Pregnancy and Delivery Outcomes Following Benzodiazepine Exposure: A Systematic Review and Meta-analysis.

OBJECTIVE: Understanding the effects of benzodiazepines (BZDs) on maternal/fetal health remains incomplete despite their frequent use. This article quantifies the effects of antenatal BZD exposure on delivery outcomes. DATA SOURCES: Medline, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched till June 30, 2018. STUDY SELECTION: English-language cohort studies comparing antenatal BZD exposure to an unexposed group on any delivery outcome were eligible. In all, 23,909 records were screened, 56 studies were assessed, and 14 studies were included. DATA EXTRACTION: Two reviewers independently assessed quality and extracted data. Estimates were pooled using random effects meta-analysis. Sub-analyses examined several potential moderators including timing of exposure. RESULTS: There were 9 outcomes with sufficient data for meta-analysis. Antenatal BZD exposure was significantly associated with increased risk of 6 outcomes initially: spontaneous abortion (pooled odds ratio = 1.86; 95% confidence interval [CI], 1.43 to 2.42), preterm birth (1.96; 95% CI, 1.25 to 3.08), low birth weight (2.24; 95% CI, 1.41 to 3.88), low Apgar score (2.19; 95% CI, 1.94 to 2.47), Neonatal Intensive Care Unit (NICU) admission (2.61; 95% CI, 1.64 to 4.14), and induced abortion (2.04; 95% CI, 1.23 to 3.40). There was significant heterogeneity between studies for most outcomes without consistent moderators. Birth weight (mean difference [MD]: -151.35 g; 95% CI, -329.73 to 27.03), gestational age (-0.49 weeks; 95% CI, -1.18 to 0.19), and small for gestational age (SGA; 1.42; 95% CI, 1.00 to 2.01) did not show significant associations although after adjusting for publication bias, gestational age, and SGA became significant, totaling 8 significant outcomes. CONCLUSIONS: Antenatal BZD exposure appears to be statistically associated with increased risk of several adverse perinatal outcomes. Although confounds cannot be ruled out, NICU admission does appear clinically relevant and consistent with the antidepressant literature.

Benzodiazepine Use During Pregnancy Alone or in Combination With an Antidepressant and Congenital Malformations: Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize the effects of antenatal benzodiazepine exposure as monotherapy and in combination with antidepressants on the risk of congenital malformations. DATA SOURCES: MEDLINE, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched from inception to June 30, 2018, using controlled vocabulary and keywords (eg, prenatal, benzodiazepines, malformation). STUDY SELECTION: English-language cohort studies with prospectively collected data on the risk of malformations in benzodiazepine-exposed and -unexposed offspring were evaluated. 23,909 records were screened, 56 studies were assessed for eligibility, and 8 studies were included. DATA EXTRACTION: Quality was assessed by 2 independent reviewers and data extracted. Random-effects models were used for outcomes (≥ 3 studies). Subanalyses examined effect of potential moderators including study quality and timing of exposure, among others. RESULTS: Prenatal benzodiazepine use was not associated with an increased risk of congenital malformations (odds ratio [OR] = 1.13; 95% CI, 0.99 to 1.30, 8 studies, n = 222/5,195 exposed and 64,335/2,082,467 unexposed), including with first trimester exposure specifically (OR = 1.08; 95% CI, 0.93 to 1.25, P = .33; 5 studies, n = 181/4,331 exposed and 64,308/2,081,463 unexposed). There was no significant association with cardiac malformation following exposure (OR = 1.27; 95% CI, 0.98 to 1.65, P = .07; 4 studies, n = 61/4,414 exposed and 19,260/2,033,402 unexposed). However, concurrent use of benzodiazepine and antidepressants during pregnancy was associated with a significantly increased risk of congenital malformations (OR = 1.40; 95% CI, 1.09 to 1.80, P = .008; 3 studies). CONCLUSIONS: Benzodiazepine exposure during pregnancy does not appear to be associated with congenital malformations or with cardiac malformations specifically. There may be an increased risk of congenital malformations when benzodiazepines are used in conjunction with antidepressants, suggesting that caution with this combination is warranted.

