No abstract

BackgroundIn 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication.MethodsThe study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs).ResultsTwenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32).ConclusionsThe evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1193-5) contains supplementary material, which is available to authorized users.

Objective. Nowadays, body mass index (BMI) is used to evaluate the risk stratification of obesity-related pregnancy complications in clinics. However, BMI cannot reflect fat distribution or the proportion of adipose to nonadipose tissue. The objective of this study is to evaluate the association of maternal first or second trimester central obesity with the risk of GDM. Research Design and Methods. We searched in PubMed, Embase, and Web of Science for English-language medical literature published up to 12 May 2019. Cohort studies were only included in the search. Abdominal subcutaneous fat thickness, waist circumference, waist-hip ratio or body fat distribution were elected as measures of maternal central obesity, and all diagnostic criteria for GDM were accepted. The random effect meta-analysis was performed to evaluate the relationship between central obesity and the risk of GDM. Results. A total of 11 cohort studies with an overall sample size of 27,675 women and 2,226 patients with GDM were included in the analysis. The summary estimate of GDM risk in the central obesity pregnant women was 2.76 (95% confidence interval [CI]: 2.35–3.26) using the adjusted odds ratio (OR). The degree of heterogeneity among the studies was low (I2=14.4, P=0.307). The subgroup analyses showed that heterogeneity was affected by selected study characteristics (methods of exposure and trimesters). After adjusting for potential confounds, the OR of adjusted BMI was significant (OR=3.07, 95% CI: 2.35–4.00). Conclusions. Our findings indicate that the risk of GDM was positively associated with maternal central obesity.

The results of this meta-analysis indicate maternal fluoxetine use is associated with a slightly increased risk of cardiovascular malformations in infants. Health care providers and pregnant women must weigh the risk-benefit potential of these drugs when making decisions about whether to treat with fluoxetine during pregnancy.

This meta-analysis suggested that the use of sertraline use by pregnant women in the first trimester had an increased risk of cardiovascular-related malformations as well as atrial and/or ventricular septal defects in infants. Meanwhile, nonsignificant associations between sertraline use and other congenital anomalies were found. More cohort studies are warranted to provide detailed results of other congenital anomalies.