The Effects of Malaria in Pregnancy on Neurocognitive Development in Children at 1 and 6 Years of Age in Benin: A Prospective Mother-Child Cohort.

BACKGROUND: Malaria in pregnancy (MiP) contributes significantly to infant mortality rates in sub-Saharan Africa and has consequences on survivors, such as preterm birth and low birth weight. However, its impact on long-term neurocognitive development in children remains unknown. METHODS: Our prospective cohort included pregnant women and their live-born singletons from the Malaria in Pregnancy Preventive Alternative Drugs clinical trial. MiP was assessed using microscopy and real-time quantitative polymerase chain reaction (qPCR). Neurocognitive development in children was assessed using the Mullen Scales of Early Learning and the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), at 1 and 6 years of age, respectively. RESULTS: Of 493 pregnant women, 196 (40%) were infected with malaria at least once: 121 (31%) with placental malaria diagnosed by qPCR. Multiple linear regression B-coefficients showed that impaired gross motor scores were associated with MiP at least once (-2.55; confidence interval [95% CI]: -5.15, 0.05), placental malaria by qPCR (-4.95; 95% CI: -7.65, -2.24), and high parasite density at delivery (-1.92; 95% CI: -3.86, 0.02) after adjustment. Malaria and high parasite density at the second antenatal care visit were associated with lower KABC-II Non-Verbal Index scores at 6 years (-2.57 [95% CI: -4.86, -0.28] and -1.91 [-3.51, -0.32]), respectively. CONCLUSIONS: This prospective cohort study provides evidence that MiP, particularly late term, could have important negative consequences on child development at 1 and 6 years of age. Mechanisms behind this association must be further investigated and diagnostic methods in low-income countries should be strengthened to provide adequate treatment. CLINICAL TRIALS REGISTRATION: NCT00811421.

The Impact of Maternal Depression and Parent-Child Interactions on Risk of Parasitic Infections in Early Childhood: A Prospective Cohort in Benin.

OBJECTIVES: Maternal depression occurs in 13-20% of women from low-income countries, which is associated with negative child health outcomes, including diarrheal disease. However, few studies have investigated its impact on child risk of infectious disease. We studied the impacts of maternal depressive symptoms and parent-child interactions, independently, on the risk of Plasmodium falciparum malaria and soil-transmitted helminth infection in Beninese children. METHODS: Our population included mothers and children enrolled in a clinical trial during pregnancy (MiPPAD) in Benin. The Edinburgh Postnatal Depression Scale (EPDS) assessed maternal depressive symptoms and the home observation measurement of the environment (HOME) assessed parent-child interactions. Blood and stool sample analyses diagnosed child malaria and helminth infection at 12, 18, and 24 months. Negative binomial and Poisson regression models with robust variance tested associations. RESULTS: Of the 302 mother-child pairs, 39 (12.9%) mothers had depressive symptoms. Median number of malaria episodes per child was 3 (0-14) and 29.1% children had at least one helminth infection. Higher EPDS scores were associated with lower HOME scores; relative risk (RR) 0.97 (95% confidence interval (CI) 0.95, 0.99), particularly with lower acceptance, involvement, and variety subscales; RR 0.92 (95% CI 0.85, 0.99), RR 0.82 (95% CI 0.77, 0.88), RR 0.93 (95% CI 0.88, 0.99), respectively. However, neither exposure was associated with risk of parasitic infection in children. CONCLUSIONS FOR PRACTICE: Maternal depressive symptoms are associated with poor parent-child interactions, particularly acceptance of behavior, involvement with children, and variety of interactions, but these exposures do not independently impact risk of parasitic infection in children.

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.

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. STUDY DESIGN: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. RESULTS: Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2." CONCLUSIONS: Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.

Relationship between Stunting, Wasting, Underweight and Geophagy and Cognitive Function of Children.

