Florence Bodeau-Livinec

Maternal Anemia at First Antenatal Visit: Prevalence and Risk Factors in a Malaria-Endemic Area in Benin

The risk factors for maternal anemia (hemoglobin level less than 110 g/L) were studied in human immunodeficiency virus-negative pregnant women in Benin at the time of first antenatal visit and prior to any prevention. Data for the first 1,005 pregnant women included in a multicentre randomized controlled trial were analyzed. Anemia was common (68.3%), and malaria and helminth infestations were prevalent in 15.2% and 11.1% of the women. A total of 33.3%, 31.3% and 3.6% of the women were iron, folic acid and vitamin B12 deficient, respectively. These parasitic infections and nutrient deficiencies were associated with a high risk of anemia. Twenty-one percent, 15%, 12%, 11% and 7% of anemia were attributable to malnutrition, malaria, iron, folic acid deficiencies, and helminth infestations, respectively. Most anemia was caused by factors that could be prevented by available tools, stressing the need to reinforce their implementation and to evaluate their effectiveness throughout the course of the pregnancy.

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]).

Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks' gestation in France in 2011: EPIPAGE-2 cohort study.

Objectives To describe neurodevelopmental outcomes at 2 years corrected age for children born alive at 22-26, 27-31, and 32-34 weeks’ gestation in 2011, and to evaluate changes since 1997. Design Population based cohort studies, EPIPAGE and EPIPAGE-2. Setting France. Participants 5567 neonates born alive in 2011 at 22-34 completed weeks’ gestation, with 4199 survivors at 2 years corrected age included in follow-up. Comparison of outcomes reported for 3334 (1997) and 2418 (2011) neonates born alive in the nine regions participating in both studies. Main outcome measures Survival; cerebral palsy (2000 European consensus definition); scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ; at least one of five domains below threshold) if completed between 22 and 26 months corrected age, in children without cerebral palsy, blindness, or deafness; and survival without severe or moderate neuromotor or sensory disabilities (cerebral palsy with Gross Motor Function Classification System levels 2-5, unilateral or bilateral blindness or deafness). Results are given as percentage of outcome measures with 95% confidence intervals. Results Among 5170 liveborn neonates with parental consent, survival at 2 years corrected age was 51.7% (95% confidence interval 48.6% to 54.7%) at 22-26 weeks’ gestation, 93.1% (92.1% to 94.0%) at 27-31 weeks’ gestation, and 98.6% (97.8% to 99.2%) at 32-34 weeks’ gestation. Only one infant born at 22-23 weeks survived. Data on cerebral palsy were available for 3599 infants (81.0% of the eligible population). The overall rate of cerebral palsy at 24-26, 27-31, and 32-34 weeks’ gestation was 6.9% (4.7% to 9.6%), 4.3% (3.5% to 5.2%), and 1.0% (0.5% to 1.9%), respectively. Responses to the ASQ were analysed for 2506 children (56.4% of the eligible population). The proportion of children with an ASQ result below threshold at 24-26, 27-31, and 32-34 weeks’ gestation were 50.2% (44.5% to 55.8%), 40.7% (38.3% to 43.2%), and 36.2% (32.4% to 40.1%), respectively. Survival without severe or moderate neuromotor or sensory disabilities among live births increased between 1997 and 2011, from 45.5% (39.2% to 51.8%) to 62.3% (57.1% to 67.5%) at 25-26 weeks’ gestation, but no change was observed at 22-24 weeks’ gestation. At 32-34 weeks’ gestation, there was a non-statistically significant increase in survival without severe or moderate neuromotor or sensory disabilities (P=0.61), but the proportion of survivors with cerebral palsy declined (P=0.01). Conclusions In this large cohort of preterm infants, rates of survival and survival without severe or moderate neuromotor or sensory disabilities have increased during the past two decades, but these children remain at high risk of developmental delay.

Impact of helminth infection during pregnancy on cognitive and motor functions of one-year-old children.

