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Purpose of ReviewEvidence suggests neurotoxicity of endocrine disrupting chemicals (EDCs) during sensitive periods of development. We present an overview of pediatric population neuroimaging studies that examined brain influences of EDC exposure during prenatal period and childhood.Recent FindingsWe found 46 studies that used magnetic resonance imaging (MRI) to examine brain influences of EDCs. These studies showed associations of prenatal exposure to phthalates, organophosphate pesticides (OPs), polyaromatic hydrocarbons and persistent organic pollutants with global and regional brain structural alterations. Few studies suggested alteration in functional MRI associated with prenatal OP exposure. However, studies on other groups of EDCs, such as bisphenols, and those that examined childhood exposure were less conclusive.SummaryThese findings underscore the potential profound and lasting effects of prenatal EDC exposure on brain development, emphasizing the need for better regulation and strategies to reduce exposure and mitigate impacts. More studies are needed to examine the influence of postnatal exposure to EDC on brain imaging.

Background: We aimed to examine the national and subnational prevalence of vulnerable newborn phenotypes in Peru, 2012–2021. Methods: Newborn phenotypes were defined using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight [LBW], non-LBW) using the Peruvian National Birth Registry as six (by excluding birthweight) and ten newborn phenotypes (using all three outcomes). Small phenotypes (with at least one classification of PT, SGA, or LBW) were further considered. Using individual-level data, we stratified the phenotypes by maternal educational level, maternal age, healthcare insurance, altitude of residence, and geographic region (Coast, Andes, and Amazon). Findings: The prevalence of the five vulnerable newborn phenotypes for the study period was LGA+T (15.2%), AGA+PT (5.2%), SGA+T (4.6%), LGA+PT (0.8%), and SGA+PT (0.7%). The Coast had a higher prevalence of newborns with large phenotypes (19.4%) and the Highlands a higher prevalence of newborns with small phenotypes (12.5%). Mothers with poor socioeconomic status, extreme ages and living at high altitude had a higher prevalence of newborns with small phenotypes, and mothers who were wealthier, more educated, and older had a higher prevalence of infants with large phenotypes. Interpretation: Our findings cautiously suggest that socioeconomic and geographic disparities may play a crucial role in shaping vulnerable newborn phenotypes at national and subnational level in Peru. Further studies using longitudinal data are needed to corroborate our findings and to identify individual-level risk factors.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

Background/objectives: Cardiovascular diseases are the leading cause of global mortality. Systematic studies on cardiovascular-related mortality at national and subnational levels in Peru are lacking. We aimed to describe the trends in cardiovascular-related mortality between 2017 and 2022 in Peru at national and subnational levels and by socioeconomic indicators. Subjects/methods: We used data from the Peruvian death registry 2017–2022. Using ICD-10 codes, mortality was categorized into: hypertensive-, coronary-, and cerebrovascular- related deaths. We estimated age-standardized cardiovascular-related mortality rates by sex at national and regional levels, and by natural regions (Coast, Highlands, Amazon). We estimated the change in mortality rates between 2017–2019 and 2020–2022 and explored factors that contributed to such a change. We explored ecological relationships between mortality rates and socioeconomic indicators.Findings: Overall 183,386 cardiovascular-related deaths were identified. Coronary-related deaths (37.2 %) were followed by hypertensive-related (25.1 %) and cerebrovascular-related deaths (22.6 %). Peru showed a marked increasing trend in cardiovascular-related mortality in 2020–2022 (77.8 %). The increase clustered in the Coast and Highlands, with the highest change observed in Lima (132.1 %). Mortality was highest in subjects with lower education and subjects with public health insurance. Gini coefficient was associated with lower mortality rates while unemployment was associated with higher mortality rates.Interpretation: There was a notable rise in cardiovascular-related mortality in Peru, particularly during the Covid-19 pandemic with a slight decrease in 2022. Gaining a comprehensive understanding of the factors that contribute to the increase in cardiovascular deaths in Peru will facilitate the development of precise interventions at both the national and regio

Fetal tobacco exposure has persistent effects on growth and metabolism. The underlying mechanisms of these relationships are yet unknown. We investigated the associations of fetal exposure to maternal smoking with neonatal metabolite profiles. In a population-based cohort study among 828 mother-infant pairs, we assessed maternal tobacco use by questionnaire. Metabolite concentrations of amino acids, non-esterified fatty acids, phospholipids and carnitines were determined by using LC-MS/MS in cord blood samples. Metabolite ratios reflecting metabolic pathways were computed. Compared to non-exposed neonates, those exposed to first trimester only tobacco smoking had lower neonatal mono-unsaturated acyl-alkyl-phosphatidylcholines (PC.ae) and alkyl-lysophosphatidylcholines (Lyso.PC.e) 18:0 concentrations. Neonates exposed to continued tobacco smoking during pregnancy had lower neonatal mono-unsaturated acyl-lysophosphatidylcholines (Lyso.PC.a), Lyso.PC.e.16:0 and Lyso.PC.e.18:1 concentration (False discovery rate (FDR) p-values < 0.05). Dose-response associations showed the strongest effect estimates in neonates whose mothers continued smoking ≥5 cigarettes per day (FDR p-values < 0.05). Furthermore, smoking during the first trimester only was associated with altered neonatal metabolite ratios involved in the Krebs cycle and oxidative stress, whereas continued smoking during pregnancy was associated with inflammatory, transsulfuration, and insulin resistance markers (p-value < 0.05). Thus, fetal tobacco exposure seems associated with neonatal metabolite profile adaptations. Whether these changes relate to later life metabolic health should be studied further.

