Search

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. [ABSTRACT FROM AUTHOR]

Background: Public health education aims at producing a competent workforce. The WHO-ASPHER framework proposes a set of relevant public health competencies organised in 10 sections (e.g. science practice, leadership, law policies and ethics etc). As part of the Europubhealth (EPH) consortium, eight universities collaborate for the delivery of a 2-year international public health master course. The training pathway includes a first "foundation" year, with a choice of four options (components), and a second "specialisation" year with a choice of seven components. In 2020, EPH consortium decided to use the WHO-ASPHER framework in order to map the competencies addressed and the level of proficiency targeted by each component of its master course. Methods: An 84-item questionnaire covering the whole WHO-ASPHER framework was sent to the 11 EPH component coordinators, asking them to rate the proficiency levels targeted at the end of their courses. Answers from each coordinator were summarised by calculating mean proficiency levels for each of the 10 competency sections. We used Bland & Altman plots to explore heterogeneity of answers and then calculated transformed scores to account for rating heterogeneity. We use tabulation and a heat map to explore patterns of proficiency levels across components. Results: There were differences in overall proficiency levels between years with, as expected, higher scores in year two. Year one components reached medium to high proficiency scores for the sections "science practice", "health promotion" and "communication" with scores ranging from 2.6 to 3 (on a 1-low to 4-high scale). When compared with year one on a heat-map, year two components displayed more contrasted profiles, typically aiming for high proficiency level (i.e. scores above 3.5) on 3 out of the 10 sections of competencies. Except for the "collaborations and partnership" section, the training pathways offered by the EPH master course seem to offer opportunities for a high proficiency level in all domains of competencies. Conclusions: The mapping proved a useful exercise to identify strengths and complementarities among the EPH consortium. The results suggest that the EPH master course is coherent and offers students opportunities to gain proficiency in most competencies relevant to public health practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (β = -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. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

Highlights • 4-year old kids did better than 3-year olds on the Mullen Scales of Early Learning. • 6-year old kids did better than 5-yr olds on the Kaufman Assessment Battery – 2nd edition (KABC-II). • These age differences were less consistent when standardizing with HIC norms. • Mullen and KABC-II performance predicted by maternal Ravens Matrices, HOME, & SES. • Mullen and KABC-II performance were not correlated with maternal depression. Abstract 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. [ABSTRACT FROM AUTHOR]

Purpose REtard de Croissance Intra-uterin et PALudisme (RECIPAL) is an original preconceptional cohort designed to assess the consequences of malaria during the first trimester of pregnancy, which is a poorly investigated period in Africa and during which malaria may be detrimental to the fetus. Participants For this purpose, a total of 1214 women of reproductive age living in Sô-Ava and Akassato districts (south Benin) were followed up monthly from June 2014 to December 2016 until 411 of them became pregnant. A large range of health determinants was collected both before and during pregnancy from the first weeks of gestation to delivery. Five Doppler ultrasound scans were performed for early dating of the pregnancy and longitudinal fetal growth assessment. Findings to date Pregnant women were identified at a mean of 6.9 weeks of gestation (wg). Preliminary results confirmed the high prevalence of malaria in the first trimester of pregnancy, with more than 25.4% of women presenting at least one microscopic malarial infection during this period. Most infections occurred before six wg. The prevalence of low birth weight, small birth weight for gestational age (according to INTERGROWTH-21st charts) and preterm birth was 9.3%, 18.3% and 12.6%, respectively. Future plans REtard de Croissance Intra-uterin et PALudisme (RECIPAL) represents at this time a unique resource that will provide information on multiple infectious (including malaria), biological, nutritional and environmental determinants in relation to health outcomes in women of reproductive age, pregnant women and their newborns. It will contribute to better define future recommendations for the prevention of malaria in early pregnancy and maternal malnutrition in Africa. It confirms that it is possible to constitute a preconceptional pregnancy cohort in Africa and provides valuable information for researchers starting cohorts in the future. [ABSTRACT FROM AUTHOR]

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 ironsupplemented 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. [ABSTRACT FROM AUTHOR]

Introduction: Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Materials and Methods: Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. Results: At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Conclusion: Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the Institute of Health Metrics. In conclusion, due to the high prevalence of elevated BLL, health interventions should look forward to minimize the exposure to lead to better protect the population in West Africa. [ABSTRACT FROM AUTHOR]

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. Author Summary: The WHO recommends anthelmintics for pregnant women after their first trimester but the benefits remain unequivocal. Although the consequences of helminth infection during pregnancy on the health of pregnant women have been well studied, the impact on the early development of offspring has been understudied. Studies suggest that helminth infection in children may be associated with poor cognitive development, but very little is known whether a similar consequence exists for offspring of women infected with helminths during pregnancy. From our study, we found that women who had intestinal worm infection at least once during pregnancy, had children with lower cognitive and motor scores. Moreover, hookworm infection in pregnant women prior to receiving anthelminthic treatment was associated with poor gross motor functions of children at one-year of age. Based on the findings of this study, measures to prevent helminth infections during pregnancy should be reinforced. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]