Objective To determine the effect of helminth infection during pregnancy on the cognitive and motor functions of one-year-old children. Methods Six hundred and thirty five singletons born to pregnant women enrolled before 29 weeks of gestation in a trial comparing two intermittent preventive treatments for malaria were assessed for cognitive and motor functions using the Mullen Scales of Early Learning, in the TOVI study, at twelve months of age in the district of Allada in Benin. Stool samples of pregnant women were collected at recruitment, second antenatal care (ANC) visit (at least one month after recruitment) and just before delivery, and were tested for helminths using the Kato-Katz technique. All pregnant women were administered a total of 600 mg of mebendazole (100 mg two times daily for 3 days) to be taken after the first ANC visit. The intake was not directly observed. Results Prevalence of helminth infection was 11.5%, 7.5% and 3.0% at first ANC visit, second ANC visit and at delivery, respectively. Children of mothers who were infected with hookworms at the first ANC visit had 4.9 (95% CI: 1.3–8.6) lower mean gross motor scores compared to those whose mothers were not infected with hookworms at the first ANC visit, in the adjusted model. Helminth infection at least once during pregnancy was associated with infant cognitive and gross motor functions after adjusting for maternal education, gravidity, child sex, family possessions, and quality of the home stimulation. Conclusion Helminth infection during pregnancy is associated with poor cognitive and gross motor outcomes in infants. Measures to prevent helminth infection during pregnancy should be reinforced.

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.

Prenatal Hemoglobin Levels and Early Cognitive and Motor Functions of One-Year-Old Children.

OBJECTIVE: To explore the relationship between prenatal hemoglobin (Hb) concentration and infant cognitive and motor functions. METHODS: Our prospective cohort study included 1-year-old children born to women enrolled at their first antenatal care (ANC) visit in Allada, Benin, before 29 weeks of pregnancy, within a trial comparing the efficacy of sulfadoxine-pyrimethamine and mefloquine. Hb concentrations of pregnant women were determined from venous blood samples collected at first and second ANC visits of at least 1-month interval and at delivery. Women were prescribed oral iron, folic acid, and anthelminthics after the first ANC visit. A total of 636 children (76.8% of eligible children) were assessed by trained research nurses for cognitive and motor functions by using the Mullen Scales of Early Learning. RESULTS: Prevalence of anemia (Hb < 110 g/L) decreased from 67.0% at first ANC visit (mean gestational age [SD], 22.1 [4.0] weeks) to 38.4% at delivery. Mean (SD) Hb concentrations increased from 103.7 (12.3) at first ANC visit to 112.4 (14.1) at delivery. We observed a significant negative quadratic relationship between infant gross motor (GM) function and Hb concentration at first and second ANC visits. Thus, infant GM scores increased sharply with increasing maternal Hb concentration until 90 g/L where increasing GM was mild, and began to decline after 110 g/L. CONCLUSIONS: There appears to be an Hb concentration range that may be optimal for GM function of 1-year-old children. This may reflect the importance of physiologic hemodilution, which occurs after the second trimester until 34 weeks of gestation.

Epistatic Interactions between Apolipoprotein E and Hemoglobin S Genes in Regulation of Malaria Parasitemia

Apolipoprotein E is a monomeric protein secreted by the liver and responsible for the transport of plasma cholesterol and triglycerides. The APOE gene encodes 3 isoforms Ɛ4, Ɛ3 and Ɛ2 with APOE Ɛ4 associated with higher plasma cholesterol levels and increased pathogenesis in several infectious diseases (HIV, HSV). Given that cholesterol is an important nutrient for malaria parasites, we examined whether APOE Ɛ4 was a risk factor for Plasmodium infection, in terms of prevalence or parasite density. A cross sectional survey was performed in 508 children aged 1 to 12 years in Gabon during the wet season. Children were screened for Plasmodium spp. infection, APOE and hemoglobin S (HbS) polymorphisms. Median parasite densities were significantly higher in APOE Ɛ4 children for Plasmodium spp. densities compared to non-APOE Ɛ4 children. When stratified for HbS polymorphisms, median Plasmodium spp. densities were significantly higher in HbAA children if they had an APOE Ɛ4 allele compared to those without an APOE Ɛ4 allele. When considering non-APOE Ɛ4 children, there was no quantitative reduction of Plasmodium spp. parasite densities for HbAS compared to HbAA phenotypes. No influence of APOE Ɛ4 on successful Plasmodium liver cell invasion was detected by multiplicity of infection. These results show that the APOE Ɛ4 allele is associated with higher median malaria parasite densities in children likely due to the importance of cholesterol availability to parasite growth and replication. Results suggest an epistatic interaction between APOE and HbS genes such that sickle cell trait only had an effect on parasite density in APOE Ɛ4 children. This suggests a linked pathway of regulation of parasite density involving expression of these genes. These findings have significance for understanding host determinants of regulation of malaria parasite density, the design of clinical trials as well as studies of co-infection with Plasmodium and other pathogens.

