BACKGROUND:Sudden unexpected death in infancy (SUDI) remains poorly understood, and the potential contribution of air pollution exposure is largely unexplored. Given its known impact on infant health, air pollution may influence the risk of SUDI, particularly through short-term effects. OBJECTIVES:We aimed to evaluate the short-term effect of exposure to ambient air pollutants on SUDI in France. METHODS:Using data from the French national SUDI registry (2015-2022) and modelled air pollution data, we assigned daily concentrations of particulate matter (PM10 and PM2.5, μg/m3), nitrogen dioxide (NO2, μg/m3) and ozone (O3, μg/m3) at each infant's residence. We conducted a time-stratified case-crossover analysis comparing single- and multi-pollutant exposure on the day of death with matched control days, considering lagged effects up to 6 days. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression, adjusted for public holiday, influenza-like syndrome and daily mean temperature. We assessed the potential effect of several effect modifiers, such as biological sex, age at death, season, urban or rural residence, social deprivation and sleeping position at discovery. RESULTS:A total of 1078 SUDI cases were included. Exposure to PM was consistently associated with higher odds of SUDI, with a lag effect of 3 to 5 days before death and during the last week of life. NO2 exposure presented a trend of association. Higher effects were observed for PM and NO2 with cumulative exposure, especially for PM and consistent with the multi-pollutant model. We observed seasonal heterogeneity, with higher ORs in the spring for PM and O3. CONCLUSIONS:Our findings support a plausible short-term trigger effect of air pollution on SUDI. These results highlight the need to integrate environmental determinants, particularly for NO2 and PM, into SUDI prevention strategies.
BACKGROUND:Clinical prediction becomes actionable only when estimated risk is connected to a decision boundary. The prevalence threshold is a likelihood-ratio-derived landmark that may complement conventional risk stratification, but its empirical behaviour in obstetric populations is incompletely described. OBJECTIVES:To evaluate how fixed probability cutoffs and a formally derived prevalence threshold partition predicted preterm birth risk in a national cohort. METHODS:We analysed singleton births to U.S. residents in the 2024 natality public-use file. Preterm birth was delivery before 37 completed weeks using the obstetric estimate. A logistic model generated predicted probabilities, and adjusted risk ratios were estimated by modified Poisson regression with robust variance. We assessed discrimination, calibration across risk tenths, fixed cutoffs of 5%, 10%, 15% and 20%, and a cervical-length prevalence threshold derived from a sensitivity of 23.3% and a specificity of 93.6%. RESULTS:Among 3,004,719 complete-case pregnancies, 263,034 (8.8%) were preterm. The c-statistic was 0.634 (95% CI 0.633, 0.636), with close agreement between predicted and observed risk across tenths. Predicted risk had a mean of 8.75%, a median of 7.40%, and a range of 4.83%-84.22%. At the 10%, 15% and 20% cutoffs, 17.7%, 7.1% and 4.5% of pregnancies were above threshold, with observed preterm birth rates of 16.9%, 24.4% and 27.4%, respectively. The cervical-length likelihood ratio was 3.64, giving a prevalence threshold of 34.4%; 21,212 pregnancies (0.71%) were above this landmark, with an observed preterm birth rate of 38.1%. CONCLUSIONS:Higher fixed cutoffs selected smaller, more outcome-enriched groups while capturing fewer preterm births. The derived prevalence threshold supplied a transparent evidentiary landmark for a specified downstream test, but it was not a utility-derived treatment threshold or a screening recommendation.
BACKGROUND:Cardiovascular health before pregnancy may influence maternal and pregnancy outcomes; however, evidence among women undergoing frozen embryo transfer (FET) remains limited. OBJECTIVE:This retrospective cohort study aims to investigate the association between pre-pregnancy biomedical cardiovascular health (CVH), defined by the American Heart Association, and adverse pregnancy outcomes (APOs) after FET. METHODS:This retrospective cohort study was conducted from January 2019 to August 2023 and included 1521 women undergoing FET in their first in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle. The main APOs included hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), preterm birth (PTB), offspring being large for gestational age (LGA) and small for gestational age (SGA). Modified Poisson regression models with restricted cubic splines were used to investigate the relationship between biomedical CVH and APOs, and adjusted population-attributable fraction (PAF) and partial population-attributable fraction(partial PAFs) models were used to quantify the theoretical reduction in APOs with CVH improvement. RESULTS:Compared with the high CVH group, the low-to-moderate CVH group was associated with higher risks of HDP (relative risk [RR] 2.61, 95% confidence interval [CI] 1.83, 3.73), GDM (RR 1.82, 95% CI 1.40, 2.38), PTB (RR 2.03, 95% CI 1.47, 2.81), and LGA (RR 1.28, 95% CI 1.08, 1.52). CVH was linearly associated with the log risk of HDP and PTB. In contrast, CVH showed nonlinear associations with the log risk of GDM and LGA. PAF estimates suggest that 11.0%-36.1% of these APOs could be associated with low-to-moderate CVH (CVH score < 80). Specifically, for individual CVH components, elevated blood pressure was the leading risk factor for HDP, whereas overweight and obesity (BMI) were the strongest risk factors for GDM, PTB, and offspring LGA. CONCLUSIONS:Biomedical CVH is negatively associated with APOs in pregnancies after FET. Women undergoing FET might benefit from preventive strategies to improve CVH, especially BMI and blood pressure.
