Few population studies have sufficient follow-up period to examine early-life exposures with later life diseases. A critical question is whether involuntary exposure to tobacco smoke from conception to adulthood increases the risk of cardiometabolic diseases (CMD) in midlife. In the Collaborative Perinatal Project, serum-validated maternal smoking during pregnancy (MSP) was assessed in the 1960s. At a mean age of 39 years, 1623 offspring were followed-up for the age at first physician-diagnoses of any CMDs, including diabetes, heart disease, hypertension, or hyperlipidemia. Detailed information on their exposure to environmental tobacco smoke (ETS) in childhood and adolescence was collected with a validated questionnaire. Cox regression was used to examine associations of in utero exposure to MSP and exposure to ETS from birth to 18 years with lifetime incidence of CMD, adjusting for potential confounders. We calculated midlife cumulative incidences of hyperlipidemia (25.2%), hypertension (14.9%), diabetes (3.9%), and heart disease (1.5%). Lifetime risk of hypertension increased by the 2nd -trimester exposure to MSP (adjusted hazard ratio: 1.29, 95% confidence interval: 1.01–1.65), ETS in childhood (1.11, 0.99–1.23) and adolescence (1.22, 1.04–1.44). Lifetime risk of diabetes increased by joint exposures to MSP and ETS in childhood (1.23, 1.01–1.50) or adolescence (1.47, 1.02–2.10). These associations were stronger in males than females, in never-daily smokers than lifetime ever smokers. In conclusion, early-life involuntary exposure to tobacco smoke increases midlife risk of hypertension and diabetes in midlife.

This study aimed to evaluate the association between parental and infant birth weights in Japan. In total, 37,504 pregnant Japanese women and their partners were included in this birth cohort study. A multinomial logistic regression model was used to evaluate the associations of parental birth weights with small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants. Associations between parental birth weight and low birth weight (LBW) infants or macrosomia were also examined, and linear associations between parental birth weight and SGA or LGA were found. The adjusted odds ratios (aORs) for SGA infants per 500 g decrease in maternal and paternal birth weights were 1.50 (95% confidence interval [CI],1.43–1.58) and 1.31 (95% CI, 1.25–1.38), respectively. The aORs for LGA infants per 500 g increase in maternal and paternal birth weights were 1.53 (95% CI, 1.47–1.60) and 1.41 (95% CI, 1.35–1.47), respectively. The association between parental birth weight and LBW infants or macrosomia was also linear. The aORs for LBW infants per 500 g decrease in maternal and paternal birth weights were 1.47 (95% CI, 1.40–1.55) and 1.25 (95% CI, 1.19–1.31), respectively. The aORs for macrosomia per 500 g increase in maternal and paternal birth weights were 1.59 (95% CI, 1.41–1.79) and 1.40 (95% CI, 1.23–1.60), respectively. Parental birth weight was found to be associated with infant birth weight even after adjusting for various parental factors. Furthermore, maternal birth weight was more strongly associated with infant birth weight than with paternal birth weight.

We investigated the influence of maternal yellow-pea fiber supplementation in obese pregnancies on offspring metabolic health in adulthood. Sixty newly-weaned female Sprague-Dawley rats were randomized to either a low-calorie control diet (CON) or high calorie obesogenic diet (HC) for 6-weeks. Obese animals were then fed either the HC diet alone or the HC diet supplemented with yellow-pea fiber (HC + FBR) for an additional 4-weeks prior to breeding and throughout gestation and lactation. On postnatal day (PND) 21, 1 male and 1 female offspring from each dam were weaned onto the CON diet until adulthood (PND 120) for metabolic phenotyping. Adult male, but not female, HC offspring demonstrated increased body weight and feed intake vs CON offspring, however no protection was offered by maternal FBR supplementation. HC male and female adult offspring demonstrated increased serum glucose and insulin resistance (HOMA-IR) compared with CON offspring. Maternal FBR supplementation improved glycemic control in male, but not female offspring. Compared with CON offspring, male offspring from HC dams demonstrated marked dyslipidemia (higher serum cholesterol, increased number of TG-rich lipoproteins, and smaller LDL particles) which was largely normalized in offspring from HC + FBR mothers. Male offspring born to obese mothers (HC) had higher hepatic TG, which tended to be lowered (p = 0.07) by maternal FBR supplementation.