OBJECTIVES: The aim of this study was to investigate the relationship between anthropometric characteristics and both geophagy and cognitive function of children. STUDY DESIGN: The study prospectively followed singleton children whose mothers participated in the MiPPAD clinical trial in Allada, Benin, from birth to age 12 months. Anthropometric measurements were taken at birth and 9 and 12 months. Wasting, stunting and underweight were defined as weight-for-length, length-for-age and weight-for-age Z-scores less than -2, respectively. Cognitive and motor functions were assessed using the Mullen Scales of Early Learning. Parent-reported geophageous habits of children were collected when the children were 12 months. Multiple linear and logistic regressions were used to analyse the data. RESULTS: A total of 632 children (49.7% girls) were involved in the study. Stunting, wasting and underweight were observed in 14.1%, 13.6% and 17.7%, respectively, at 9 months and 17.3%, 12.7% and 17.2%, respectively, at 12 months. The prevalence of geophagy among the children was 48.2%. Impaired growth at 9 and 12 months was consistently associated with low cognitive and gross motor (GM) score. Children stunted at 9 months had lower GM scores at 12 months compared with their non-stunted peers (ß = -3.48, 95% confidence interval -6.62 to -0.35). CONCLUSIONS: Stunting, wasting and underweight are associated with cognitive and GM deficits in infants. In this setting, impaired growth was not associated with geophagy. Further research evaluating geophagy and growth prospectively and concurrently from birth to 36 months is needed.

Specialist health care services use in a European cohort of infants born very preterm.

AIM: Children born very preterm require additional specialist care because of the health and developmental risks associated with preterm birth, but information on their health service use is sparse. We sought to describe the use of specialist services by children born very preterm in Europe. METHOD: We analysed data from the multi-regional, population-based Effective Perinatal Intensive Care in Europe (EPICE) cohort of births before 32 weeks' gestation in 11 European countries. Perinatal data were abstracted from medical records and parents completed a questionnaire at 2 years corrected age (4322 children; 2026 females, 2296 males; median gestational age 29wks, interquartile range [IQR] 27-31wks; median birthweight 1230g, IQR 970-1511g). We compared parent-reported use of specialist services by country, perinatal risk (based on gestational age, small for gestational age, and neonatal morbidities), maternal education, and birthplace. RESULTS: Seventy-six per cent of the children had consulted at least one specialist, ranging across countries from 53.7% to 100%. Ophthalmologists (53.4%) and physiotherapists (48.0%) were most frequently consulted, but individual specialists varied greatly by country. Perinatal risk was associated with specialist use, but the gradient differed across countries. Children with more educated mothers had higher proportions of specialist use in three countries. INTERPRETATION: Large variations in the use of specialist services across Europe were not explained by perinatal risk and raise questions about the strengths and limits of existing models of care. WHAT THIS PAPER ADDS: Use of specialist services by children born very preterm varied across Europe. This variation was observed for types and number of specialists consulted. Perinatal risk was associated with specialist care, but did not explain country-level differences. In some countries, mothers' educational level affected use of specialist services.

UTILIZACIÓN DE SERVICIOS DE SALUD ESPECIALIZADOS EN UN ESTUDIO DE COHORTE EUROPEO DE NIÑOS NACIDOS MUY PREMATUROS: OBJETIVO: Niños nacidos muy prematuramente requieren cuidados especializados adicionales debido a su salud y a los riesgos asociados con la prematuros, sin embargo la información sobre el uso de servicios de salud es escasa. Buscamos describir la utilización de servicios especializados por niños nacidos muy prematuramente, en Europa. MÉTODO: Analizamos datos de una cohorte de nacimientos ocurridos antes de las 32 semanas de gestación tomados del Effective Perinatal Intensive Care in Europe (EPICE), basado en la población y multirregional, en 11 países europeos. Los datos perinatales fueron extraídos de las historias clínicas y los padres completaron un cuestionario a los 2 años de edad corregida (4.322 niños; 2026 sexo femenino, 2.296 masculino; edad gestacional mediana 29 semanas, rango intercuartílico (IQR) 27-31 semanas; mediana de peso de nacimiento 1.230 gr, IQR 970-1.511 gr). Comparamos el uso de servicios especializados (según informe de los padres) por país, riesgo perinatal (basado en edad gestacional, bajo peso para edad gestacional y morbilidades neonatales), educación materna y lugar de nacimiento. RESULTADOS: En total 65% de los niños habían consultado por lo menos a un especialista, con un rango entre países de 53,7% a 100%. Los especialistas más frecuentemente consultados fueron Oftalmólogos (53,4%) y Fisioterapeutas (48%) pero los especialistas consultados por cada individuo variaron mucho según el país. El riesgo perinatal se asoció al uso de especialista, pero el gradiente varió entre los países. Niños de madres con mayor nivel educativo tuvieron mayor proporción de uso de especialistas en tres países. INTERPRETACIÓN: Las grandes variaciones en el uso de servicios especializados en Europa no fueron explicadas por el riesgo perinatal y arrojan cuestionamientos sobre las fortalezas y limitaciones de los modelos de cuidados existentes.

