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.

Cytokine production by newborns: influence of sex and season of birth.

BACKGROUND: Immune signatures at birth could be associated with clinical outcomes and will improve our understanding of immunity prenatal programming. METHODS: Data come from 235 newborns from the cohort study NELA. Production of cytokines was determined using Luminex technology. Associations between cytokine concentrations with sex and season of birth were examined by multivariate regression models. RESULTS: Umbilical cord blood cells produced high levels of inflammatory cytokines, moderate levels of Th1/Th2/Tr-related cytokines, and low levels of Th17 cytokines. Compared to females, male newborn cells secreted higher levels of Th2 (peptidoglycan-stimulated IL-13, odds ratio [OR] = 2.26; 95% CI 1.18, 4.31, p value = 0.013) and Th17 (polyinosinic:polycytidylic acid-stimulated IL-23, OR = 1.82, 95% CI 1.01, 3.27, p value = 0.046) and lower levels of Th1 (olive-stimulated IL-2, OR = 0.56, 95% CI 0.31, 0.99, p value = 0.047) cytokines. Also, children born during warm seasons showed decreased innate cytokine response to peptidoglycan (IL-6, OR = 0.28, 95% CI 0.15, 0.52, p value < 0.001) compared to those born in cold seasons; meanwhile, adaptive immunity cytokines were more frequently secreted by children born during warm seasons in response to allergen extracts (IL-10, OR = 2.11, 95% CI 1.12, 3.96, p value = 0.020; IL-17F, OR = 3.31, 95% CI 1.83, 5.99, p value < 0.001). CONCLUSION: Newborns showed specific cytokines signatures influenced by sex and season of birth. IMPACT: There is a limited number of population-based studies on the immune status at birth and the influence of prenatal and perinatal factors on it. Characterization of cytokine signatures at birth related to the prenatal environment could improve our understanding of immunity prenatal programming. Newborns exhibit specific unstimulated and stimulated cytokine signatures influenced by sex and season of birth. Unstimulated and stimulated cytokine signatures in newborns may be associated with the development of related clinical outcomes later in 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.

Cytokine profiles in cord blood in relation to prenatal traffic-related air pollution: The NELA cohort.

BACKGROUND: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. METHODS: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-ß, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. RESULTS: NO2 during the whole pregnancy increased the odds of detection of IL-1ß (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. CONCLUSIONS: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.

Air pollution from traffic during pregnancy impairs newborn's cord blood immune cells: The NELA cohort.

BACKGROUND: Hazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. METHODS: In-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Long-term (whole pregnancy and trimesters) and short-term (15-days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. RESULTS: Mean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 µg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 µg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 µg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. CONCLUSIONS: Prenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.

Neurodevelopmental effects of prenatal vitamin D in humans: systematic review and meta-analysis.

Diverse studies have investigated the impact of prenatal exposure to vitamin D levels on brain development; however, evidence in humans has never been systematically reviewed. This article summarized evidence of the association between 25-hydroxyvitamin D [25(OH)D] levels in maternal blood in pregnancy or newborn blood at birth and neurodevelopmental outcomes, including cognition, psychomotor performance, language development, behavioral difficulties, attention deficit and hyperactivity disorder (ADHD), and autistic traits. PubMed, Web of Science and SCOPUS databases were systematically searched for epidemiologic studies published through May 2018 using keywords. Random-effects meta-analyses were conducted. Of 260 identified articles, 25 were included in the present review. Comparing the highest vs. the lowest category of prenatal 25(OH)D levels, the pooled beta coefficients were 0.95 (95% CI -0.03, 1.93; p = 0.05) for cognition, and 0.88 (95% CI -0.18, 1.93; p = 0.10) for psychomotor development. The pooled relative risk for ADHD was 0.72 (95% CI, 0.59, 0.89; p = 0.002), and the pooled odds ratio for autism-related traits was 0.42 (95% CI, 0.25, 0.71; p = 0.001). There was little evidence for protective effects of high prenatal 25(OH)D for language development and behavior difficulties. This meta-analysis provides supporting evidence that increased prenatal exposure to 25(OH)D levels is associated with improved cognitive development and reduced risk of ADHD and autism-related traits later in life. Associations represent a potentially high public health burden given the current prevalence of vitamin D deficiency and insufficiency among childbearing aging and pregnant women.