Hilary K. Brown

Neonatal morbidity associated with late preterm and early term birth: the roles of gestational age and biological determinants of preterm birth

BACKGROUND The aim of this study was to elucidate the role of gestational age in determining the risk of neonatal morbidity among infants born late preterm (34-36 weeks) and early term (37-38 weeks) compared with those born full term (39-41 weeks) by examining the contribution of gestational age within the context of biological determinants of preterm birth. METHODS This was a retrospective cohort study. The sample included singleton live births with no major congenital anomalies, delivered at 34-41 weeks of gestation to London-Middlesex (Canada) mothers in 2002-11. Data from a city-wide perinatal database were linked with discharge abstract data. Multivariable models used modified Poisson regression to directly estimate adjusted relative risks (aRRs). The roles of gestational age and biological determinants of preterm birth were further examined using mediation and moderation analyses. RESULTS Compared with infants born full term, infants born late preterm and early term were at increased risk for neonatal intensive care unit triage/admission [late preterm aRR=6.14, 95% confidence interval (CI) 5.63, 6.71; early term aRR=1.54, 95% CI 1.41, 1.68] and neonatal respiratory morbidity (late preterm aRR=6.16, 95% CI 5.39, 7.03; early term aRR=1.46, 95% CI 1.29, 1.65). The effect of gestational age was partially explained by biological determinants of preterm birth acting through gestational age. Moreover, placental ischaemia and other hypoxia exacerbated the effect of gestational age on poor outcomes. CONCLUSIONS Poor outcomes among infants born late preterm and early term are not only due to physiological immaturity but also to biological determinants of preterm birth acting through and with gestational age to produce poor outcomes.

Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children

Importance Previous observations of a higher risk of child autism spectrum disorder with serotonergic antidepressant exposure during pregnancy may have been confounded. Objective To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder. Design, Setting, and Participants Retrospective cohort study. Health administrative data sets were used to study children born to mothers who were receiving public prescription drug coverage during pregnancy in Ontario, Canada, from 2002-2010, reflecting 4.2% of births. Children were followed up until March 31, 2014. Exposures Serotonergic antidepressant exposure was defined as 2 or more consecutive maternal prescriptions for a selective serotonin or serotonin-norepinephrine reuptake inhibitor between conception and delivery. Main Outcomes and Measures Child autism spectrum disorder identified after the age of 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores (computerized algorithm used to select a large number of potential confounders) and by comparing exposed children with unexposed siblings. Results There were 35 906 singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%) of children were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 4.51 per 1000 person-years among children exposed to antidepressants vs 2.03 per 1000 person-years among unexposed children (between-group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio [HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After inverse probability of treatment weighting based on the high-dimensional propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997-2.59]). The association was also not significant when exposed children were compared with unexposed siblings (incidence of autism spectrum disorder was 3.40 per 1000 person-years vs 2.05 per 1000 person-years, respectively; adjusted HR, 1.60 [95% CI, 0.69-3.74]). Conclusions and Relevance In children born to mothers receiving public drug coverage in Ontario, Canada, in utero serotonergic antidepressant exposure compared with no exposure was not associated with autism spectrum disorder in the child. Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors.

Pregnancy in Women With Intellectual and Developmental Disabilities

OBJECTIVE Our objectives were to describe the general fertility rate (GFR) and age-specific fertility rates (ASFRs) of women with intellectual and developmental disabilities (IDD) and the social and health characteristics of those with a singleton live birth, and to compare these to women without IDD. METHODS In this population-based retrospective cohort study using linked Ontario health and social services administrative data, we identified 18- to 49-year-old women with IDD (N = 21 181) and without IDD (N = 990 776). The GFR and ASFRs (2009) were calculated for both groups and compared using rate ratios (RR) and 95% confidence intervals (CI). Among women with a singleton live birth (N = 423 with, N = 42 439 without IDD), social and health characteristics were compared using Pearsons Chi square tests. RESULTS The GFR in women with IDD (20.3 per 1000) was lower than that in women without IDD (43.4 per 1000) (RR 0.47; 95% CI 0.43 to 0.51). ASFRs in 18- to 24-year-olds were similar in both groups. Among women with a singleton live birth, those with IDD were younger and had higher rates of poverty, epilepsy, obesity, and mental health issues. They also had high rates of medication use during pregnancy. CONCLUSION In the largest study of fertility in women with IDD to date, we found that ASFRs are similar in young women with and without IDD. Women with IDD with a singleton live birth experience significant social and health disparities during pregnancy. These findings suggest the need to develop services to support the reproductive health of this vulnerable group.

