Emerging evidence demonstrates a link between preterm birth (PTB) and later life cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to compare conventional CVD risk factors between those born preterm and at term. PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. The review protocol is registered in PROSPERO (CRD42018095005). CVD risk factors including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index, lipid profile, blood glucose, and fasting insulin among those born preterm (<37 weeks’ gestation) were compared with those born at term (≥37 weeks’ gestation). Subgroup analyses based on gender, age, gestational at birth (<32 weeks’ gestation and <28 weeks’ gestation), and PTB associated with small for gestational age or average for gestational age were also performed. Fifty-six studies provided data on 308,987 individuals. Being born preterm was associated with 3.26 mmHg (95% confidence interval [CI] 2.08 to 4.44) higher mean SBP and 1.32 mmHg (95% CI: 0.61 to 2.04) higher mean DBP compared to being born at term. Subgroup analyses demonstrated that SBP was higher among (a) preterm compared to term groups from early adolescence until adulthood; (b) females born preterm but not among males born preterm compared to term controls; and (c) those born at <32 weeks or <28 weeks compared to term. Our meta-analyses demonstrate higher SBP and DBP among those born preterm compared to term. The difference in SBP is evident from early adolescence until adulthood.

Preeclampsia (PE) and gestational hypertension (GH) are pregnancy-specific diseases that occur in around 10% of pregnancies worldwide. Increasing evidence suggests that women whose pregnancies were complicated by PE or GH, and their offspring, are at increased risk of cardiovascular disease (CVD) later in life. We hypothesised that PE and GH would associate with CVD risk factors 8–10 years after the first pregnancy in the mother and child and that differences in cardiovascular risk profile would be seen between 8- and 10-year-old male and female children. This is a follow-up study of the Adelaide SCOPE pregnancy cohort where 1164 nulliparous women and their babies were recruited between 2005 and 2008. Haemodynamic function was assessed using non-invasive USCOMBP+ and USCOM1A devices. Microvascular function was assessed by post-occlusive reactive hyperaemia. Of the 273 mother–child pairs followed up, 38 women had PE and 20 had GH during pregnancy. Augmentation index (Aix) and suprasystolic pulse pressure (ssPP) were increased, whereas measures of microvascular function were decreased in children who were born to PE compared to uncomplicated pregnancies. Female children had decreased Aix and ssPP compared to male children after in utero exposure to PE. Women who developed GH during their first pregnancy had increased systolic, diastolic and mean arterial pressures compared to women who had uncomplicated pregnancy. Our data suggest that GH is associated with increased cardiovascular risk in women 8–10 years after first pregnancy and PE is associated with increased offspring risk at 8–10 years of age, highlighting differences between these two hypertensive disorders of pregnancy.

Estimation of pre-pregnancy weight is difficult because measurements taken before pregnancy are rarely available. No studies have compared various ‘proxy’ measures using recalled weight or based on early pregnancy weight with actual measurements of pre-pregnancy weight. The Southampton Women’s Survey recruited women during 1998–2002 who were not pregnant. Data on 198 women with an estimated date of conception within 3 months of recruitment were analysed. Three proxy measures were considered: (1) recalled pre-pregnancy weight obtained during early pregnancy, (2) measured weight in early pregnancy and (3) estimated pre-pregnancy weight using a published model. Mean (standard deviation) recalled weight was 1.65 (3.03) kg lighter than measured pre-pregnancy weight, while early pregnancy weight and weights from the published model were 0.88 (2.34) and 0.88 (2.33) kg heavier, respectively. The Bland–Altman limits of agreement for recalled weight were −7.59 to 4.29 kg, wider than those for the early pregnancy weight: −3.71 to 5.47 kg and the published model: −3.68 to 5.45 kg. For estimating pre-pregnancy weight, we recommend subtraction of 0.88 kg from early pregnancy weight or the published model, or addition of 1.65 kg to recalled weight. Estimates of pre-pregnancy body mass index and gestational weight gain categories were very similar when using early pregnancy and published model weights, but they differed from those using recalled weight. Our findings indicate that calculations of first trimester weight gain using recalled weight must be treated cautiously, and a measured weight in early pregnancy provides a more precise assessment of pre-pregnancy weight than recalled weight.

