The Association among Malaria in Pregnancy, Neonatal inflammation, and Neurocognitive Development in a Cohort of Malawian Infants.
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SUBMITTER: Buchwald AG
PROVIDER: S-EPMC9709022 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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The Association among Malaria in Pregnancy, Neonatal inflammation, and Neurocognitive Development in a Cohort of Malawian Infants.
Buchwald Andrea G AG Boudova Sarah S Peterson Ingrid I Divala Titus T Mungwira Randy R Mawindo Patricia P Gladstone Melissa M Cairo Cristiana C Laufer Miriam K MK
The American journal of tropical medicine and hygiene 20221017 5
Malaria in pregnancy (MIP) causes poor birth outcomes, but its impact on neurocognitive development has not been well characterized. Between 2012 and 2014, we enrolled 307 mother-infant pairs and monitored 286 infants for neurocognitive development using the Malawi Developmental Assessment Tool at 6, 12, and 24 months of age. MIP was diagnosed from peripheral blood and placental specimens. Cord blood cytokine levels were assessed for a subset of neonates. Predictors of neurodevelopment were exam ...[more]
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Project description:BackgroundAnnually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring.Methods and findingsBetween April 2014 and April 2015, we followed 421 Malawian mother-baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur-Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], -7.53 [-13.04, -2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], -8.57 [-13.09, -4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies.ConclusionsThis mother-baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children.
| S-EPMC8478258 | biostudies-literature
Project description:We tested the hypotheses that a more mature or diverse gut microbiota will be positively associated with infant growth and inversely associated with inflammation. We characterized gut microbiota from the stool samples of Malawian infants at 6 mo (n = 527), 12 mo (n = 632) and 18 mo (n = 629) of age. Microbiota diversity and maturity measurements were based on Shannon diversity index and microbiota for age Z-score (MAZ), respectively. Growth was calculated as change in Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and head circumference-for-age (HCZ) from 6 to 12 mo and 12 to 18 mo. Biomarkers of inflammation (alpha-1-acid glycoprotein (AGP) and C-reactive protein (CRP)) were measured at 6 and 18 mo. Multivariable models were used to assess the association of each independent variable with each outcome. Microbiota diversity and maturity were related to growth in weight from 6 to 12 mo, but not to growth in length or head circumference or to growth from 12 to 18 mo. Microbiota diversity and maturity may also be linked to inflammation, but findings were inconsistent.
| S-EPMC6733848 | biostudies-literature
Project description:BackgroundNeuropsychological sequelae from pediatric cerebral malaria (CM) have been well-documented. Although malaria-specific retinopathy during acute illness has become a defining criterion for CM, its relationship to neurocognitive sequelae has not been documented. This relationship is important if malaria-specific retinopathy reflects the possible brain neuropathogenesis leading to long-term neurocognitive deficits.MethodsFrom 2008 to 2012, 49 Malawian children 4.5-12 years of age surviving retinopathy-positive CM (CM-R) were tested 1-6 yrs after illness with the Kaufman Assessment Battery for Children, 2 edition, the tests of variables of attention and the Achenbach Child Behavior Checklist. In an observational study of a cohort of cerebral malaria survivors, these neurocognitive and behavioral outcomes were statistically related to types and severity of retinopathy measures, while controlling for age, sex, body mass index, socioeconomic status and time interval between illness and testing.ResultsWorse scores for hemorrhages, papilledema, optic disk hyperemia, retinal whitening of macula and foveal annulus were associated with poorer Kaufman Assessment Battery for Children, 2 edition mental processing index and global scale scores. Disk hyperemia was also predictive of tests of variables of attention D prime overall attention performance (inattention) and commission errors (impulsivity). Few associations were found between retinopathy scores and Achenbach Child Behavior Checklist (emotional and behavioral) outcomes.ConclusionsWe are the first to report the relationship between severity of malaria-specific retinopathy during acute illness in CM survivors and persisting neurocognitive problems. These findings support earlier studies documenting that severity of retinopathy during acute illness is medically prognostic in CM survivors. We extend these findings to include long-term neurocognitive outcomes.
