Paediatric and perinatal epidemiology最新文献

Background: Prior studies report associations between periconceptional exposure to natural and synthetic oestrogen and progesterone and autism spectrum disorder (ASD). Hormonal contraception contains synthetic forms of one or both hormones. Although hormonal contraception is highly effective when consistently used, unintended pregnancy can occur with irregular use. Given the popularity of hormonal contraception, foetal exposure in utero is possible, yet the potential consequences are unknown.

Objectives: We investigated the association between periconceptional hormonal contraception use and the development of ASD in offspring.

Methods: We analysed data from the Study to Explore Early Development (SEED), a population-based case-control study conducted in select US states, from 2007 to 2020. Children with and without ASD were identified from clinical/education sources and vital records, respectively, and enrolled at ages 2.5-5 years. We confirmed the ASD case status by in-person developmental assessment. We assessed hormonal contraception via a structured interview. We assessed the associations between ASD and hormonal contraception exposure separately for contraception discontinued in the 3 months prior to pregnancy and contraception continued during pregnancy using logistic models to estimate odds ratios (OR) adjusted for biological mother age, education, parity, pre-pregnancy body mass index (BMI), and presence of gynaecologic conditions and 95% confidence intervals (CI).

Results: Of 5210 participants, 9.9% reported discontinuing hormonal contraception use before pregnancy and 2.3% reported continuing use during pregnancy. A suggestive association was found between ASD and hormonal contraception use during pregnancy (aOR 1.38,95% CI 0.93, 2.05). There was no association with use prior to pregnancy (aOR 1.02, 95% CI 0.84, 1.25).

Conclusions: Discontinuation of hormonal contraception prior to conception was not associated with ASD. The prevalence of hormonal contraception use during pregnancy was low. Results were imprecise and may be impacted by recall bias and unmeasured confounding by indication and health behaviours related to planning pregnancy.

Background: Estimating the causal effect of third-stage management approaches on preventing postpartum haemorrhage (PPH) in the context of physiologic birth using observational data requires conditioning on specific variables, with selection relying on assumptions about their roles in the exposure-outcome pathway that are rarely made explicit.

Objectives: To apply the evidence synthesis for constructing DAGs approach, incorporating findings from a systematic review, to develop a causal directed acyclic graph (DAG) that clarifies these assumptions and identifies the minimum set of variables needed to reduce bias in estimating the causal effects of physiologic third-stage care versus oxytocin prophylaxis on PPH.

Data sources: MEDLINE, Embase, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials (to December 15, 2023), ClinicalTrials.gov (to July 8, 2024), and reference lists of eligible studies.

Study selection and data extraction: The systematic review included randomised and non-randomised studies involving individuals with physiologic birth or minimal obstetric interventions. Two authors independently screened studies. DAG development was based on the subset of non-randomised studies. For each, one reviewer extracted outcome, exposure, control variables and mediators.

Synthesis: Eligible studies were analysed in three stages: (i) mapping each study's saturated implied graph; (ii) translating each posited connection using causal criteria to create study-specific DAGs; (iii) synthesising individual DAGs into an integrated DAG. The assumptions underlying this process were specific to the midwifery context in Ontario, Canada and translation was guided by midwifery expertise and existing literature.

Results: Four non-randomised studies were included. Expert consultation identified 20 factors influencing third-stage management. The integrated DAG comprised 339 directed edges connecting 35 covariates, yielding four minimal sufficient adjustment sets.

Conclusions: The integrated DAG and minimal sufficient adjustment sets are valuable tools for informing future study design and analysis, helping to minimise bias in estimating the causal effect of physiologic third-stage care versus oxytocin prophylaxis on PPH in the context of physiologic birth, while also exposing the assumptions about causal relationships between variables to scrutiny.

Background: Studies show that foetal and birthweight-for-gestational age centiles are poor predictors of serious neonatal morbidity and neonatal mortality (SNMM) in univariable models.

Objective: We assessed the predictive performance of multivariable SNMM models based on maternal/pregnancy characteristics, with and without birthweight centiles.

Methods: The study was based on all live births in the United States, 2019-2021, with data obtained from the period live birth-infant death files of the National Center for Health Statistics. SNMM was defined as any one or more of the following: 5-minute Apgar score < 4, seizures, assisted ventilation for> 30 or neonatal death. SNMM was modelled by log-linear regression on maternal/pregnancy characteristics as predictors, with and without birthweight centiles. Models were developed for live births at 24-42 weeks' and 39 weeks' gestation to all women and those with hypertensive disorders or pre-existing diabetes. Model performance was assessed using area under the curve (AUC).

Results: The study population included 10,487,243 live births and 221,728 SNMM cases (2.1 per 100 live births). The models with all live births at 24-42 weeks' gestation had AUCs of 0.83 (95% confidence interval [CI] 0.82, 0.83) based on maternal/pregnancy characteristics and 0.83 (95% CI 0.83, 0.84) based on maternal/pregnancy characteristics and birthweight centiles. However, AUCs of models based on all live births at 39 weeks' gestation were 0.66 (95% CI 0.64, 0.68) with maternal/pregnancy characteristics and 0.69 (95% CI 0.68, 0.71) with maternal/pregnancy characteristics and birthweight centiles. AUCs of the models with live births at 39 weeks' gestation to women with pre-existing diabetes were 0.69 (95% CI 0.66, 0.72) based on maternal/pregnancy characteristics, and 0.77 (95% CI 0.74, 0.79) with the addition of birthweight centiles.

Conclusions: Birthweight centiles improve multivariable SNMM predictive performance in specific subpopulations, although evaluation of decision thresholds is required to determine the clinical importance of improvement in predictive ability.