Adipocytokines, which are secreted during fetal development by both mothers and fetuses, may influence fetal lung development, but little human data are available. We used data from the HOME Study to investigate the associations of cord blood adipocytokine concentrations with children’s lung forced expiratory volume (FEV1; N = 160) and their risk of wheeze (N = 281). We measured umbilical cord serum adipocytokine concentrations using enzyme-linked immunosorbent assays and FEV1 using a portable spirometer at ages 4 and 5 to calculate the percent predicted FEV1 (%FEV1). Parents completed standardized questionnaires of their child’s wheeze symptoms every 6 months from birth to age 5, then again at ages 6 and 8. We used multivariable linear mixed models and modified Poisson regression with generalized estimating equations to estimate associations of adipocytokine concentrations (log2-transformed) with children’s %FEV1 and the risk of wheeze, respectively, adjusting for sociodemographic, perinatal, and child factors. Cord serum leptin was not associated with children’s %FEV1. Higher cord serum adiponectin concentrations were associated with higher %FEV1 in girls (β = 3.1, 95% confidence interval [CI]: 0.6, 5.6), but not in boys (β = −1.3, 95% CI: −5.9, 3.3) (sex × adiponectin p-value = 0.05). Higher leptin was associated with lower risk of wheeze in girls (RR = 0.74, 95% CI: 0.66, 0.84), but not boys (RR = 0.87, 95% CI: 0.69, 1.11) (sex × leptin p-value = 0.01). In contrast, higher adiponectin concentrations were associated with lower risk of wheeze (RR = 0.84, 95% CI: 0.73, 0.96) in both boys and girls. These data suggest that fetal adipocytokines may impact lung development and function in early childhood. Future studies are needed to confirm these findings and explore the mechanisms underlying these associations.

Maternal milk consumption can cause changes in the mammary epithelium of the offspring that result in the expression of molecules involved in the induction of differentiation, reducing the risk of developing mammary cancer later in life. We previously showed that animals that maintained a higher intake of maternal milk had a lower incidence of mammary cancer. In the present study, we evaluated one of the possible mechanisms by which the consumption of maternal milk could modify the susceptibility to mammary carcinogenesis. We used Sprague Dawley rats reared in litters of 3 (L3), 8 (L8), or 12 (L12) pups per mother in order to generate a differential consumption of milk. Whole mounts of mammary glands were performed to analyze the changes in morphology. Using real-time polymerase chain reaction (PCR), we analyzed the expression of mammary Pinc, Tbx3, Stat6, and Gata3 genes. We use the real-time methylation-specific polymerase chain reaction method to assess the methylation status of Stat6 and Gata3 CpG sites. Our findings show an increase in the size of the epithelial tree and a smaller number of ducts called terminal end buds in L3 vs. L12. We observed an increased expression of mRNA of Stat6, Gata3, Tbx3, and a lower expression of Pinc in L3 with respect to L12. Stat6 and Gata3 are more methylated in the CpG islands of the promoter analyzed in L12 vs. L3. In conclusion, the increased consumption of maternal milk during the postnatal stage generates epigenetic and morphological changes associated with the differentiation of the mammary gland.

Prenatal hypoxia (PH) has negative consequences on the cardiovascular system in adulthood and can affect the responses to additional insults later in life. We explored the effects of PH imposed during embryonic day 20 (10.5% O2 for 12 h) on circadian rhythms of systolic blood pressure (BP) and heart rate (HR) in mature male rat offspring measured by telemetry. We evaluated: (1) stability of BP and HR changes after PH; (2) circadian variability of BP and HR after 2 and 5 weeks of exposure to artificial light at night (ALAN; 1–2 lx); and (3) response of BP and HR to norepinephrine. PH increased BP in the dark (134 ± 2 mmHg vs. control 127 ± 2 mmHg; p = 0.05) and marginally in the light (125 ± 1 mmHg vs. control 120 ± 2 mmHg) phase of the day but not HR. The effect of PH was highly repeatable between 21- and 27-week-old PH male offspring. Two weeks of ALAN decreased the circadian variability of HR (p < 0.05) and BP more in control than PH rats. After 5 weeks of ALAN, the circadian variability of HR and BP were damped compared to LD and did not differ between control and PH rats (p < 0.05). Responses of BP and HR to norepinephrine did not differ between control and PH rats. Hypoxia at the end of the embryonic period increases BP and affects the functioning of the cardiovascular system in mature male offspring. ALAN in adulthood decreased the circadian variability of cardiovascular parameters, more in control than PH rats.

