Maternal schizophrenia and pregnancy outcome: Does the use of antipsychotics make a difference?

Lin, Herng-Ching; Chen, I-Ju; Chen, Yihua; Lee, Hsin Chien; Wu, Fang-Jen

doi:10.1016/j.schres.2009.10.011

Cited by 93 publications

(63 citation statements)

References 12 publications

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“…An elevated risk for prematurity OR 2.46 (1.50-4.11), in those receiving FGAs, was also found in a Taiwanese study [Lin et al 2010]. Further studies have found antipsychotic medications to be associated with both low birth weight and large-for-dates babies; the latter mainly associated with exposure to SGAs [McKenna et al 2005;Newham et al 2008].…”

Section: Risk Of Adverse Obstetric Outcomementioning

confidence: 65%

Antipsychotic drugs in pregnancy: a review of their maternal and fetal effects

Galbally

Snellen

Power

2014

Therapeutic Advances in Drug Safety

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Understanding the risks of antipsychotic medication use in pregnancy is becoming an important clinical concern given the evidence of their increasing rate of prescription in the general population for a range of disorders. Despite antipsychotics being amongst the earliest of psychotropic medications to be introduced, the evidence for their effects secondary to pregnancy exposure is extremely limited. While this review does not identify clear evidence for a risk of malformation, there is evidence for risks associated with pregnancy and neonatal outcomes. Studies identified found risks that included prematurity, low and high birth weight, and gestational diabetes. There have also been studies that suggest neonatal withdrawal and abnormal muscles movements. The longer term neurodevelopmental outcomes for children exposed in utero remain unclear with only four studies identified: two of first generation antipsychotics and two of second generation antipsychotics. When considering the risk of these medications in pregnancy, the risk of untreated maternal illness (particularly schizophrenia and bipolar disorder) on both maternal and child outcomes is relevant. Future research needs to focus on prospective, longitudinal studies with adequate measures of key confounding variables including maternal mental illness, other exposures (such as smoking, alcohol and illicit drug use) and adequate length of follow up where accurate child developmental measures are obtained.

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Section: Risk Of Adverse Obstetric Outcomementioning

confidence: 65%

Antipsychotic drugs in pregnancy: a review of their maternal and fetal effects

Galbally

Snellen

Power

2014

Therapeutic Advances in Drug Safety

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“…Other research on antipsychotic treatment in pregnancy includes pharmacovigilance studies from drug companies' safety databases 76,77 as well as cohort studies based on various data sources. 38,50,[78][79][80][81][82][83][84][85] A systematic review 19 of many of these studies suggested that women requiring antipsychotic treatment during pregnancy have a higher risk of adverse birth outcomes. However, there was substantial heterogeneity between the studies and Coughlin et al 19 emphasise that most studies had limited adjustment for potential confounding and therefore the observed associations may not be causal.…”

Section: Antipsychoticsmentioning

confidence: 99%

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records

Petersen

McCrea

Sammon

et al. 2016

Health Technol Assess

133

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BackgroundAlthough many women treated with psychotropic medication become pregnant, no psychotropic medication has been licensed for use in pregnancy. This leaves women and their health-care professionals in a treatment dilemma, as they need to balance the health of the woman with that of the unborn child. The aim of this project was to investigate the risks and benefits of psychotropic medication in women treated for psychosis who become pregnant.Objective(s)(1) To provide a descriptive account of psychotropic medication prescribed before pregnancy, during pregnancy and up to 15 months after delivery in UK primary care from 1995 to 2012; (2) to identify risk factors predictive of discontinuation and restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers and antipsychotic medication; (3) to examine the extent to which pregnancy is a determinant for discontinuation of psychotropic medication; (4) to examine prevalence of records suggestive of adverse mental health, deterioration or relapse 18 months before and during pregnancy, and up to 15 months after delivery; and (5) to estimate absolute and relative risks of adverse maternal and child outcomes of psychotropic treatment in pregnancy.DesignRetrospective cohort studies.SettingPrimary care.ParticipantsWomen treated for psychosis who became pregnant, and their children.InterventionsTreatment with antipsychotics, lithium or anticonvulsant mood stabilisers.Main outcome measuresDiscontinuation and restarting of treatment; worsening of mental health; acute pre-eclampsia/gestational hypertension; gestational diabetes; caesarean section; perinatal death; major congenital malformations; poor birth outcome (low birthweight, preterm birth, small for gestational age, low Apgar score); transient poor birth outcomes (tremor, agitation, breathing and muscle tone problems); and neurodevelopmental and behavioural disorders.Data sourcesClinical Practice Research Datalink database and The Health Improvement Network primary care database.ResultsPrescribing of psychotropic medication was relatively constant before pregnancy, decreased sharply in early pregnancy and peaked after delivery. Antipsychotic and anticonvulsant treatment increased over the study period. The recording of markers of worsening mental health peaked after delivery. Pregnancy was a strong determinant for discontinuation of psychotropic medication. However, between 40% and 76% of women who discontinued psychotropic medication before or in early pregnancy restarted treatment by 15 months after delivery. The risk of major congenital malformations, and neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers) users was twice that in users of other anticonvulsants. The risks of adverse maternal and child outcomes in women who continued antipsychotic use in pregnancy were not greater than in those who discontinued treatment before pregnancy.LimitationsA few women would have received parts of their care outside primary care, which may not be captured in this analysis. Likewise, the analyses were based on prescribing data, which may differ from usage.ConclusionsPsychotropic medication is prescribed before, during and after pregnancy. Many women discontinue treatment before or during early pregnancy and then restart again in late pregnancy or after delivery. Our results support previous associations between valproate and adverse child outcomes but we found no evidence of such an association for antipsychotics.Future workFuture research should focus on (1) curtailing the use of sodium valproate; (2) estimating the benefits of psychotropic drug use in pregnancy; and (3) investigating the risks associated with lifestyle choices that are more prevalent among women using psychotropic drugs.Funding detailsThe National Institute for Health Research Health Technology Assessment programme.

