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.

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.

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.

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.

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.

Multifetal pregnancies are at risk of adverse maternal, neonatal and long-term health outcomes, and gestational weight gain (GWG) is a potentially modifiable risk factor for several of these. However, studies assessing the associations of GWG with long-term health in twins are rare, and studies which do assess these associations in twins often do not account for gestational age. Since longer gestations are likely to lead to larger GWG and lower risk of adverse outcomes, adjusting for gestational age is necessary to better understand the association of GWG with twin health outcomes. We aimed to explore long-term associations of GWG-for-gestational-age with twin anthropometric measures. The Peri/Postnatal Epigenetic Twins Study (PETS) is a prospective cohort study, which recruited women pregnant with twins from 2007 to 2009. Twins were followed-up at 18 months and 6 years of age. GWG-for-gestational-age z-scores were calculated from pre-pregnancy weight and weight at delivery. We fitted regression models to assess associations of GWG with twin weight, height and BMI at birth, 18 months, and 6 years. Of the 250 women in the PETS, 172 had GWG measured throughout pregnancy. Overall, higher GWG-for-gestational-age z-scores were associated with higher birthweight (β: 0.32 z-scores, 95% Confidence Interval (95% CI): 0.19, 0.45), BMI (β: 0.29 z-scores, 95% CI: 0.14, 0.43) and length (β: 0.27 z-scores, 95% CI: 0.09, 0.45). However, these associations were not observed at 18 months or 6 years of age. GWG was associated with twin length, weight and BMI at birth but not during childhood. Further research is needed to determine the long-term effects of GWG on twin health outcomes.

Maternal obesity increases the risk of nonalcoholic fatty liver disease (NAFLD) in offspring. The Roux-en-Y gastric bypass (RYBG) is effective for achieving weight loss and ameliorates NAFLD. To determine whether these benefits are maintained after pregnancy and/or lactation, and whether they modulate hepatic morphofunction in the next generation, we evaluated hepatic lipid metabolism in Western diet (WD)-obese female rats that underwent RYGB and in their F1 offspring at adulthood. Female Wistar rats consumed a WD from 21 to 130 days of age, before being submitted to RYGB (WD-RYGB-F0) or SHAM (WD-SHAM-F0) operations. After 5 weeks, these females were mated with control male breeders, and the male and female F1 offspring were identified as WD-RYGB-F1 and WD-SHAM-F1. WD-RYGB-F0 dams exhibited lower serum lipids levels, but severe hepatic steatosis and pathological features of advanced liver injury. The hepatic proteins involved in lipogenesis were reduced in WD-RYGB-F0, as were the genes related to β-oxidation and bile acids (BAs). Although the female and male WD-RYGB-F1 groups did not exhibit hepatic steatosis, the livers of female WD-RYGB-F1 demonstrated higher amounts of lipogenic genes and proteins, while male WD-RYGB-F1 presented a similar downregulation of lipogenic factors to that seen in WD-RYGB-F0 dams. In contrast, maternal and offspring groups of both sexes displayed reductions in the expressions of genes involved in BAs physiology and gluconeogenesis. As such, RYGB aggravates NAFLD after pregnancy and lactation and induces a gender-dependent differential expression of the hepatic lipogenesis pathway in offspring, indicating that female WD-RYGB-F1 may be an increased risk of developing NAFLD.

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.

Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.

The mental health of adult extremely low birth weight (ELBW) (<1000 g) survivors is poorer than their normal birth weight (NBW) peers. An understanding of the modifiable factors that affect this risk could provide targets for intervention. We set out to determine the extent to which a maternal history of mental health problems influenced mental health in ELBW and NBW offspring in adulthood. A total of 85 ELBW and 88 NBW individuals born between 1977 and 1982 in central west Ontario, Canada self-reported on internalizing (depression, anxiety) and externalizing (attention-deficit hyperactivity and antisocial) problems using the Diagnostic and Statistical Manual of Mental Disorders (DSM) scales of the Young Adult Self-Report at ages 22–26 and 30–35. They also reported on their mother’s maternal mental health using the Family History Screen. An interaction was found between birth weight status and maternal history of an anxiety disorder such that ELBW survivors showed a greater increase in internalizing scores than NBW participants at 22–26 (β = 10.27, p = 0.002) and at 30–35 years of age (β = 12.65, p = 0.002). An interaction was also observed between birth weight and maternal history of mood disorder, with higher externalizing scores in ELBW survivors than NBW adults at 22–26 (β = 7.21, p < 0.0001). ELBW adults appear to be more susceptible to the adverse mental health effects of exposure to maternal mood and anxiety disorders than those born at NBW. These links further highlight the importance of detecting and treating mental health problems in the parents of preterm survivors as a means of attempting to reduce the burden of psychopathology in this population.

