Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones secreted from the intestine in response to enteral feeding to stimulate insulin secretion. We investigated the relationship serum GIP and GLP-1 levels with gestational age, and insulin secretion in preterm infants. Serum GIP and GLP-1 levels were measured at birth and at 1, 2 and 4 weeks after birth in 30 infants, including 12 born before 30th week of gestation (early group) and 18 born after 30th week of gestation (late group). Blood glucose and serum insulin levels were measured, and the quantitative insulin sensitivity check index (QUICKI) was also calculated. The levels of GLP-1 at 2 and 4 weeks were significantly higher in the early group than those in the late group. The levels of GIP were not significantly different between two groups. At 4 weeks, serum insulin level was significantly higher and QUICKI was significantly lower in the early group. Furthermore, GLP-1 levels were significantly correlated with QUICKI and the serum insulin levels in all infants at 4 weeks. In preterm infants, enteral feeding to premature intestine may be associated with GLP-1 secretion. GLP-1 is also related to stimulated insulin secretion in early postnatal period.

The associations between school performance and cognitive abilities with birth characteristics have mostly been studied without taking into consideration the effects of gestational age (GA). Our aim was to study the association between prenatal growth and cognitive function in term-born Chilean school children. A cohort of over 200,000 term-born fourth graders who took the regular national test for school performance was studied. Outcome parameters were language and mathematics test scores in relation to prenatal growth. A total of 256,040 subjects took the test and 220,940 were included in the final study sample. Prenatal growth was modestly, but significantly, associated with school performance. Adjusted β coefficients for 1 cm increase in birth length were 1.28 and 0.77 for mathematics and language, respectively; the corresponding values for 100 g increase in birth weight were 0.59 and 0.34, respectively. Increased GA was associated with lower test scores. Adjusted β coefficients for the birth measurements generally had a lower strength of association than those of socio-economic factors. However, the confounders most strongly associated with educational achievements were socio-economic factors, known to be associated with birth size. Lower socio-economic status is known to negatively influence both prenatal growth and cognitive function, supporting the overall importance of prenatal growth in relation to cognitive outcomes.

Hyperglycemia during the first trimester leads to an increased risk of innate malformations as well as death at times close to delivery dates. The methylated genes include those from paternal H19 and PEG3 and those from maternal MEST and MEG3 that are necessary for the growth and regulation of the human fetus and its placenta. The aim of this study was to evaluate and compare the expression of these genes in the cord blood of healthy infants born to mothers with gestational diabetes mellitus (GDM) and healthy mothers.

This case-control study was conducted on the cord blood of 40 infants born to mothers with GDM and 35 infants born to healthy mothers. Mothers were identified by measuring oral glucose tolerance in the 24th–26th week of pregnancy. Cord blood was obtained post-delivery, and cord blood mononuclear cells were immediately extracted, using Ficoll solution. Then, RNA extraction and cDNA synthesis were performed, and gene expression of MEG3, PEG3, H19, and MEST was assessed through quantitative real-time PCR.

Findings show that the expression levels of MEG3, PEG3, H19, and MEST genes were significantly decreased in mononuclear cord blood cells of infants born to mothers with GDM when compared to those of the healthy control group.

These findings reveal that the reduction of imprinted genes in mothers with GDM is most likely due to changes in their methylation by an epigenetic process. Considering the importance of GDM due to its high prevalence and its side effects both for mother and fetus, recognizing their exact mechanisms is of high importance. This has to be studied more widely.

In this study, we empirically analyse whether in utero exposure to the Ramadan fasting period is negatively associated with child nutrition. The data for the analyses come from a retrospective assessment of 759,799 children from 103 Demographic and Health Surveys (DHS) across 56 countries during 2003–2020. Considering the month-long Ramadan exposure as a natural experiment, we implement an intent-to-treat framework, comparing stunting and underweight among children aged 0–5 years who were exposed to Ramadan fasting at any time in utero with those who were not exposed. Our findings do not show significant evidence to conclude that in utero exposure to the Ramadan fasting period is negatively associated with child nutrition. On the contrary, except for stunting in Muslim children who had in utero exposure to Ramadan fasting during the first months of pregnancy, we find no significant association between in utero exposure to Ramadan fasting and child stunting and underweight. Our main results are robust to multiple robustness checks.