A systematic review and meta-analysis of the effects of antenatal anxiety on postpartum outcomes.

To systematically review and meta-analyze research investigating the association between maternal anxiety during pregnancy and outcomes for mother and baby following the immediate delivery period. MEDLINE, Medline In-Process & Other Non-Indexed Citations, PsycINFO, Embase, CINAHL, and the Cochrane library were searched. English-language, prospective studies providing data on outcomes following delivery in women with and without antenatal anxiety (defined by clinical diagnosis or score on validated scale) were included. Three-hundred-fifty-eight articles were retrieved and 13 were included. Titles and abstracts were screened; two reviewers independently reviewed full text articles, conducted quality assessments, extracted, and checked the data. Where available for > 2 studies, random effect meta-analysis was conducted and heterogeneity was quantified. Subanalyses explored moderators, regardless of heterogeneity, including type of anxiety assessment and timing, among others. There were two outcomes that were amenable to meta-analysis. Antenatal anxiety was significantly associated with postpartum depression (PPD) measured within 6 months postpartum (pooled odds ratio [OR] = 2.64, 95% CI 2.02-3.46; 8 studies), regardless of restricting analyses to those studies controlling for prenatal depression (2.45, 1.77-3.39; 6 studies). Associations were also significant when PPD was measured at 1-3 months (2.57, 1.94-3.40; 7 studies) and 6-10 months (4.42, 1.45-13.49; 3 studies). Maternal anxiety was also associated with reduced odds of breastfeeding (0.63, 0.53-0.74; 5 studies). Antenatal anxiety is associated with PPD up to the first 10 months, independent of prenatal depression, and with lower odds of breastfeeding.

Maternal Anxiety During Pregnancy and the Association With Adverse Perinatal Outcomes: Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis examined the association between maternal antenatal anxiety (AA) and a range of perinatal outcomes. DATA SOURCES: Ovid MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched to May 31, 2016, using controlled vocabulary and keywords (eg, prenatal, anxiety, preterm). STUDY SELECTION: Perinatal outcomes of women with and without AA (diagnosed or self-reported using validated scale) derived from English language, prospectively collected data were included. 1,458 abstracts were reviewed, 306 articles were retrieved, and 29 articles were included. DATA EXTRACTION: Two independent reviewers extracted data and assessed quality. Random-effects models were utilized for outcomes (≥ 3 studies). Subanalyses examined potential effect moderators including study quality and diagnostic versus self-reported anxiety among others. RESULTS: Antenatal anxiety was associated with increased odds for preterm birth (pooled odds ratio [OR] = 1.54; 95% confidence interval [CI], 1.39 to 1.70, 16 studies) and spontaneous preterm birth (OR = 1.41; 95% CI, 1.13 to 1.75), lower mean birth weight (mean difference = -55.96 g; 95% CI, -93.62 to -18.31 g), increased odds for low birth weight (OR = 1.80; 95% CI, 1.48 to 2.18), earlier gestational age (mean difference = -0.13 wk; 95% CI, -0.22 to -0.04 wk), increased odds for being small for gestational age (OR = 1.48; 95% CI, 1.26 to 1.74), and smaller head circumference (mean difference = -0.25 cm; 95% CI, -0.45 to -0.06 cm). Heterogeneity between studies was not significant for most outcomes. Subanalyses for birth weight found women with diagnosed anxiety had infants with significantly lower birth weight (P < .03) compared to those identified with rating scales (although both subanalyses were significant [P < .01]). Associations between anxiety and preeclampsia, cesarean delivery, and Apgar scores were nonsignificant. CONCLUSIONS: Antenatal anxiety is associated with multiple adverse perinatal outcomes and is not benign. The impact of treating anxiety on these associations is unknown.