Alterations in the circadian cycle are known to cause physiological disorders in the hypothalamic–pituitary–adrenal and the hypothalamic–pituitary–gonadal axes in adult individuals. Therefore, the present study aimed to evaluate whether exposure of pregnant rats to constant light can alter the reproductive system development of male offspring. The dams were divided into two groups: a light–dark group (LD), in which pregnant rats were exposed to an LD photoperiod (12 h/12 h) and a light–light (LL) group, in which pregnant rats were exposed to a photoperiod of constant light during the gestation period. After birth, offspring from both groups remained in the normal LD photoperiod (12 h/12 h) until adulthood. One male of each litter was selected and, at adulthood (postnatal day (PND) 90), the trunk blood was collected to measure plasma testosterone levels, testes and epididymis for sperm count, oxidative stress and histopathological analyses, and the spermatozoa from the vas deferens to perform the morphological and motility analyses. Results showed that a photoperiod of constant light caused a decrease in testosterone levels, epididymal weight and sperm count in the epididymis, seminiferous tubule diameter, Sertoli cell number, and normal spermatozoa number. Histopathological damage was also observed in the testes, and stereological alterations, in the LL group. In conclusion, exposure to constant light during the gestational period impairs the reproductive system of male offspring in adulthood.

Consumption of sugar-sweetened beverages (SSBs) during pregnancy has been associated with childhood obesity. Research in which rodent dams have been given high-fat/high-sugar diets has consistently found metabolic alterations in their offspring. However, what remains unclear is the potential impact on the developing fetus of giving sugar in isolation at concentrations similar to SSBs to the mothers. Therefore, we conducted a systematic review and meta-analysis (Protocol No: 127115 on Prospero) to identify potential relationships between maternal sucrose consumption and metabolic outcomes in offspring of rodent (rat or mouse) models. We analysed studies that provided rodent mothers dams with access to sucrose solutions (8–20% w/v) prior to conception, during pregnancy and/or lactation and that reported offspring outcomes of body weight (BW), body composition and glycaemic control. Following a systematic search of four databases (PubMed, EMBASE, Web of Science and Scopus) performed on 15 January 2019, maternal and offspring data from 15 papers were identified for inclusion. Only rat studies were identified. Meta-analyses were performed on standardised mean differences for maternal and offspring BW and fasting glucose levels, with subgroup analyses of strain, sucrose concentration, exposure period and sex of offspring. A bias towards the inclusion of only data from male offspring was identified and this limited interpretation of potential sexually dimorphic outcomes. Maternal sucrose exposure was associated with an increased risk of obesity and poor glucose disposal in adult and aged offspring.

Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6–51 and HR = 7.0, 95% CI 1.5–33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88–1.5) or diabetes (HR = 1.1, 95% CI 0.9–1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84–20) or general population (SIR: 1.9, 95% CI 1.0–3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.