| S-EPMC4165781 | biostudies-literature
Project description:BackgroundMalaria antibody responses measured at delivery have been associated with protection from maternal anaemia and low birth weight deliveries. Whether malarial antibodies present in the first half of pregnancy may protect from these or other poor birth outcomes is unclear. To determine whether malaria antibodies in the first half of pregnancy predict pregnancy outcomes, antibodies were measured to a range of merozoite antigens and to antigens expressed on the surface of parasitized red blood cells (pRBCs) in plasma samples collected at 14-20 weeks of gestation from Malawian women. The latter antibodies were measured as total IgG to pRBCs, and antibodies promoting opsonic phagocytosis of pRBCs. Associations between antibodies and maternal haemoglobin in late pregnancy or newborn size were investigated, after adjusting for potential covariates.ResultsAntibodies to pRBC surface antigens were associated with higher haemoglobin concentration at 36 weeks. Total IgG to pRBCs was associated with 0.4 g/l [(95% confidence interval (0.04, 0.8)] increase in haemoglobin, and opsonizing antibody with 0.5 (0.05, 0.9) increase in haemoglobin for each 10% increase in antibody. These antibodies were not associated with birthweight, placental malaria, or newborn anthropometrics. Antibodies to merozoite antigens and non-placental-binding IEs were not associated with decreased risk of any of these outcomes. In some instances, they were negatively associated with outcomes of interest.ConclusionAntibodies to placental-binding infected erythrocytes may be associated with higher haemoglobin levels in pregnancy, whereas antibodies to other malaria antigens may instead be markers of malaria exposure. Trial registration clinicaltrials.gov NCT01239693. Registered Nov 10, 2010.
| S-EPMC5103486 | biostudies-literature
Project description:BackgroundAlthough poor complementary feeding is associated with poor child growth, nutrition interventions only have modest impact on child growth, due to high burden of infections. We aimed to assess the association of malaria with linear growth, hemoglobin, iron status, and development in children aged 6-18 months in a setting of high malaria and undernutrition prevalence.MethodsProspective cohort study, conducted in Mangochi district, Malawi. We enrolled six-months-old infants and collected weekly data for 'presumed' malaria, diarrhea, and acute respiratory infections (ARI) until age 18 months. Change in length-for-age z-scores (LAZ), stunting, hemoglobin, iron status, and development were assessed at age 18 months. We used ordinary least squares regression for continuous outcomes and modified Poisson regression for categorical outcomes.ResultsOf the 2723 children enrolled, 2016 (74.0%) had complete measurements. The mean (standard deviation) incidences of 'presumed' malaria, diarrhea, and ARI, respectively were: 1.4 (2.0), 4.6 (10.1), and 8.3 (5.0) episodes/child year. Prevalence of stunting increased from 27.4 to 41.5% from 6 to 18 months. 'Presumed' malaria incidence was associated with higher risk of stunting (risk ratio [RR] = 1.04, 95% confidence interval [CI] = 1.01 to 1.07, p = 0.023), anemia (RR = 1.02, 95%CI = 1.00 to 1.04, p = 0.014) and better socio-emotional scores (B = - 0.21, 95%CI = - 0.39 to - 0.03, p = 0.041), but not with change in LAZ, haemoglobin, iron status or other developmental outcomes. Diarrhea incidence was associated with change in LAZ (B = - 0.02; 95% CI = - 0.03 to - 0.01; p = 0.009), stunting (RR = 1.02; 95% CI = 1.01 to 1.03; p = 0.005), and slower motor development. ARI incidence was not associated with any outcome except for poorer socio-emotional scores.ConclusionIn this population of young children living in a malaria-endemic setting, with active surveillance and treatment, 'presumed' malaria is not associated with change in LAZ, hemoglobin, or iron status, but could be associated with stunting and anemia. Diarrhea was more consistently associated with growth than was malaria or ARI. The findings may be different in contexts where active malaria surveillance and treatment is not provided.Trial registrationNCT00945698 (July 24, 2009) and NCT01239693 (November 11, 2010).