BACKGROUND:Perinatal mortality appears to have increased recently in Greece; however, it is unclear whether this increase can be solely attributed to the 2018 change in the defined gestational age threshold for stillbirth registration. OBJECTIVES:To examine temporal trends in perinatal mortality rates in Greece during the period 2014-2024 and evaluate the potential impact of changes in stillbirth registration practices. METHODS:Nationwide data from the Hellenic Statistical Authority (2014-2024; Ν = 926,154 total births) were analysed to estimate trends in perinatal mortality. Changes in stillbirth recording after 2018, following the adoption of a 22-week gestational viability threshold, were taken into account. Poisson Regression, Interrupted Time Series (ITS) and Joinpoint Regression analyses were used. RESULTS:Perinatal mortality was 5.6 in 2014 versus 8.2 in 2024 per 1000 total births. Poisson regression showed an overall increase in perinatal mortality rates (4.4% annually, 95% confidence interval [CI] 3.5 to 5.3), driven by rising stillbirth rates (6.8% annually, 95% CI 5.5 to 8.1), while early neonatal mortality rates declined (-2.0% annually; 95% CI -3.0 to -1.1). Stillbirth rates at < 26 weeks' gestation increased sharply (36.1% annually, 95% CI 24.9 to 47.4), whereas a smaller increase was observed at ≥ 26 weeks (1.7% annually, 95% CI 0.4 to 2.9). ITS analysis showed a level increase in 2019 and an increasing post-2019 trend in stillbirth rates at < 26 weeks, whereas no corresponding level or post-2019 trend changes were detected at ≥ 26 weeks. Joinpoint regression also identified 2019 as a breakpoint for stillbirths at < 26 weeks. CONCLUSIONS:The rise in perinatal mortality in Greece over the past decade has been driven by increased stillbirth rates, largely attributable to changes in stillbirth recording practices at gestational ages < 26 weeks. The modest upward trend in stillbirths at ≥ 26 weeks' gestation warrants further investigation and ongoing monitoring.
BACKGROUND:Pregnancy represents a crucial period for understanding key pathways contributing to the intergenerational effects of adverse childhood experiences (ACEs). However, prenatal mechanisms linking maternal ACEs to subsequent child mental health outcomes are still poorly understood compared to postnatal ones. OBJECTIVE:To review the biopsychosocial mechanisms during pregnancy that may contribute to the relationship between maternal ACEs and child socio-emotional and behavioural development. DATA SOURCES:We systematically searched PubMed, PsycInfo and Web of Science from inception up to February 2026. STUDY SELECTION AND DATA EXTRACTION:We included peer-reviewed observational studies (cohort, case-control, cross-sectional) evaluating prenatal biological, psychological, or social mechanisms linking maternal ACEs to child socio-emotional/behavioural outcomes (Ages 0-18); qualitative studies and grey literature were excluded. Two reviewers independently screened studies and extracted data on study design, mediators and effect sizes, with disagreements resolved by a third reviewer. SYNTHESIS:Narrative synthesis was used to summarise study characteristics, mediation pathways and analytical strategies in tabular form. Results were synthesised by type of prenatal mechanism. RESULTS:Of 2641 records identified, 122 full texts were assessed and 13 studies met inclusion criteria. Prenatal maternal depression and anxiety emerged as the most frequently studied mechanisms, showing some evidence of independent effects irrespective of postnatal factors, but most of the findings point towards a 'chain-of-risk' model, where prenatal mental health interacts with the postnatal environment. Biomedical antepartum risks and maternal-fetal attachment also showed mediating effects, but without accounting for postnatal influences. The small number of eligible studies underscores the limited exploration of prenatal transmission pathways. CONCLUSIONS:Prenatal mental health difficulties, particularly in interaction with postnatal factors, may play a role in the intergenerational transmission of ACEs. Further studies using robust methods to disentangle prenatal and postnatal contributions are needed to inform targeted interventions.