Visual processing problems may be one underlying factor for cognitive impairments related to autism spectrum disorders (ASDs). We examined associations between ASD-traits (Autism-Spectrum Quotient) and visual processing performance (Rey–Osterrieth Complex Figure Test; Block Design task of the Wechsler Adult Intelligence Scale-III) in young adults (mean age=25.0, s.d.=2.1 years) born preterm at very low birth weight (VLBW; <1500 g) (n=101) or at term (n=104). A higher level of ASD-traits was associated with slower global visual processing speed among the preterm VLBW, but not among the term-born group (P<0.04 for interaction). Our findings suggest that the associations between ASD-traits and visual processing may be restricted to individuals born preterm, and related specifically to global, not local visual processing. Our findings point to cumulative social and neurocognitive problems in those born preterm at VLBW.

Women with a history of preeclampsia (PE) have a greater risk of pulmonary arterial hypertension (PAH). In turn, pregnancy at high altitude is a risk factor for PE. However, whether women who develop PE during highland pregnancy are at risk of PAH before and after birth has not been investigated. We tested the hypothesis that during highland pregnancy, women who develop PE are at greater risk of PAH compared to women undergoing healthy highland pregnancies. The study was on 140 women in La Paz, Bolivia (3640m). Women undergoing healthy highland pregnancy were controls (C, n = 70; 29 ± 3.3 years old, mean±SD). Women diagnosed with PE were the experimental group (PE, n = 70, 31 ± 2 years old). Conventional (B- and M-mode, PW Doppler) and modern (pulsed wave tissue Doppler imaging) ultrasound were applied for cardiovascular íííassessment. Spirometry determined maternal lung function. Assessments occurred at 35 ± 4 weeks of pregnancy and 6 ± 0.3 weeks after birth. Relative to highland controls, highland PE women had enlarged right ventricular (RV) and right atrial chamber sizes, greater pulmonary artery dimensions and increased estimated RV contractility, pulmonary artery pressure and pulmonary vascular resistance. Highland PE women had lower values for peripheral oxygen saturation, forced expiratory flow and the bronchial permeability index. Differences remained 6 weeks after birth. Therefore, women who develop PE at high altitude are at greater risk of PAH before and long after birth. Hence, women with a history of PE at high altitude have an increased cardiovascular risk that transcends the systemic circulation to include the pulmonary vascular bed.

Intrauterine growth restriction (IUGR) and fetal growth restriction (FGR) are pregnancy complications associated with morbidity in later life. Despite a growing body of evidence from current research on developmental origins of health and disease (DOHaD), little information is currently provided to parents on long-term metabolic, cardiovascular and neurologic consequences. As parents strongly rely on internet-based health-related information, we examined the quality of information on IUGR/FGR sequelae and DOHaD in webpages used by laypersons. Simulating non-clinicians experience, we entered the terms ‘IUGR consequences’ and ‘FGR consequences’ into Google and Yahoo search engines. The quality of the top search-hits was analyzed with regard to the certification through the Health On the Net Foundation (HON), currentness of cited references, while reliability of information and DOHaD-related consequences were assessed via the DISCERN Plus score (DPS). Overall the citation status was not up-to-date and only a few websites were HON-certified. The results of our analysis showed a dichotomy between the growing body of evidence regarding IUGR/FGR-related sequelae and lack of current guidelines, leaving parents without clear directions. Furthermore, detailed information on the concept of DOHaD is not provided. These findings emphasize the responsibility of the individual physician for providing advice on IUGR/FGR-related sequelae, monitoring and follow-up.

