Gregory A. Reinhart

Rationale design methodology and sample characteristics for the Vietnam pre-conceptual micronutrient supplementation trial (PRECONCEPT): a randomized controlled study.

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

Neither Preconceptional Weekly Multiple Micronutrient nor Iron–Folic Acid Supplements Affect Birth Size and Gestational Age Compared with a Folic Acid Supplement Alone in Rural Vietnamese Women: A Randomized Controlled Trial

BACKGROUNDnMaternal nutritional status before and during early pregnancy plays a critical role in fetal growth and development. The benefits of periconception folic acid (FA) supplementation in the prevention of neural tube defects is well recognized, but the evidence for preconception micronutrient interventions for improving pregnancy outcomes is limited.nnnOBJECTIVEnThis study aimed to evaluate whether preconception supplementation with weekly iron and folic acid (IFA) or multiple micronutrients (MMs) improves birth outcomes compared with FA alone.nnnMETHODSnWe recruited 5011 women of reproductive age in a double-blind, randomized controlled trial in Vietnam and provided weekly supplements containing either 2800 μg FA, 60 mg Fe and 2800 μg FA (IFA), or the same amount of FA and iron plus other MMs until they conceived (n = 1813). All pregnant women received daily IFA through delivery, and were followed up for birth outcomes, including birth weight, gestational age, preterm delivery and small for gestational age (SGA). Group comparisons were done with the use of ANOVA or chi-square tests for both intention-to-treat (n = 1599) and per-protocol analyses (women consumed supplements ≥26 wk before conception; n = 824). Effect modification by baseline underweight or anemia status was tested with the use of generalized linear models.nnnRESULTSnThe mean age of the women was 26 y, 30% were underweight, and <10% were nulliparous. The groups were similar for most baseline characteristics. The mean ± SD duration of the preconception intervention was 33 ± 25 wk and compliance was high (>90%). Infants born to the 3 groups of women did not differ (P ≥ 0.05) on mean ± SD birth weight (3076.8 ± 444.5 g) or gestational age (39.2 ± 2.0 wk), or prevalence of SGA (12%), low birth weight (5%) and preterm delivery (10%). There were no significant differences in women who consumed supplements ≥26 wk before conception or by baseline underweight or anemia.nnnCONCLUSIONnWeekly 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.

Double-Fortified Salt Is Efficacious in Improving Indicators of Iron Deficiency in Female Indian Tea Pickers

Poor iron status affects 50% of Indian women and compromises work productivity, cognitive performance, and reproduction. Among the many strategies to reduce iron deficiency is the commercial fortification of iodized table salt with iron to produce a double-fortified salt (DFS). The objective of this study was to test the efficacy of DFS in reducing iron deficiency in rural women of reproductive age from northern West Bengal, India. The participants were 212 women between 18 and 55 y of age who worked as full-time tea pickers on a large tea estate. Participants in the randomized, controlled, double-blind study were assigned to use either DFS or a control iodized salt for 7.5 to 9 mo. The DFS was fortified with 3.3-mg ferrous fumarate (1.1-mg elemental iron) per kg of iodized salt, whereas the control salt contained only iodine (47 mg/kg potassium iodate), and both salt varieties were distributed gratis to the families of participants at 0.5 kg/mo for each 2 household members. At baseline, 53% of participants were anemic (hemoglobin <120 g/L), 25% were iron deficient (serum ferritin <12 μg/L), and 23% were iron-deficient anemic. Also, 22% had a transferrin receptor concentration >8.6 mg/L and 22% had negative (<0.0 mg/kg) body iron stores. After 9 mo the participants receiving DFS showed significant improvements compared with controls in hemoglobin (+2.4 g/L), ferritin (+0.13 log10 μg/L), soluble transferrin receptor (−0.59 mg/L), and body iron (+1.43 mg/kg), with change in status analyzed by general linear models controlling for baseline values. This study demonstrated that DFS is an efficacious approach to improving iron status and should be further evaluated for effectiveness in the general population. This trial was registered at clinicaltrials.gov as NCT01032005.

