Prolonged Breastfeeding and the Risk of Plasmodium vivax Infection and Clinical Malaria in Early Childhood: A Birth Cohort Study.

BACKGROUND: Relatively few Amazonian infants have clinical malaria diagnosed, treated and notified before their first birthday, either because they are little exposed to an infection or remain asymptomatic once infected. Here we measure the proportion of children who have experienced Plasmodium vivax infection and malaria by 2 years of age in the main transmission hotspot of Amazonian Brazil. METHODS: We measured IgG antibodies to 3 blood-stage P. vivax antigens at the 1- and 2-year follow-up assessment of 435 participants in a population-based birth cohort. Children's malaria case notifications were retrieved from the electronic database of the Ministry of Health. We used multiple Poisson regression models to identify predictors of serologically proven P. vivax infection and clinical vivax malaria during the first 2 years of life. RESULTS: Overall, 23 [5.3%; 95% confidence interval (CI): 3.5-7.8%) children had antibodies to ≥2 antigens detected during at least one follow-up assessment, consistent with past P. vivax infection(s). Fifteen (3.4%; 95% CI: 2.1-5.6%) children had clinical vivax episodes notified during the first 2 years of life; 7 of them were seronegative. We estimate that half of the infections remained unnotified. Children born to women who experienced P. vivax infection during pregnancy were more likely to be infected and develop clinical vivax malaria, while those breast-fed for ≥12 months had their risk of being P. vivax -seropositive (which we take as evidence of blood-stage P. vivax infection during the first 2 years of life) decreased by 79.8% (95% CI: 69.3-86.7%). CONCLUSION: P. vivax infections in early childhood are underreported in the Amazon, are associated with anemia at 2 years of age, and appear to be partially prevented by prolonged breastfeeding.

Leisure-time physical activity in Amazonian pregnant women and offspring birth weight: A prospective cohort study.

Compelling evidence supports the current international recommendation of at least 150 min/week of leisure-time physical activity (LTPA) during pregnancy. However, the potential relationship between LTPA and birth weight (BW) remains unclear in low- and middle-income countries. The purpose of this study was to examine the association between LTPA during pregnancy and offspring BW in an Amazonian population. Prospective cohort study was carried-out with 500 pregnant women and their offspring followed-up in the MINA-Brazil study, which was conducted in Cruzeiro do Sul, Western Brazilian Amazon. LTPA was assessed in the second (mean 19.6, SD 2.4 weeks) and third (mean 27.8, SD 1.6 weeks) gestational trimesters by a standardised interview and categorised according to the recommended cut-off of at least 150 min/week. We calculated offspring BW z-scores by sex and gestational age. We then explored the effect of LTPA during pregnancy on offspring BW, the association between LTPA and small-for-gestational-age (SGA) or large-for-gestational-age (LGA) births, and the mediating role of excessive and insufficient gestational weight gain (GWG). At least 150 min/week of LTPA during the third gestational trimester was associated with an offspring BW decrease of -0.35 z-score (95% CI: -0.65, -0.05) or -147.9 grams (95% CI: -260.9, -14.8), without increasing the frequency of SGA foetuses either in the second or third gestational trimester (p > 0.05). Excessive GWG mediated the effect of LTPA on the offspring BW (indirect effect = -0.05 z-score [95% CI: -0.10, -0.00] or -34.7 grams (95% CI: -66.1, -3.3]). This mediation effect was not observed for insufficient GWG. LTPA in the third, but not in the second, trimester of pregnancy was inversely associated with offspring BW without increasing the frequency of SGA, an effect that was partly mediated by excessive GWG.

Prenatal care and preterm birth in the Western Brazilian Amazon: A population-based study.

Brazil is among the top ten countries in preterm delivery worldwide. This study assesses the factors associated with preterm birth in the Western Brazilian Amazon. A population-based cross-sectional study was held between July 2015 to June 2016 in Cruzeiro do Sul, Brazilian Amazon. A total of 1525 births were included in this analysis. Preterm birth was defined as births at gestational age < 37 weeks. A stepwise multiple logistic regression was used to identify factors associated with preterm delivery. The prevalence rate of preterm birth was 7.9% (n = 120; 95% CI: 6.5-9.3). After adjusting for confounding factors, a positive association with preterm birth was observed for pregnant women who completed less than six antenatal care visits (OR: 2.93; 95% CI: 1.89-4.56), who had a birth interval of < 18 months (OR: 2.65; 95% CI: 1.04-6.75), and who experienced bleeding (OR: 2.17; 95% CI: 1.39-3.38) and hypertension during pregnancy (OR: 1.74; 95% CI: 1.07-2.82). Factors associated with preterm birth in the Western Brazilian Amazon were mostly related to the aspects of health care provided to women, and thus could be prevented. Proper, timely, and regular antenatal care visits can help reduce adverse outcomes, such as hypertension and bleeding.

Low-level Plasmodium vivax exposure, maternal antibodies, and anemia in early childhood: Population-based birth cohort study in Amazonian Brazil.