We examined the association between life course body weight percentile trajectories and risk for preterm delivery (PTD). Data about women’s weight at birth, age 18, and before pregnancy were obtained by retrospective self-report in a cohort of 1410 black women in metropolitan Detroit. Growth mixture models were used to categorize women with similar weight percentile trajectories across these time points. Log-Poisson models were used to examine the association between the trajectory groups and PTD. Four trajectory groups with different beginning and endpoints of their weight percentiles (high-high, high-low, low-high and low-low) best fit the data. The groups with the highest prevalence of PTD were those that started low (low-high, 21%; low-low, 18%). The low-high group had a higher prevalence of PTD than the high-high trajectory group in unadjusted models (prevalence ratio=1.49 [95% confidence interval (CI) 1.11, 2.00]). The association became not significant after adjusting for maternal age at delivery, income, diabetes and hypertension. When compared with the high-high trajectory group, the low-low trajectory seemed to also have a higher prevalence of PTD after adjusting for maternal age at delivery, income, diabetes and hypertension (prevalence ratio=1.35 [95% CI 1.00, 1.83]). Results suggest that a woman’s risk for PTD is influenced by her body weight trajectory across the life course.

There is a strong relationship between low birth weight (LBW) and an increased risk of developing cardiovascular disease (CVD). In postnatal life, LBW offspring are becoming more commonly exposed to the additional independent CVD risk factors, such as an obesogenic diet. However, how an already detrimentally programmed LBW myocardium responds to a secondary insult, such as an obesogenic diet (western diet; WD), during postnatal life is ill defined. Herein, we aimed to determine in a pre-clinical guinea pig model of CVD, both the independent and interactive effects of LBW and a postnatal WD on the molecular pathways that regulate cardiac growth and metabolism. Uterine artery ablation was used to induce placental insufficiency (PI) in pregnant guinea pigs to generate LBW offspring. Normal birth weight (NBW) and LBW offspring were weaned onto either a Control diet or WD. At ˜145 days after birth (young adulthood), male and female offspring were humanely killed, the heart weighed and left ventricle tissue collected. The mRNA expression of signalling molecules involved in a pathological hypertrophic and fibrotic response was increased in the myocardium of LBW male, but not female offspring, fed a WD as was the mRNA expression of transcription factors involved in fatty acid oxidation. The mRNA expression of glucose transporters was downregulated by LBW and WD in male, but not female hearts. This study has highlighted a sexually dimorphic cardiac pathological hypertrophic and fibrotic response to the secondary insult of postnatal WD consumption in LBW offspring.

Maternal prenatal diet can exert a powerful influence on the health of children when they reach adulthood – an orienting phenomenon in the Developmental Origins of Health and Disease research paradigm. Similar to other subsistence-based communities experiencing a rapid nutrition transition, obesity is increasing among Yup’ik Alaskans. Diabetes prevalence, however, remains relatively low and may reflect developmental nutritional processes that have yet to be thoroughly considered. Here we investigate recall of Yup’ik women’s diets during a past pregnancy using a mixed-methods approach as a critical first step in exploring such alternative developmental hypotheses. For certain populations, retrospective dietary reports might be the only source of information on factors relevant to understanding developmental pathways to health and disease. Our analysis identified community-specific factors that will likely improve the accuracy of future retrospective dietary analyses investigating the role of prenatal nutrition in the developmental origins of metabolic disease, especially among Alaska Natives.

It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

There is some evidence that perinatal factors, specifically birth weight (BW), may be related to the onset of prostate cancer (PRCA). This case–control study, nested within the Malmö Diet and Cancer Cohort Study, used archived birth record data from 308 incident PRCA cases diagnosed between 1991 and 2005, and 637 age-matched controls among 4781 men born (1923–1945) in Malmö and Lund, Sweden. We applied conditional logistic regression to examine the birth size–PRCA association, including tumour subtypes, adjusting for perinatal and adult factors. Compared with controls, cases had a non-significantly higher mean BW and were more likely to have high (>4000 g) BW (21% v. 18%), but did not differ in other birth size measures, nor in mean adult body mass index . We observed a non-linear association between BW and PRCA risk. Compared with BWs between 3000 and 3500 g (reference), the fully adjusted odds ratios (OR, 95% CI) were 0.55 (0.33–0.91) for <3000 g, 0.86 (0.61–1.22) for 3500–4000 g and 0.98 (0.64–1.50) for >4000 g. Among men with aggressive tumours, the reduction in risk for those with BWs <3000 g (OR 0.26, 95% CI 0.09–0.72) was stronger than the rate of risk for PRCA overall. Crude risk estimates were minimally attenuated when adjusted for gestational age, maternal age, birth order and adult factors. Birth length, head circumference and placental weight were not associated with prostate cancer. Our results indicate a protective effect of lower BW on risk of total and aggressive prostate cancer, rather than any direct effect of larger birth size.