Supplementation of a maternal high calorie diet with yellow-pea fiber in prepregnancy and throughout gestation and lactation protects male offspring from metabolic dysfunction in the absence of any change in body weight status in adulthood.

Birthweight has been associated with diabetes in a reverse J-shape (highest risk at low birthweight and moderately high risk at high birthweight) and inversely associated with hypertension in adulthood with inconsistent evidence for cardiovascular disease. There is a lack of population-based studies examining the incidence of cardiometabolic outcomes in young adults born with low and high birthweights. To evaluate the association between birthweight and diabetes, hypertension, and ischemic heart disease (IHD) in young adulthood, we conducted a retrospective cohort study of 874,904 singletons born in Ontario, Canada, from 1994 to 2002, identified from population-based health administrative data. Separate Cox regression models examined birthweight in association with diabetes, hypertension, and IHD adjusting for confounders. Among adults 18–26 years, the diabetes incidence rate was 18.15 per 100,000 person-years, hypertension was 15.80 per 100,000 person-years, and IHD was 1.85 per 100,000 person-years. Adjusted hazard ratios (AHR) for the hazard of diabetes with low (<2500g) and high (>4000g), compared with normal (2500–4000g) birthweight, were 1.46 (95% CI 1.28, 1.68) and 1.09 (0.99, 1.21), respectively. AHR for hypertension with low and high birthweight were 1.34 (1.15, 1.56) and 0.86 (0.77, 0.97), respectively. AHR for IHD with low and high birthweight were 1.28 (0.80, 2.05) and 0.97 (0.71, 1.33), respectively. Overall, birthweight was associated with diabetes in young adults in a reverse J-shape and inversely with hypertension. There was insufficient evidence of an association with IHD. Further evidence is needed to understand the causal mechanisms between birthweight and cardiometabolic diseases in young adults.

Meta-analysis is used to test a variant of a Developmental Origins of Adult Health and Disease (DOHaD)’s conjecture known as predictive adaptive response (PAR). According to it, individuals who are exposed to mismatches between adverse or constrained in utero conditions, on the one hand, and postnatal obesogenic environments, on the other, are at higher risk of developing adult chronic conditions, including obesity, type 2 diabetes (T2D), hypertension and cardiovascular disease. We argue that migrant populations from low and middle to high-income countries offer a unique opportunity to test the conjecture. A database was constructed from an exhaustive literature search of peer-reviewed papers published prior to May 2021 contained in PUBMED and SCOPUS using keywords related to migrants, DOHaD, and associated health outcomes. Random effects meta-regression models were estimated to assess the magnitude of effects associated with migrant groups on the prevalence rate of T2D and hypertension in adults and overweight/obesity in adults and children. Overall, we used 38 distinct studies and 78 estimates of diabetes, 59 estimates of hypertension, 102 estimates of overweight/obesity in adults, and 23 estimates of overweight/obesity in children. Our results show that adult migrants experience higher prevalence of T2D than populations at destination (PR 1.48; 95% CI 1.35–1.65) and origin (PR 1.80; 95% CI 1.40–2.34). Similarly, there is a significant excess of obesity prevalence in children migrants (PR 1.22; 95% CI 1.04–1.43) but not among adult migrants (PR 0.89; 95% CI 0.80–1.01). Although the total effect of migrant status on prevalence of hypertension is centered on zero, some migrant groups show increased risks. Finally, the size of estimated effects varies significantly by migrant groups according to place of destination. Despite limitations inherent to all meta-analyses and admitting that some of our findings may be accounted for alternative explanations, the present study shows empirical evidence consistent with selected PAR-like conjectures.

