Pre-conception serum ferritin concentrations are associated with metal concentrations in blood during pregnancy: A cohort study in Benin.

BACKGROUND: Iron deficiency is a common nutritional deficiency that impacts maternal health and fetal development and is also associated with increased uptake of toxic metals. Women in sub-Saharan Africa are highly exposed to both iron deficiency and metals in the environment. As research on the developmental origins of health and disease increasingly shows impacts of pre-conception maternal health on pregnancy and fetal health, these environmental exposures are of concern. OBJECTIVES: This study investigated the association between iron status pre-pregnancy and blood metal concentrations in the first trimester of pregnancy with potential implications for iron supplementation. METHODS: Pre-conception and first trimester blood samples taken from 262 Beninese women were tested for serum ferritin, inflammation markers, manganese (Mn), cadmium (Cd), lead (Pb), copper, zinc, selenium, mercury and arsenic. Associations between serum ferritin adjusted for inflammation and metal concentrations were analyzed using multivariate linear regression. RESULTS: Women with iron deficiency before conception (13%) were more likely to remain iron deficient in the first trimester (4%) (adjusted OR = 41.2, 95%CI 6.2; 275.0) even within the context of routine iron supplementation during pregnancy. Lower pre-pregnancy serum ferritin concentrations were significantly related to higher concentrations of Mn, Cd and Pb in the first trimester. Every 1% increase in serum ferritin concentration was associated with a 0.13% decrease in Mn (adjusted ß = -0.13, 95%CI -0.18; -0.07), a 0.22% decrease in Cd (adjusted ß = -0.22, 95%CI -0.28; -0.15) and a 0.06% decrease in Pb concentration (adjusted ß = -0.06, 95%CI -0.12; -0.006). DISCUSSION: These results suggest that increasing iron stores prior to pregnancy may prevent excessive uptake of toxic concentrations of the metals Mn, Cd and Pb and argue in favour of testing the effects of iron supplementation prior to pregnancy on metal concentrations.

Consequences of prenatal geophagy for maternal prenatal health, risk of childhood geophagy and child psychomotor development.

OBJECTIVE: To investigate the relationship between prenatal geophagy, maternal prenatal haematological indices, malaria, helminth infections and cognitive and motor development among offspring. METHODS: At least a year after delivery, 552 of 863 HIV-negative mothers with singleton births who completed a clinical trial comparing the efficacy of sulfadoxine-pyrimethamine and mefloquine during pregnancy in Allada, Benin, responded to a nutrition questionnaire including their geophagous habits during pregnancy. During the clinical trial, helminth infection, malaria, haemoglobin and ferritin concentrations were assessed at 1st and 2nd antenatal care visits (ANV) and at delivery. After the first ANV, women were administered daily iron and folic acid supplements until three what? post-delivery. Singleton children were assessed for cognitive function at age 1 year using the Mullen Scales of Early Learning. RESULTS: The prevalence of geophagy during pregnancy was 31.9%. Pregnant women reporting geophagy were more likely to be anaemic (AOR = 1.9, 95% CI [1.1, 3.4]) at their first ANV if they reported geophagy at the first trimester. Overall, prenatal geophagy was not associated with maternal haematological indices, malaria or helminth infections, but geophagy during the third trimester and throughout pregnancy was associated with poor motor function (AOR = -3.8, 95% CI [-6.9, -0.6]) and increased odds of geophagous behaviour in early childhood, respectively. CONCLUSIONS: Prenatal geophagy is not associated with haematological indices in the presence of micronutrient supplementation. However, it may be associated with poor child motor function and infant geophagy. Geophagy should be screened early in pregnancy.

Prenatal Iron Deficiency, Neonatal Ferritin, and Infant Cognitive Function.