The ‘DOHaD’ literature argues that stressors encountered at age t ‘program’ individual health at age t+n, and that this programming appears strongest when t defines critical developmental periods including gestation. Accordingly, children of ill-nourished pregnant women suffer greater later life morbidity than do offspring of well-nourished mothers. The possibility that circumstances other than access to nutritious food drive both a mother’s diet and fetal development remains, however, a threat to the inference of programming in utero. Attempts to rule out this threat include tests of the hypothesis that birth cohorts in gestation during famines exhibit shorter life spans than other cohorts. The tests produce conflicting results attributed to confounding by autocorrelation, selective migration and introduction of modern medicine. We offer a test in which neither medicine nor migration nor autocorrelation could obscure the presumed effect. We apply time-series regression methods to the life span of Swedes born between 1751 and 1800 to test the hypothesis that cohorts exposed in utero to the Swedish Famine of 1773 lived shorter lives than expected from trends and other forms of autocorrelation. We use these 50 birth cohorts not only because they included those exposed to severe famine but also because they may well be the only human birth cohorts that completed life unaffected by selective migration and unaided by modern medicine and for which we know life span. We find that the cohort born in 1773 live 4.2 years longer than expected from trends over the last half of the 18th century.

The thymus undergoes a critical period of growth and development early in gestation and, by mid-gestation, immature thymocytes are subject to positive and negative selection. Exposure to undernutrition during these periods may permanently affect phenotype. We measured thymulin concentrations, as a proxy for thymic size and function, in children (n = 290; aged 9–13 years) born to participants in a cluster-randomized trial of maternal vitamin A or β-carotene supplementation in rural Nepal (1994–1997). The geometric mean (95% confidence interval) thymulin concentration was 1.37 ng/ml (1.27, 1.47). A multivariate model of early-life exposures revealed a positive association with gestational age at delivery (β = 0.02; P = 0.05) and higher concentrations among children born to β-carotene-supplemented mothers (β = 0.19; P < 0.05). At ∼9–12 years of age, thymulin was positively associated with all anthropometric measures, with height retained in our multivariate model (β = 0.02; P < 0.001). There was significant seasonal variation: concentrations tended to be lower pre-monsoon (β = −0.13; P = 0.15), during the monsoon (β = −0.22; P = 0.04), and pre-harvest (β = −0.34; P = 0.01), relative to the post-harvest season. All early-life associations, except supplementation, were mediated in part by nutritional status at follow-up. Our findings underscore the known sensitivity of the thymus to nutrition, including potentially lasting effects of early nutritional exposures. The relevance of these findings to later disease risk remains to be explored, particularly given the role of thymulin in the neuroendocrine regulation of inflammation.

Previous studies have suggested that maternal active smoking can increase the risk of birth defects, but evidence on second-hand tobacco smoke (SHS) is limited. We aimed to assess the association between maternal exposure to SHS and birth defects in a Chinese population. The data were based on a large-scale cross-sectional survey conducted in Shaanxi Province, China. Considering the characteristics of survey design and the potential impact of confounding factors, we adopted propensity score matching (PSM) to match the SHS exposure group and the non-exposure group to attain a balance of the confounders between the two groups. Subsequently, conditional logistic regression was employed to estimate the effect of SHS exposure on birth defects. Furthermore, sensitivity analyses were conducted to verify the key findings. After nearest neighbor matching of PSM with a ratio of 2 and a caliper width of 0.03, there were 6,205 and 12,410 participants in the exposure and control group, respectively. Pregnant women exposed to SHS were estimated to be 58% more likely to have infants with overall birth defects (OR = 1.58, 95% CI: 1.30–1.91) and 75% more likely to have infants with circulatory system defects (OR = 1.75, 95% CI: 1.26–2.44). We also observed that the risk effect of overall birth defects had an increasing trend as the frequency of exposure increased. Additionally, sensitivity analyses suggested that our results had good robustness. These results indicate that maternal exposure to SHS likely increases the risk of overall birth defects, especially circulatory system defects, in Chinese offspring.

