The 1918 Influenza pandemic had long-term impacts on the cohort exposed in utero which experienced earlier adult mortality, and more diabetes, ischemic heart disease, and depression after age 50. It is possible that the Coronavirus Disease 2019 (COVID-19) pandemic will also have long-term impacts on the cohort that was in utero during the pandemic, from exposure to maternal infection and/or the stress of the pandemic environment. We discuss how COVID-19 disease during pregnancy may affect fetal and postnatal development with adverse impacts on health and aging. Severe maternal infections are associated with an exaggerated inflammatory response, thromboembolic events, and placental vascular malperfusion. We also discuss how in utero exposure to the stress of the pandemic, without maternal infection, may impact health and aging. Several recently initiated birth cohort studies are tracking neonatal health following in utero severe acute respiratory syndrome virus 2 (SARS-CoV-2) exposure. We suggest these cohort studies develop plans for longer-term observations of physical, behavioral, and cognitive functions that are markers for accelerated aging, as well as methods to disentangle the effects of maternal infection from stresses of the pandemic environment. In utero exposure to COVID-19 disease could cause developmental difficulties and accelerated aging in the century ahead. This brief review summarizes elements of the developmental origins of health, disease, and ageing and discusses how the COVID-19 pandemic might exacerbate such effects. We conclude with a call for research on the long-term consequences of in utero exposure to maternal infection with COVID-19 and stresses of the pandemic environment.

Recent studies have used Mendelian randomization (MR) to investigate the observational association between low birth weight (BW) and increased risk of cardiometabolic outcomes, specifically cardiovascular disease, glycemic traits, and type 2 diabetes (T2D), and inform on the validity of the Barker hypothesis. We used simulations to assess the validity of these previous MR studies, and to determine whether a better formulated model can be used in this context. Genetic and phenotypic data were simulated under a model of no direct causal effect of offspring BW on cardiometabolic outcomes and no effect of maternal genotype on offspring cardiometabolic risk through intrauterine mechanisms; where the observational relationship between BW and cardiometabolic risk was driven entirely by horizontal genetic pleiotropy in the offspring (i.e. offspring genetic variants affecting both BW and cardiometabolic disease simultaneously rather than a mechanism consistent with the Barker hypothesis). We investigated the performance of four commonly used MR analysis methods (weighted allele score MR (WAS-MR), inverse variance weighted MR (IVW-MR), weighted median MR (WM-MR), and MR-Egger) and a new approach, which tests the association between maternal genotypes related to offspring BW and offspring cardiometabolic risk after conditioning on offspring genotype at the same loci. We caution against using traditional MR analyses, which do not take into account the relationship between maternal and offspring genotypes, to assess the validity of the Barker hypothesis, as results are biased in favor of a causal relationship. In contrast, we recommend the aforementioned conditional analysis framework utilizing maternal and offspring genotypes as a valid test of not only the Barker hypothesis, but also to investigate hypotheses relating to the Developmental Origins of Health and Disease more broadly.

Globally, the availability and formulations for the administration of cannabis are changing with decriminalization or legalization of recreational use in some jurisdictions, and the prescription of cannabis also occurring. These changes are likely to affect the prevalence of use, including by women of childbearing age. The effects of in utero and infant alcohol and tobacco exposure are well-documented, but the outcomes of cannabis exposure are less certain. The content of delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis has progressively increased over several decades. This review explores the limited knowledge surrounding the epidemiology of gestational and postnatal cannabis exposure and implications for the mother–placenta–fetus/neonate triad. We examine cannabis’ effects from antenatal and lactation exposure on (a) pregnancy and perinatal outcomes, (b) placental health, and (c) longer term cardiometabolic and neurodevelopmental risks and outcomes. Though definitive outcomes are lacking, gestational cannabis has been associated with increased risk of other substance use during pregnancy; impaired placental blood flow; increased risk of small for gestational age births; and associated complications. Childhood and adolescent outcomes are sparsely assessed, with suggested outcomes including increased risk of depression and attention-deficit hyperactivity disorder. Cardiometabolic implications of gestational cannabis use may include maternal fatty liver, obesity, insulin resistance, and increased risk of gestational diabetes mellitus (GDM), with potential consequences for the fetus. Clinical implications for pediatric practice were explored in a bid to understand any potential risk or impact on child health and development.