USO DE SERVIÇOS DE SAÚDE ESPECIALIZADOS EM UMA COORTE EUROPÉIA DE LACTENTES NASCIDOS MUITO PREMATUROS: OBJETIVO: Crianças nascidas muito prematuras requerem cuidado especializado adicional por causa dos riscos à saúde e ao desenvolvimento associados ao nascimento premature, mas informações sobreo uso de serviços de saúde são escassas. Procuramos descrever o uso de serviços especializados por crianças nascidas muito prematuras na Europa. MÉTODO: Analisamos dados de uma coorte populacional multi-regional, do Cuidado Intensivo Neonatal Efetivo na Europa (EPICE), com lactentes nascidos antes de 32 semanas de gestação em 11 países europeus. Dados perinatais foram extraídos dos registros médicos, e os pais completaram um questionário com 2 anos de idade corrigida (4.322 crianças; 2.026 do sexo feminino, 2.296 do sexo masculino; idade gestacional mediana 29semanas, intervalo interquartile [IIQ] 27-31sem; peso ao nascimento mediano 1,230g, IIQ 970-1511g). Comparamos o uso de serviços especializados reportados pelos pais por país, risco perinatal (com base na idade gestacional, pequeno para a idade gestacional e morbidades neonatais), educação materna e local de nascimento. RESULTADOS: Setenta e seis por cento das crianças consultou pelo menos um especialista, variando entre países de 53,7 a 100%. Oftalmologistas (53,4%) e fisioterapeutas (48,0%) foram os mais frequentemente consultados, mas os especialistas individuais variaram bastante por país. O risco perinatal se associou com uso de serviços especializados, mas o gradient diferiu entre países. Crianças com mães mais educadas tinham maior proporção de uso de especialistas em três países. INTERPRETAÇÃO: Grandes variações no uso de serviços especializados na Europa não foram explicadas pelo risco perinatal, e levantam questões sobre as forças e limitações dos modelos de cuidado existentes.

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.

Toxics (Pb, Cd) and trace elements (Zn, Cu, Mn) in women during pregnancy and at delivery, South Benin, 2014-2015.

During pregnancy, fetal development can be hindered by maternal exposure to toxic elements and abnormal concentrations of trace elements. Few data are available in African countries. Our goal was to assess the body burden of lead (Pb), cadmium (Cd), manganese (Mn), zinc (Zn) and copper (Cu) in pregnant women in Benin. The study was carried out in Sô-Ava district, from November 2015 to April 2016. Sixty women were recruited from the RECIPAL pre-conceptional cohort study. In all women, blood samples were collected during the first trimester of pregnancy. Thirty-two women had additional maternal and cord blood samples collected at delivery. Blood samples were analyzed by inductively coupled plasma mass spectrometry. At delivery, Cd median (IQR) concentration in maternal blood was 0.34 µg/L (0.24-0.46) in this non-smoking population. Pb median (IQR) concentration in maternal blood at delivery was 37.4 µg/L (30.5-52.0), with 31.3% of blood Pb levels above the 50 µg/L threshold. These pregnant women lived in semi-rural lakeside villages. Potential sources of Pb exposure identified during pregnancy were having water supply by drill pump and activities such as smoking fish by the woman and fishing by the household head. At delivery, Zn, Cu, and Mn median (IQR) concentrations in maternal blood were, respectively, 5415 µg/L (4894-5822), 1609 µg/L (1295-1771) and 16.0 µg/L (12.5-20.8). Pb, Cd, Mn and Cu blood concentrations were significantly higher at delivery than during the first trimester of pregnancy. Pb, Cd, Zn and Cu concentrations were significantly lower in cord blood than in maternal blood, contrary to Mn concentration, which was significantly higher in cord blood than in maternal blood at delivery. This exploratory study is the first one performed in Benin, and warns us about exposition of women from Sô-Ava district to Pb and Cd during pregnancy.

Perinatal exposure to chlordecone and infant growth.

