Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.
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SUBMITTER: Petry CJ
PROVIDER: S-EPMC8308651 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVES/BACKGROUND: Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births). RESULTS: We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ? 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ? 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)]. CONCLUSION: This review provides evidence of a significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.
| S-EPMC3231892 | biostudies-other
Project description:BackgroundAntenatal multiple micronutrient supplementation (MMS) with iron, folic acid, and other micronutrients might improve birth outcomes, but it is not currently universally recommended by WHO.MethodsIn this observational cohort study, we surveyed pregnancies for adverse birth outcomes at eight hospitals from July, 2014, to July, 2018, and 18 hospitals from August, 2018, to December, 2020, in Botswana to assess four routine supplementation strategies in women presenting before 24 weeks' gestation: folic acid only, iron only, iron and folic acid supplementation (IFAS), and MMS. Women with singleton pregnancies; a known HIV status, age, and delivery site; haemoglobin measured within 7 days of presenting to antenatal care; and weight measured within 31 days of presenting to care were included in our analysis. Data were abstracted from the maternity obstetric record (a record of antenatal care) at the time of birth from all women giving birth at selected hospitals throughout the country. We estimated risk differences overall and in key subgroups, adjusting for demographic and clinical factors.FindingsBetween July 6, 2014, and Dec 8, 2020, 96 341 eligible women (21 659 [22·5%] of whom had HIV) were included in the study. 36 334 (37·7%) women initiated iron only supplementation, 1133 (11·8%) initiated folic acid only supplementation, 23 101 (24·0%) initiated IFAS, and 31 588 (32·8%) women initiated MMS. Women who initiated iron only and folic acid only supplementation had higher risks of stillbirth, preterm birth, very preterm birth, low and very low birthweight, and neonatal death compared with women who received IFAS (adjusted risk differences for iron only supplementation vs IFAS ranged from 0·22% [95% CI 0·04 to 0·40] for neonatal death to 2·39% [1·78 to 3·00] for preterm birth; and adjusted risk differences for folic acid only supplementation vs IFAS ranged from 0·77% [-0·80 to 2·34] for neonatal death to 5·75% [1·38 to 10·13] for preterm birth), with greater difference in women with HIV and those aged 35 years and older. Compared with IFAS, women who initiated MMS had lower risks of preterm and very preterm births, and low and very low birthweight (adjusted risk differences ranged from -0·50% [-0·77 to 0·23] for very preterm birth to -1·06% [-1·69 to -0·42] for preterm birth).InterpretationNationwide data from Botswana support improved birth outcomes with MMS compared with IFAS.FundingNational Institutes of Health, National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.
| S-EPMC9309424 | biostudies-literature
Project description:Multiple micronutrient supplementation (MMS) in pregnancy has previously been associated with positive effects on fetal growth, but its value in high-income countries remains controversial. In this study, we investigated effects of pregnancy MMS on offspring size at birth and adiposity, along with risks of various maternal outcomes of pregnancy, using the prospective Cambridge Baby Growth Study. Maternal MMS was reported in 528 out of 970 women who completed pregnancy questionnaires. Gestational diabetes (GDM) was assessed using results from 75 g oral glucose tolerance tests at week 28 of pregnancy. Offspring size at birth was assessed using standard anthropometric measurements and adiposity using skinfold calipers. MMS was associated with increased risk of developing GDM (risk ratio = 1.86 (1.13-3.08), p = 0.02), as well as increased offspring size at birth in terms of weight (p = 0.03), head circumference (p = 0.04), and flank, and subscapular and triceps skinfold thicknesses (p = 0.04, 0.03, and 0.003, respectively). There was no association with quadriceps skinfold thickness (p = 0.2), suggesting that the increased adiposity was partially regionalized. In women who underwent oral glucose tolerance testing, nearly all of these associations were attenuated by adjusting for GDM. These results suggest that the increased offspring size at birth, including (regionalized) adiposity associated with pregnancy, and MMS may be partially related to the development of GDM.