Background: Antimicrobial resistance (AMR) poses a critical public health issue, exacerbated by the overuse and misuse of antibiotics. Children are particularly susceptible to bacterial infections and are frequently prescribed antibiotics.

Objective: This study examined trends in antibiotic dispensing to children aged under 13 years in Australia between 2013 and 2023.

Methods: This retrospective observational study used a 10% random sample of dispensing records for nationally subsidised prescription antibiotics. The number of children dispensed an antibiotic was calculated for each year and expressed per 100 children. Trends were analysed using joinpoint regression overall and by age group, sex, the World Health Organisation's Access, Watch, Reserve (AWaRe) system of antibiotic classification and antibiotic subtype.

Results: Between 2013 and 2023, 3,406,208 antibiotic prescriptions were dispensed to 554,837 children. There was a decrease in the total number of antibiotic prescriptions dispensed, falling from 103 prescriptions dispensed for every 100 children in 2013 to 63 prescriptions in 2023 (annual percent change [APC]: -6.9, 95% CI: -9.8, -4.4). While decreases were observed for medications classified as 'Access' (APC: -5.8, 95% CI: -8.7, -3.1), the largest decrease was observed in 'Watch' medications (APC: -15.0, 95% CI: -19.4, -11.7). Decreases were observed in the proportion of children dispensed an antibiotic, declining from 45.7% in 2013 to 33.6% in 2023 (APC: -4.7%, 95% CI: -7.1%, -2.5%). Reductions in dispensing were observed overall and by sex, age groups and most antibiotic types.

Conclusions: Antibiotic dispensing in Australian children has decreased over the past decade, for all ages, sexes and antibiotic sub-classes, likely reflecting implemented policies and efforts to curb overuse of antibiotic medicines and AMR during this period.

Background: Maternal acetaminophen use during pregnancy is common globally. However, its potential risks for neurodevelopmental disorders in offspring, including attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID), remain uncertain in Asian populations.

Objective: We examined the association between maternal acetaminophen use during pregnancy and diagnoses of neurodevelopmental disorders in offspring.

Methods: This nationwide birth cohort study included 217,602 children contributing 966,546 person-years using a nationwide administrative database from 2005 to 2022. We investigated the association between maternal acetaminophen use during pregnancy and offspring's neurodevelopmental outcomes using Cox proportional hazards models, with primary analyses based on 1:1 propensity score (PS) matching. The robustness of the primary findings was evaluated through alternative statistical approaches (adjusted model and inverse probability of treatment weighting [IPTW]), sibling comparison, probabilistic bias analyses for exposure misclassification, and negative exposure control methods.

Results: Of the 217,602 children, 85,853 (39.5%) were exposed to acetaminophen during pregnancy. PS-matched analyses (N = 42,123 children per comparator) yielded hazard ratios of 1.08 (95% CI: 1.00, 1.16) for composite neurodevelopmental outcomes, 1.22 (95% CI: 1.09, 1.36) for ADHD, 1.06 (95% CI: 0.98, 1.15) for ASD, and 1.02 (95% CI: 0.90, 1.19) for ID. Similar findings were observed in adjusted models and IPTW methods. Sibling comparisons (n = 23,593) showed point estimates in the opposite direction (e.g., HR of ADHD, 0.86; 95% CI, 0.52, 1.44). Probabilistic bias analysis for exposure misclassification suggested overestimation due to unrecorded over-the-counter acetaminophen use, with effect estimates shifting towards the null as misclassification increased. Negative exposure controls (e.g., NSAIDs and acetaminophen use after pregnancy) indicated potential positive bias in the observed associations.

Conclusions: Although PS-matched analyses indicated small increases in risk, sensitivity analyses suggested that unmeasured confounding, misclassification and other biases may partially explain these associations.

Background: Early-onset neonatal infections are among the most common neonatal diseases. However, the long-term outcomes of the infections are not well understood.

Objective: To study the association between early-onset neonatal infection and attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

Methods: A nationwide register-based cohort study was conducted, including near-term and term children born between 1997 and 2013 with follow-up until 2021. An early-onset infection was defined as an invasive bacterial infection occurring within the first week of life, including both physician-assigned diagnoses and positive bacterial cultures. ADHD and ASD were defined by diagnoses or prescriptions of relevant medication. Associations between sepsis and the neurodevelopmental disorders were investigated using multivariable Cox regression to estimate adjusted hazard ratios (HR), whereas associations with meningitis were examined using person-time incidence rate ratios (IRR). Sibling-matched analyses were also conducted for associations with sepsis.

Results: A total of 981,869 children were included, with 8154 defined as having sepsis and 152 defined as having meningitis. Among these, only 257 children had culture-positive sepsis, whereas 32 had culture-positive meningitis. The incidence rate of ADHD and ASD for children with sepsis was 4.5 per 1000 and 3.3 per 1000 person-years, respectively. Sepsis was associated with an increased adjusted likelihood of both ADHD (HR 1.28, 95% CI 1.17, 1.39) and ASD (HR 1.43, 95% CI 1.30, 1.58). However, sibling-matched analyses especially attenuated the association with ADHD (HR 1.12, 95% CI 0.93, 1.34). Point estimates suggested that children with meningitis also had an increased likelihood of both ADHD (IRR 1.77, 95% CI 0.88, 3.17) and ASD (IRR 2.05, 95% CI 0.89, 4.04).

Conclusions: Early-onset sepsis was associated with an increased likelihood of ASD, whereas the majority of the association with ADHD could be explained by unmeasured shared familial confounding.