Prenatal Iron Deficiency and Replete Iron Status Are Associated with Adverse Birth Outcomes, but Associations Differ in Ghana and Malawi

Background Previous literature suggests a U-shaped relation between hemoglobin concentration and adverse birth outcomes. There is less evidence on associations between iron status and birth outcomes. Objective Our objective was to determine the associations of maternal hemoglobin concentration and iron status with birth outcomes. Methods We conducted a secondary data analysis of data from 2 cohorts of pregnant women receiving iron-containing nutritional supplements (20–60 mg ferrous sulfate) in Ghana (n = 1137) and Malawi (n = 1243). Hemoglobin concentration and 2 markers of iron status [zinc protoporphyrin and soluble transferrin receptor (sTfR)] were measured at ≤20 weeks and 36 weeks of gestation. We used linear and Poisson regression models and birth outcomes included preterm birth (PTB), newborn stunting, low birth weight (LBW), and small-for-gestational-age. Results Prevalence of iron deficiency (sTfR \u3e6.0 mg/L) at enrollment was 9% in Ghana and 20% in Malawi. In early pregnancy, iron deficiency was associated with PTB (9% compared with 17%, adjusted RR: 1.63; 95% CI: 1.14, 2.33) and stunting (15% compared with 23%, adjusted RR: 1.44; 95% CI: 1.09, 1.94) in Malawi but not Ghana, and was not associated with LBW in either country; replete iron status (sTfR \u3c10th \u3epercentile) was associated with stunting (9% compared with 15%, adjusted RR: 1.71; 95% CI: 1.06, 2.77) in Ghana, but not PTB or LBW, and was not associated with any birth outcomes in Malawi. In late pregnancy, iron deficiency was not related to birth outcomes in either country and iron-replete status was associated with higher risk of LBW (8% compared with 16%, adjusted RR: 1.90; 95% CI: 1.17, 3.09) and stunting (6% compared with 13%, adjusted RR: 2.14; 95% CI: 1.21, 3.77) in Ghana, but was not associated with birth outcomes in Malawi. Conclusions The associations of low or replete iron status with birth outcomes are population specific. Research to replicate and extend these findings would be beneficial. These trials were registered at clinicaltrials.gov as NCT00970866 (Ghana) and NCT01239693 (Malawi)

Safety of universal provision of iron through home fortification of complementary foods in malaria-endemic areas.

Home fortification of complementary foods with iron and other micronutrients is a low-cost strategy for filling nutrient gaps in the diets of infants and young children, but there has been uncertainty about the safety of universal provision of iron via home fortification in malaria-endemic areas. Based on the current understanding of the potential mechanisms of adverse effects of iron, the risk can probably be minimized by using the lowest possible efficacious dose of iron, preferably delivered in small amounts throughout the day with food, to minimize spikes in plasma nontransferrin-bound iron and large amounts of unabsorbed iron in the gastrointestinal tract. Results from 6 home fortification studies in malaria-endemic areas showed no increased risk of morbidity (including malaria), but these studies were not powered to rule out a modest increase in the risk of severe adverse events. At present, the safest option is to implement home fortification in the context of comprehensive malaria control strategies, as recommended in recent WHO guidelines

Effects of lipid-based nutrient supplements or multiple micronutrient supplements compared with iron and folic acid supplements during pregnancy on maternal haemoglobin and iron status.

We examined the effect of three types of prenatal supplements containing different amounts of iron on haemoglobin (Hb) and iron status (zinc protoporphyrin [ZPP] and soluble transferrin receptor [sTfR]) in late pregnancy among 1,379 women in rural Malawi. Participants were recruited at ≤20 gestational weeks (gw) and randomly assigned to consume daily (1) 60-mg iron and folic acid (IFA); (2) 20-mg iron plus 17 micronutrients in a capsule (MMN); or (3) lipid-based nutrient supplement (LNS; 118 kcal) with 20-mg iron plus 21 micronutrients, protein, and fat. We analysed differences between intervention groups in mean Hb, ZPP, and sTfR at 36 gw, and the proportion with anaemia (Hb < 100 g L-1 ) and iron deficiency (ZPP > 60 μmol mol-1 haem or sTfR > 6 mg L-1 ) at 36 gw. Women in the IFA group had higher Hb at 36 gw than women in the LNS group (P = 0.030) and higher iron status (lower ZPP and sTfR) than women in both the LNS (P < 0.001 for both ZPP and sTfR) and MMN (P = 0.025 and P = 0.046) groups. Results for anaemia and iron deficiency showed similar trends. Further research is needed to elucidate the appropriate amount of iron to improve Hb and iron status, while improving birth outcomes