Women with thyroid diseases at the beginning of pregnancy may have suboptimal thyroid hormone levels because of potential difficulties in compensating for the physiological thyroid hormone changes occurring in pregnancy. Our objective was to study the association between preexisting thyroid diseases, pregnancy complications, and neonatal anthropometry. In total, 16,395 women from the ELFE French longitudinal birth cohort were included, and 273 declared pre-pregnancy thyroid diseases. Associations were investigated with multivariable regression models, with adjustment for relevant potential confounders. Body mass index (BMI) was additionally adjusted for in a second stage. As compared with other women, women with pre-pregnancy thyroid diseases were more frequently obese (19.6% vs. 9.8%) and had greater odds of gestational diabetes development (odds ratio [OR] = 1.58 [95% confidence interval [CI] 1.08, 2.30]) or had undergone treatment for infertility (OR = 1.57 [95% CI 1.07, 2.31]). After adjustment for BMI, the association with gestational diabetes was no longer significant (OR = 1.27 [95% CI 0.86, 1.88]). After excluding women with another medical history, those with pre-pregnancy thyroid diseases had increased odds of premature rupture of membranes (OR = 1.51 [95% CI 1.01, 2.25]). Children born from mothers with hypothyroidism before conception due to a disease or as a potential side effect of treatment had a smaller head circumference at birth than other children (β = −0.23 [95% CI −0.44, −0.01] cm). In conclusion, pre-pregnancy thyroid diseases were associated with risk of infertility treatment, gestational diabetes, and premature rupture of membranes. The association between history of hypothyroidism and moderate adverse effects on fetal head circumference growth needs replication.

Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.

Prenatal insults during fetal development result in increased likelihood of developing chronic disease. Obesity, the biggest risk factor for the development of metabolic disease, is affected by several genetic and environmental factors. High-fat diet (HFD) consumption is usually linked with the development of obesity. The main goal of this study was to analyze the impact of the exposure to a HFD in prenatally stressed animals. For this purpose, we subjected pregnant BALB/c mice to restraint stress for 2 h a day between gestational day (GD) 14 and GD 21. Prenatally stressed and control offspring of both sexes were postnatally exposed to a HFD for 24 weeks. We found that prenatal stress (PS) per se produced disturbances in males such as increased total blood cholesterol and triglycerides, with a decrease in mRNA expression of sirtuin-1. When these animals were fed a HFD, we observed a rise in glucose and insulin levels and an increase in visceral adipose tissue gene expression of leptin, resistin, and interleukin-1 beta. Although females proved to be more resilient to PS consequences, when they were fed a HFD, they showed significant metabolic impairment. In addition to the changes observed in males, females also presented an increase in body weight and adiposity and a rise in cholesterol levels.

Nutrition during the periconceptional period influences postnatal cardiovascular health. We determined whether in vitro embryo culture and transfer, which are manipulations of the nutritional environment during the periconceptional period, dysregulate postnatal blood pressure and blood pressure regulatory mechanisms. Embryos were either transferred to an intermediate recipient ewe (ET) or cultured in vitro in the absence (IVC) or presence of human serum (IVCHS) and a methyl donor (IVCHS+M) for 6 days. Basal blood pressure was recorded at 19–20 weeks after birth. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after varying doses of phenylephrine (PE). mRNA expression of signaling molecules involved in blood pressure regulation was measured in the renal artery. Basal MAP did not differ between groups. Baroreflex sensitivity, set point, and upper plateau were also maintained in all groups after PE stimulation. Adrenergic receptors alpha-1A (αAR1A), alpha-1B (αAR1B), and angiotensin II receptor type 1 (AT1R) mRNA expression were not different from controls in the renal artery. These results suggest there is no programmed effect of ET or IVC on basal blood pressure or the baroreflex control mechanisms in adolescence, but future studies are required to determine the impact of ET and IVC on these mechanisms later in the life course when developmental programming effects may be unmasked by age.

