Prenatal glucocorticoid overexposure has been shown to programme adult cardiovascular function in a range of species, but much less is known about the long-term effects of neonatal glucocorticoid overexposure. In horses, prenatal maturation of the hypothalamus–pituitary–adrenal axis and the normal prepartum surge in fetal cortisol occur late in gestation compared to other precocious species. Cortisol levels continue to rise in the hours after birth of full-term foals and increase further in the subsequent days in premature, dysmature and maladapted foals. Thus, this study examined the adult cardiovascular consequences of neonatal cortisol overexposure induced by adrenocorticotropic hormone administration to full-term male and female pony foals. After catheterisation at 2–3 years of age, basal arterial blood pressures (BP) and heart rate were measured together with the responses to phenylephrine (PE) and sodium nitroprusside (SNP). These data were used to assess cardiac baroreflex sensitivity. Neonatal cortisol overexposure reduced both the pressor and bradycardic responses to PE in the young adult males, but not females. It also enhanced the initial hypotensive response to SNP, slowed recovery of BP after infusion and reduced the gain of the cardiac baroreflex in the females, but not males. Basal diastolic pressure and cardiac baroreflex sensitivity also differed with sex, irrespective of neonatal treatment. The results show that there is a window of susceptibility for glucocorticoid programming during the immediate neonatal period that alters cardiovascular function in young adult horses in a sex-linked manner.

People commonly face adverse circumstances throughout life, which increases risk for psychiatric disorders, such as anxiety, depression, psychosis, and posttraumatic stress disorder (PTSD). Adversities may occur during different periods in life. Especially adversity during early periods has been suggested to put individuals at risk for adverse mental health outcomes. Here, we investigated whether timing of adversity during the prenatal period, childhood, or mid-to-late adulthood differentially impacted classification into late adulthood symptom profiles. We performed sex-stratified Latent Profile Analysis to identify latent profiles regarding anxious, depressive, psychotic, and PTSD symptoms in n = 568 Dutch famine birth cohort members (n = 294 women, n = 274 men, mean age(SD) = 72.9(0.8)). Cross-sectional late adulthood symptomatology, childhood traumatic maltreatment, and adulthood trauma were based on self-report questionnaires. Prenatal adversity was considered present when individuals were prenatally exposed to the 1944-45 Dutch famine. In both men and women we identified one anxious/depressive profile and three profiles with approximately equal severity of all symptom types within each profile, yet differentiating in overall severity (low, mild, high) between profiles. We additionally found a PTSD symptom profile in women. In men, logistic regression models showed significant associations between prenatal, childhood and adulthood adversity, and profile classification, with differential effects depending on timing and most profound effects of child maltreatment. In women, childhood and adulthood adversity significantly increased classification probability into almost all profiles, with no significant effect of prenatal adversity. These findings support a time-dependent and sex-specific impact of adversity during different periods across the lifespan on psychological health, with consequences into late adulthood.

Neurocognitive development is a dynamic process over the life course and is influenced by intrauterine factors as well as later life environment. Using data from the Pune Maternal Nutrition Study from 1994 to 2008, we investigate the association of in utero, birth, and childhood conditions with offspring neurocognitive development in 686 participants of the cohort, at age 12 years. The life course exposure variables in the analysis include maternal pre-pregnancy size and nutrition during pregnancy, offspring birth measurements, nutrition and physical growth at age 12 years along with parental education and socio-economic status. We used the novel Bayesian Model Averaging (BMA) approach; which has been shown to have better predictive performance over traditional tests of associations. Our study employs eight standard neurocognitive tests that measure intelligence, working memory, visuo-conceptual and verbal learning, and decision-making/attention at 12 years of age. We control for nutritional-metabolic information based on blood measurements from the pregnant mothers and the children at 12 years of age. Our findings highlight the critical role of parental education and socio-economic background in determining child neurocognitive performance. Maternal characteristics (pre-pregnancy BMI, fasting insulin during pregnancy) and child height at 12 years were also robust predictors on the BMA. A range of early factors – such as maternal folate and ferritin concentrations during pregnancy, and child’s head circumference at birth – remained important determinants of some dimensions of child’s neurocognitive development, but their associations were not robust once we account for model uncertainty. Our results suggest that intrauterine influences on long- term neurocognitive outcomes may be potentially reversible by post-birth remediation. In addition to the current nutritional interventions, public health policy should also consider social interventions in children born into families with low socio-economic status to improve human capital.