Effects of lipid‐based nutrient supplements or multiple micronutrient supplements compared with iron and folic acid supplements during pregnancy on maternal haemoglobin and iron status

We examined the effect of three types of prenatal supplements containing different amounts of iron on haemoglobin (Hb) and iron status (zinc protoporphyrin [ZPP] and soluble transferrin receptor [sTfR]) in late pregnancy among 1,379 women in rural Malawi. Participants were recruited at ≤20 gestational weeks (gw) and randomly assigned to consume daily (1) 60-mg iron and folic acid (IFA); (2) 20-mg iron plus 17 micronutrients in a capsule (MMN); or (3) lipid-based nutrient supplement (LNS; 118 kcal) with 20-mg iron plus 21 micronutrients, protein, and fat. We analysed differences between intervention groups in mean Hb, ZPP, and sTfR at 36 gw, and the proportion with anaemia (Hb < 100 g L-1 ) and iron deficiency (ZPP > 60 μmol mol-1 haem or sTfR > 6 mg L-1 ) at 36 gw. Women in the IFA group had higher Hb at 36 gw than women in the LNS group (P = 0.030) and higher iron status (lower ZPP and sTfR) than women in both the LNS (P < 0.001 for both ZPP and sTfR) and MMN (P = 0.025 and P = 0.046) groups. Results for anaemia and iron deficiency showed similar trends. Further research is needed to elucidate the appropriate amount of iron to improve Hb and iron status, while improving birth outcomes

Impact of small-quantity lipid-based nutrient supplement on hemoglobin, iron status and biomarkers of inflammation in pregnant Ghanaian women

We examined hemoglobin (Hb, g/L), iron status (zinc protoporphyrin, ZPP, µmol/mol heme, and transferrin receptor, TfR, mg/L) and inflammation (C-reactive protein, CRP and alpha-1 glycoprotein, AGP) in pregnant Ghanaian women who participated in a randomized controlled trial. Women (n = 1320) received either 60 mg Fe + 400-µg folic acid (IFA); 18 micronutrients including 20-mg Fe (MMN) or small-quantity lipid-based nutrient supplements (SQ-LNS, 118 kcal/d) with the same micronutrient levels as in MMN, plus four additional minerals (LNS) daily during pregnancy. Intention-to-treat analysis included 349, 354 and 354 women in the IFA, MMN and LNS groups, respectively, with overall baseline mean Hb and anemia (Hb <100) prevalence of 112 and 13.3%, respectively. At 36 gestational weeks, overall Hb was 117, and anemia prevalence was 5.3%. Compared with the IFA group, the LNS and MMN groups had lower mean Hb (120 ± 11 vs. 115 ± 12 and 117 ± 12, respectively; P < 0.001), higher mean ZPP (42 ± 30 vs. 50 ± 29 and 49 ± 30; P = 0.010) and TfR (4.0 ± 1.3 vs. 4.9 ± 1.8 and 4.6 ± 1.7; P < 0.001), and greater prevalence of anemia (2.2% vs. 7.9% and 5.8%; P = 0.019), elevated ZPP (>60) [9.4% vs. 18.6% and 19.2%; P = 0.003] and elevated TfR (>6.0) [9.0% vs. 19.2% and 15.1%; P = 0.004]. CRP and AGP concentrations did not differ among groups. We conclude that among pregnant women in a semi-urban setting in Ghana, supplementation with SQ-LNS or MMN containing 20 mg iron resulted in lower Hb and iron status but had no impact on inflammation, when compared with iron (60 mg) plus folic acid (400 µg). The amount of iron in such supplements that is most effective for improving both maternal Hb/iron status and birth outcomes requires further evaluation. This trial was registered at ClinicalTrials.gov as: NCT00970866

Effects of a lipid-based nutrient supplement during pregnancy and lactation on maternal plasma fatty acid status and lipid profile: Results of two randomized controlled trials.