Obesity is a chronic condition associated with dyslipidemia and insulin resistance. Here, we show that the offspring of obese mothers are dyslipidemic and insulin resistant from the outset.

Maternal and cord blood and placental tissues were collected following C-section at term. Patients were grouped as being normal weight (NW, BMI = 18–24.9) or obese (OB, BMI ≥ 30), and separated by fetal sex. We measured plasma lipids, insulin, and glucose in maternal and cord blood. Insulin resistance was quantified using the HOMA-IR. Placental markers of lipid and energy metabolism and relevant metabolites were measured by western blot and metabolomics, respectively.

For OB women, total cholesterol was decreased in both maternal and cord blood, while HDL was decreased only in cord blood, independent of sex. In babies born to OB women, cord blood insulin and insulin resistance were increased. Placental protein expression of the energy and lipid metabolism regulators PGC1α, and SIRT3, ERRα, CPT1α, and CPT2 decreased with maternal obesity in a sex-dependent manner (P < 0.05). Metabolomics showed lower levels of acylcarnitines C16:0, C18:2, and C20:4 in OB women’s placentas, suggesting a decrease in β-oxidation. Glutamine, glutamate, alpha-ketoglutarate (αKG), and 2-hydroxyglutarate (2-HG) were increased, and the glutamine-to-glutamate ratio decreased (P < 0.05), in OB placentas, suggesting induction of glutamate into αKG conversion to maintain a normal metabolic flux.

Newly-born offspring of obese mothers begin their lives dyslipidemic and insulin resistant. If not inherited genetically, such major metabolic perturbations might be explained by abnormal placental metabolism with potential long-term adverse consequences for the offspring’s health and wellbeing.

In low-income countries, prospective data on combined effects of in utero teratogen exposure are lacking and necessitates new research. The aim of the present study was to explore the effect of in utero teratogen exposure on the size of the kidneys and pancreas 5 years after birth in a low-income paediatric population. Data was collected from 500 mother–child pairs from a low-income setting. Anthropometric measurements included body weight, (BW) body height, mid-upper arm and waist circumference (WC). Clinical measurements included blood pressure (BP), mean arterial pressure and heart rate. Ultrasound measurements included pancreas, and kidney measurements at age 5 years. The main outcome of interest was the effect of maternal smoking and alcohol consumption on ultrasound measurements of organ size at age 5 years. Left and right kidney length measurements were significantly lower in smoking exposed children compared to controls (p = 0.04 and p = 0.03). Pancreas body measurements were significantly lower in smoking exposed children (p = 0.04). Multiple regression analyses were used to examine the associations between the independent variables (IDVs), maternal age, body mass index (BMI), mid-upper arm circumference (MUAC) and BW of the child, on the dependent variables (DVs) kidney lengths and kidney volumes. Also, the association between in utero exposure to alcohol and nicotine and pancreas size. WC was strongest (r = 0.28; p < 0.01) associated with pancreas head [F (4, 454) = 13.44; R2 = 0.11; p < 0.01] and tail (r = 0.30; p < 0.01) measurements at age 5 years, with in utero exposure, sex of the child and BMI as covariates. Kidney length and pancreas body measurements are affected by in utero exposure to nicotine at age 5 years and might contribute to cardiometabolic risk in later life. Also, findings from this study report on ultrasound reference values for kidney and pancreas measurements of children at age 5 years from a low-income setting.

