Serum Vitamins A and E at Mid-Pregnancy and Their Relationships with Both Maternal and Cord Blood Antioxidant Status and Perinatal Conditions: The NELA Cohort.

INTRODUCTION: Most of the pregnant women do not achieve the recommended dietary intake of vitamins A and E. These vitamins may counteract oxidative stress involved in some adverse perinatal outcomes. We aimed to assess the associations between maternal vitamin A and E at mid-pregnancy with both maternal and fetal outcomes and to identify possible early biomarkers during pregnancy to predict and prevent oxidative stress in the offspring. METHODS: Data on dietary and serum levels of vitamins A and E were collected from 544 pregnant women from the Nutrition in Early Life and Asthma (NELA) study, a prospective mother-child cohort set up in Spain. RESULTS: There were large discrepancies between low dietary vitamin E intake (78% of the mothers) and low serum vitamin E levels (3%) at 24 weeks of gestation. Maternal serum vitamins A and E at mid-pregnancy were associated with higher antioxidant status not only in the mother at this time point (lower hydroperoxides and higher total antioxidant activity [TAA]) but also with the newborn at birth (higher TAA). Gestational diabetes mellitus (GDM) was negatively associated with maternal serum vitamin A (OR: 0.95 CI: 0.91-0.99, p = 0.009) at mid-pregnancy. Nevertheless, we could not detect any association between GDM and oxidative stress parameters. CONCLUSIONS: In conclusion, maternal vitamin A and E serum levels may be used as an early potential biomarker of antioxidant status of the neonate at birth. Control of these vitamins during pregnancy could help avoid morbid conditions in the newborn caused by oxidative stress in GDM pregnancies.

The Nutrition in Early Life and Asthma (NELA) birth cohort study: Rationale, design, and methods.

BACKGROUND: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests. OBJECTIVES: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility. POPULATION: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19-22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the "Virgen de la Arrixaca" University Clinical Hospital over a 36-month period, from March 2015 to April 2018. DESIGN: Prospective, population-based, maternal-child, birth cohort study. METHODS: Questionnaires on exposures and outcome variables were administered to mothers at 20-24 gestation week; 32-36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points. PRELIMINARY RESULTS: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months' visit and 532 children (72%) attending the 18 months' visit. CONCLUSION: The NELA cohort will add original and unique knowledge to the developmental origins of asthma.

Iron bioavailability of four iron sources used to fortify infant cereals, using anemic weaning pigs as a model.

PURPOSE: Iron (Fe) deficiency anemia in young children is a global health concern which can be reduced by Fe fortification of foods. Cereal is often one of the first foods given to infants, providing adequate quantities of Fe during weaning. In this work, we have compared iron bioavailability and iron status of four iron sources used to fortify infant cereals, employing piglets as an animal model. METHOD: The study was conducted on 36 piglets, 30 of them with induced anemia. From day 28 of life, the weaned piglets were fed with four experimental diets (n = 6) each fortified with 120 mg Fe/kg by ferrous sulfate heptahydrate (FSH), electrolytic iron (EI), ferrous fumarate (FF), or micronized dispersible ferric pyrophosphate (MDFP) for another 21 days. In addition, one group of six anemic piglets fed with the basal diet with no iron added (Control-) and a Control+ group of non-anemic piglets (n = 6) were also studied. Blood indicators of iron status were measured after depletion and during the repletion period. The Fe content in organs, hemoglobin regeneration efficiency, and relative bioavailability (RBV) was also determined. RESULTS: The Fe salts adequately treated anemia in the piglets, allowing the animals to recover from the anemic state, although EI was less efficient with regard to replenishing Fe stores giving lower concentrations of plasma ferritin and iron in the spleen, liver, lung, and kidney. In addition, the RBV of EI was 88.27% with respect to the reference iron salt (FSH). CONCLUSIONS: Ferrous fumarate and MDFP were equally as bioavailable as the reference salt, and were used significantly better than EI in piglets. These results contribute to extend the evidence-based results for recommending the most suitable fortificant for infant cereals.

Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study.

BACKGROUND & AIMS: Prenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. METHODS: Data come from 325 mother-child pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. RESULTS: A reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception (-0.50; 95% CI: -0.91, -0.09; P = 0.016), and from preconception up to 12 weeks of gestation (-0.48; 95% CI: -0.88, -0.08; P = 0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth (-0.77; 95% CI: -1.52, -0.02; P = 0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth. CONCLUSIONS: Maternal non-compliance with the use of FA supplement recommendations from preconception up to 12 weeks of gestation reduces offspring global DNA methylation levels at birth.

Infant gut microbiota colonization: influence of prenatal and postnatal factors, focusing on diet.

Maternal microbiota forms the first infant gut microbial inoculum, and perinatal factors (diet and use of antibiotics during pregnancy) and/or neonatal factors, like intra partum antibiotics, gestational age and mode of delivery, may influence microbial colonization. After birth, when the principal colonization occurs, the microbial diversity increases and converges toward a stable adult-like microbiota by the end of the first 3-5 years of life. However, during the early life, gut microbiota can be disrupted by other postnatal factors like mode of infant feeding, antibiotic usage, and various environmental factors generating a state of dysbiosis. Gut dysbiosis have been reported to increase the risk of necrotizing enterocolitis and some chronic diseases later in life, such as obesity, diabetes, cancer, allergies, and asthma. Therefore, understanding the impact of a correct maternal-to-infant microbial transfer and a good infant early colonization and maturation throughout life would reduce the risk of disease in early and late life. This paper reviews the published evidence on early-life gut microbiota development, as well as the different factors influencing its evolution before, at, and after birth, focusing on diet and nutrition during pregnancy and in the first months of life.

