Association of labor induction with offspring risk of autism spectrum disorders

IMPORTANCE: Induction of labor is a frequently performed obstetrical intervention. It would thus be of great concern if reported associations between labor induction and offspring risk of autism spectrum disorders (ASD) reflected causal influence. OBJECTIVE: To assess the associations of labor induction with ASD, comparing differentially exposed relatives (siblings and cousins discordant for induction). DESIGN, SETTING, AND PARTICIPANTS: Follow-up of all live births in Sweden between 1992 and 2005, defined in the Medical Birth Register. The register was linked to population registers of familial relations, inpatient and outpatient visits, and education records. Diagnoses of ASD were from 2001 through 2013, and data were analyzed in the 2015-2016 year. EXPOSURES: Induction of labor. MAIN OUTCOMES AND MEASURES: Autism spectrum disorders identified by diagnoses from inpatient and outpatient records between 2001 and 2013. Hazard ratios (HRs) quantified the association between labor induction and offspring ASD. In addition to considering a wide range of measured confounders, comparison of exposure-discordant births to the same woman allowed additional control for all unmeasured factors shared by siblings. RESULTS: The full cohort included 1362950 births, of which 22077 offspring (1.6%) were diagnosed with ASD by ages 8 years through 21 years. In conventional models of the full cohort, associations between labor induction and offspring ASD were attenuated but remained statistically significant after adjustment for measured potential confounders (HR, 1.19; 95% CI, 1.13-1.24). When comparison was made within siblings whose births were discordant with respect to induction, thus accounting for all environmental and genetic factors shared by siblings, labor induction was no longer associated with offspring ASD (HR, 0.99; 95% CI, 0.88-1.10). CONCLUSIONS AND RELEVANCE: In this nationwide sample of live births we observed no association between induction of labor and offspring ASD within sibling comparison. Our findings suggest that concern for ASD should not factor into the clinical decision about whether to induce labor.NonePublishe

Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring.

Importance: Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding. Objective: To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems. Design, Setting, and Participants: This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations. Exposures: Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations. Main Outcomes and Measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring. Results: Among 1580629 offspring (mean gestational age, 279 days; 48.6% female; 1.4% [n = 22544] with maternal first-trimester self-reported antidepressant use) born to 943776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons. Conclusions and Relevance: Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.National Institute of Mental Health of the National Institutes of Health (NIH), T32MH103213National Institute on Drug Abuse of NIH, K99DA040727National Science Foundation Graduate Research Fellowship, 1342962Indiana Clinical and Translational Sciences Institute: Pediatric Project Development TeamSwedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM), 340-2013-5867Swedish Research Council for Health, Working Life, and Welfare, FORTE; 50623213Swedish Research Council, 2014-38313831Accepte

Paternal age at childbirth and eating disorders in offspring

Background. Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age’s relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence. Method. Data for 2 276 809 individuals born in Sweden 1979–2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987–2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history. Results. Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25–29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14–1.53] for AN and 1.26 (95% CI 1.13–1.40) for AED. Conclusions. In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline.NonePublishe

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Evaluation and management of congenital tracheal stenosis.

To outline an expert-based consensus of recommendations for the diagnosis and management of pediatric patients with congenital tracheal stenosis. Expert opinions were sought from members of the International Pediatric Otolaryngology Group (IPOG) via completion of an 18-item survey utilizing an iterative Delphi method and review of the literature. Forty-three members completed the survey providing recommendations regarding the initial history, clinical evaluation, diagnostic evaluation, temporizing measures, definitive repair, and post-repair care of children with congenital tracheal stenosis. These recommendations are intended to be used to support clinical decision-making regarding the evaluation and management of children with congenital tracheal stenosis. Responses highlight the diverse management strategies and the importance of a multidisciplinary approach to care of these patients