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.

Many studies have reported on relations between birth size and adult size but the findings to date are hard to compare due to the lack of uniform measures across studies. Interpretation of findings is also hampered by potential confounding by ethnic, socioeconomic and family factors. The purpose of this study is to explore these relationships in a comprehensive fashion, with multiple measures of birth size and adult size, using same-sex sibling controls discordant in birth weight to address potential confounding at the family level. Study subjects include pregnant women enrolled during 1959–1966 in the Child Health and Development Study in Oakland, CA and the Boston, MA, and providence, RI, sites of the Collaborative Perinatal Project in New England, currently combined into the New England Family Study. We assessed 392 offspring (mean age 43 years), the great majority as sibships as available. Our analyses confirm the positive association between birth weight and adult length reported in other studies, with a change in adult height of 1.25 cm (95% CI: 0.79 to 1.70 cm) for each quintile change in standardized birth weight. No associations were seen between birth weight and adult fatness for which findings in other studies are highly variable. As adult weight is likely to reflect recent variations in the adult nutritional environment rather than the early environment, it may be more useful for studies of birth size and adult size to focus on adult length rather than weight measures in evaluating the role of early influences on adult health.

The in utero and immediate postnatal environments are recognized as critical windows of developmental plasticity where offspring are highly susceptible to changes in the maternal metabolic milieu. Maternal hypercholesterolemia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy which can program metabolic dysfunction in offspring, including dysregulation of hepatic lipid metabolism. Although there is currently no established reference range MHC, a loosely defined cutoff point for total cholesterol >280 mg/dL in the third trimester has been suggested. There are several unanswered questions regarding this condition particularly with regard to how the timing of cholesterol exposure influences hepatic lipid dysfunction and the mechanisms through which these adaptations manifest in adulthood. Gestational hypercholesterolemia increased fetal hepatic lipid concentrations and altered lipid regulatory mRNA and protein content. These early changes in hepatic lipid metabolism are evident in the postweaning environment and persist into adulthood. Further, changes to hepatic epigenetic signatures including microRNA (miR) and DNA methylation are observed in utero, at weaning, and are evident in adult offspring. In conclusion, early exposure to cholesterol during critical developmental periods can predispose offspring to the early development of nonalcoholic fatty liver disease (NAFLD) which is characterized by altered regulatory function beginning in utero and persisting throughout the life cycle.

Epidemiological studies suggest that glucocorticoid excess in the fetus may contribute to the pathophysiology of cardiovascular diseases in adulthood. However, the impact of maternal glucocorticoid on the cardiovascular system of the offspring has not been much explored in studies involving humans, especially in childhood. The objective of this study was to assess the influence of maternal cortisol concentrations on child arterial elasticity. One hundred and thirty pregnant women followed from 1997 to 2000, and respective children 5–7 years of age followed from 2004 to 2006 were included in the study. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of nine samples of saliva. Arterial elasticity was assessed by the large artery elasticity index (LAEI; the capacitive elasticity of large arteries) by recording radial artery pulse wave, utilizing the equipment HDI/PulseWave CR-2000 Cardiovascular Profiling System®. The nutritional status of the children was determined by the body mass index (BMI). Insulin concentration was assessed by chemiluminescence, and insulin resistance by the homeostasis model assessment. Blood glucose, total cholesterol and fractions (LDL-c and HDL-c) and triglyceride concentrations were determined by automated enzymatic methods. The association between maternal cortisol and child arterial elasticity was assessed by multivariate linear regression analysis. There was a statistically significant association between maternal cortisol and LAEI (P = 0.02), controlling for birth weight, age, BMI and HDL-c of the children. This study suggests that exposure to higher glucocorticoid concentrations in the prenatal period is associated to lower arterial elasticity in childhood, an earlier cardiovascular risk marker.