| S-EPMC7697774 | biostudies-literature
Project description:Increasing evidence suggests an inverse association between cadmium (Cd) and size at birth, potentially greatest among female neonates. We evaluated whether greater maternal body burden of Cd is associated with reduced neonatal anthropometry (birthweight, birth length, head circumference, and ponderal index) and assessed whether these associations differ by infant sex. The analytic sample for the present study (n=396) was derived from a subcohort of 750 women randomly drawn from among all participants (N=4344) in the Omega Study, a prospective pregnancy cohort. Creatinine-corrected Cd in maternal clean-catch spot urine samples (U-Cd) was quantified by inductively coupled plasma mass spectrometry. Continuous log2-transformed Cd (log2-Cd) and U-Cd tertiles (low<0.29μg/g creatinine, middle 0.29-0.42μg/g creatinine, high≥0.43μg/g creatinine) were used in multivariable linear regression models. Females had reduced birth length with greater U-Cd tertile, whereas males birth length marginally increased [β(95% CI) females: low=reference, middle=-0.59cm (-1.37, 0.19), high=-0.83cm (-1.69, 0.02), p-trend=0.08; males: low=reference, middle=0.18cm (-0.59, 0.95), high=0.78cm (-0.04, 1.60), p-trend=0.07; p for interaction=0.03]. The log2-Cd by infant sex interaction was statistically significant for ponderal index [p=0.003; β(95% CI): female=0.25kg/m(3) (-0.20, 0.70); male=-0.63kg/m(3) (-1.01, -0.24)] and birth length [p<0.001; β(95% CI): female=-0.47cm (-0.74, -0.20), male=0.32cm (0.00, 0.65)]. Our findings suggest potential sex-specific reversal of Cd's associations on birth length and contribute to the evidence suggesting Cd impairs fetal growth.
| S-EPMC4866807 | biostudies-literature
Project description:The effect of pre and periconceptional multiple micronutrient supplementation on methylation of CpG loci within CpG islands associated with 14,000 genes across the human genome has been investigated in the offspring of a cohort of Gambian women participating in a controlled double blinded trial. Methylation levels in placebo and micronutrient supplemented cohorts were compared in genomic DNA from cord blood (35 placebo and 21 micronutrient supplemented) and in circulating blood samples (14 placebo and 9 micronutrient supplemented) drawn from the same cohort at 9 months old. A small number of differentially methylated CpG loci were identified in cord blood (14 in males and 21 in females) and a larger number in the 9 month infant comparison (108 in males and 106 in females). Seven differentially methylated loci in males and 8 in females persisted from cord to infant. These findings indicate that micronutrient supplementation pre-conception or early in embryonic development is potentially associated with programming of gene activity at birth, which is maintained into early infanthood. Strikingly, the loci affected by micronutrient supplementation differed between males and females, with no shared changes in cord blood and only 5 shared changes at 9 months. Additionally, a large number of CpG loci showed variation in methylation level when comparing 9-month samples to cord blood samples. These postnatal changes were more consistent between sexes, with 85% of female alterations being found as a subset of male changes in the placebo cohort and 62% of the female changes shared with males in the supplemented cohort. Taken together, the results suggest that there is a core developmental program shared between the sexes that is unaffected by nutrient supplementation, but that there are also sex-specific developmental changes which are altered under conditions of micronutrient supplementation and deficiency.
2012-03-15 | GSE34257 | GEO
Project description:BACKGROUND: Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth weight. OBJECTIVE: Our aim was to assess the relationships between prenatal exposures to phthalates and phenols and fetal growth among male newborns. METHODS: We conducted a case-control study on male malformations of the genitalia nested in two French mother-child cohorts with recruitment between 2002 and 2006. We measured, in maternal urinary samples collected between 6 and 30 gestational weeks, the concentrations (micrograms per liter) of 9 phenol (n = 191 pregnant women) and 11 phthalate metabolites (n = 287). Weight, length, and head circumference at birth were collected from maternity records. Statistical analyses were corrected for the oversampling of malformation cases. RESULTS: Adjusted birth weight decreased by 77 g [95% confidence interval (CI): -129, -25] and by 49 g (95% CI: -86, -13) in association with a 1-unit increase in ln-transformed 2,4-dichlorophenol (DCP) and 2,5-DCP urinary concentrations, respectively. Benzophenone-3 (BP3) ln-transformed concentrations were positively associated with weight (26 g; 95% CI: -2, 54) and head circumference at birth (0.1 cm; 95% CI: 0.0, 0.2). Head circumference increased by 0.3 cm (95% CI: 0.0, 0.7) in association with a 1-unit increase in ln-transformed BPA concentration. For phthalate metabolites there was no evidence of monotonic associations with birth weight. CONCLUSIONS: Consistent with findings of a previous study, we observed evidence of an inverse association of 2,5-DCP and a positive association of BP3 with male birth weight.
