Fetal growth restriction (FGR) is a major complication of human pregnancy, frequently resulting from placental vascular diseases and prenatal malnutrition, and is associated with adverse neurocognitive outcomes throughout life. However, the mechanisms linking poor fetal growth and neurocognitive impairment are unclear. Here, we aimed to correlate changes in gene expression induced by FGR in rats and abnormal cerebral white matter maturation, brain microstructure, and cortical connectivity in vivo. We investigated a model of FGR induced by low-protein-diet malnutrition between embryonic day 0 and birth using an interdisciplinary approach combining advanced brain imaging, in vivo connectivity, microarray analysis of sorted oligodendroglial and microglial cells and histology. We show that myelination and brain function are both significantly altered in our model of FGR. These alterations, detected first in the white matter on magnetic resonance imaging significantly reduced cortical connectivity as assessed by ultrafast ultrasound imaging. Fetal growth retardation was found associated with white matter dysmaturation as shown by the immunohistochemical profiles and microarrays analyses. Strikingly, transcriptomic and gene network analyses reveal not only a myelination deficit in growth-restricted pups, but also the extensive deregulation of genes controlling neuroinflammation and the cell cycle in both oligodendrocytes and microglia. Our findings shed new light on the cellular and gene regulatory mechanisms mediating brain structural and functional defects in malnutrition-induced FGR, and suggest, for the first time, a neuroinflammatory basis for the poor neurocognitive outcome observed in growth-restricted human infants. GLIA 2016;64:2306-2320.

These findings illustrate the complex etiology of anemia and provide a useful framework for designing, targeting and evaluating appropriate strategies for the prevention and control of anemia. Contrary to expectations, iron deficiency accounted for a very small proportion of anemia in Northern Vietnam.

BackgroundLow birth weight and maternal anemia remain intractable problems in many developing countries. The adequacy of the current strategy of providing iron-folic acid (IFA) supplements only during pregnancy has been questioned given many women enter pregnancy with poor iron stores, the substantial micronutrient demand by maternal and fetal tissues, and programmatic issues related to timing and coverage of prenatal care. Weekly IFA supplementation for women of reproductive age (WRA) improves iron status and reduces the burden of anemia in the short term, but few studies have evaluated subsequent pregnancy and birth outcomes.The Preconcept trial aims to determine whether pre-pregnancy weekly IFA or multiple micronutrient (MM) supplementation will improve birth outcomes and maternal and infant iron status compared to the current practice of prenatal IFA supplementation only. This paper provides an overview of study design, methodology and sample characteristics from baseline survey data and key lessons learned.Methods/designWe have recruited 5011 WRA in a double-blind stratified randomized controlled trial in rural Vietnam and randomly assigned them to receive weekly supplements containing either: 1) 2800 μg folic acid 2) 60 mg iron and 2800 μg folic acid or 3) MM. Women who become pregnant receive daily IFA, and are being followed through pregnancy, delivery, and up to three months post-partum. Study outcomes include birth outcomes and maternal and infant iron status. Data are being collected on household characteristics, maternal diet and mental health, anthropometry, infant feeding practices, morbidity and compliance.DiscussionThe study is timely and responds to the WHO Global Expert Consultation which identified the need to evaluate the long term benefits of weekly IFA and MM supplementation in WRA. Findings will generate new information to help guide policy and programs designed to reduce the burden of anemia in women and children and improve maternal and child health outcomes in resource poor settings.Trial registrationNCT01665378

Weekly supplementation with MMs or IFA before conception did not affect birth outcomes compared with FA in rural Vietnamese women. The trial was registered at clinicaltrials.gov as NCT01665378.

No abstract

BackgroundMicronutrient deficiencies are a public health concern worldwide negatively affecting maternal and child health outcomes. The primary underlying causes of micronutrient deficiencies are insufficient intake and poor bioavailability of micronutrients. However, reliable data on micronutrient intakes are sparse. The objectives of this study were to identify the key local food sources providing the majority of micronutrients and assess the adequacy and determinants of micronutrient intakes.MethodsThe study used data from a survey of 4,983 rural women of reproductive age (WRA) participating in a preconception micronutrient supplementation trial in Vietnam. Micronutrient intakes were assessed using a validated 107-item semi-quantitative food-frequency questionnaire. Multivariate linear and logistic regression analyses were used to examine the association between socioeconomic status and micronutrient intakes.ResultsStarchy staples were the main source of iron and zinc (37% and 54%, respectively) with only a small proportion from meat (10% and 18%, respectively). The primary source of folate and vitamin A were vegetables; vitamin B12 came from meat and eggs. The proportion of the population with intakes below the estimated average requirement was 25% for iron, 16% for zinc, 54% for folate, 64% for vitamin B12 and 27% for vitamin A. Socioeconomic status was the main determinant of micronutrient intakes. WRA in the highest quintile consumed 26% more iron, 19% more zinc, 36% more folate, 82% more vitamin B12 and 47% more vitamin A compared to those in the lowest quintile. Women in the upper quintiles of SES were more likely to obtain nutrients from more nutritious and higher bioavailable foods than those in the lowest quintile.ConclusionsUnderprivileged women were at increased risk for insufficient micronutrient intakes due to poor diet quality. Targeted efforts to promote the consumption of local nutrient rich foods along with educational programs and social development are needed.

This study provides new evidence that iNO could be effective in preventing brain damage and/or enhancing repair of the developing brain.

ObjectivePreconception micronutrient interventions may be a promising approach to reduce anemia and iron deficiency during pregnancy, but currently we have limited data to inform policies. We evaluated whether providing additional pre-pregnancy weekly iron-folic acid (IFA) or multiple micronutrient (MM) supplements compared to only folic acid (FA) improves iron status and anemia during pregnancy and early postpartum.MethodsWe conducted a double blind randomized controlled trial in which 5011 Vietnamese women were provided with weekly supplements containing either only 2800 μg FA (control group), IFA (60 mg Fe and 2800 μg FA) or MM (15 micronutrients with similar amounts of IFA). All women who became pregnant (n = 1813) in each of the 3 groups received daily IFA (60 mg Fe and 400 μg FA) through delivery. Hematological indicators were assessed at baseline (pre-pregnancy), during pregnancy, 3 months post-partum, and in cord blood. Adjusted generalized linear models were applied to examine the impact of preconception supplementation on anemia and iron stores, using both intention to treat and per protocol analyses (women consumed supplements ≥ 26 weeks before conception).ResultsAt baseline, 20% of women were anemic, but only 14% had low iron stores (ferritin <30 μg/L) and 3% had iron deficiency (ferritin <12 μg/L). The groups were balanced for baseline characteristics. Anemia prevalence increased during pregnancy and post-partum but was similar among intervention groups. In intention to treat analyses, prenatal ferritin was significantly higher among women receiving MM (geometric mean (μg/L) [95% CI]: 93.6 [89.3–98.2]) and IFA (91.9 [87.6–96.3]) compared to control (85.3 [81.5–89.2]). In per protocol analyses, women receiving MM or IFA had higher ferritin 3 months postpartum (MM 118.2 [109.3–127.8]), IFA 117.8 [108.7–127.7] vs control 101.5 [94.0–109.7]) and gave birth to infants with greater iron stores (MM 184.3 [176.1–192.9]), IFA 189.9 [181.6–198.3] vs control 175.1 [167.9–182.6]).ConclusionPreconception supplementation with MM or IFA resulted in modest increases in maternal and infant iron stores but did not impact anemia. Further research is needed to characterize the etiology of anemia in this population and identify effective interventions for reducing prenatal anemia.Trial RegistrationClinicalTrials.Gov NCT01665378