Biological determinants of spontaneous late preterm and early term birth: a retrospective cohort study.

Our aim was to examine the association between biological determinants of preterm birth (infection and inflammation, placental ischaemia and other hypoxia, diabetes mellitus, other) and spontaneous late preterm (34–36 weeks) and early term (37–38 weeks) birth.

The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis

OBJECTIVE This systematic review and meta-analysis examines the relationship between antenatal selective serotonin reuptake inhibitor (SSRI) exposure and child autism, with specific attention to maternal mental illness (MMI) as a potential confounding factor. DATA SOURCES We searched MEDLINE, Embase, PsycINFO, and CINAHL from database inception to January 28, 2016. STUDY SELECTION Keywords included terms for SSRIs, pregnancy, and autism. We included published, peer-reviewed articles written in English. DATA EXTRACTION Two reviewers used standardized instruments for data extraction and quality assessment. We generated pooled estimates for studies of the same design for SSRI exposure at any time during pregnancy and exposure during the first trimester. Subanalyses were conducted among studies with analyses (1) adjusted for MMI and (2) restricted to MMI. RESULTS We included in the meta-analysis 4 case-control studies and 2 cohort studies. In the case-control studies, the adjusted pooled odds ratio (aPOR) values were 1.4 (95% CI, 1.0-2.0) (any) and 1.7 (95% CI, 1.1-2.6) (first trimester). In MMI-adjusted analyses, only first trimester exposure remained statistically significant (aPOR = 1.8; 95% CI, 1.1-3.1). In MMI-restricted analyses, neither exposure period was statistically significant. In the cohort studies, MMI-adjusted relative risk values were 1.5 (95% CI, 0.9-2.7) (any) and 1.4 (95% CI, 1.0-1.9) (first trimester). In MMI-restricted analyses, SSRI exposure at any time during pregnancy was nonsignificant. CONCLUSIONS It remains unclear whether the association between first trimester SSRI exposure and child autism that was present in the case-control studies even after adjustment for MMI is a true association or a product of residual confounding. Future studies require robust measurement of MMI prior to and during pregnancy.

Mild Prematurity, Proximal Social Processes, and Development

OBJECTIVE: To elucidate the role of gestational age in determining the risk of poor developmental outcomes among children born late preterm (34–36 weeks) and early term (37–38 weeks) versus full term (39–41 weeks) by examining the contribution of gestational age to these outcomes in the context of proximal social processes. METHODS: This was an analysis of the Canadian National Longitudinal Survey of Children and Youth. Developmental outcomes were examined at 2 to 3 (N = 15 099) and 4 to 5 years (N = 12 302). The sample included singletons, delivered at 34 to 41 weeks, whose respondents were their biological mothers. Multivariable modified Poisson regression was used to directly estimate adjusted relative risks (aRRs). We assessed the role of parenting by using moderation analyses. RESULTS: In unadjusted analyses, children born late preterm appeared to have greater risk for developmental delay (relative risk = 1.26; 95% confidence interval [CI], 1.01 to 1.56) versus full term. In adjusted analyses, results were nonsignificant at 2 to 3 years (late preterm aRR = 1.13; 95% CI, 0.90 to 1.42; early term aRR = 1.11; 95% CI, 0.96 to 1.27) and 4 to 5 years (late preterm aRR = 1.06; 95% CI, 0.79 to 1.43; early term aRR = 1.03; 95% CI, 0.85 to 1.25). Parenting did not modify the effect of gestational age but was a strong predictor of poor developmental outcomes. CONCLUSIONS: Our findings show that, closer to full term, social factors (not gestational age) may be the most important influences on development.