| S-EPMC3295340 | biostudies-other
Project description:The effect of pre and periconceptional multiple micronutrient supplementation on methylation of CpG loci within CpG islands associated with 14,000 genes across the human genome has been investigated in the offspring of a cohort of Gambian women participating in a controlled double blinded trial. Methylation levels in placebo and micronutrient supplemented cohorts were compared in genomic DNA from cord blood (35 placebo and 21 micronutrient supplemented) and in circulating blood samples (14 placebo and 9 micronutrient supplemented) drawn from the same cohort at 9 months old. A small number of differentially methylated CpG loci were identified in cord blood (14 in males and 21 in females) and a larger number in the 9 month infant comparison (108 in males and 106 in females). Seven differentially methylated loci in males and 8 in females persisted from cord to infant. These findings indicate that micronutrient supplementation pre-conception or early in embryonic development is potentially associated with programming of gene activity at birth, which is maintained into early infanthood. Strikingly, the loci affected by micronutrient supplementation differed between males and females, with no shared changes in cord blood and only 5 shared changes at 9 months. Additionally, a large number of CpG loci showed variation in methylation level when comparing 9-month samples to cord blood samples. These postnatal changes were more consistent between sexes, with 85% of female alterations being found as a subset of male changes in the placebo cohort and 62% of the female changes shared with males in the supplemented cohort. Taken together, the results suggest that there is a core developmental program shared between the sexes that is unaffected by nutrient supplementation, but that there are also sex-specific developmental changes which are altered under conditions of micronutrient supplementation and deficiency. Bisulphite converted DNA from 59 cord (36 placebo and 23 treated) and 25 infant peripheral blood (15 placebo and 10 treated) samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2. (For further analysis, five were excluded during quality control leaving 56 cord (35 placebo and 21 treated) and 23 infant peripheral blood (14 placebo and 9 treated) samples. Full data set of 84 samples were submitted to GEO)
2012-03-15 | E-GEOD-34257 | biostudies-arrayexpress
Project description: Not available
| S-EPMC6464025 | biostudies-literature
Project description: Not available
| S-EPMC6418471 | biostudies-literature
Project description:Abstract Objectives Vitamin D may have an adjunctive role in the prevention and treatment of iron deficiency (ID) through its proposed role in the regulation of erythropoiesis and circulating hepcidin concentrations. Observational studies have shown associations between low vitamin D and iron status; however, there are few data from intervention trials. In participants of the Maternal Vitamin D for Infant Growth Trial (MDIG; NCT01924013), among whom the baseline prevalence of vitamin D deficiency was 64%, we examined the effect of prenatal vitamin D supplementation on iron status during pregnancy by testing the effect of vitamin D supplementation on serum ferritin concentrations. Methods In this double-blind, dose-response, randomized trial in Dhaka, Bangladesh, women were recruited at 17–24 weeks’ gestation and randomly assigned to receive a prenatal vitamin D3 dose of 4200, 16,800, 28,000 IU/week or placebo. Serum ferritin was quantified using an electro-chemiluminescence immunoassay. Plasma C-reactive protein (CRP) was analysed by enzyme-linked immunoassay. Linear regression was used to test the hypothesized effect of vitamin D supplementation on serum ferritin (n = 1011 of 1300 enrolled). In a sensitivity analysis, we adjusted for concurrent CRP to correct for inflammation (n = 920). Regression correction was used to generate an inflammation-corrected estimate of the prevalence of ID (n = 920). Results Prevalence of ID (serum ferritin <15 µg/L) was high overall (27% corrected for inflammation; 12% uncorrected). Geometric mean (95% confidence interval) serum ferritin concentrations were lower in each of the vitamin D supplementation groups [43.1 (38.1, 48.7), 44.8 (40.4, 49.7) and 45.1 (41.5, 49.1) µg/L in the 4200, 16,800 and 28,000 IU/week groups, respectively] compared to the placebo group [50.3 µg/L (45.0, 56.2)], although none of the pairwise differences between each vitamin D group and placebo were statistically significant at the P < 0.05 threshold. Adjusting for CRP did not change the inferences. Conclusions In a population with concurrently high prevalence rates of iron and vitamin D deficiency, prenatal vitamin D supplementation did not lead to improvements in iron status by late gestation. The possibility of a negative effect of vitamin D supplementation on iron status should be further explored. Funding Sources The Bill and Melinda Gates Foundation.
| S-EPMC7258216 | biostudies-literature