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“…Of the 12 studies, 8 controlled for maternal age, 8,[10][11][12][13][14]16,17 4 studies controlled for gestational age at time of patient contact, [10][11][12]14 and 4 studies presented adjusted ORs controlling for factors including smoking, body mass index, drinking, previous abortions, birth order, country of origin, diabetes, hypertension, and previous malformed children. 8,13,16,17 All studies reported the general timing of fetal exposure; however, only one of the studies recorded the dosage of SGAs that subjects were taking, 10 and only 2 studies recorded the exact duration of exposure.…”

Section: Risk Of Bias Within Studiesmentioning

confidence: 99%

“…8,13,16,17 All studies reported the general timing of fetal exposure; however, only one of the studies recorded the dosage of SGAs that subjects were taking, 10 and only 2 studies recorded the exact duration of exposure. 10,17 No studies reported whether disease symptoms were well controlled or the severity of the underlying disease. Furthermore, 1 study measured SGA use during pregnancy as prescriptions filled, 16 which does not necessarily coincide with in utero SGA exposure.…”

Section: Risk Of Bias Within Studiesmentioning

confidence: 99%

“…For all other studies, exposure was self-reported by the subject. Of the 12 studies, 7 reported concomitant drug use among their subjects, 8,10,11,[16][17][18]24 which was not controlled for. Eight of the studies included in this analysis reported data obtained from a teratology information service (Motherisk, Teratogen Information Service, Drug Safety Unit Research database, Teratology Information Service, French Regional Pharmacovigilence Centre).…”

Section: Risk Of Bias Within Studiesmentioning

confidence: 99%

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Pregnancy Outcomes Following In Utero Exposure to Second-Generation Antipsychotics

Terrana

Koren

Pivovarov³

et al. 2015

Journal of Clinical Psychopharmacology

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Second-generation antipsychotics (SGAs) are increasingly used for a variety of mental illnesses; however, the data regarding the safety of these medications during pregnancy are inconclusive and contradictory. We examined the risk of adverse pregnancy outcomes associated with in utero exposure to SGAs by conducting a systematic review and meta-analysis. We searched the databases EMBASE and MEDLINE from January 1990 to December 2014. Eligible studies had to report pregnant women who took SGAs during pregnancy (first trimester exposure if analyzing congenital malformations), follow a healthy comparison group in a similar manner, and report data on pregnancy outcomes. There was no restriction on language, sample size, or publication date. The primary outcome analyzed was major congenital malformations, and secondary outcomes included miscarriages, stillbirths, preterm births, small or large for gestational age neonates, and differences in gestational ages and birth weights. A total of 12 studies met our inclusion criteria, totalling 1782 cases and 1,322,749 controls. The use of SGA during the first trimester of pregnancy was associated with a significant increased risk for major congenital malformations (odds ratio, 2.03; 95% confidence interval, 1.41-2.93); however, no specific pattern of malformations was found. An increased risk was also found for preterm births (odds ratio, 1.85; 95% CI, 1.20-2.86). The use of SGA during pregnancy was not found to be associated with an increased risk for secondary outcomes analyzed. The absence of a specific pattern of malformations makes it difficult to identify an explicit risk posed by SGAs, and therefore, further studies sufficiently controlling for confounding factors are needed to validate these findings.

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Maternal schizophrenia and pregnancy outcome: Does the use of antipsychotics make a difference?

Cited by 93 publications

References 12 publications

Antipsychotic drugs in pregnancy: a review of their maternal and fetal effects

Antipsychotic drugs in pregnancy: a review of their maternal and fetal effects

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records

Pregnancy Outcomes Following In Utero Exposure to Second-Generation Antipsychotics

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