In this study, we investigate if children born following assisted reproduction technologies (ARTs) are at an increased risk for long-term ophthalmic complications. For this purpose, a population-based cohort analysis was conducted which included all deliveries between 1991 and 2014 at a single tertiary medical center. Offspring were classified relative to conception method as ART or spontaneous pregnancies. Offspring hospitalizations up to the age of 18 years involving ophthalmic morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan–Meier survival curve was used to compare cumulative hospitalization rates in exposed (ART) and unexposed offspring (spontaneous), and a Cox proportional hazards model was used to control for potential confounders. A total of 243,682 deliveries were included in the study. In that, 1.8% of the deliveries (4364) were of mothers who underwent fertility treatments and 98.2% (239,318) were conceived spontaneously. Offspring born to mothers who underwent fertility treatments had a significantly higher hospitalization rate involving ophthalmic morbidity, as compared to spontaneously conceived offspring (1.2% vs. 1.0%, p = 0.04). The Kaplan–Meier survival curve pointed to a significantly higher cumulative incidence of ophthalmic morbidity following ART (log rank p = 0.02). Cox proportional hazards model was adjusted for maternal age, preterm delivery, maternal hypertensive disorders, diabetes, and mode of delivery which demonstrated ART as an independent risk factor for long-term pediatric ophthalmic morbidity (adjusted hazard ratio = 1.37, CI 1.04–1.80, p-value = 0.02). We concluded that ART is an independent risk factor for long-term ophthalmic morbidity of the offspring.

According to the World Health Organization, smoking is the most important risk factor for adverse pregnancy outcomes in industrialized nations. We aimed to establish how fetal gender and smoking interact with regard to perinatal outcomes, especially preterm delivery. Data from 220,339 singleton pregnancies, obtained from the German Perinatal Survey in Schleswig-Holstein and registered between 2004 and 2017 were analyzed in regard to smoking behavior, fetal gender, and preterm delivery. The rate of preterm births was directly proportional to the women’s consumption of nicotine. The rate of preterm deliveries was 6.8% among nonsmokers, and 13.2% in women who were very heavy smokers (≥22 cigarettes/day). Very heavy smoking (≥22 cigarettes/day) had a marked impact on extremely preterm births (<28 weeks of gestation) and very preterm births (28–31 weeks of gestation). Preterm births increased by 1.2% from heavy smokers to very heavy smokers; the differences between the other groups ranged between 0.1% and 0.4%. Fetal gender also had an impact on preterm birth: male infants were predominant in nearly all groups of women who delivered preterm infants. Smoking during pregnancy and male gender are both risk factors for preterm delivery. Fetal gender should be given greater attention as one of the several risk factors of preterm birth. Due to the high rate of morbidity among preterm infants and enormous costs for the healthcare system, women should be encouraged to cease or at least reduce smoking during pregnancy.

Donor-conceived neonates have poorer birth outcomes, including low birth weight and preterm delivery that are associated with poorer long-term health in adulthood through the developmental origins of health and disease (DOHaD) theory. The aim of this study was to conduct the first investigation of the adult health outcomes of donor-conceived people. An online health survey was completed by 272 donor sperm-conceived adults and 877 spontaneously conceived adults from around the world. Donor and spontaneously conceived groups were matched for age, sex, height, smoking, alcohol consumption, exercise, own fertility and maternal smoking. Donor sperm-conceived adults had significantly higher reports of being diagnosed with type 1 diabetes (P = 0.031), thyroid disease (P = 0.031), acute bronchitis (P = 0.008), environmental allergies (P = 0.046), sleep apnoea (P = 0.037) and having ear tubes/grommets surgically implanted (P = 0.046). This is the first study to investigate the health outcomes of adult donor sperm-conceived people. Donor sperm-conceived adults self-reported elevated frequencies of various health conditions. The outcomes are consistent with birth defect data from donor sperm treatment and are consistent with the DOHaD linking perturbed early growth and chronic disease in adulthood.