Despite high altitude was implicated in adverse birth outcomes, there remained a paucity of evidence on low-to-medium altitude effect. This study aimed to explore the association of low-to-medium altitude with birth outcomes. A population-based cross-sectional survey was performed using a stratified multistage random sampling method among women with their infants born during 2010–2013 in Northwestern China. Altitude was determined in meters based on the village or community of the mother’s living areas. Birth outcomes involved birth weight, gestational age, and small for gestational age (SGA). Generalized linear models were fitted to investigate the association of altitude with birth outcomes. Moreover, the dose–response relationship between altitude and birth outcomes was evaluated with a restricted cubic spline function. A total of 27 801 women with their infants were included. After adjusting for potential confounders, every 100-m increase in the altitude was associated with reduced birth weight by 6.4 (95% CI −8.1, −4.6) g, the slight increase of gestational age by 0.015 (95% CI 0.010, 0.020) week, and an increased risk of SGA birth (odds ratio 1.03, 95% CI 1.02, 1.04). Moreover, there was an inversely linear relationship between altitude and birth weight (P for overall < 0.001 and P for nonlinear = 0.312), and a positive linear relationship between altitude and SGA (P for overall < 0.001 and P for nonlinear = 0.194). However, a nonlinear relationship was observed between altitude and gestational age (P for overall < 0.001 and P for nonlinear = 0.010). The present results suggest that low-to-medium altitude is possibly associated with adverse birth outcomes.

The theory of developmental programming is supported by accumulating evidence, both observational and experimental. The direct application of the principles of developmental programming by clinicians to benefit pregnant women remains an area of limited attention. Examining a selection of inpatients at an obstetric referral center, I searched for situations in which clinical decision making could be driven by the principles of developmental programming. I also looked for situations in which the clinical research agenda could be dictated by these concepts. In the decision to undertake preventive measures to avoid preeclampsia, the offspring’s perspective may support more liberal application of calcium and aspirin. Consideration of the long-term health perspective of the offspring could drive choices in the management of obesity and diabetes in pregnancy. The administration of corticosteroids in women delivering by elective cesarean at term may have modest short-term benefits, but additional trials are necessary to investigate long-term offspring health. The offspring of women suffering hyperemesis gravidarum may benefit from nutritional therapy. The long-term health of the offspring could affect couples’ choice for IVF or expectant management. Applying the principles of developmental programming to the management of pregnant women could drive clinical decision making and is driving the clinical research agenda. Increasingly, developmental programming concepts are becoming an integral part of clinical practice, as well as determining the choice of outcomes in trials in obstetrics and fertility medicine. The presented cases underscore the need for more research to guide clinical practice.

Zinc is an important nutrient involved in cell division, physical growth, and immune system function. Most studies evaluating the nutritional status related to zinc and prematurity were conducted with hospitalized preterm infants. These studies show controversial results regarding the prevalence of deficiency, clinical implications, and the effect of zinc supplementation on mortality, infectious diseases, and growth in these groups. This study aimed to compare serum and erythrocyte zinc levels in a group of preterm and full-term infants after 9 months of age, and related the zinc levels to dietary intake and anthropometric indicators in both groups. This cross-sectional study compared 43 preterm infants (24 to 33 weeks) aged 9–24 months to 47 full-term healthy infants. Outcome measures: anthropometric indicators and dietary intake. Blood sample for serum and erythrocyte zinc levels (ICP-MS, Inductively Coupled Plasma Mass Spectrometry). There was no difference between the groups regarding the mean of serum and erythrocyte zinc. Variables associated with higher serum zinc levels were breastfeeding at evaluation (β = 20.11 µg/dL, 95% CI 9.62–30.60, p < 0.001) and the later introduction of solid foods (β = 6.6 µg/dL, 95% CI 5.3–11.4, p < 0.001). Breastfeeding was also associated with higher erythrocyte zinc levels. The zinc levels were adequate in both groups, there was no association with anthropometric indicators or dietary intake and were slightly influenced by breastfeeding and time of solid food introduction.