Low birth weight (BW) is consistently correlated with increased parental risk of subsequent cardiovascular disease, but the links with offspring placental weight (PW) are mostly unexplored. We have investigated the associations between parental coronary heart disease (CHD) and offspring BW and PW using the Walker cohort, a collection of 48,000 birth records from Dundee, Scotland, from the 1950s and 1960s. We linked the medical history of 13,866 mothers and 8,092 fathers to their offspring’s records and performed Cox survival analyses modelling maternal and paternal CHD risk by their offspring’s BW, PW, and the ratio between both measurements. We identified negative associations between offspring BW and both maternal (hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.88–0.95) and paternal (HR: 0.96, 95% CI: 0.93–1.00) CHD risk, the stronger maternal correlation being consistent with previous reports. Offspring PW to BW ratio was positively associated with maternal CHD risk (HR: 1.14, 95% CI: 1.08–1.21), but the associations with paternal CHD were not significant. These analyses provide additional evidence for intergenerational associations between early growth and parental disease, identifying directionally opposed correlations of maternal CHD with offspring BW and PW, and highlight the importance of the placenta as a determinant of early development and adult disease.

The developmental origins of health and disease (DOHaD) framework has highlighted the importance of the early life period on disease risk in later life with impacts that can span generations. A primary focus to date has been around maternal health and the ‘First Thousand Days’ as a key developmental window whereby an adverse environment can have lasting impacts on both mother and offspring. More recently, the impact of paternal health has gathered increasing traction as a key window for early life developmental programming. However, to date, adolescents, the next generation of parents, have attracted less attention as a key DOHaD window although many behavioural traits become entrained during adolescence and track into adulthood. This systematic review examined literature focused on identifying adolescent understanding of DOHaD concepts. Consistent across the eligible articles was that overall understanding of DOHaD-related concepts in adolescents was low. Three key themes emerged: 1. Individual-level awareness of DOHaD concepts (cognitive engagement and action of the adolescents themselves); 2. Interpersonal communication and social awareness of DOHaD concepts (cognitive engagement and communication of the DOHaD concepts to family and wider community); and 3. Health literacy and the promotion of adolescence as a key DOHaD life stage. These findings highlight the need to develop strategic approaches to increase DOHaD awareness that are not only appealing to adolescents but can also support sustained changes in health behaviour. Investment in today’s adolescents has the potential to act as a NCD ‘circuit breaker’ and thus will yield significant dividends for future generations.

Polyunsaturated fatty acids are critically important for newborn nutrition and in the trajectory of growth and developmental processes throughout early life. This systematic review (PROSPERO ID: CRD42023400059) critically analyzes literature pertaining to how omega-3 and omega-6 fatty acids in human milk are related to health outcomes in early life. Literature selected for the review were published between 2005 and 2020 and included assessments in healthy term children between 0 and 5 years of age. The studies reported the relation between human milk fatty acids docosahexaenoic acid (C22:6n-3, DHA), eicosapentaenoic acid (C20:5n-3, EPA), alpha-linolenic acid (C18:3n-3, ALA), arachidonic acid (C20:4n-6, AA), and linoleic acid (C18:2n-6, LA) with three domains of health outcomes: neurodevelopment, body composition, and allergy, skin & eczema. Results from the 21 studies consistently suggested better health outcomes across the three domains for infants consuming milk with higher concentrations of total n-3, DHA, EPA, and ALA. Negative health outcomes across the three domains were associated with higher levels of total n-6, AA, and LA in milk. N-3 and n-6 content of milk were related to neurodevelopmental, body composition, and allergy, skin & eczema outcomes with moderate certainty. Maternal diet impacting milk fatty acid content and fatty acid desaturase genotype modifying physiologic responses to fatty acid intake were prominent gaps identified in the review using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and GRADE approach. This research study can inform baby nutrition product development, and fatty acid intake recommendations or dietary interventions for mothers and children.