Impact of Preconception Micronutrient Supplementation on Anemia and Iron Status during Pregnancy and Postpartum: A Randomized Controlled Trial in Rural Vietnam

Objective Preconception 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. Methods We 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). Results At 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]). Conclusion Preconception 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 Registration ClinicalTrials.Gov NCT01665378

Consumption of a Double-Fortified Salt Affects Perceptual, Attentional, and Mnemonic Functioning in Women in a Randomized Controlled Trial in India

Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory.Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function.Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18-55 y.Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function.Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.

Impact of preconceptional micronutrient supplementation on maternal mental health during pregnancy and postpartum: results from a randomized controlled trial in Vietnam

BackgroundMicronutrient malnutrition has been associated with maternal depressive symptoms (MDS), but little is known about the effects of preconceptional micronutrient supplementation. This paper examined the effects of preconceptional micronutrient supplementation on MDS during pregnancy and postpartum.MethodsWe used data from a double-blind controlled trial (PRECONCEPT) in which 5011 Vietnamese women were randomized to receive weekly supplements containing either a) multiple micronutrients (MM) b) iron and folic acid (IFA) or c) folic acid (FA) until conception (nxa0=xa01813). Maternal mental health was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline (preconception), and the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and 3xa0months postpartum. Elevated MDS was defined as EPDS scorexa0≥xa04. All group comparisons were done using ANOVA or chi-square tests of proportions intention to treat and per protocol analyses (women consumed supplements ≥26xa0weeks before conception). We also conducted stratified analyses by preconception CES-D scores, underweight, or anemia status using generalized linear models.ResultsBaseline CES-D scores were similar across treatment groups. The proportion of women experiencing elevated MDS was 11.3, 8.1 and 4.9% at first, second and third trimesters of pregnancy, respectively, and 3.6% at 3 mo postpartum. Mean EPDS scores at first (1.5xa0±xa02.7), second (1.1xa0±xa02.4), and third trimester of pregnancy (0.7xa0±xa02.0) and early postpartum (0.6xa0±xa01.8) were low and did not differ by treatment group. However, among women in the highest tertile of CES-D scores at preconception, mean EPDS scores in the first and second trimesters of pregnancy were lower in the MM and IFA groups compared to FA only (Pxa0<xa00.05).ConclusionsWeekly preconceptional micronutrient supplements containing iron did not improve depression measures relative to folic acid alone among all women, but may have benefitted women who were at risk for depression.Trial registrationThe trial was registered retrospectively at ClinicalTrials.Gov as NCT01665378 on August 13, 2012.

Double Fortified Salt Intervention Improved Iron Intake But Not Energy and Other Nutrient Intakes in Female Tea Plantation Workers From West Bengal, India:

Background: Iron deficiency is a global public health concern and has implications on the health status of women in reproductive age. Objective: We hypothesized that improving iron intake with double fortified salt would improve food intake, resulting in higher energy, nutrient intakes, and weight indicators of female tea plantation workers. Methods: In this randomized double-masked study, the participants (n = 245) were assigned to receive salt double fortified with iron and iodine (DFS; treatment) or salt fortified with iodine (control) and followed for 7.5 to 9 months. Dietary intakes were measured at three time points, baseline, midpoint, and end line using (1) food frequency questionnaire, (2) 24-hour recall, and (3) weighed lunch intake. Anthropometric measures of height (cm), weight (kg), and mid-upper arm circumference (cm) were also recorded at three time points. Mixed-model repeated-measures approach was used to detect group differences across time. Results: Double fortified salt improved dietary iron intake in the treatment group compared to the control group (P < .001). No other dietary or anthropometric differences could be attributed to treatment. Significant effect of time was observed in the intake frequency of major food groups and calcium, vitamin A and C (P <.001 for all), suggesting an equal effect of seasonality in both the groups. Conclusion: Addition of DFS in the diet improved dietary iron intake but did not affect the intake of energy, other nutrients, or nutritional status indicators. The improvement observed in the dietary iron intake demonstrates that fortification is an effective strategy to address iron deficiency in at-risk populations.