BACKGROUND:Male preconception health remains a critically under-addressed area of family planning. While research suggests air pollution may harm semen quality, downstream impacts on pregnancy, particularly for more vulnerable infertility treatment populations, are understudied. OBJECTIVES:Among couples seeking infertility treatment, we examined the relationship between men's exposure to ambient air pollution and intrauterine insemination (IUI) cycle treatment outcomes. METHODS:In the Folic Acid and Zinc Supplementation Trial (2013-2018), 592 male partners resided in the Salt Lake City area with at least one IUI cycle in 9 months of follow-up (n = 1223 cycles). Residential air pollution exposure was estimated using Community Multiscale Air Quality models and averaged across the 74-day window of spermatogenesis prior to the insemination date, as well as across developmental windows of mitosis, meiosis I-II, spermiogenesis, and spermiation. Treatment-cycle probabilities of hCG+ pregnancy, pregnancy loss, and livebirth were evaluated using generalised linear mixed models adjusted for age, season, income, and co-pollutants (fine particulate matter [PM2.5], nitrogen dioxide [NO2], ozone [O3], and sulfur dioxide [SO2]). RESULTS:In multivariable models, we observed a lower probability of pregnancy per 5 ppb increase in O3 and NO2 across the 74-day spermatogenesis window (relative risk [RR] 0.71, 95% confidence interval [CI] 0.55, 0.93; RR 0.73, 95% CI 0.50, 1.05, respectively), with associations noted during mitosis and meiosis. PM2.5 and SO2 were less consistently associated with IUI outcomes. Findings from mixture models were similar, as were findings for air pollutants and a lower probability of live birth. No clear patterns emerged between air pollutants and pregnancy loss. CONCLUSIONS:Ambient air pollution during spermatogenesis, especially during mitosis and meiosis, was associated with a lower chance of pregnancy and live birth in an IUI treatment population. Further understanding pathways between men's air pollution exposure and pregnancy and live birth is an important future research need. TRIAL REGISTRATION:clinicaltrials.gov identifier: NCT01857310.
BACKGROUND:Fertility treatments have been associated with an increased risk of congenital anomalies. Most studies have compared births conceived through fertility treatment with unassisted conceptions; consequently, these estimates reflect the combined effects of fertility treatment and the underlying infertility, potentially resulting in confounding by indication. OBJECTIVES:To estimate the association between infertility, independent of fertility treatment, and the risk of congenital anomalies. METHODS:This population-based cohort study included all live births and stillbirths at ≥ 20 weeks' gestation to women aged 15-50 in Ontario, Canada, 2006-2021. Infertility without treatment was defined as a history of one or more infertility consultations with a physician within 2 years before conception, in the absence of fertility treatment. Modified Poisson regression generated relative risks (RR) adjusted for maternal age, income quintile, rurality, pre-existing comorbidities, and smoking, alcohol use, and substance use during pregnancy. RESULTS:Of the 1,415,324 deliveries, the prevalence of congenital anomalies was 5.3% in unassisted conception and 5.9% among births to women with infertility who did not use fertility treatment. A small increase in risk was observed for any congenital anomaly (RR 1.12, 95% confidence interval [CI] 1.09, 1.14). Among organ system anomalies, the highest relative risks were observed for eye anomalies (0.11% vs 0.14%; RR 1.22, 95% CI 1.03, 1.45) and ear, face, and neck anomalies (0.06% vs 0.08%; RR 1.19, 95% CI 1.05, 1.35). Among specific anomalies, the highest relative risk was observed for other penile malformations (0.03% vs 0.04%; RR 1.41, 95% CI 1.09, 1.83). CONCLUSIONS:Although the overall risk of congenital anomalies was low, infants born to women with infertility who did not use fertility treatment had small increased risks of any congenital anomaly, selected organ system anomalies, and specific anomalies compared with infants born from unassisted conceptions.