OBJECTIVE: To investigate the impact of prenatal maternal iron deficiency (ID) on cord blood serum ferritin (CBSF) concentration and infant cognitive and motor development. METHODS: Our prospective cohort study included 636 mother-singleton child pairs from 828 eligible pregnant women who were enrolled during their first antenatal care (ANC) visit in Allada, Benin, into a clinical trial comparing the efficacy of mefloquine and sulfadoxine-pyrimethamine. Venous blood samples of women were assessed for ferritin and hemoglobin concentrations at the first and second ANC visits (occurring at least 1-month apart) and at delivery. Women were prescribed daily iron and folic acid supplements throughout pregnancy. Hematologic examinations were repeated for cord blood at birth. At age 1 year, cognitive and motor functions of children were assessed by using the Mullen Scales of Early Learning. RESULTS: The prevalence of prenatal ID at first and second ANC visits, and at delivery was 30.5%, 34.0%, and 28.4%, respectively. CBSF concentrations were similar between ID and non-ID pregnant women. Neither prenatal ID nor CBSF concentration was associated with poor cognitive or gross motor function of children at age 1 year. CBSF concentrations were lower among mothers who had ID anemia (IDA) at delivery compared with non-IDA pregnant women (adjusted mean difference: -0.2 [95% confidence interval: -0.4 to -0.0]). CONCLUSIONS: In a malaria-endemic region, ID in pregnancy in the context of iron supplementation is neither associated with CBSF concentration nor with infant cognitive and motor development. Prenatal IDA around the time of delivery is associated with lower CBSF concentrations.

Iron and malaria: a dangerous liaison?

Malaria increases the burden of anemia in low-income countries, where, according to 2012 data from the World Health Organization, 40% of children are anemic. Moreover, iron is a cofactor for Plasmodium falciparum development, raising fears that iron supplementation might be harmful in patients with P. falciparum infection. The primary objective of this narrative review is to describe current knowledge on the iron-malaria association, including recent findings and substantive qualitative results. Between 2012 and 2016 the MEDLINE database was searched for literature published about malaria and iron levels. Observational studies reported some protection of iron supplementation against malaria among iron-deficient children, while older clinical trials reported increased susceptibility to malaria among iron-supplemented children. However, iron supplements were not significantly associated with increased malaria risk in recent clinical trials or in a 2016 Cochrane review. Evidence of an iron-malaria association is limited by the following factors: the protective effect of control interventions, the limited follow-up of children, and the lack of homogenous iron indicators. The effects of previous health status and possible thresholds in iron levels should be investigated using a gold-standard combination of iron markers. Moreover, the benefits of iron supplementation require further evaluation.

Maternal anemia in pregnancy: assessing the effect of routine preventive measures in a malaria-endemic area.

We investigated the effectiveness of routine preventive measures for anemia in Beninese pregnant women during pregnancy. Anemia (hemoglobin < 110 g/L) was common: 68.3% at first antenatal visit (ANV1), 64.7% at second antenatal visit (ANV2), and 40.6% at delivery. Parasitic infections and nutritional deficiencies were the most preventable causes. After intermittent preventive treatment (IPTp) and antihelminthic treatments, malaria prevalence decreased from 15.1% (ANV1) to 4.0% (ANV2) and increased again to 9.6% at delivery. Helminth infections dropped from 11.1% (ANV1) to 7.2% (ANV2) and 2.4% at delivery. Malaria was associated with lower mean hemoglobin on ANV1 and delivery, and iron deficiency was associated with lower mean hemoglobin on ANV1 and ANV2. IPTp and antihelminthic treatments were efficacious to clear parasitic infections and improve hematologic status, whereas the effectiveness of daily iron and folic acid supplements to correct iron and folate deficiencies and decrease anemia was less marked, possibly because of lack of compliance.

Maternal anemia in Benin: prevalence, risk factors, and association with low birth weight.

We studied the prevalence of anemia during pregnancy and its relationship with low birth weight (LBW; birth weight < 2,500 g) in Benin. We analyzed 1,508 observations from a randomized controlled trial conducted from 2005 to 2008 showing equivalence on the risk of LBW between two drugs for Intermittent Preventive Treatment of malaria during pregnancy (IPTp). Despite IPTp, helminth prophylaxis, and iron and folic acid supplementations, the proportions of women with severe anemia (hemoglobin [Hb] concentration < 80 g/L) and anemia (Hb < 110 g/L) were high throughout pregnancy: 3.9% and 64.7% during the second and 3.7% and 64.1% during the third trimester, but 2.5% and 39.6% at the onset of labor, respectively. Compared with women without anemia (Hb ≥ 110 g/L) during the third trimester, women with severe anemia (Hb < 80 g/L) were at higher risk of LBW after adjustment for potential confounding factors (prevalence ratio [PR] = 2.8; 95% confidence interval [1.4-5.6]).