuptake Inhibitors: A Systematic Review and Meta-Analysis of Observational Studies

Wang, Jianjun; Cosci, Fiammetta

doi:10.1159/000516031

Cited by 25 publications

(21 citation statements)

References 57 publications

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“…Such widespread use of SRIs during pregnancy is justified by the concerns that an untreated antenatal depression would affect early development of the offspring ( Hanley et al, 2015 ; Gentile, 2017 ; Kautzky et al, 2021 ) while the SRIs are not known to associate with major teratogenic effects other than possible cardiac issues ( Reefhuis et al, 2015 ; Wemakor et al, 2015 ; Wisner et al, 2020 ; Kolding et al, 2021 ). However, recent clinical findings have challenged the current liberal practice showing that newborn infants exposed to SRIs in utero show markedly high rates of SRI withdrawal symptoms requiring medical attention ( Ulbrich et al, 2021 ; Wang and Cosci, 2021 ). In addition, recent studies on magnetic resonance (MR) imaging ( Lugo-Candelas et al, 2018 ; Rotem-Kohavi et al, 2019 ) and cortical activity ( Videman et al, 2017 ) have suggested that SRIs may clearly have measurable effects, prompting further studies on the associated brain mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Cortical Cross-Frequency Coupling Is Affected by in utero Exposure to Antidepressant Medication

et al. 2022

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Up to five percent of human infants are exposed to maternal antidepressant medication by serotonin reuptake inhibitors (SRI) during pregnancy, yet the SRI effects on infants’ early neurodevelopment are not fully understood. Here, we studied how maternal SRI medication affects cortical frequency-specific and cross-frequency interactions estimated, respectively, by phase-phase correlations (PPC) and phase-amplitude coupling (PAC) in electroencephalographic (EEG) recordings. We examined the cortical activity in infants after fetal exposure to SRIs relative to a control group of infants without medical history of any kind. Our findings show that the sleep-related dynamics of PPC networks are selectively affected by in utero SRI exposure, however, those alterations do not correlate to later neurocognitive development as tested by neuropsychological evaluation at two years of age. In turn, phase-amplitude coupling was found to be suppressed in SRI infants across multiple distributed cortical regions and these effects were linked to their neurocognitive outcomes. Our results are compatible with the overall notion that in utero drug exposures may cause subtle, yet measurable changes in the brain structure and function. Our present findings are based on the measures of local and inter-areal neuronal interactions in the cortex which can be readily used across species, as well as between different scales of inspection: from the whole animals to in vitro preparations. Therefore, this work opens a framework to explore the cellular and molecular mechanisms underlying neurodevelopmental SRI effects at all translational levels.

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Section: Introductionmentioning

confidence: 99%

Cortical Cross-Frequency Coupling Is Affected by in utero Exposure to Antidepressant Medication

et al. 2022

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“…It is important to clinically prioritize disproportionality signals to provide further clarification assisting clinicians in the prescription or monitoring of antidepressant treatment in pregnant women. Venlafaxine has previously been associated with the neonatal withdrawal syndrome (Holland & Brown, 2017;Wang & Cosci, 2021), but our evidence suggests, for the first time, that mianserin, mirtazapine and trazodone may also be involved.…”

Section: Discussionmentioning

confidence: 53%

“…As in the total sample, the network analysis in the subset of neonates exposed to antidepressant monotherapy suggested a quartet of core symptoms including respiratory symptoms, irritability/agitation, tremor and feeding problems. There is a strong overlap between this symptom cluster and the clinical characterisation provided for SSRI-related neonatal withdrawal syndrome previously (Wang & Cosci, 2021).…”

Section: Discussionmentioning

confidence: 78%

Neonatal withdrawal syndrome following in utero exposure to antidepressants: a disproportionality analysis of VigiBase, the WHO spontaneous reporting database

et al. 2022

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Background Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitor (SSRIs). Methods In our case/non-case pharmacovigilance study, based on VigiBase®, the WHO database of suspected adverse drug reactions, we estimated reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence/credibility intervals (CI) as measures of disproportionate reporting of antidepressant-related neonatal withdrawal syndrome. Antidepressants were first compared to all other medications, then to methadone, and finally within each class of antidepressants: SSRIs, tricyclics (TCA) and other antidepressants. Antidepressants were ranked in terms of clinical priority, based on semiquantitative score ratings. Serious v. non-serious reports were compared. Results A total of 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants were included. Disproportionate reporting was detected for antidepressants as a group as compared to all other drugs (ROR: 6.18, 95% CI 5.45–7.01, IC: 2.07, 95% CI 1.92–2.21). Signals were found for TCAs (10.55, 95% CI 8.02–13.88), followed by other antidepressants (ROR: 5.90, 95% CI 4.74–7.36) and SSRIs (ROR: 4.68, 95% CI 4.04–5.42). Significant disproportionality emerged for all individual antidepressants except for bupropion, whereas no disproportionality for any antidepressant was detected v. methadone. Eleven antidepressants had a moderate clinical priority score and four had a weak one. Most frequent symptoms included respiratory symptoms (n = 106), irritability/agitation (n = 75), tremor (n = 52) and feeding problems (n = 40). Conclusions Most antidepressants are associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome, which should be considered when prescribing an antidepressant during pregnancy, irrespective of class.

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“…1). There are concerns for psychotropic medication use during pregnancy regarding the risks of various adverse outcomes in offspring [32]. However, we did not exclude pregnant women who were on antidepressants or other psychotropic medication in view of the low exposure rates in the control groups (antidepressants: 0.67%, antipsychotics: 0.23%; antiepileptics: 0.07%; antiparkinson drugs: 0.07%; stimulants: 0.002%).…”

Section: Exposure and Comparator Cohortsmentioning

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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Neonatal Withdrawal Syndrome following Late in utero Exposure to Selective Serotonin Reuptake Inhibitors: A Systematic Review and Meta-Analysis of Observational Studies

Cited by 25 publications

References 57 publications

Cortical Cross-Frequency Coupling Is Affected by in utero Exposure to Antidepressant Medication

Cortical Cross-Frequency Coupling Is Affected by in utero Exposure to Antidepressant Medication

Neonatal withdrawal syndrome following in utero exposure to antidepressants: a disproportionality analysis of VigiBase, the WHO spontaneous reporting database

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

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