Neurodevelopment of Children Whose Mothers Were Randomized to Low-Dose Aspirin During Pregnancy.

OBJECTIVE: Because low-dose aspirin is now commonly prescribed in pregnancy, we sought to assess the association between early antenatal exposure and child neurodevelopment. METHODS: We performed a noninferiority, masked, neurodevelopmental follow-up study of children between age 33 and 39 months whose mothers had been randomized to daily low-dose aspirin (81 mg) or placebo between 6 0/7 and 13 6/7 weeks of gestation through 37 weeks. Neurodevelopment was assessed with the Bayley-III (Bayley Scales of Infant and Toddler Development, 3rd Edition) and the ASQ-3 (Ages and Stages Questionnaire, 3rd Edition). The primary outcome was the Bayley-III cognitive composite score with a difference within 4 points demonstrating noninferiority. RESULTS: A total of 640 children (329 in the low-dose aspirin group, 311 in the placebo group) were evaluated between September 2021 and June 2022. The Bayley-III cognitive composite score was noninferior between the two groups (-1, adjusted mean -0.8, 95% CI, -2.2 to 0.60). Significant differences were not seen in the language composite score (difference 0.7, 95% CI, -0.8 to 2.1) or the motor composite score (difference -0.6, 95% CI, -2.5 to 1.2). The proportion of children who had any component of the Bayley-III score lower than 70 did not differ between the two groups. Similarly, the communication, gross motor, fine motor, problem-solving, and personal-social components of the ASQ-3 did not differ between groups. Maternal characteristics, delivery outcomes, breastfeeding rates, breastfeeding duration, and home environment as measured by the Family Care Indicators were similar. CONCLUSION: Antenatal low-dose aspirin exposure was not associated with altered neurodevelopmental outcomes at age 3 years. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04888377.

Exposure to perfluoroalkyl and polyfluoroalkyl substances and pediatric obesity: a systematic review and meta-analysis.

INTRODUCTION: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are potentially obesogenic for children. We undertook a systematic review to synthesize this literature and explore sources of heterogeneity in previously published epidemiological studies. METHODS: Studies that collected individual-level PFAS and anthropometric data from children up to 12 years of age were identified by searching six databases. We excluded studies that only evaluated obesity measures at the time of birth. A full-text review and quality assessment of the studies was performed using the Office of Health Assessment and Translation (OHAT) criteria. Forest plots were created to summarize measures of association and assess heterogeneity across studies by chemical type and exposure timing. Funnel plots were used to assess small-study effects. RESULTS: We identified 24 studies, of which 19 used a cohort design. There were 13 studies included in the meta-analysis examining various chemicals and outcomes. Overall prenatal exposures to four different types of PFAS were not statistically associated with changes in body mass index (BMI) or waist circumference. In contrast, for three chemicals, postnatal exposures were inversely related to changes in BMI (i.e., per log10 increase in PFOS: BMI z-score of -0.16 (95% CI: -0.22, -0.10)). There was no substantial heterogeneity in the reported measures of association within prenatal and postnatal subgroups. We observed modest small-study effects, but correction for these effects using the Trim and Fill method did not change our summary estimate(s). CONCLUSION: Our review found no evidence of a positive association between prenatal PFAS exposure and pediatric obesity, whereas an inverse association was found for postnatal exposure. These findings should be interpreted cautiously due to the small number of studies. Future research that can inform on the effects of exposure mixtures, the timing of the exposure, outcome measures, and the shape of the exposure-response curve is needed.

Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in the Blood of Pakistani Children with and without Autism Spectrum Disorder and Their Associated Factors.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with early onset in utero or childhood. Environmental exposure to six metals (Pb, Hg, As, Cd, Mn, Al) is believed to be associated with ASD directly or interactively with genes. Objective: To assess the association of ASD among Pakistani children with the six metals and genotype frequencies of three GST genes (GSTP1, GSTM1, GSTT1). METHODS: We enrolled 30 ASD cases, age 2-12 years old, and 30 age- and sex-matched typically developing (TD) controls in Karachi, Pakistan. We assessed associations of ASD status with various factors using Conditional Logistic Regression models. We also used General Linear Models to assess possible interaction of blood Mn and Pb concentrations with the three GST genes in relation to ASD status. RESULTS: The unadjusted difference between ASD and TD groups in terms of geometric mean blood Pb concentrations was marginally significant (p = 0.05), but for Al concentrations, the adjusted difference was marginally significant (p = 0.06). CONCLUSIONS: This is the first study reporting six blood metal concentrations of Pakistani children with ASD. Estimates provided for possible interactions of GST genes with Mn and Pb in relation to ASD status are valuable for designing future similar studies.

Risk of Injury in Older Adults Using Gastrointestinal Antispasmodic and Anticholinergic Medications.

OBJECTIVES: To determine the risk of injury associated with gastrointestinal (GI) antispasmodic and anticholinergic use in elderly adults. DESIGN: Retrospective case-control study. SETTING: Integrated healthcare system. PARTICIPANTS: Healthcare system members aged 65 and older (N = 260,010; 54,152 cases, 205,858 controls). MEASUREMENTS: Cases were identified as individuals with an injury resulting in a hospitalization, emergency department, or urgent care visit (index date) from January 2009 through December 2010. Cases and controls were matched in a 1:4 ratio based on age and sex. GI antispasmodic and anticholinergic current and past exposure for cases and controls was evaluated. Individuals were classified as current users if the days' supply of the GI prescription overlapped the index date and past users if the days' supply ended more than 60 days before the index date. Duration of use for current users was analyzed for short- and long-term use. Conditional logistic regression produced adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Of the total population, 1,068 (0.4%) had current exposure to a GI antispasmodic or anticholinergic (302 (0.6%) cases, 766 (0.4%) controls). Current users had a small but significantly greater risk of injury than nonusers (OR = 1.16, 95% CI = 1.01-1.34, P = .03). Past use was not significantly different from no use. Short-term users had a significantly greater risk of injury (OR = 1.31, 95% CI = 1.01-1.70, P = .04) than nonusers. Long-term use was associated with greater risk, but the difference was not statistically significant. CONCLUSION: Older adults using GI antispasmodic and anticholinergic drugs have greater risk of injury. These findings support recommendations to limit the prescribing of GI antispasmodics and anticholinergics in elderly adults.