BACKGROUND: The intensive use of chlordecone (an organochlorine insecticide) in the French West Indies until 1993 resulted in a long-term soil and water contamination. Chlordecone has known hormonal properties and exposure through contaminated food during critical periods of development (gestation and early infancy) may affect growth. OBJECTIVES: We aimed to assess the impact of prenatal and postnatal exposure to chlordecone on the growth of children from the TIMOUN mother-child cohort. METHODS: Chlordecone was determined in cord plasma at birth (N=222) and in breast milk samples (at 3 months). Dietary chlordecone intake was estimated at 7 and 18 months, with food-frequency questionnaires and food-specific contamination data. Anthropometric measurements were taken at the 3-, 7- and 18-month visits and measurements reported in the infants' health records were noted. Structured Jenss-Bayley growth models were fitted to individual height and weight growth trajectories. The impact of exposure on growth curve parameters was estimated directly with adjusted mixed non-linear models. Weight, height and body mass index (BMI), and instantaneous height and weight growth velocities at specific ages were also analyzed relative to exposure. RESULTS: Chlordecone in cord blood was associated with a higher BMI in boys at 3 months, due to greater weight and lower height, and in girls at 8 and 18 months, mostly due to lower height. Postnatal exposure was associated with lower height, weight and BMI at 3, 8 and 18 months, particularly in girls. CONCLUSION: Chlordecone exposure may affect growth trajectories in children aged 0 to 18 months.

Is Neurodevelopmental Assessment in Early Childhood Predictive of Performance Assessed Later in Childhood and Adolescence in Sub-Saharan Africa? A Systematic Review of the Literature.

BACKGROUND: Most neurodevelopmental tests used to assess child development in sub-Saharan Africa were developed in western or high-income countries, raising the question of their usefulness with African children. OBJECTIVE: This systematic review identified and synthesized key findings from studies measuring development in children in Sub-Saharan Africa in early childhood and again at school age, to assess neurocognitive associations longitudinally from infancy through middle childhood. METHODS: The study was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, selecting articles referenced in the PubMed, PsycInfo, and Embase databases using the following inclusion criteria: published between 2000 and 2022, written in French or English, and presenting results dealing with the objective assessment of child's neurodevelopment. All articles were registered in the Zotero reference manager and analyzed by title, abstract, and full text. RESULTS: Several of the seven selected studies confirmed that attention and working memory in infancy can predict children's neurocognitive performance, including mathematical ability, at school age. In two of the studies, children with poor mental development at 1 year of age are more likely to present with poorer behavioral development at school age, including learning difficulties in school and risk for grade repetition. CONCLUSION: Cognitive ability assessed in early childhood is strongly associated with performance at school age in cohorts of African children followed longitudinally. Even with assessments adapted cross-culturally, infants and preschoolers at risk for poor developmental outcomes can be identified to better receive strategic early interventions to enhance their development.

Malaria and gravidity interact to modify maternal haemoglobin concentrations during pregnancy.

BACKGROUND: Primigravidity 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. METHODS: Data 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. RESULTS: In 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. CONCLUSION: In 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.

Lead Exposure in Infancy and Subsequent Growth in Beninese Children.

Studies suggest that elevated postnatal blood lead levels (BLLs) are negatively associated with child growth. This study aimed to investigate the associations of childhood BLLs at age one year and growth outcomes at age six years (n = 661) in a cohort of children in Allada, Benin. The growth outcomes studied are weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), BMI-for-age Z-score (BMIZ), weight-for-height Z-score (WHZ), head circumference (HC), growth velocities, underweight, stunting, and wasting. Multivariable regression models examined the associations between BLLs and growth outcomes, with adjustment for potential confounders. The geometric mean BLLs was 59.3 µg/L and 82% of children had BLLs >35 µg/L at the age of 12.8 months. After adjusting for confounding factors, no overall association was found between BLL quartiles and HAZ, WAZ, BMIZ, WHZ, growth velocities, wasting, and underweight. However, boys in the highest quartile had a 1.02 cm lower HC (95% CI: [−1.81, −0.24]) as compared to the lowest quartile. Furthermore, an increased odds of being stunted was observed in children in the highest quartile of exposure compared to the first (OR: 2.43; 95% CI: [1.11−5.33]) which remained statistically significant only among girls in sex-specific strata. Blood lead was found to be associated with an increased risk of childhood stunting and a lower head circumference in a resource-limited setting.

[Formula: see text]Neurodevelopmental assessment at one year of age predicts neuropsychological performance at six years in a cohort of West African Children.