The consistently high prevalence of cardiovascular disease (CVD) has urged the need for punctual and effective prevention. Extended research on this specific area has demonstrated the influence of fetal and neonatal periods on the risk of developing CVD in adulthood. Thus, the role of traditional and novel biological markers to the effective screening of CVD among the neonatal population is widely investigated. The objective of the present narrative review is to examine those neonatal biomarkers that may play a role in the development of CVD, to exhibit scientific data that appertain to their association with various perinatal conditions leading to CVD predisposition, and their potential role on prediction and prevention strategies. Multiple biomarkers, traditional and novel, have been mined across the studied literature. Adiposity, insulin resistance, altered lipid profile, inflammation, and endothelial dysfunction seem among the headliners of CVD. Even though various novel molecules have been studied, their clinical utility remains controversial. Therefore, it is quite important for the scientific community to find elements with strong predictive value and practical clinical use.

Early-life intervention to reduce obesity and poor dental health through early-life nutrition will improve health outcomes in later life. This study examined the prevalence of overweight and obesity and visual dental decay in 4-year old children in New Zealand between 2013 and 2017, and the impact of a nutrition and physical activity intervention programme, Under-5-Energize (U5E), on prevalence of these conditions within ethnic groups and by deprivation. The data set included 277,963 4-year-old children, including 25,140 from the Waikato region children of whom 8067 attended one of the 121 early childhood centres (ECC) receiving the U5E programme from 2014. Purposively the U5E-ECC selected were attended by higher proportions of indigenous Māori children and children living in higher deprivation areas than non-U5E-ECC. From 2013 to 2017, the overall prevalence of obesity, as defined by World Health Organisation criteria, declined slightly but rates of dental decay did not change. In the Waikato region, the prevalence of obesity declined in non-Māori children from 2015 to 2017 and children attending U5E-ECC had lower rates of dental decay than non-U5E children. Binary logistic regression showed that between 2015 and 2017 visible dental decay was more likely in children who were Māori (3.06×3.17), living in high deprivation (1.54×1.66) and male (1.10) but less likely if attending an U5E-ECC (0.83×0.79). Early-life intervention had efficacy at reducing dental decay, and demonstrated that the origins of disparities in health such as ethnicity and deprivation need to be addressed further to break the intergenerational cycles of poor health.

Epigenetic age acceleration (AA) has been associated with adverse environmental exposures and many chronic conditions. We estimated, in the NINFEA birth cohort, infant saliva epigenetic age, and investigated whether parental socio-economic position (SEP) and pregnancy outcomes are associated with infant epigenetic AA. A total of 139 saliva samples collected at on average 10.8 (range 7–17) months were used to estimate Horvath’s DNA methylation age. Epigenetic AA was defined as the residual from a linear regression of epigenetic age on chronological age. Linear regression models were used to test the associations of parental SEP and pregnancy outcomes with saliva epigenetic AA. A moderate positive association was found between DNA methylation age and chronological age, with the median absolute difference of 6.8 months (standard deviation [SD] 3.9). The evidence of the association between the indicators of low SEP and epigenetic AA was weak; infants born to unemployed mothers or with low education had on average 1 month higher epigenetic age than infants of mothers with high education and employment (coefficient 0.78 months, 95% confidence intervals [CIs]: −0.79 to 2.34 for low/medium education; 0.96, 95% CI: −1.81 to 3.73 for unemployment). There was no evidence for association of gestational age, birthweight or caesarean section with infant epigenetic AA. Using the Horvath’s method, DNA methylation age can be fairly accurately predicted from saliva samples already in the first months of life. This study did not reveal clear associations between either pregnancy outcomes or parental socio-economic characteristics and infant saliva epigenetic AA.