In recent years, the rapidly increasing incidence of obesity is becoming a worldwide public health problem. Obesity is a chronic disease which may have a major negative effect on the people’s quality of life. Previous studies on the comprehensive effects of multivitamins on central obesity and general obesity are relatively few. The aim of this study was to evaluate association of vitamins exposure with obesity risk and obesity-related indicators. We fitted three statistical models (linear regression model, logistic regression model, and Bayesian kernel machine regression model) to evaluate the correlation between vitamin levels and obesity in the study population. The vitamin score represents the overall level of vitamin in serum, which was mutually verified with the results obtained from statistical model. The vitamin (A, C, and D) levels were significantly higher among non-obesity group compared to the obesity group. Using the lowest quartile of vitamin level as a referent, vitamin A, C, and D levels showed significantly negative correlation with the obesity risk in both adjusted and unadjusted models. When considering all vitamin as a mixed exposure, we found a generally negative relationship between vitamin mixtures with binary outcome (obesity) and continuous outcome (BMI, waist circumference, and hsCRP). Reduced levels of vitamins (A, C and D) increased the risk of obesity. Increased levels of vitamin mixtures can significantly reduce obesity risk and obesity-related indicators. Vitamins may reduce the risk of obesity by suppressing inflammatory responses.

Maternal prenatal and postnatal psychological distress, including depression and anxiety, may affect children’s cognitive development. However, the findings have been inconsistent. We aimed to use the dataset from the Japan Environment and Children’s Study, a nationwide prospective birth cohort study, to examine this association. We evaluated the relationship between the maternal six-item version of the Kessler Psychological Distress Scale (K6) scores and cognitive development among children aged 4 years. K6 was administered twice during pregnancy (M-T1; first half of pregnancy, M-T2; second half of pregnancy) and 1 year postpartum (C-1y). Cognitive development was assessed by trained testers, using the Kyoto Scale of Psychological Development 2001. Multiple regression analysis was performed with the group with a K6 score ≤ 4 for both M-T1 and M-T2 and C-1y as a reference. Records from 1,630 boys and 1,657 girls were analyzed. In the group with K6 scores ≥ 5 in both M-T1 and M-T2 and C-1Y groups, boys had significantly lower developmental quotients (DQ) in the language-social developmental (L-S) area (partial regression coefficient: −4.09, 95% confidence interval: −6.88 – −1.31), while girls did not differ significantly in DQ for the L-S area. Among boys and girls, those with K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, or C-1y did not have significantly lower DQ for the L-S area. Persistent maternal psychological distress from the first half of pregnancy to 1 year postpartum had a disadvantageous association with verbal cognitive development in boys, but not in girls aged 4 years.

Maternal obesity may trigger long-term neurodevelopmental disorders in offspring. Considering the benefits of the Brazil nut (Bertholletia excelsa H.B.K.), a rich source of nutrients such as selenium, this study aimed to evaluate its effect on the behavior of obese rat offspring and its relationship with oxidative stress. From 60 days of age until weaning, female Wistar rats were fed a high-fat diet (mHF) or an HF diet supplemented with 5% Brazil nut (mHF/BN), while control mothers (mCTL) were fed a standard diet or a standard diet supplemented with 5% Brazil nut (mBN). Male pups received a standard diet throughout life and, at 30 and 90 days old, were subjected to behavioral tasks to evaluate anxiety and cognition. Biochemical evaluations were performed at 90 days of age. No alterations were observed in the anxiety behavior of the offspring. However, the offspring of the mHF group (oHF) exhibited impaired short-term memory at 30 and 90 days of age and impaired long-term memory at 30 days. Short-term memory impairment was prevented by Brazil nuts in young rats (30 days). While the serum selenium concentration was reduced in the oHF group, the serum catalase concentration was reduced in all groups, without changes in lipid peroxidation or protein carbonylation. Brazil nut maternal diet supplementation prevented short- and long-term cognitive impairment in the offspring, which may be related to the selenium levels.