Rural children from Benin, west Africa were evaluated with the Mullen Scales of Early Learning (MSEL) at one year of age and then at six years with the Kaufman Assessment Battery for Children (KABC-II), the visual computerized Tests of Variables of Attention (TOVA), and the Bruininks-Oseretsky Test (BOT-2) of motor proficiency (N = 568). Although both the MSEL and KABC-II were available to the assessors in French, instructions to the mother/child were in local language of Fon. Mothers were evaluated with the Edinburgh Postpartum Depression Scale (EPDS), Caldwell HOME Scale, educational level and literacy, and a Socio-Economic Scale - also in their local language (Fon). After adjusting for maternal factors, MSEL cognitive composite was correlated with KABC-II with moderate effect sizes, but not with TOVA scores. Overall eta-squared effect for the multivariate models were moderately to strongly correlated (.07 to .37). Neurodevelopmental assessments in early childhood adapted cross-culturally are predictive of school-age neuropsychological cognitive ability.

Soil-transmitted helminth infection in pregnancy and long-term child neurocognitive and behavioral development: A prospective mother-child cohort in Benin.

BACKGROUND: An estimated 30% of women in Sub-Saharan Africa suffer from soil-transmitted helminth infection during pregnancy (SHIP), which has been shown to increase risk of pre-term birth, low birth weight, and maternal anemia. A previous study in Benin found that SHIP was associated with impaired cognitive and gross motor development scores in 635 one-year-old children. The objective of the present study was to follow children prospectively to investigate whether the association between SHIP and child neurocognitive and behavioral development persisted at age six. PRINCIPAL FINDINGS: Our prospective child cohort included 487 live-born singletons of pregnant women enrolled in the Malaria in Pregnancy Preventive Alternative Drugs clinical trial in Allada, Benin. SHIP was assessed at three antenatal visits (ANVs) through collection and testing of stool samples. Neurocognitive and behavioral development was assessed in six-year-old children by trained investigators using the Kaufman Assessment Battery for Children 2nd edition and the parent-reported Strengths and Difficulties Questionnaire (SDQ). Multiple linear regression models generated coefficients and 95% confidence intervals and potential mediating factors were tested. Prevalence of SHIP was 13% at the 1st ANV, 9% at the 2nd ANV, and 1% at delivery. SHIP was not associated with low neurocognitive scores in children at six years. Higher SDQ internalizing scores, indicating increased emotional impairments in children, were associated with helminth infection at the 2nd ANV/delivery 1.07 (95% CI 0.15, 2.00) and at least once during pregnancy 0.79 (95% CI 0.12, 1.46) in adjusted models. Mediation analysis did not reveal significant indirect effects of several mediators on this association. CONCLUSIONS: Our study shows that while SHIP is not associated with impaired long-term neurocognitive development, infections may have significant negative impacts on emotional development in six-year-old children. SHIP remains a critical public health issue, and adequate prevention and treatment protocols should be enforced in low- and middle-income countries.

Comparison of growth models to describe growth from birth to 6 years in a Beninese cohort of children with repeated measurements.

OBJECTIVE: To select a growth model that best describes individual growth trajectories of children and to present some growth characteristics of this population. SETTINGS: Participants were selected from a prospective cohort conducted in three health centres (Allada, Sekou and Attogon) in a semirural region of Benin, sub-Saharan Africa. PARTICIPANTS: Children aged 0 to 6 years were recruited in a cohort study with at least two valid height and weight measurements included (n=961). PRIMARY AND SECONDARY OUTCOME MEASURES: This study compared the goodness-of-fit of three structural growth models (Jenss-Bayley, Reed and a newly adapted version of the Gompertz growth model) on longitudinal weight and height growth data of boys and girls. The goodness-of-fit of the models was assessed using residual distribution over age and compared with the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC). The best-fitting model allowed estimating mean weight and height growth trajectories, individual growth and growth velocities. Underweight, stunting and wasting were also estimated at age 6 years. RESULTS: The three models were able to fit well both weight and height data. The Jenss-Bayley model presented the best fit for weight and height, both in boys and girls. Mean height growth trajectories were identical in shape and direction for boys and girls while the mean weight growth curve of girls fell slightly below the curve of boys after neonatal life. Finally, 35%, 27.7% and 8% of boys; and 34%, 38.4% and 4% of girls were estimated to be underweight, wasted and stunted at age 6 years, respectively. CONCLUSION: The growth parameters of the best-fitting Jenss-Bayley model can be used to describe growth trajectories and study their determinants.