| S-EPMC6309082 | biostudies-literature
Project description:BackgroundMalaria 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.MethodsOur 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.ResultsOf 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.ConclusionsThis 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 registrationNCT00811421.
| S-EPMC8906760 | biostudies-literature
Project description:BackgroundThe relationship between antenatal corticosteroids (ACS) and preterm infants born to mothers with hypertensive disorders of pregnancy (HDP) remains a subject of debate. To evaluate whether the use of ACS before delivery was associated with neonatal outcomes in very preterm infants born to mothers with HDP.MethodsThis multicenter cohort study enrolled all infants with gestational age at 24 to 31 week and admitted to tertiary NICUs of the Chinese Neonatal Network (CHNN) within 24 h of birth from 2019 to 2021. ACS administration was defined as at least one dose of dexamethasone or betamethasone before delivery. The primary outcome was surfactant and/ or invasive mechanical ventilation (IMV) within 72 h of life. Multivariable logistic regression analyses were performed to assess the association between ACS and neonatal outcomes.ResultsAmong the 4,582 study infants born to mothers with HDP, 3,806 (83.1%) were exposed to ACS. ACS treatment was significantly associated with lower risk of requirement of surfactant and/ or IMV within 72 h of life (adjusted Odds Ratio = 0.60, 95% confidence interval 0.49-0.74). ACS exposure was also independently associated with decreased mortality, surfactant use, IMV, combined surfactant and IMV use and moderate or severe bronchopulmonary dysplasia. The severity of maternal HDP did not appear to influence the correlation between ACS treatment and neonatal outcomes. Our analysis also indicated that a single complete course seemed to have the most significant protective effect.ConclusionsOur study reinforces the significant role of ACS in reducing severe respiratory morbidity and mortality in very preterm infants born to mothers with HDP.
| S-EPMC11905651 | biostudies-literature
Project description:IntroductionPrevious evidence examining the association between socioeconomic status and pregnancy complications are conflicted and often limited to using area-based measures of socioeconomic status. In this study, we aimed to examine the association between individual-level socioeconomic factors and a wide range of adverse pregnancy and neonatal outcomes using data from the IMPROvED birth cohort conducted in Sweden, the Netherlands and Republic of Ireland.Material and methodsThe study cohort consisted of women who participated in the IMPROvED birth cohort between 2013 and 2017. Data on socioeconomic factors were self-reported and obtained at 15 weeks' gestation, and included level of education, employment status, relationship status, and income. Data on pregnancy and neonatal outcomes included gestational hypertension, pre-eclampsia, gestational diabetes mellitus, emergency cesarean section, preterm birth, post term delivery, small for gestational age and Apgar score at 1 min. These data were obtained within 72 h following delivery and confirmed using medical records. Multivariable logistic regression examined the association between each socioeconomic variable and each outcome separately adjusting for maternal age, maternal body mass index, maternal smoking, maternal alcohol consumption and cohort center. We also examined the effect of exposure to any ≥2 risk factors compared to none.ResultsA total of 2879 participants were included. Adjusted results suggested that those with less than third level of education had an increased odds of gestational hypertension (OR: 1.74, 95% CI: 1.23-2.46), while those on a middle level of income had a reduced odds of emergency cesarean section (OR: 0.59, 95% CI: 0.42-0.84). No significant associations were observed between socioeconomic variables and neonatal outcomes. Exposure to any ≥2 socioeconomic risk factors was associated with an increased risk of preterm birth (OR: 1.75, 95% CI: 1.06-2.89).ConclusionsWe did not find strong evidence of associations between individual-level socioeconomic factors and pregnancy and neonatal outcomes in high-income settings overall, with only few significant associations observed among pregnancy outcomes.