Labour and delivery interventions in women with intellectual and developmental disabilities: a population-based cohort study

Background Our objectives were to: (1) examine the occurrence of labour induction, caesarean section, and operative vaginal delivery in women with intellectual and developmental disabilities compared to those without and (2) determine whether pre-pregnancy health conditions and pregnancy complications explain any elevated occurrence of these interventions. Methods We conducted a population-based study using linked Ontario (Canada) administrative data. We identified deliveries to women with (N=3932) and without (N=382 774) intellectual and developmental disabilities (2002–2011). Modified Poisson regression was used to estimate adjusted relative risks (aRR) and 95% CIs for interventions, controlling for sociodemographic characteristics. We used generalised estimating equations to determine whether pre-pregnancy health conditions and pregnancy complications explained any statistically significantly elevated aRRs. Results After controlling for socio-demographic characteristics, women with intellectual and developmental disabilities were more likely to have labour inductions (aRR, 1.13; 95% CI 1.06 to 1.20) and caesarean sections (aRR, 1.09; 95% CI 1.03 to 1.16) but not operative vaginal deliveries, compared to the referent group. Pre-pregnancy health conditions explained 12.9% of their elevated aRR for labour induction. Pre-pregnancy health conditions and maternal complications explained 27.8% and 13.3%, respectively, of their elevated aRR for caesarean section. Conclusions Women with intellectual and developmental disabilities are slightly more likely to have labour inductions and caesarean sections than women without intellectual and developmental disabilities. The elevated occurrence of these interventions is not fully explained by their pre-pregnancy health conditions or pregnancy complications. Non-medical issues should be evaluated for their influence on the timing of labour and delivery in this population.

Maternal and offspring outcomes in women with intellectual and developmental disabilities: a population‐based cohort study

To compare the risks for adverse maternal and offspring outcomes in women with and without intellectual and developmental disabilities.

Identifying women at risk for postpartum anxiety: a prospective population-based study.

To develop a multifactorial model to predict anxiety symptomatology at 8 weeks postpartum.

Changes in Smoking During Pregnancy in Ontario, 1995 to 2010: Results From the Canadian Community Health Survey

OBJECTIVE The objectives of this study were (1) to examine changes in smoking behaviour across time in pregnant women in Ontario (relative to non-pregnant women and men) and (2) to assess whether, among pregnant women, changes across time vary as a function of sociodemographic characteristics. METHODS This study used data from the Canadian Community Health Survey. The study sample included 15- to 49-year-old residents of Ontario. Multivariable logistic regression, with interactions between time period and the characteristic of interest, was used to examine whether changes varied across time according to (1) group (pregnant women, non-pregnant women, men; two-year intervals, 2001 to 2010) and (2) pregnant subgroup (maternal age, maternal marital status, maternal education; 1995 to 2000 [n = 3745], 2001 to 2005 [n = 5084], and 2006 to 2010 [n = 2900]). RESULTS A decrease in the prevalence of smoking across time was seen in all groups but was smaller in pregnant women than in non-pregnant women (23.5% vs. 30.8%). Among pregnant women, interactions between time period and maternal age, maternal marital status, and maternal education were statistically significant. The prevalence of smoking during pregnancy decreased in older, married, and more highly educated women, but increased in younger women (by 8.2%) and less educated women (by 12.8%). Although the prevalence of smoking during pregnancy decreased in unmarried women, the change was smaller than in married women. CONCLUSION Although the prevalence of smoking in pregnant women is decreasing over time, the decrease is smaller than that in non-pregnant women. Pregnant subgroups particularly resistant to change include younger, unmarried, and less educated mothers. These findings suggest there are subgroups that should be targeted more deliberately by public health interventions.