Follow-Up of Elevated Blood Lead Levels and Sources in a Cohort of Children in Benin.

Lead exposure is associated with poor cognitive development in children. Very few studies in sub-Saharan Africa (SSA) have studied blood lead levels (BLLs) and non-gasoline sources of exposure in children. Data from a birth cohort in Benin (2011-2013) suggested that 58% of 1-year-old children had BLLs > 50 ug/L. We aimed to investigate the prevalence of elevated BLLs (>50 µg/L and >100 µg /L) among 425 of these children at 6 years of age in 2016-2018 and to compare BLLs between age 1 and 6 years, and study sources of lead at age 6 years. BLLs were analysed by inductively coupled plasma mass spectrometry. Multiple linear regression and quantile regressions were used to study potential sources of lead. The prevalence of BLLs > 50 µg/L in children was 59.5% (Geometric Mean (GM) 56.4 µg/L, 95% CI: 54.1-58.7) at 6 years of age compared to 54.8% (GM 56.5 µg/L, 95% CI: 53.4-59.6) at 1 year of age. The prevalence of children with BLLs > 100 µg/L decreased from 14.4% at 1 year of age to 8.2% at 6 years of age. After adjustment for all other covariates, consumption of peanuts more than once per month was significantly associated with a 22.0% (95% CI: 4.6, 42.5) increment in BLLs at age 6 years compared with no consumption. Consumption of bushmeat killed by lead bullets at age 6 years was associated with an increase in the higher percentiles of BLLs (P75) compared with the absence of this source. Other potential sources of lead associated with BLLs with marginal significance were consumption of rice, paternal occupational exposure, and the presence of activity with the potential use of lead. This prospective cohort confirms the persistently high prevalence of elevated BLLs in children residing in a rural region in the south of Benin, as well as the presence of multiple and continuous sources of lead. These results highlight the need for prevention programs to reduce and eliminate lead exposure in children.

Neurocognitive testing in West African children 3-6 years of age: Challenges and implications for data analyses.

OBJECTIVE: When testing African children with developmental and cognitive standardized tests from high-income countries (HIC), investigators are uncertain as to whether to apply the HIC norms for these tests when standardizing a child's raw-score performance on the basis of age. The present study compared the construct validity of both raw and HIC-based standardized scores for the Mullen Scales of Early Learning (MSEL) and the Kaufman Assessment Battery in Children - 2nd edition (KABC-II) for Beninese children in a rural setting from three to six years of age. METHODS: Seventy-four children 3-4 yrs of age were assessed with the MSEL, and 61 eligible older children (5-6 yrs of age) were assessed with the KABC-II. Assessors spoke the instructions to the children and caregivers for the assessment items in the local language. The developmental quality of the home environment was evaluated with the Caldwell Home Observation for Measurement of the Environment (HOME) inventory, and a material possessions and housing quality checklist was used as a measure of socio-economic status (SES). Children's mothers were given the Raven's Progressive Matrices test (nonverbal cognitive ability), and the Edinburgh Postpartum Depression Scale (EPDS) (emotional wellbeing). RESULTS: For the MSEL, the 4-yr old group performed significantly better than the 3-yr old group on both the raw and standardized score comparisons for all scales. These differences were attenuated when using standardized scores, although the MSEL standardized cognitive composite score was still highly significant between years of age. When comparing 5- to 6-yr olds on KABC-II subtest and global scale performance, comparisons between the raw and standardized mean score performances were much less consistent. Generally, 6-yr olds performed significantly better than 5-yr olds on the raw score comparisons on the KABC-II subtests, but not so for standardized scores. Parent-child interactions assessed through the HOME measure was associated with both raw and standardized MSEL cognitive composite score outcomes on a multiple regression analysis. SES was the only significant predictor for KABC-II raw and standardized outcomes. CONCLUSION: Standardization using HIC norms was not optimal, resulting in minimal impact to account for age when using the MSEL, and lower scores for oldest children compared with youngest children when using the KABC2. This is likely due to children in Benin drifting away from HIC-based norms with each passing year of age, systematically lowering standardized performance measures. These findings support the importance of having a local comparison group of reference or control children to allow for adjusted (for age, HOME, and SES) raw score comparisons when using western-based tests for developmental and neuropsychological evaluation.

Blood lead level in infants and subsequent risk of malaria: A prospective cohort study in Benin, Sub-Saharan Africa.