| S-EPMC10577636 | biostudies-literature
Project description:In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association.In the context of a randomised, placebo-controlled trial of intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) in 1030 Mozambican pregnant women, 997 newborns were followed up until 12 months of age. There were 500 live borns to women who received placebo and 497 to those who received SP.There were 58 infant deaths; 60.4% occurred in children born to women who received placebo and 39.6% to women who received IPTp (p = 0.136). There were 25 neonatal deaths; 72% occurred in the placebo group and 28% in the IPTp group (p = 0.041). Of the 20 deaths that occurred in the first week of life, 75% were babies born to women in the placebo group and 25% to those in the IPTp group (p = 0.039). IPTp reduced neonatal mortality by 61.3% (95% CI 7.4%, 83.8%); p = 0.024].Malaria prevention with SP in pregnancy can reduce neonatal mortality. Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group. Alternatively, SP may have reduced the risk of neonatal infections. These findings are of relevance to promote the implementation of IPTp with SP, and provide insights into the understanding of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health.ClinicalTrials.gov NCT00209781.
| S-EPMC2829080 | biostudies-literature
Project description:ImportanceMaternal tobacco use during pregnancy (MTDP) persists across the globe. Longitudinal assessment of the association of MTDP with neurocognitive development of offspring at late childhood is limited.ObjectivesTo examine whether MTDP is associated with child neurocognitive development at ages 9 to 12 years.Design, setting, and participantsThis cohort study included children aged 9 and 10 years at wave 1 (October 2016 to October 2018) and aged 11 to 12 years at a 2-year follow-up (wave 2, August 2018 to January 2021) across 21 US sites in the Adolescent Brain Cognitive Development (ABCD) Study. Data were analyzed from June 2022 to December 2023.ExposureMTDP.Main outcomes and measuresOutcomes of interest were neurocognition, measured by the National Institutes of Health (NIH) Toolbox Cognition Battery, and morphometric brain measures through the region of interest (ROI) analysis from structural magnetic resonance imaging (sMRI).ResultsAmong 11 448 children at wave 1 (mean [SD] age, 9.9 [0.6] years; 5990 [52.3%] male), 1607 children were identified with MTDP. In the NIH Toolbox Cognition Battery, children with MTDP (vs no MTDP) exhibited lower scores on the oral reading recognition (mean [SE] B = -1.2 [0.2]; P < .001), picture sequence memory (mean [SE] B = -2.3 [0.6]; P < .001), and picture vocabulary (mean [SE] B = -1.2 [0.3]; P < .001) tests and the crystallized cognition composite score (mean [SE] B = -1.3 [0.3]; P < .001) at wave 1. These differential patterns persisted at wave 2. In sMRI, children with MTDP (vs no MTDP) had smaller cortical areas in precentral (mean [SE] B = -104.2 [30.4] mm2; P = .001), inferior parietal (mean [SE] B = -153.9 [43.4] mm2; P < .001), and entorhinal (mean [SE] B = -25.1 [5.8] mm2; P < .001) regions and lower cortical volumes in precentral (mean [SE] B = -474.4 [98.2] mm3; P < .001), inferior parietal (mean [SE] B = -523.7 [136.7] mm3; P < .001), entorhinal (mean [SE] B = -94.1 [24.5] mm3; P < .001), and parahippocampal (mean [SE] B = -82.6 [18.7] mm3; P < .001) regions at wave 1. Distinct cortical volume patterns continued to be significant at wave 2. Frontal, parietal, and temporal lobes exhibited differential ROI, while there were no notable distinctions in the occipital lobe and insula cortex.Conclusions and relevanceIn this cohort study, MTDP was associated with enduring deficits in childhood neurocognition. Continued research on the association of MTDP with cognitive performance and brain structure related to language processing skills and episodic memory is needed.
| S-EPMC10865146 | biostudies-literature