BACKGROUND: Malaria causes significant morbidity and mortality in children under 5 years of age in sub-Saharan Africa and the Asia-Pacific region. Neonates and young infants remain relatively protected from clinical disease and the transplacental transfer of maternal antibodies is hypothesized as one of the protective factors. The adverse health effects of Plasmodium vivax malaria in early childhood-traditionally viewed as a benign infection-remain largely neglected in relatively low-endemicity settings across the Amazon. METHODOLOGY/PRINCIPAL FINDINGS: Overall, 1,539 children participating in a birth cohort study in the main transmission hotspot of Amazonian Brazil had a questionnaire administered, and blood sampled at the two-year follow-up visit. Only 7.1% of them experienced malaria confirmed by microscopy during their first 2 years of life- 89.1% of the infections were caused by P. vivax. Young infants appear to be little exposed to, or largely protected from infection, but children >12 months of age become as vulnerable to vivax malaria as their mothers. Few (1.4%) children experienced ≥4 infections during the 2-year follow-up, accounting for 43.4% of the overall malaria burden among study participants. Antenatal malaria diagnosed by microscopy during pregnancy or by PCR at delivery emerged as a significant correlate of subsequent risk of P. vivax infection in the offspring (incidence rate ratio, 2.58; P = 0.002), after adjusting for local transmission intensity. Anti-P. vivax antibodies measured at delivery do not protect mothers from subsequent malaria; whether maternal antibodies transferred to the fetus reduce early malaria risk in children remains undetermined. Finally, recent and repeated vivax malaria episodes in early childhood are associated with increased risk of anemia at the age of 2 years in this relatively low-endemicity setting. CONCLUSIONS/SIGNIFICANCE: Antenatal infection increases the risk of vivax malaria in the offspring and repeated childhood P. vivax infections are associated with anemia at the age of 2 years.

Effect of Vitamin A status during pregnancy on maternal anemia and newborn birth weight: results from a cohort study in the Western Brazilian Amazon.

PURPOSE: Inadequate Vitamin A (VA) status during pregnancy has been associated with maternal anemia and suboptimal newborn birth weight (BW). We assessed the effect of gestational serum retinol and ß-carotene (µmol/L), in different moments during pregnancy, on maternal hemoglobin (Hb, g/L) and anemia (Hb < 110.0 g/L) at delivery, and newborn BW (kg). METHODS: In a prospective cohort study in Cruzeiro do Sul, Western Brazilian Amazon, biomarkers of the VA status were assessed in the second and third trimesters in pregnancy. Serum retinol and ß-carotene were analyzed considering their effects in each and in both assessments (combined VA status), and the difference of serum values between assessments. Multiple linear and Poisson regression models were used with a hierarchical selection of covariates. RESULTS: A total of 488 mother-newborn pairs were surveyed. Combined VA deficiency status increased the risk for maternal anemia (adjusted prevalence ratio: 1.39; 95% CI 1.05-1.84), and was negatively associated with maternal Hb (ß - 3.30 g/L; 95% CI - 6.4, - 0.20) and newborn BW (ß - 0.10 kg; 95% CI - 0.20, - 0.00), adjusted for socioeconomic, environmental, obstetric, and antenatal characteristics, and nutritional indicators. However, the association for newborn BW was no longer significant after further adjustment for plasma ferritin. There were no significant associations between serum ß-carotene and the outcomes studied. CONCLUSION: Poor serum retinol status throughout pregnancy was associated with maternal anemia at delivery in Amazonian women. The current World Health Organization protocols for supplementation during antenatal care should consider VA status for planning recommendations in different scenarios.

High prevalence of gestational night blindness and maternal anemia in a population-based survey of Brazilian Amazonian postpartum women.

Nutrition during pregnancy is one of the key elements to good maternal and child health, as well as to lifetime landmarks. However, many pregnant women go undernourished in less developed settings. The purpose of this study was to estimate the prevalence and factors associated with gestational night blindness (GXN) and maternal anemia in a cross-sectional population-based study in Cruzeiro do Sul, Acre State, Western Brazilian Amazon. All women living in the municipality admitted at the only maternity-hospital in the city to delivery of a singleton infant were eligible to this study (n = 1,525). Recruitment of participants took place between July 2015 to June 2016. GXN was assessed in the postpartum period by WHO standardized interview. Maternal anemia was defined as hemoglobin at delivery < 110.0 g/L. We estimated prevalence rates and adjusted prevalence ratios (aPR), alongside 95% confidence intervals (95% CI), of the factors associated with the outcomes through multiple Poisson regression models with robust variance. Alarming prevalence of GXN (11.5%; 95% CI, 9.97-13.25) and maternal anemia (39.4%; 95% CI, 36.84-41.95) were found. Factors associated with GXN were (aPR; 95% CI): ≥ 5 residents in the household (2.06; 1.24-3.41), smoking during pregnancy (1.78; 1.15-2.78), and attending < 6 antenatal care visits (1.61; 1.08-2.40). Factors associated with maternal anemia were (aPR; 95% CI): maternal age < 19 years (1.18; 1.01-1.38), gestational malaria (1.22; 1.01-1.49), not taking micronutrient supplements during pregnancy (1.27; 1.01-1.62), and attending < 6 antenatal care visits (1.40; 1.15-1.70). High prevalence rates of GXN and maternal anemia in these postpartum women may reflect poor assistance during antenatal care, underlying the importance of rethinking current protocols related to nutrition in pregnancy.