Lead and malaria both present significant health risks to children in Sub-Saharan Africa. Previous studies have shown that high blood lead levels in children act as a protective factor against subsequent malaria incidence. The main objective of this study was to investigate associations between blood lead level and malaria outcomes prospectively in Beninese children from 12 to 24 months of age. Two-hundred and four children were assessed for lead at 12 months and closely followed until 24 months for malaria; when symptoms and parasite density were also recorded. Univariate and multivariate negative binomial and linear regression models tested associations between blood lead level quartile and total episodes of malaria (total symptomatic and asymptomatic episodes) and parasite density, respectively. Median blood lead level among children measured at 12 months was 56.50 (4.81-578) µg/L. During the 12-month follow-up, 172 (84.31%) children had at least one malaria episode. Univariate and multivariate negative binomial and linear regressions did not reveal significant associations between blood lead level quartile and malaria outcomes. Iron deficiency was not found to be an effect modifier. Results from this prospective child-cohort study investigating associations between blood lead level and malaria did not confirm results from previous cross-sectional studies. Further research is needed to further explore this relationship and other co-morbidities due to malaria and lead.

Hunting, Sale, and Consumption of Bushmeat Killed by Lead-Based Ammunition in Benin.

Human consumption of animal meat killed by lead ammunition has been reported as a risk factor for elevated blood lead levels. However, little is known about how meat killed by lead ammunition is hunted, prepared, sold, and consumed. We explored the process from hunting to consumption within communities in Benin from the perspective of preventive measures. We conducted 38 semi-structured interviews with hunters (n = 9) and sellers (n = 8) of bushmeat and families (n = 21) as consumers of bushmeat killed by lead ammunition. Data were transcribed, translated, and coded for analysis. We conducted content analysis to identify and describe key themes and processes from hunting to consumption. Many hunters (n = 7/9) used lead-based ammunition. After the meat is hunted, market sellers often buy it directly from the hunters. Amongst the hunters and sellers, few (n = 4/17) acknowledged removing the meat impacted by lead shot prior to sale. Many families (n = 15/21) mentioned consumption of the hunted bushmeat. The meat is cooked before sharing with children. Many families (n = 19/21) mentioned they look for the remains of the lead shot or remove the meat impacted by the shot. The finding suggests that hunting, sale, and consumption of bushmeat killed by lead ammunition are well-known practices in Allada, Benin. The bushmeat often hunted illegally with lead shot is sold in the markets and eventually consumed by families who attempt to clean the meat impacted by the lead shot before cooking it.

Neurodevelopmental outcomes in HIV-infected and uninfected African children.

OBJECTIVE: HIV infection is associated with cognitive impairments, but outcomes are poorly explored in children starting antiretroviral therapy (ART) early or in those exposed but uninfected. DESIGN: Nested cross-sectional evaluation of the neurocognitive and behavioural outcomes of HIV-infected, HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) Cameroonian children at age 4-9 years prospectively followed. METHODS: Cognitive development was assessed in 127 HIV-infected, 101 HEU, 110 HUU children using the KABC-II, neurologic dysfunction using the Touwen examination and behavioural difficulties using the Strength and Difficulties Questionnaire (SDQ). Analyses were adjusted for children age, sex and primary language. Contextual factors were included in a second step to assess their effects on outcomes. RESULTS: All HIV-infected children were treated before 12 months. There was a negative linear gradient in KABC-II scores from HUU children to HEU and HIV-infected children [gradient: -6.0 (-7.7; -4.3) for nonverbal index, NVI, and -8.8 (-10.7; -6.8) for mental processing index, MPI]. After adjusting for contextual factors, scores of HEU children were not significantly different from those of HUU children (all P > 0.1) and differences between HIV-uninfected and HUU children reduced [NVI: from -11.9 (-15.3; -8.5) to -3.4 (-6.8; -0.01), MPI: from -17.6 (-21.3; -13.8) to -5.5 (-9.3; -1.7)]. Compared with uninfected children, HIV-infected children had more neurological dysfunctions and higher SDQ scores (P = 0.002). CONCLUSION: Despite early ART, perinatal-HIV infection is associated with poorer neurocognitive scores and increased behavioural difficulties during childhood. Contextual factors play an important role in this association, which emphasizes the need for early nutritional and developmental interventions targeting both HIV-affected infants and their relatives.