The hypothesis was that maternal intake of the antioxidant alpha-lipoid acid (ALA), during the developmental period of the hypothalamic orexigenic neurons, causes a permanent beneficial effect in offspring metabolism. Pregnant Wistar rats were fed with standard diet (food) + ALA (0.4% wt/wt) from day 14 of gestation to day 20 of lactation (n = 4) or food (n = 4). At 3 months of age, male offspring born from ALA-fed rats or controls (CT) were randomly assigned to be fed with food + 10% fructose solution in drinking water (F) or food + tap water (C), resulting in four groups: ALAF, ALAC, CTF, and CTC (n = 5/group). Food intake and body weight (BW) were measured twice a week for 31 days. Metabolites’ levels in blood, mRNA expressions of Npy, Agrp (hypothalamus), Fasn, Srebf1, Ppard, and Pparg (liver), and the antioxidant capacity of the liver were determined. Results significance was set at p < 0.05. Average BW gain, daily BW gain, and intraabdominal fat tissue at necropsy were higher in CTF group followed by CTC, ALAF, and ALAC groups. There were no differences between groups in Kcal intake per day. mRNA expressions of hypothalamic and hepatic genes and plasmatic levels of glucose and triglycerides were higher in CTF group followed by ALAF, CTC, and ALAC groups. Fructose intake affected the oxidative capacity of the liver, but this effect was not observed in the ALAF group. In conclusion, maternal ALA intake protected the adult offspring to develop metabolic symptoms associated with high fructose in the drinking water.

Adverse childhood experiences (ACEs) are associated with a high risk of developing chronic diseases and decreased life expectancy, but no ACE epigenetic biomarkers have been identified until now. The latter may result from the interaction of multiple factors such as age, sex, degree of adversity, and lack of transcriptional effects of DNA methylation changes. We hypothesize that DNA methylation changes are related to childhood adversity levels and current age, and these markers evolve as aging proceeds. Two Gene Expression Omnibus datasets, regarding ACE, were selected (GSE72680 and GSE70603), considering raw- and meta-data availability, including validated ACE index (Childhood Trauma Questionnaire (CTQ) score). For DNA methylation, analyzed probes were restricted to those laying within promoters and first exons, and samples were grouped by CTQ scores terciles, to compare highly (ACE) with non-abused (control) cases. Comparison of control and ACE methylome profile did not retrieve differentially methylated CpG sites (DMCs) after correcting by false discovery rate < 0.05, and this was also observed when samples were separated by sex. In contrast, grouping by decade age ranges (i.e., the 20s, 30s, 40s, and 50s) showed a progressive increase in the number of DMCs and the intensity of changes, mainly related with hypomethylation. Comparison with transcriptome data for ACE subjects in the 40s, and 50s showed a similar age-dependent effect. This study provides evidence that epigenetic markers of ACE are age-dependent, but not defined in the long term. These differences among early, middle, and late adulthood epigenomic profiles suggest a window for interventions aimed to prevent the detrimental effects of ACE.

Nutrition during the first 1000 days of life represents a window of opportunity to reduce the risk of metabolic dysfunctions later in life. Exclusive breastfeeding (EBF) and adequate introduction of solid foods are essential to promote metabolic and nutritional benefits. We evaluated the association of infant feeding practices from birth to 6 months (M) with adiposity indicators at 12 M. We performed a secondary analysis of 106 healthy term infants born from a cohort of healthy pregnant women. Type of breastfeeding (exclusive or nonexclusive), the start of complementary feeding (CF) (before (<4 M) or after (≥4 M)), and adiposity (body mass index – BMI, body mass index-for-age – BMI/A, waist circumference – WC, and waist circumference–length ratio – WLR) were evaluated at 12 M using descriptive statistics, mean differences, X2, and linear regression models. During the first 6 M, 28.3% (n = 30) of the infants received EBF. Early CF (<4 M) was present in 26.4% (n = 28) of the infants. Children who started CF < 4 M were less breastfed, received added sugars as the most frequently introduced food category, and showed higher BMI, BMI/A, WC, and WLR; those who consumed added sugars early (<4 M) had a higher WC. Starting CF < 4 M was the main factor associated with a higher WC at 12 M. Unhealthy infant feeding practices, such as lack of EBF, early CF, and early introduction of sugars, may be associated with higher adiposity at 12 M.