Factors affecting exclusive breastfeeding in the first month of life among Amazonian children.

Early life feeding practices can directly affect the growth, development, and survival of a child. This study aimed to estimate the frequency of and factors associated with exclusive breastfeeding (EBF) in the first month of life among Amazonian infants. We used data of 1,523 mother-child pairs of the MINA-Brazil birth cohort study. Mothers were interviewed soon after delivery at baseline and by telephone at 30-45 days postpartum (n = 962, 63.2% of those eligible). Kaplan-Meier survival analysis and accelerated failure-time (AFT) models were used to estimate the probability of EBF and the factors associated with EBF duration in the first month. At 30 days of age, 36.7% of the studied population (95% confidence interval [CI] 33.6-39.8) were exclusively breastfed, with a median duration of 16 days. Considering all eligible children for follow-up, the probability of EBF in the first month was 43.7% (95% CI 40.4-46.8), and the median duration was 30 days. The duration of EBF (time-ratio, TR) was 28% longer among multiparous mothers (TR 1.28; 95% CI 1.11-1.48). The use of a pacifier and the occurrence of wheezing were associated with a reduced EBF duration by 33% (TR 0.67; 95% CI 0.58-0.77) and 19% (TR 0.80; 95% CI 0.70-0.93), respectively. These results highlight that EBF among children in the Brazilian Amazon is considerably below international recommendations, and indicate the immediate need to plan and implement actions to promote and support breastfeeding early in life.

Predictors of vitamin A status among pregnant women in Western Brazilian Amazon.

Determining the predictors of serum retinol at mid-pregnancy is relevant for planning interventions aimed at improving vitamin A status of pregnant women and their offspring. This prospective study assessed predictors of serum retinol at the beginning of the third trimester of pregnancy. We enrolled 442 pregnant women living in the urban area of Cruzeiro do Sul, Western Brazilian Amazon. Demographic, socio-economic, environmental and clinical characteristics as well as obstetric history, anthropometric, dietary and biochemical data, including serum retinol, were gathered between 16 and 20 gestational weeks. Serum retinol also measured at the beginning of the third trimester of pregnancy (approximately 28 gestational weeks) was the outcome of interest. Multiple linear regression models were used to evaluate associations with the outcome. Overall, the following variables explained serum retinol at the beginning of the third trimester of pregnancy in the adjusted model (R 2 = 11·1 %): seasonality (winter season - November to April; ß=0·134; 95 % CI 0·063, 0·206), weekly consumption of Amazonian fruits (ß=0·087; 95 % CI 0·012, 0·162) and retinol concentrations between 16 and 20 gestational weeks (ß=0·045; 95 % CI 0·016, 0·074) were positively associated, whereas having a smoker in the house was negatively associated (ß=-0·087; 95 % CI: -0·166, -0·009). Consumption of pro-vitamin A-rich fruits by pregnant women should be encouraged. Passive smoking may play a role in decreasing vitamin A status as a proxy of smoking exposure during pregnancy.

The Hidden Burden of Plasmodium vivax Malaria in Pregnancy in the Amazon: An Observational Study in Northwestern Brazil.

We measured the prevalence of malaria in pregnancy and estimated its impact on birth weight and length and maternal hemoglobin in 1,180 women from Juruá Valley, the main malaria hotspot in Brazil. Antenatal malaria episodes, 74.6% of them due to Plasmodium vivax, were microscopically diagnosed in 8.0% of the women and were associated with an average reduction in birth weight z-scores of 0.35 (95% confidence interval [CI] = 0.14-0.57) and in birth length z-scores of 0.31 (95% CI = 0.08-0.54), compared with malaria-free pregnancies. Affected mothers had a mean decrease in hemoglobin concentration at delivery of 0.33 g/100 mL (95% CI = 0.05-0.62 g/100 mL); 51.6% were anemic. The timing and frequency of antenatal infections influenced pregnancy outcomes and first- or second-trimester infections were not associated with decreased birth weight and length and maternal hemoglobin at delivery. Although repeated antenatal vivax infections were associated with poorer birth outcomes, even a single vivax malaria episode was associated with a significant reduction in birth weight and length and maternal hemoglobin. Overall, 7.5% women had the parasite's DNA found in peripheral blood at delivery. Most (83.1%) of these 89 perinatal infections were due to P. vivax and only 7.9% of them progressed to symptomatic disease after delivery. Plasmodium vivax and Plasmodium falciparum DNA was found in 0.6% and 0.3% of 637 cord blood samples examined, respectively, but only one newborn developed clinical neonatal malaria. Our results further challenge the notion that vivax malaria is relatively benign during pregnancy and call for better strategies for its prevention.