Dietary Patterns in Pregnancy and Biomarkers of Oxidative Stress in Mothers and Offspring: The NELA Birth Cohort.

Background: Although adherence to the Mediterranean and antioxidant-rich diets during pregnancy is suggested to improve maternal-fetal health by reducing oxidative stress, yet there is no study available. Objective: We examined whether maternal dietary patterns in pregnancy impact the biomarkers of oxidative stress in mothers and their offspring. Methods: Study population included 642 mothers and 335 newborns of the "Nutrition in Early Life and Asthma" (NELA) birth cohort. Maternal diet during pregnancy was assessed by a validated food frequency questionnaire and a priori-defined dietary indices (relative Mediterranean Diet [rMED], alternative Mediterranean Diet [aMED], Dietary Approach to Stop Hypertension [DASH], Alternate Healthy Index [AHEI], and AHEI-2010) were calculated. Biomarkers measured were: hydroperoxides, carbonyl groups, and 8-hydroxydeoxyguanosine (8OHdG) determined in maternal blood and newborn cord blood, and urinary maternal and offspring 15-F2t-isoprostane. Multivariate linear regression models were performed. Results: Maternal rMED score was inversely associated with the maternal levels of 8OHdG at mid-pregnancy (beta per 1-point increase = -1.61; 95% CI -2.82, -0.39) and the newborn levels of hydroperoxides (beta per 1-point increase = -4.54; 95% CI -9.32, 0.25). High vs. low maternal rMED score was marginally associated with the decreased levels of 8OHdG in newborns (beta = -9.17; 95% CI -19.9, 1.63; p for trend 0.079). Maternal DASH score tended to be inversely associated with maternal urinary 15-F2t-isoprostane (beta per 1-point increase = -0.69; 95% CI, -1.44, 0.06). High vs. low maternal AHEI score was associated with reduced offspring urinary levels of 15-F2t-isoprostane (beta = -20.2; 95% CI -38.0, -2.46; p for trend 0.026). Conclusion: These results suggest that maternal adherence to healthy dietary patterns during pregnancy may reduce DNA damage and lipid oxidation in mothers and offspring.

Adherence to the Mediterranean Diet and Determinants Among Pregnant Women: The NELA Cohort.

The Mediterranean diet represents one of the most studied dietary patterns; however, there is no single tool for measuring the grade of adherence and no single set of criteria for adapting these indices to pregnant women. We characterized the adherence to the Mediterranean diet (MDA) of pregnant women participating in the NELA (Nutrition in Early Life and Asthma) cohort and identified the sociodemographic determinants and lifestyle habits associated with a higher risk of a low MDA. Maternal diet during gestation was assessed by a validated Food Frequency Questionnaire (FFQ) (n = 665). We estimated the Relative Mediterranean Diet score (rMED), Alternative Mediterranean Diet score (aMED), and the Alternate Healthy Eating Index-2010 (AHEI-2010). Multivariate regression models were performed to identify the sociodemographic and lifestyle factors associated with each index. Mothers with a lower age and more previous deliveries had a greater probability of low MDA (p < 0.05). For the aMED index only, mothers with university education and/or who practiced sport activities for two or more hours per week had a lower probability of a low MDA (p < 0.01). The three indices classified the NELA cohort as having a medium level of adherence. These results may be improved by designing intervention strategies and dietary recommendations for both maternal and offspring health.

Self-Reported DHA Supplementation during Pregnancy and Its Association with Obesity or Gestational Diabetes in Relation to DHA Concentration in Cord and Maternal Plasma: Results from NELA, a Prospective Mother-Offspring Cohort.

Maternal supplementation of docosahexaenoic acid (DHA) during pregnancy has been recommended due to its role in infant development, but its effect on materno-fetal DHA status is not well established. We evaluated the associations between DHA supplementation in pregnant women with obesity or gestational diabetes mellitus (GDM) and maternal and neonatal DHA status. Serum fatty acids (FA) were analyzed in 641 pregnant women (24 weeks of gestation) and in 345 venous and 166 arterial cord blood samples of participants of the NELA cohort. Obese women (n = 47) presented lower DHA in serum than those lean (n = 397) or overweight (n = 116) before pregnancy. Linoleic acid in arterial cord was elevated in obese women, which indicates lower fetal retention. Maternal DHA supplementation (200 mg/d) during pregnancy was associated with enhanced maternal and fetal DHA levels regardless of pre-pregnancy body mass index (BMI), although higher arterial DHA in overweight women indicated an attenuated response. Maternal DHA supplementation was not associated with cord venous DHA in neonates of mothers with GDM. The cord arteriovenous difference was similar for DHA between GDM and controls. In conclusion, maternal DHA supplementation during pregnancy enhanced fetal DHA status regardless of the pre-pregnancy BMI while GDM may reduce the effect of DHA supplementation in newborns.