Muscle and bone have been considered a functional unit that grows together early in life, deteriorates with aging, and can cause osteosarcopenia. Due to its importance in public health, detecting risk factors in early life is desirable. This study examined whether birth weight (BW) was associated with muscle–bone unit using dual energy X-ray absorptiometry (DXA) parameters in young women from the Nutritionists’ Health Study (NutriHS), a cohort study of undergraduates and Nutrition graduates. This cross-sectional analysis included 170 young healthy women who answered early life events-questionnaire, and had anthropometric, muscle tests and DXA-determined body composition and bone densitometry (iDXA-Lunar®). A blood sample was obtained for a subsample of 148 participants. Appendicular skeletal muscle mass index (ASMI) was calculated. BW was categorized in quartiles (BWq) and variables of interest compared by ANOVA. Associations of BWq with calf circumference (CC), handgrip, muscle performance tests, ASMI, bone mineral density and content (BMD and BMC), and plasma glucose, lipids, insulin, and 25-hydroxyvitamin D were performed using multiple linear regression and directed acyclic graph-recommended adjustments. Mean values of age, body mass index, and BW were 23.0 years (20.0–28.0), 22.9 ± 2.9 kg/m2, and 3199 ± 424 g, respectively. Comparing variables across BWq, significant differences in CC, handgrip, ASMI, and total body BMC were detected. Regression models adjusted for confounders showed associations of BWq with CC (β = 0.72, p = 0.005), handgrip (β = 1.53, p = 0.001), ASMI (β = 0.16, p = 0.022), total body BMC (β = 64.8, p = 0.005), total femur BMC (β = 0.70, p = 0.041), total body BMD (β = 0.02, p = 0.043), and lumbar spine BMD (β = 0.03, p = 0.028). We conclude that BW is associated with muscle–bone unit using DXA-parameters in Brazilian young healthy women from the NutriHS, suggesting a role for intrauterine environment for musculoskeletal health.

Nicotine is the main psychoactive substance present in cigarette smoke that is transferred to the baby by breast milk. In rats, maternal nicotine exposure during breastfeeding induces obesogenesis and hormone dysfunctions in adult male offspring. As glucocorticoid (GC), insulin, and vitamin D change both adipogenesis and lipogenesis processes, we assessed parameters related to metabolism and action of these hormones in visceral and subcutaneous adipose tissues (VAT and SAT) of adult male and female rats in a model of neonatal nicotine exposure. At postnatal (PN) day 2, dams were kept with six pups (three per sex) and divided into nicotine and control groups for implantation of osmotic minipumps that released 6 mg/kg nicotine or saline, respectively. At PN180, fat mass, hormone levels, and protein contents of biomarkers of the GC activation and receptor (11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor alpha), insulin signaling pathway [insulin receptor beta (IRβ), phosphorylated insulin receptor substrate 1, insulin receptor substrate 1 (IRS1), phosphorylated serine/threonine kinase (pAKT), serine/threonine kinase, glucose transporter type 4 (GLUT4)], and vitamin D activation and receptor (1α-hydroxylase and vitamin D receptor) were evaluated. While nicotine-exposed males showed increased fat mass, hypercorticosteronemia, hyperinsulinemia, and higher 25-hydroxyvitamin D, these alterations were not observed in nicotine-exposed females. Nicotine-exposed males only showed lower IRS1 in VAT, while the females had hyperglycemia, higher pAKT in VAT, while lower IRβ, IRS1, and GLUT4 in SAT. Parameters related to metabolism and action of GC and vitamin D were unaltered in both sexes. We evidence that exposure exclusively to nicotine during breastfeeding affects the hormone status and fat depots of the adult progeny in a sex-dependent manner.

Stunting (<−2 SD of length- or height-for-age on WHO growth curves) is the most used predictor of child neurodevelopmental (ND) risk. Occipitofrontal head circumference (OFC) may be an equally feasible, but more direct and robust predictor. We explored association of the two measurements with ND outcome, separately and combined, and examined if cutoffs are more efficacious than continuous measures in predicting ND risk. Infants and young children in rural Guatemala (n = 642; age range = 0.1–35.9 months) were enrolled in a prospective natural history study, and their ND was tested using the Mullen Scales of Early Learning (MSEL) longitudinally. Length- or height-for-age and OFC-for-age were calculated. We performed age-adjusted multivariable regression analyses to explore the association between 1) length or height and ND, 2) OFC and ND, and 3) both length or height and OFC combined, with ND; concurrently, predictively, and longitudinally, as continuous variables and using WHO z-score cutoffs. Continuous length- or height-for-age and OFC z-scores were more strongly associated with MSEL than the traditional -2 SD WHO cutoff. The combination of height-for-age z-score and OFC z-score was consistently, strongly associated with the MSEL Early Learning Composite concurrently (p-values 0.0004–0.11), predictively (p-value 0.001–0.07), with the exception of the 18–24 months age group which had very few records, and in the longitudinal model (p-value <0.0001–0.004). The combination of continuous length- or height-for-age and OFC shows additional utility in estimating ND risk in infants and young children. Measurement of OFC may improve precision of prediction of ND risk in infants and young children.