Background: National and subnational C-section rates are seldom available in low- and middle-income countries to guide policies and interventions. We aimed to describe the C-section rates at the national and subnational levels in Peru (2012-2020). Methods: Based on the Peruvian national birth registry, we quantified C-section rates at the national, regional and province levels; also, by natural regions (Coast, Highlands, and Amazon). Using individual-level data from the mother, we stratified the C-section rates by educational level, healthcare insurance and provider. Ecologically, we studied the correlations between C-section rates and human development index (HDI), altitude above sea level, proportion of the population living in poverty and proportion of rural population. Findings: C-section rate in Peru decreased slightly from 2012 (39·7%) to 2020 (38·0%). A widening gap of C-section rates was observed through the study years among the Coast that showed higher rates and the other natural regions that showed lower rates. The rates in most of the 25 regions showed a flat trend, particularly in the last four years and some provinces showed a very low rate. The rates were highest in mothers with higher education and in users of private health insurance. Higher HDI, health facility located at lower altitude, lower poverty and urbanization were positively correlated with higher C-section rates. Interpretation: C-section rates in Peru are above the international recommendations. Large differences by natural region, provinces and women socioeconomic status were found. Further efforts are needed to achieve the recommended C-section rates. Funding: Academy Ter Meulen grant of the Academy Medical Sciences Fund of the Royal Netherlands Academy of Arts & Sciences (KNAWWF/1327/TMB202116), Wellcome Trust (214185/Z/18/Z), Fogarty (D43TW011502).

Maternal tobacco and cannabis use during pregnancy are associated with adverse perinatal outcomes. We hypothesized that maternal tobacco and cannabis use are associated with placental adaptations, which subsequently lead to adverse perinatal outcomes. In a population-based prospective cohort study of 8008 pregnant women, we assessed maternal tobacco and cannabis use by questionnaires. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured in the first and second trimester and at delivery from blood samples. Placental weight and pregnancy complications were obtained from medical records. We observed that tobacco use before and during first-trimester only was not associated with any angiogenic factors. As compared to no tobacco use, continued use during pregnancy was associated with higher PlGF, lower sFlt-1 concentrations, and lower sFlt-1/PlGF ratio in second trimester (all p-values <0.05). Also, compared to no cannabis use, use before and during pregnancy was associated with higher PlGF concentrations and lower sFlt-1/PlGF ratio in first and second trimester (all p-values <0.05). First trimester only cannabis use was associated with higher sFlt-1 concentrations and higher sFlt-1/PlGF ratio at delivery (all p-values <0.05). Compared to non-use, tobacco use before pregnancy was associated with a higher placental weight, whereas continued tobacco use during pregnancy was associated with a lower placental weight. Continued tobacco or cannabis use was related to higher placental weight to birth weight ratio and higher risk of pregnancy complications (all p-values <0.05). These results suggest that maternal tobacco and cannabis use lead to placental vascular maladaptation predisposing to adverse pregnancy outcomes.

Background: Foetal tobacco and cannabis exposure may have persistent cardio-metabolic consequences in the offspring. Objective: We examined the associations of maternal and paternal tobacco and cannabis use during pregnancy with offspring body fat and cardio-metabolic outcomes. Methods: In a population-based prospective cohort study among 4792 mothers, fathers, and children, we assessed parental substance use by questionnaires. Childhood outcomes included body mass index (BMI), body fat, blood pressure, and lipid, glucose and insulin concentrations at 10 years. Results: Children exposed to maternal tobacco use during pregnancy had a higher android/gynoid fat mass ratio (difference 0.22 SDS, 95% confidence interval [CI]: 0.13, 0.30), fat mass index (difference 0.20 SDS, 95% CI: 0.12, 0.28), triglyceride concentrations (difference 0.15 SDS, 95% CI: 0.04, 0.26), and a higher risk of overweight (odds ratio [OR] 1.35, 95% CI: 1.07, 1.71), compared to non-exposed. Children exposed to maternal cannabis during pregnancy had a higher BMI (difference 0.26 SDS, 95% CI: 0.08, 0.44), android/gynoid fat mass ratio (difference 0.21 SDS, 95% CI: 0.04, 0.39), and fat-free mass index (difference 0.24 SDS, 95% CI: 0.06, 0.41), compared to non-exposed. The associations for paternal substance use with child cardio-metabolic health outcomes were similar as those for maternal use. Conclusions: Similar associations for maternal and paternal substance use during pregnancy suggest that these findings may be explained by shared family-based social and lifestyle factors, rather than by direct foetal programming.

Background: National and subnational characterization of birthweight profiles lacks in low- and middle-income countries, yet these are needed for monitoring the progress of national and global nutritional targets. We aimed to describe birthweight indicators at the national and subnational levels in Peru (2012-2019), and by selected correlates. Methods: We studied mean birthweight (g), low birthweight (<2,500 g) and small for gestational age (according to international growth curves) prevalences. We analysed the national birth registry and summarized the three birthweight indicators at the national, regional, and province level, also by geographic area (Coast, Highlands, and Amazon). With individual-level data from the mother, we described the birthweight indicators by age, educational level and healthcare provider. Following an ecological approach (province level), we described the birthweight indicators by human development index (HDI), altitude above sea level, proportion of the population living in poverty and proportion of rural population. Findings: Mean birthweight was always the lowest in the Highlands (2,954 g in 2019) yet the highest in the Coast (3,516 g in 2019). The same was observed for low birthweight and small for gestational age. In regions with Coast and Highlands, the birthweight indicators worsen from the Coast to the Highlands; the largest absolute difference in mean birthweight between Coast and Highlands in the same region was 367 g. All birthweight indicators were the worst in mothers with none/initial education, while they improved with higher HDI. Interpretation: This analysis suggests that interventions are needed at the province level, given the large differences observed between Coast and Highlands even in the same region. Funding: Wellcome Trust (214185/Z/18/Z)