Usefulness of child development assessments for low-resource settings in Francophone Africa

Objective: Few tools are available to screen or assess infants cognitive development, especially in French-speaking Africa. This study evaluated the use of the French translation of the Mullen Scales of Early Learning (MSEL), and the “Ten Questions” questionnaire (TQ) in 1-year-old children in Benin, a francophone country. Methods: A cross-sectional study was conducted in 3 health centers serving a semirural area in Benin. Three hundred fifty-seven children aged 12 months and their mothers were enrolled in 2011. Infant development was assessed at local health centers followed by a home visit to collect information on socioeconomic status, maternal Raven score, maternal depressive symptoms, and mother-child interactions (Home Observation for the Measurement of the Environment [HOME] Inventory), and to administer the TQ. Results: The infants gender (female), the HOME, and maternal education were associated with a higher Early Learning Composite score in multivariate analyses (p = .02, p = .004, p = .007, respectively). The HOME and family wealth were also associated with the Gross Motor Scale (p = .03 and p = .03, respectively). Mothers were more likely to report difficulties on the TQ when the child presented lower score on the MSEL. When considering the Gross Motor Scale as the gold standard to define moderate delays, the 2 combined motor-related questions on the TQ showed good sensitivity and specificity (76.5 and 75.7). Conclusion: In a low-resource rural setting in Africa, the TQ effectively identified 3 quarters of 1-year-old infants with delayed development. After this screening, the MSEL may be useful for further assessment as it showed good feasibility and sensitivity to known risk factors for poor child development.

Elevated Blood Lead Levels in Infants and Mothers in Benin and Potential Sources of Exposure

Lead in childhood is well known to be associated with poor neurodevelopment. As part of a study on maternal anemia and offspring neurodevelopment, we analyzed blood lead level (BLL) with no prior knowledge of lead exposure in 225 mothers and 685 offspring 1 to 2 years old from Allada, a semi-rural area in Benin, sub-Saharan Africa, between May 2011 and May 2013. Blood samples were analyzed by inductively coupled plasma mass spectrometry. Environmental assessments in households and isotopic ratio measurements were performed for eight children with BLL > 100 µg/L. High lead levels (BLL > 50 µg/L) were found in 44% of mothers and 58% of children. The median BLL was 55.1 (interquartile range 39.2–85.0) and 46.6 (36.5–60.1) µg/L, respectively. Maternal BLL was associated with offspring’s consumption of piped water and animals killed by ammunition. Children’s BLL was associated with presence of paint chips in the house and consumption of animals killed by ammunition. In this population, with 98% of children still breastfed, children’s BLL was highly associated with maternal BLL on multivariate analyses. Environmental measures and isotopic ratios supported these findings. Offspring may be highly exposed to lead in utero and probably via breastfeeding in addition to lead paint exposure.

Malaria and gravidity interact to modify maternal haemoglobin concentrations during pregnancy

BackgroundPrimigravidity is one of the main risk factors for both malaria and anaemia. Since the implementation of intermittent preventive treatment (IPTp) in sub-Saharan Africa, the relationship between anaemia and gravidity and its evolution during pregnancy has been little explored. This study aimed to evaluate the impact of gravidity on the variation of haemoglobin during pregnancy according to the timing of gestation.MethodsData from three studies carried out in nearby areas in south Benin (Ouidah, Comé, Allada) between 2005 and 2012 were analysed. At inclusion (first antenatal visit, ANV1) women’s age, area of residence, schooling, gravidity, gestational age, weight and height were recorded. Thick blood smears were performed on ANV1, second visit (ANV2) and at delivery. In Allada, women’s serum ferritin and CRP concentrations were also assessed. The impact of gravidity on maternal haemoglobin (Hb) was analysed using a logistic or linear regression depending on the outcome. The statistical significance was set to P < 0.05.ResultsIn total, data from 3,591 pregnant women were analysed. Both univariate and multivariate analyses showed a constant association between Hb concentrations and gravidity in the three periods of Hb assessment (ANV1, ANV2 and delivery). Mean Hb concentration was significantly lower in primigravidae than in multigravidae at ANV1 (mean difference = -2.4 g/L, CI 95%: [-3.4, -1.4], P < 0.001). Afterwards, there was a significant increase in primigravidae only, with a tendency to reversal between primigravidae and multigravidae, which was confirmed at delivery (mean difference = 2.8 g/L, CI 95%: [1.3, 4.2], P < 0.001). The prevalence of malaria infection was halved between ANV1 and delivery in primigravidae while it decreased by only 38% among multigravidae, who were less prone to malaria infection (prevalence at ANV1, 20% and 10% respectively). Iron deficiency was more common in multigravidae, and it decreased slightly in this group between ANV1 and delivery.ConclusionIn a context of IPTp, Hb levels improved progressively throughout pregnancy in primigravidae, likely as a result of reduction in malaria infection. In multigravidae, the improvement was less perceptible and anaemia was mainly due to iron deficiency.