BACKGROUND:Clinical guidelines now recommend administering intrapartum antibiotic prophylaxis (IAP) before skin incision at caesarean section to prevent maternal infection. However, this practice exposes the fetus to antibiotics, raising concerns about potential long-term effects on the infant microbiome and the risk of childhood obesity. OBJECTIVES:To assess whether the timing of IAP at caesarean section-before skin incision versus after umbilical cord clamping-is associated with childhood obesity at age 4-5 years. METHODS:We conducted a quasi-experimental study of a hospital-wide policy change in clinical practice using data from two birth cohorts (Born in Bradford [BiB] and Born in Bradford's Better Start [BiBBS]). The study included 1985 children of White British or Pakistani heritage born by caesarean section between 2007 and 2019. Children exposed to pre-incision IAP (n = 324) were compared with those unexposed (post-cord clamping IAP; n = 1661). The primary outcome was obesity (BMI z-score > 95th percentile) at age 4-5 years. Adjusted Risk Ratios (aRR) were estimated using multivariable Poisson regression stratified by ethnicity. RESULTS:The prevalence of obesity was 11.9%. Adjusted risk ratios for obesity were 1.25 (95% CI 0.53 to 2.98) for White British children and 1.25 (95% CI 0.64 to 2.43) for Pakistani children. Similarly, estimates for BMI z-score had wide confidence intervals indicating, limited precision. CONCLUSIONS:We did not observe a clear difference in childhood obesity at 4-5 years between pre-incision and post-cord clamping prophylactic antibiotics at caesarean section. Confidence intervals were wide, and modest clinically relevant effects cannot be excluded. Findings are compatible with no large adverse effect and may provide reassurance regarding the metabolic safety of current clinical practice.
BACKGROUND:Children conceived through assisted reproductive technologies (ART) often achieve higher school grades than spontaneously conceived peers in unadjusted analyses, a pattern largely attributed to the socio-economic advantage of parents who use ART. However, as ART is increasingly utilised by less advantaged groups, it is important to understand how ART-conceived children fare when their parents have lower levels of education. OBJECTIVE:The objective of this study is to examine whether the association between conception through assisted reproductive technologies and school grades at age 16 differs by maternal education. METHODS:We conducted a population-based cohort study of all live-born children in Norway from 1985 to 2002 who completed compulsory schooling (n = 929,017), using nationwide register data. The exposure was conception through ART (1.0%), and the outcome was the standardised grade point average (GPA) at age 16. Analyses were stratified by maternal education (primary/secondary vs. tertiary). Using linear regression models, we estimated differences in GPA between ART- and spontaneously conceived children. We progressively adjusted for child sex, birth cohort, plurality, birth order, maternal age, parental income and family structure. RESULTS:Among children of lower-educated mothers, mean GPA was higher for ART-conceived than spontaneously conceived children in baseline models (0.17, 95% confidence interval [CI] 0.14, 0.19). Among children of tertiary-educated mothers, the corresponding difference was 0.06 (95% CI 0.03, 0.09). After adjustment, the differences were slightly negative but small in magnitude in both education groups (primary/secondary: -0.18, 95% CI -0.21, -0.16; tertiary: -0.08, 95% CI -0.11, -0.05). CONCLUSIONS:Both ART-conceived children of less- and more-educated mothers appear advantaged in unadjusted analyses. After accounting for parental characteristics, differences were small in both education groups, reflecting socio-demographic selection into treatment within each group. These findings suggest that as ART use expands across more socio-economically diverse populations, it is unlikely to independently improve or worsen children's school performance across educational strata.
BACKGROUND:Early and late delivery are associated with increased risk of neurodevelopmental disabilities. Some experts emphasise direct causal effect, while others propose confounding by underlying pathologies. OBJECTIVES:We present detailed relative-risk estimates for five major neurodevelopmental disabilities by strata of gestational age. Confounding is explored through sibling-matched analyses and the relative risks of birth defects with gestational age. METHODS:Using data from Norway's Medical Birth Registry and other national health registries for 2.9 million births in 1967-2019, we conducted a prospective cohort analysis assessing gestational-age-specific relative risks for cerebral palsy (CP), intellectual impairment, epilepsy, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). We used an analysis of sibship-matched pairs to assess the role of unmeasured confounding by conditions that persist across successive pregnancies. We also compared these gestational-age-specific risk patterns with the corresponding risks of five birth defects present before delivery. RESULTS:Multivariable-adjusted relative risks (RRs) of all five neurodevelopmental disabilities were increased with early pre-term delivery. Compared with births at 40 weeks, infants born at 23-27 weeks had RRs ranging from 2-fold for ADHD (RR 2.2, 95% confidence interval [CI] 2.0, 2.5) to 50-fold for CP (95% CI 44, 58). Relative risks for post-term delivery (≥ 43 weeks) were smaller, ranging from 1.15 to 1.45. In sibship analyses, relative risks with pre-term delivery were attenuated, suggesting the influence of unmeasured confounding. The relative risks of birth defects with preterm and post-term delivery were similar to neurodevelopmental disabilities, showing that confounding alone can produce relative risks of the magnitude seen with neurodevelopmental disabilities. CONCLUSIONS:The effect of gestational age at birth on neurodevelopment is likely less-and perhaps much less-than suggested by the observed associations. Prevention of neurodevelopmental disabilities depends not just on interventions during and after delivery, but on identifying and intervening on prenatal causes of these disabilities.