It is unknown whether a novel small-quantity lipid-based nutrient supplement (SQ-LNS) containing alpha-linolenic (ALA) and linoleic acids impacts maternal plasma lipids and fatty acid status. We measured plasma fatty acids (wt%) and lipid concentrations at 36 wk gestation and breast milk fatty acids (wt%) at 6 months postpartum in a subsample of women enrolled in a randomized controlled trial studying the effects of SQ-LNS on birth outcomes and child growth. Women≤20 wk gestation in Ghana (n=1,320) and Malawi (n=1,391) were assigned to receive daily either: 1) iron-folic acid (pregnancy); 2) multiple micronutrients (pregnancy and lactation); or 3) SQ-LNS (pregnancy and lactation). At 36 wk, plasma ALA levels were higher in those receiving SQ-LNS. SQ-LNS increased breast milk ALA in Ghana but not Malawi. There was no effect on plasma lipids or other selected fatty acids. SQ-LNS may impact plasma and breast milk ALA levels depending on the population

Effects of a lipid-based nutrient supplement during pregnancy and lactation on maternal plasma fatty acid status and lipid profile: Results of two randomized controlled trials☆

It is unknown whether a novel small-quantity lipid-based nutrient supplement (SQ-LNS) containing alpha-linolenic (ALA) and linoleic acids impacts maternal plasma lipids and fatty acid status. We measured plasma fatty acids (wt%) and lipid concentrations at 36 wk gestation and breast milk fatty acids (wt%) at 6 months postpartum in a subsample of women enrolled in a randomized controlled trial studying the effects of SQ-LNS on birth outcomes and child growth. Women≤20 wk gestation in Ghana (n=1,320) and Malawi (n=1,391) were assigned to receive daily either: 1) iron-folic acid (pregnancy); 2) multiple micronutrients (pregnancy and lactation); or 3) SQ-LNS (pregnancy and lactation). At 36 wk, plasma ALA levels were higher in those receiving SQ-LNS. SQ-LNS increased breast milk ALA in Ghana but not Malawi. There was no effect on plasma lipids or other selected fatty acids. SQ-LNS may impact plasma and breast milk ALA levels depending on the population

Association of Lactase Persistence Genotypes (rs4988235) and Ethnicity with Dairy Intake in a Healthy U.S. Population.

Lactase persistence (LP) is a trait in which lactose can be digested throughout adulthood, while lactase non-persistence (LNP) can cause lactose intolerance and influence dairy consumption. One single nucleotide polymorphism (SNP ID: rs4988235) is often used as a predictor for dairy intake, since it is responsible for LP in people in European descent, and can occur in other ethnic groups. The objective of this study was to determine whether rs4988235 genotypes and ethnicity influence reported dairy consumption in the United States (U.S.). A food frequency questionnaire (FFQ) and multiple Automated Self-Administered 24-h recalls (ASA24®) were used to measure habitual and recent intake, respectively, of total dairy, cheese, cow's milk, plant-based alternative milk, and yogurt in a multi-ethnic U.S. cohort genotyped for rs4988235. Within Caucasian subjects, LP individuals reported consuming more recent total dairy and habitual total cow's milk intake. For subjects of all ethnicities, LP individuals consumed more cheese (FFQ p = 0.043, ASA24 p = 0.012) and recent total dairy (ASA24 p = 0.005). For both dietary assessments, Caucasians consumed more cheese than all non-Caucasians (FFQ p = 0.036, ASA24 p = 0.002) independent of genotype, as well as more recent intake of yogurt (ASA24 p = 0.042). LP subjects consumed more total cow's milk than LNP, but only when accounting for whether subjects were Caucasian or not (FFQ p = 0.015). Fluid milk and alternative plant-based milk consumption were not associated with genotypes or ethnicity. Our results show that both LP genotype and ethnicity influence the intake of some dairy products in a multi-ethnic U.S. cohort, but the ability of rs4988235 genotypes to predict intake may depend on ethnic background, the specific dairy product, and whether intake is reported on a habitual or recent basis. Therefore, ethnicity and the dietary assessment method should also be considered when determining the suitability of rs4988235 as a proxy for dairy intake