KOKAN region is characterized by undernutrition across all stages of lifecycle. Developmental Origins of Health & Disease hypothesis suggests that environmental influences in the early period of growth and development can contribute to the risks of noncommunicable diseases (NCD) in adulthood. Newborns and placentas of 815 pregnant mothers delivered in a rural hospital were studied. We tested the hypothesis that low placental weight will be associated with low birth weight (LBW). Mothers had a mean age of 26 years and were smaller in size at delivery [mean height of 152.1 cm (±6.1 cm), weight 52 kg (±10.2 kg), body mass index (BMI) 22.5 kg/m2 (±4.1 kg/m2)]. Mean placental weight was 488 g (±120 g). Mean birth weight, length, and head circumference of the newborn were 2.54 kg (±0.5 kg), 46.3 cm (±3.1 cm), and 32.7 cm (±1.7 cm), respectively. Prevalence of LBW, stunting, and small head size was 41.6%, 42.2%, and 18.2%, respectively. Maternal height, weight, and BMI at delivery were all positively associated with placental weight (p < 0.01 for all). Mothers with placentas in the lowest placental weight tertile had an increased likelihood of producing an LBW baby [OR 7.7, 95% CI (5.0, 11.8)], a stunted baby [OR 1.9 (1.4, 2.9)], or a baby with a small head circumference [OR 2.4 (1.4, 4.0)]. Mothers in the lowest height tertile had odds of producing a LBW baby [OR 1.8 95% CI (1.2, 2.7)] or a stunted baby [OR 1.6 (1.1, 2.3)]. There is a need to improve the nutritional status of women in KOKAN region which may reduce the risk of NCD.

The rising rate of childhood overweight follows the increase in maternal obesity, since perinatal events impact offspring in a diversity of metabolic disorders. Despite many studies that have linked dietary consumption, overnutrition, or maternal obesity as the mediators of fetal metabolic programming, there are gaps regarding the knowledge about the contribution of different maternal phenotypes to the development of metabolic disturbances in offspring. This study aimed to investigate whether maternal high-fat diet (HFD) consumption without the development of the obese phenotype would protect offspring from metabolic disturbances. Female mice were fed standard chow diet or a HFD for 4 weeks before mating. HFD females were classified into obesity-resistant (OR) or obesity-prone (OP), according to weight gain. OP females presented with higher adiposity, fasting serum glucose and insulin, cholesterol and non-esterified fatty acid (NEFA). Newborn offspring from OP dams showed higher serum glucose and insulin and alteration in hepatic gene expression that may have contributed to the rise in hepatic fat content and decline of glycogen levels in the liver. Despite offspring from OR and OP females having showed similar growth after the day of delivery, offspring from OP females had higher caloric intake, fasting glucose, serum triglycerides and altered hepatic gene expression, as well as glucose and pyruvate intolerance and lower insulin sensitivity at d28 compared with offspring from OR females. Maternal pre-pregnancy serum glucose, insulin, and NEFA positively correlated with serum glucose and fat liver content and negatively correlated with hepatic glycogen in offspring. In conclusion, our results show that maternal resistance to diet-induced obesity partially protects offspring from early metabolic disturbances.

During the early postnatal period, dietary manipulations can alter the developmental trajectory of the growing offspring, causing beneficial or adverse health outcomes later in adult life. We investigated the potential preventive effects of neonatal zingerone intake on the development of fructose-induced metabolic derangements in rats.

Four-day old male and female Sprague-Dawley rat pups (n = 79) were randomly grouped and administered: 10 ml/kg body weight (bwt) of distilled water (W), 10 ml/kg bwt 20% fructose solution (FS), 10 ml/kg bwt fructose solution + 40 mg/kg bwt of zingerone in distilled water (ZF) or 40 mg/kg bwt of zingerone in distilled water (ZW) pre-weaning. After weaning, W and ZW continued on unlimited tap water, while FS and ZF continued on unlimited fructose solution for 10 weeks. Body mass and food and fluid intake were evaluated, plasma was collected for metabolic assays and visceral fat was quantified.

Food intake was decreased, fructose and overall caloric intake were increased due to fructose feeding in both sexes (P < 0.05). When compared with the controls, the high-fructose diet significantly raised the terminal body masses of females (P < 0.0001), concentrations of triglycerides, total cholesterol, LDL-c, TG:HDL-c ratio and visceral fat mass relative to bwt in both sexes (P < 0.05). Zingerone prevented (P < 0.05) the fructose-induced increase in body mass (females) and hypercholesterolemia (both sexes). Levels of HDL-c, glycaemic parameters and adiponectin were not affected by the interventions (P > 0.05). Sex-related differences were observed in food, fluid and caloric intake, terminal mass, cholesterol subtypes and visceral fat percentage (P < 0.05).

Zingerone could be used strategically in the neonatal phase as a prophylatic management of high-fructose diet-induced metabolic syndrome.