The evolution of birth weight (BW), birth length (BL), and gestational age at delivery (GAD) and their correlation with various maternal sociodemographic variables were studied in Chilean newborns from years 1996 to 2017. A slight decrease in the mean values of these perinatal outcomes was observed; however, their risk sub-categories increased significantly, especially for GAD, indicating an important deterioration. GAD was strongly correlated with BW and BL. In the contingency tables, all sociodemographic variables, with the exemption of sex, had a higher proportion of early term 37–38-week and late pre-term 34–36-week newborns in women with a higher socioeconomic level; the strongest positive association was observed between mother’s years of education and the GAD risk category 37–38 weeks. Different maternal factors, such as a higher frequency of cesarean sections, including either obesity presence or smoking habit, could be influencing presented results.

Emerging evidence suggests that parents’ nutritional status before and at the time of conception influences the lifelong physical and mental health of their child. Yet little is known about the relationship between diet in adolescence and the health of the next generation at birth. This study examined data from Norwegian cohorts to assess the relationship between dietary patterns in adolescence and neonatal outcomes. Data from adolescents who participated in the Nord-Trøndelag Health Study (Young-HUNT) were merged with birth data for their offspring through the Medical Birth Registry of Norway. Young-HUNT1 collected data from 8980 adolescents between 1995 and 1997. Linear regression was used to assess associations between adolescents’ diet and later neonatal outcomes of their offspring adjusting for sociodemographic factors. Analyses were replicated with data from the Young-HUNT3 cohort (dietary data collected from 2006 to 2008) and combined with Young-HUNT1 for pooled analyses. In Young-HUNT1, there was evidence of associations between dietary choices, meal patterns, and neonatal outcomes, these were similar in the pooled analyses but were attenuated to the point of nonsignificance in the smaller Young-HUNT3 cohort. Overall, energy-dense food products were associated with a small detrimental impact on some neonatal outcomes, whereas healthier food choices appeared protective. Our study suggests that there are causal links between consumption of healthy and unhealthy food and meal patterns in adolescence with neonatal outcomes for offspring some years later. The effects seen are small and will require even larger studies with more state-of-the-art dietary assessment to estimate these robustly.

New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother–child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14–0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01–0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this “triple exposure” hypothesis.

Recent evidence suggests that a long inter-pregnancy interval (IPI: time interval between live birth and estimated time of conception of subsequent pregnancy) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (<6 months) and long (>60 months) IPI on long-term cardiovascular morbidity of the offspring. A population-based cohort study was performed in which all singleton live births in parturients with at least one previous birth were included. Hospitalizations of the offspring up to the age of 18 years involving cardiovascular diseases and according to IPI length were evaluated. Intermediate interval, between 6 and 60 months, was considered the reference. Kaplan–Meier survival curves were used to compare the cumulative morbidity incidence between the groups. Cox proportional hazards model was used to control for confounders. During the study period, 161,793 deliveries met the inclusion criteria. Of them, 14.1% (n = 22,851) occurred in parturient following a short IPI, 78.6% (n = 127,146) following an intermediate IPI, and 7.3% (n = 11,796) following a long IPI. Total hospitalizations of the offspring, involving cardiovascular morbidity, were comparable between the groups. The Kaplan–Meier survival curves demonstrated similar cumulative incidences of cardiovascular morbidity in all groups. In a Cox proportional hazards model, short and long IPI did not appear as independent risk factors for later pediatric cardiovascular morbidity of the offspring (adjusted HR 0.97, 95% CI 0.80–1.18; adjusted HR 1.01, 95% CI 0.83–1.37, for short and long IPI, respectively). In our population, extreme IPIs do not appear to impact long-term cardiovascular hospitalizations of offspring.