BACKGROUND:Composite indicators of neonatal morbidity specific to Métis populations in Canada are lacking. OBJECTIVES:To estimate the incidence of neonatal morbidity and neonatal death among Métis neonates in Alberta, and to identify maternal and neonatal factors associated with neonatal morbidity. METHODS:Population-based retrospective cohort study including all singleton live births to Métis mothers in Alberta between April 2006 and March 2016. Hospital discharge data were used to evaluate the Neonatal Adverse Outcome Indicator (NAOI), which comprises a set of newborn medical complications and neonatal death. We estimated overall and annual NAOI incidence proportions and overall neonatal mortality. Multilevel regression models were used to estimate adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) for maternal and neonatal characteristics associated with NAOI. RESULTS:Among 7853 neonates, the overall NAOI incidence proportion was 10.1% (95% CI 9.5, 10.8), ranging annually from 7.7% (95% CI 6.1, 9.7) to 11.9% (95% CI 8.1, 17.2). The most common conditions were respiratory conditions originating in the perinatal period (4.8%, 95% CI 4.3, 5.3) and birth trauma (3.4%, 95% CI 3.0, 3.8). The overall neonatal mortality rate was 2.9 per 1000 live births (95% CI 1.9, 4.4). Increased risk of NAOI was associated with pre-pregnancy disease (aRR 1.27, 95% CI 1.03, 1.51), pregnancy-related disease (aRR 1.92, 95% CI 1.65, 2.18), assisted vaginal delivery (aRR 2.52, 95% CI 2.09, 2.94), caesarean delivery (aRR 1.23, 95% CI 1.04, 1.41), male sex (aRR 1.27, 95% CI 1.09, 1.42), preterm birth (aRR 4.36, 95% CI 3.71, 5.00) and any congenital malformation (aRR 2.71, 95% CI 1.87, 3.56). CONCLUSIONS:The incidence of neonatal morbidity among Métis neonates in Alberta highlights the importance of continued surveillance using standardised indicators. Incorporating NAOI into perinatal and obstetric care may inform culturally responsive improvements in care.
BACKGROUND:Gestational diabetes mellitus (GDM) is a common pregnancy complication with both short- and long-term adverse outcomes for both mothers and their offspring. CenteringPregnancy group prenatal care (CPNC) model has gained popularity due to its unique design to support pregnant individuals in managing multiple risk factors during pregnancy. However, whether participation in CPNC reduces the risk of developing GDM remains uncertain. OBJECTIVE:To compare the GDM incidence between pregnant individuals receiving CPNC and those receiving traditional individual prenatal care (IPNC). METHODS:This retrospective cohort study included 8313 participants (CPNC: 1832; IPNC: 6481) from South Carolina. GDM was screened and diagnosed between 24 and 30 weeks of gestation with the two-step approach. We applied inverse probability of treatment weighting (IPTW) using stabilized propensity score (PS) weights. The weighted risk ratio (RR) of CPNC relative to IPNC for GDM was estimated using weighted marginal log-binomial models. RESULTS:In the original cohort, the incidence of GDM was 4.7% in the CPNC group and 6.8% in the IPNC group. After applying stabilized IPTW, baseline characteristics were well balanced between groups. In the weighted pseudo-cohort, CPNC was associated with a lower risk of GDM compared with IPNC (RR 0.64, 95% confidence interval [CI] 0.51, 0.81). In subgroup analyses, this inverse association was observed among non-Hispanic White (RR 0.61, 95% CI 0.43, 0.86) and non-Hispanic Black participants (RR 0.69, 95% CI 0.47, 1.00), but not among Hispanic participants (RR 1.05, 95% CI 0.62, 1.77). Results from multivariable logistic regression in the original cohort were consistent in direction but less precise. There was no evidence of additive interaction by race/ethnicity. CONCLUSIONS:Pregnant individuals receiving CPNC had a lower risk of developing GDM than those receiving IPNC.
