Abstract
To explore associations between exposure to antidepressants, their discontinuation, depression [medicated or unmediated] and preterm birth [<37 and <32 weeks], small for gestational age (SGA) [<10th and <3rd centiles], breastfeeding [any] at 6-8 weeks. Design: A population-based cohort study. Setting: The Secure Anonymised Information Linkage [SAIL] databank in Wales, linking maternal primary care data with infant outcomes. Participants: 107,573, 105,331, and 38,725 infants born 2000-2010 with information on prematurity, SGA and breastfeeding respectively, after exclusions. Exposures: Maternal antidepressant prescriptions in trimesters 2 or 3, discontinuation after trimester 1, recorded diagnosis of depression [medicated or unmediated] in pregnancy. Methods: Odds ratios for adverse pregnancy outcomes were calculated, adjusted for smoking, parity, socio-economic status, and depression. Exclusive formula feeding at 6-8 weeks was associated with prescriptions in trimesters 2 or 3 for any antidepressants (adjusted odds ratio [aOR] 0.81, 95% confidence intervals 0.67-0.98), SSRIs [aOR 0.77, 0.62-0.95], particularly higher doses [aOR 0.45, 0.23-0.86], discontinuation of antidepressants or SSRIs after trimester 1 (aOR 0.70, 0.57-0.83 and 0.66, 0.51-0.87), diagnosis of depression aOR 0.76 [0.70-0.82), particularly if medicated (aOR 0.70, 0.58-0.85), rather than unmedicated (aOR 0.87, 0.82-0.92). Preterm birth at <37 and <32 weeks' gestation was associated with diagnosis of depression (aOR 1.27, 1.17-1.38, and 1.33, 1.09-1.62), particularly if medicated (aOR 1.56, 1.23-1.96, and 1.63, 0.94-2.84); birth at <37 weeks was associated with antidepressants, (aOR 1.24, 1.04-1.49]. SGA <3rd centile was associated with antidepressants (aOR 1.43, 1.07-1.90), and SSRIs (aOR 1.46, 1.06-2.00], particularly higher doses [aOR 2.10, 1.32-3.34]. All adverse outcomes were associated with socio-economic status and smoking. Exposure to antidepressants or depression increased risks of exclusive formula feeding at 6-8 weeks, and prescription of antidepressants was associated with SGA <3rd centile. Prescription of antidepressants offers a useful marker to target additional support and additional care before and during pregnancy and lactation.
Highlights
IntroductionSome 20% women aged 16–54 report at least one common mental health problem: this figure [point prevalence of 19.5–25.2%] has remained unchanged since 2000. [1] The prevalence of depression during pregnancy is reported as between 6 and 13%,[2, 3] and around 10% pregnant women develop a depressive illness during pregnancy or postpartum, with a further 16% developing a self-limiting depressive reaction. [4]Selective serotonin reuptake inhibitors [SSRIs] are the most commonly prescribed antidepressants: [5,4] 2.8% [6] to 10.2%[7] pregnant women are prescribed SSRIs during pregnancy, with marked variation across Europe. [8] SSRIs, and their metabolites, cross the placenta, [9] and appear in cord blood [10, 11] in proportion to dose administered; [12] foetal exposure is prolonged by accumulation in amniotic fluid
Birth weight
Support before, during and after pregnancy. This analysis identified a population vulnerable to adverse outcomes, including exclusive formula feeding at 6–8 weeks
Summary
Some 20% women aged 16–54 report at least one common mental health problem: this figure [point prevalence of 19.5–25.2%] has remained unchanged since 2000. [1] The prevalence of depression during pregnancy is reported as between 6 and 13%,[2, 3] and around 10% pregnant women develop a depressive illness during pregnancy or postpartum, with a further 16% developing a self-limiting depressive reaction. [4]Selective serotonin reuptake inhibitors [SSRIs] are the most commonly prescribed antidepressants: [5,4] 2.8% [6] to 10.2%[7] pregnant women are prescribed SSRIs during pregnancy, with marked variation across Europe. [8] SSRIs, and their metabolites, cross the placenta, [9] and appear in cord blood [10, 11] in proportion to dose administered; [12] foetal exposure is prolonged by accumulation in amniotic fluid. [25, 26] despite biological plausibility, not all studies report an increase in preterm birth, [27] and poor parental perinatal mental health can adversely affect childhood outcomes. Many studies are unable to account for the effects of underlying mental illness, discontinuation of medication, social stress or smoking and some associations with adverse outcomes may be shared with non-SSRI antidepressants [28] or depressive illness. The aim of this study is to investigate any associations between antidepressants, SSRIs at standard and higher doses, their discontinuation after trimester 1, and depression [medicated or unmedicated] and the range of adverse outcomes important to women: preterm birth, intra-uterine growth as SGA and, for the first time, breastfeeding [any] at 6–8 weeks, complementing reports of increased prevalence of congenital anomalies [17].
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