Early Nutritional Exposures Research Articles

Nutrition and the gut-brain axis in neonatal brain injury and development

Early nutritional exposures, including during embryogenesis and the immediate postnatal period, affect offspring outcomes in both the short- and long-term. Alterations of these modifiable exposures shape the developing gut microbiome, intestinal development, and even neurodevelopmental outcomes. A gut-brain axis exists, and it is intricately connected to early life feeding and nutritional exposures. Here, we seek to discuss the (1) origins of the gut-brain access and relationship with neurodevelopment, (2) components of human milk (HM) beyond nutrition and their role in the developing newborn, and (3) clinical application of nutritional practices, including fluid management and feeding on the development of the gut-brain axis, and long-term neurodevelopmental outcomes. We conclude with a discussion on future directions and unanswered questions that are critical to provide further understanding and insight into how clinicians and healthcare providers can optimize early nutritional practices to ensure children not only survive, but thrive, free of neurodevelopmental impairment.

Prenatal and childhood exposures are associated with thymulin concentrations in young adolescent children in rural Nepal.

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.

Stooling pattern and early nutritional exposures associated with necrotizing enterocolitis in premature infants.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency affecting premature infants. A better understanding of the clinical signs and symptoms associated with the disease may result in an improved ability to more effectively intervene in patient care. One of the clinical signs that have not been fully explored is the stooling pattern of preterm infants. This retrospective case-control study included 258 premature infants born prior to 29 weeks of gestation: 129 infants with NEC and 129 gestational age-matched controls. Data were collected from the medical record for the first 28 postnatal days. The relationships between the stooling pattern of premature infants and NEC were assessed via nonparametric techniques and linear mixed models. We identified few differences in the stooling pattern among infants with NEC and their unaffected counterparts. During the first week following birth, infants with NEC passed stool more frequently than controls. However, we found that these infants were taking nothing by mouth for fewer days in the first week following birth compared with controls. We also found that infants who developed NEC were fed smaller proportions of breast milk than healthy controls. Aberrant gut motility has been associated with prematurity and inflammatory bowel disease. However, our analyses did not identify any major differences in the stooling pattern among NEC case patients and controls. While further analyses may be needed, clinical suspicion for NEC should not be overwhelmingly influenced by the stooling pattern observed during the early neonatal period.

Maternal and Early Postnatal Nutrition and Mental Health of Offspring by Age 5 Years: A Prospective Cohort Study

Diet quality is related to the risk for depression and anxiety in adults and adolescents; however, the possible impact of maternal and early postnatal nutritional exposures on children's subsequent mental health is unexplored. The large prospective Norwegian Mother and Child Cohort Study recruited pregnant women between 1999 and 2008. Data were collected from mothers during pregnancy and when children were 6 months and 1.5, 3, and 5 years of age. Latent growth curve models were used to model linear development in children's internalizing and externalizing problems from 1.5 to 5 years of age as a function of diet quality during pregnancy and at 1.5 and 3 years. Diet quality was evaluated by dietary pattern extraction and characterized as "healthy" or "unhealthy." The sample comprised 23,020 eligible women and their children. Adjustments were made for variables including sex of the child, maternal depression, maternal and paternal age, maternal educational attainment, household income, maternal smoking before and during pregnancy, mothers' parental locus of control, and marital status. Higher intakes of unhealthy foods during pregnancy predicted externalizing problems among children, independently of other potential confounding factors and childhood diet. Children with a high level of unhealthy diet postnatally had higher levels of both internalizing and externalizing problems. Moreover, children with a low level of postnatal healthy dietalso had higher levels of both internalizing and externalizing problems. Among this large cohort of mothers and children, early nutritional exposures were independently related to the risk for behavioral and emotional problems in children.

Maternal micronutrients can modify colonic mucosal microbiota maturation in murine offspring

Epidemiologic data suggest that early nutritional exposures may inflict persistent changes in the developing mammalian “super-organism” (i.e., the host and its residing microbiota). Such persistent modifications could predispose young adults to inflammatory bowel diseases (IBD). We recently observed that the dietary supplementation of four micronutrients to dams augmented colitis susceptibility in murine offspring in association with mucosal microbiota composition changes. In this study the effects of the four micronutrients on the microbiota of dams and female mice was examined. Additionally, age dependent microbiota composition shifts during pediatric development were delineated from the previous offspring data sets. Maternal and adult female microbiota did not separate secondary to the nutritional intervention. Significant microbiota composition changes occurred from postnatal day 30 (P30) to P90 at the level of 1 phylum and 15 genera. Most of these changes were absent or opposite in the maternally supplemented offspring. Nutritionally induced alterations in mucosal microbiota maturation may be contributors to colitis susceptibility in mammals.

The Mediterranean diet and fetal size parameters: the Generation R Study

Developmental adaptations due to early nutritional exposures may have permanent health consequences. Studies of diet and fetal size have mainly focused on individual nutrients despite evidence that the pattern of food consumption may be of significance. Hence, we evaluated the associations of dietary habits in early pregnancy (gestational age < 18 weeks) with fetal size, uteroplacental vascular resistance, placental weight and birth weight in a prospective observational study of 3207 Caucasian pregnant mothers in Rotterdam, the Netherlands. Participants completed a semiquantitative FFQ during early pregnancy. Logistic regression analysis was used to predict the occurrence of intra-uterine growth retardation at birth as a function of food intake. The derived solution was considered as the dietary pattern. As it was characterised by higher intakes of fruit, vegetables, vegetable oil, fish, pasta and rice, and lower intakes of meat, potatoes and fatty sauces, it was labelled the 'Mediterranean' diet. The degree of adherence to the diet was positively associated with plasma folate and serum vitamin B12 concentrations and showed an inverse relationship with homocysteine and high-sensitivity C-reactive protein plasma concentrations (P <0·05). Important fetal size and placental parameters were associated with the degree of adherence to the diet, revealing a 72 g lower birth weight (95% CI -110·8, -33·3) and a 15 g lower placental weight (95% CI -29·8, -0·2) for women with low adherence to the diet. To conclude, low adherence to a Mediterranean diet in early pregnancy seems associated with decreased intra-uterine size with a lower placental and a lower birth weight.

Data collected on maternal dietary exposures in the Danish National Birth Cohort

Recent research suggests that the diet consumed in, or shortly before, pregnancy can potentially lead to maldevelopment and diseases in the offspring, which may become apparent at any time from the embryonic stage until old age. For example, maternal diet may affect the chance of twinning (and associated complications), malformation risk, brain development, and the offspring's fecundity and risk of contracting cardiovascular diseases and cancer in adult life. Prospectively designed longitudinal studies with sufficient size and data quality are much needed to substantiate or refute these hypotheses. At present, the Danish National Birth Cohort is likely to be the largest epidemiological database containing extensive information on maternal dietary exposures. By October 2002, 100 000 women had been recruited in early pregnancy, for long-term follow-up of themselves and their offspring. The present paper details the information available in the database on early nutritional exposures with emphasis on maternal dietary intake. We also present distributions of selected nutritional exposures.