The functional differentiation of the mammary gland (MG) is fundamental for the prevention of mammary pathologies. This process occurs throughout pregnancy and lactation, making these stages key events for the study of pathologies associated with development and differentiation. Many studies have investigated the link between mammary pathologies and thyroid diseases, but most have ignored the role of thyroid hormone (TH) in the functional differentiation of the MG. In this work, we show the long-term impact of hypothyroidism in an animal model whose lactogenic differentiation occurred at low TH levels. We evaluated the ability of the MG to respond to hormonal control and regulate cell cycle progression. We found that a deficit in TH throughout pregnancy and lactation induces a long-term decrease in Rb phosphorylation, increases p53, p21, Cyclin D1 and Ki67 expression, reduces progesterone receptor expression, and induces nonmalignant lesions in mammary tissue. This paper shows the importance of TH level control during mammary differentiation and its long-term impact on mammary function.

The aim of this study is to determine if the offspring of mothers with obesity, present disorders in the expression of genes related to atrophy or protein synthesis in the muscle and if these disorders are modified with the (−)-epicatechin (Epi) treatment. Six male offspring per group were randomly assigned to the control groups [C and offspring of maternal obesity (MO)] or the Epi intervention groups, Epi treatment for 13 weeks (C + Epi long or MO + Epi long), or Epi administration for two weeks (C + Epi short or MO + Epi short). The effect of Epi in the gastrocnemius tissue was evaluated, analyzing mRNA and protein levels of Murf1, MAFbx, Foxo1, NFkB, and p70S6K-alpha. After the analysis by two-way ANOVA, we found an influence of the Epi long treatment over the model, by decreasing the Murf1 gene expression in both groups treated with the flavonoid (C + Epi long and MO + Epi long) (p = 0.036). Besides, Epi long treatment over the NFκB expression, by decreasing the fold increase in both groups treated with the flavonoid (C + Epi long and MO + Epi long) (p = 0.038). We not find any interaction between the variables or changes in the MAFbx, Foxo1 mRNA, neither in the phosphorylated/total protein ratio of NFκB, Foxo1, or p70S6K-alpha. In conclusions, treatment with a long protocol of Epi, reduces the mRNA of the muscle atrophy genes Murf 1 and NFkB, in the gastrocnemius muscle; however, these changes are not maintained at protein level.

Characterizing and quantifying the trajectories of variables of interest through time in their field of study is of interest to a range of disciplines. The aim of this study was to investigate the growth speed in height of children and its determinants. A total of 3401 males and 3200 females from four low- and middle-income countries with measured height on five occasions from 2002 to 2016 were included in the study. Data were analyzed using a latent growth model. The results of the study reported that children in four low- and middle-income countries exhibited substantial growth inequalities. There was a significant gender difference in change of growth with males had a higher baseline, rate of change, and acceleration in height growth than females. Comparing the component of slopes across countries, the growth change inequalities were observed among children. These inequalities were statistically significant, with the highest rate of change observed in Peru and Vietnam.

The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02–9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02–0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

An adverse early life environment is associated with increased cardiovascular disease in offspring. Work in animal models has shown that maternal undernutrition (UN) during pregnancy leads to hypertension in adult offspring, with effects thought to be mediated in part via altered renal function. We have previously shown that growth hormone (GH) treatment of UN offspring during the pre-weaning period can prevent the later development of cardiometabolic disorders. However, the mechanistic basis for these observations is not well defined. The present study examined the impact of GH treatment on renal inflammatory markers in adult male offspring as a potential mediator of these reversal effects. Female Sprague-Dawley rats were fed either a chow diet fed ad libitum (CON) or at 50% of CON intake (UN) during pregnancy. All dams were fed the chow diet ad libitum during lactation. CON and UN pups received saline (CON-S/UN-S) or GH (2.5 µg/g/day; CON-GH/UN-GH) from postnatal day 3 until weaning (p21). Post-weaning males were fed a standard chow diet for the remainder of the study (150 days). Histological analysis was performed to examine renal morphological characteristics, and gene expression of inflammatory and vascular markers were assessed. There was evidence of renal hypotrophy and reduced nephron number in the UN-S group. Tumour necrosis factor-α, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecular-1 and vascular cell adhesion molecule-1 gene expression was increased in UN-S offspring and normalized in the UN-GH group. These findings indicate that pre-weaning GH treatment has the potential to normalize some of the adverse renal and cardiovascular sequelae that arise as a consequence of poor maternal nutrition.

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.