Vitamin D insufficiency, excessive weight gain, and insulin resistance during pregnancy.

BACKGROUND AND AIMS: Vitamin D insufficiency has been related to metabolic complications during pregnancy, including insulin resistance. There is evidence that excessive weight gain can negatively influence 25-hydroxyvitamin D (25(OH)D) concentrations. We aimed to investigate the association of vitamin D insufficiency during pregnancy (25(OH)D3 < 75 nmol/L in the second and third trimesters) with insulin resistance, and explore whether excessive gestational weight gain (GWG) could modify such relationship. METHODS AND RESULTS: A prospective longitudinal analysis was conducted within the MINA-Brazil Study among 444 pregnant women enrolled in antenatal care and with complete data on 25(OH)D3, weight gain, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). Quantile and logistic regression models were conducted with adjustment for sociodemographic, obstetric, and lifestyle characteristics, as well as gestational age and seasonality at outcome assessment. Predicted probabilities for insulin resistance (HOMA-IR>2.71) were estimated according to excessive GWG. Persistent vitamin D insufficiency was associated with increasing insulin concentrations (p for trend = 0.04); pregnant women with vitamin D insufficiency in the second or third trimester had an odds ratio of 1.83 (95% confidence interval (95% CI) = 1.03, 3.27) for insulin resistance, with significant modification by GWG (p = 0.038). Among participants without excessive GWG, the predicted probability for insulin resistance was 0.345 (95% CI = 0.224, 0.467) for those with persistent vitamin D insufficiency, and 0.134 (95% CI = 0.046, 0.221) for those who were sufficient in vitamin D. Probabilities for insulin resistance did not vary according to vitamin D status among participants with excessive GWG. CONCLUSION: Vitamin D insufficiency was associated with insulin resistance in the third trimester of pregnancy, dependent on excessive GWG.

Interacting Epidemics in Amazonian Brazil: Prior Dengue Infection Associated With Increased Coronavirus Disease 2019 (COVID-19) Risk in a Population-Based Cohort Study.

BACKGROUND: Immunity after dengue virus (DENV) infection has been suggested to cross-protect from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality. METHODS: We tested whether serologically proven prior DENV infection diagnosed in September-October 2019, before the coronavirus disease 2019 (COVID-19) pandemic, reduced the risk of SARS-CoV-2 infection and clinically apparent COVID-19 over the next 13 months in a population-based cohort in Amazonian Brazil. Mixed-effects multiple logistic regression analysis was used to identify predictors of infection and disease, adjusting for potential individual and household-level confounders. Virus genomes from 14 local SARS-CoV-2 isolates were obtained using whole-genome sequencing. RESULTS: Anti-DENV immunoglobulin G (IgG) was found in 37.0% of 1285 cohort participants (95% confidence interval [CI]: 34.3% to 39.7%) in 2019, with 10.4 (95% CI: 6.7-15.5) seroconversion events per 100 person-years during the follow-up. In 2020, 35.2% of the participants (95% CI: 32.6% to 37.8%) had anti-SARS-CoV-2 IgG and 57.1% of the 448 SARS-CoV-2 seropositives (95% CI: 52.4% to 61.8%) reported clinical manifestations at the time of infection. Participants aged >60 years were twice more likely to have symptomatic COVID-19 than children under 5 years. Locally circulating SARS-CoV-2 isolates were assigned to the B.1.1.33 lineage. Contrary to the cross-protection hypothesis, prior DENV infection was associated with twice the risk of clinically apparent COVID-19 upon SARS-CoV-2 infection, with P values between .025 and .039 after adjustment for identified confounders. CONCLUSIONS: Higher risk of clinically apparent COVID-19 among individuals with prior dengue has important public health implications for communities sequentially exposed to DENV and SARS-CoV-2 epidemics.

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.

Vitamin D sufficiency in young Brazilian children: associated factors and relationship with vitamin A corrected for inflammatory status.

OBJECTIVE: To assess sociodemographic, nutritional and health conditions associated with vitamin D sufficiency among young Brazilian children living at different latitudes. DESIGN: Cross-sectional analysis with a four-level model of inflammation to correct micronutrient concentrations. Prevalence ratios (PR; 95 % CI) were estimated for factors associated with vitamin D sufficiency (≥50 nmol/l), adjusting for child's sex, age, skin colour, stunting and vitamin A+D supplementation. SETTING: Primary health-care units in four Brazilian cities located at lower (7°59'26·9016″S and 9°58'31·3864″S) and higher latitudes (16°41'12·7752″S and 30°2'4·7292″S). PARTICIPANTS: In total 468 children aged 11-15 months were included in the analysis. RESULTS: Only 31·8 % of children were vitamin D sufficient (concentration <30 nmol/l and <50 nmol/l among 32·9 and 68·2 %, respectively). Living at higher latitudes was associated with reduced prevalence of vitamin D sufficiency compared with lower latitudes (PR = 0·65; 95 % CI 0·49, 0·85). Maternal education ≥9 years positively influenced a sufficient vitamin D status in children. After correction for inflammatory status, each increase of 1 µmol/l in vitamin A concentration was associated with a 1·38-fold higher prevalence of vitamin D sufficiency (95 % CI 1·18, 1·61). Progressive decline in the prevalence of vitamin D sufficiency was associated with marginal and deficient status of vitamin A (Ptrend = 0·001). CONCLUSIONS: Lower latitude, higher maternal education and vitamin A concentration were positively associated with vitamin D sufficiency in young Brazilian children. These findings are relevant for planning public health strategies for improving vitamin D status starting in early infancy.

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.

Serum folate and vitamin B12 status in young Brazilian children.

OBJECTIVE: To assess the nutritional status of folate and vitamin B12 with anaemia in young children. DESIGN: A cross-sectional study was conducted at the primary health-care centres of four Brazilian cities. Folate and vitamin B12 were assessed by fluoroimmunoassay. Multilevel Poisson regression models were used to explore the association of folate and vitamin B12 status in relation to anaemia in young children. SETTING: Brazil.ParticipantsChildren (n 460) aged 11 to 15 months. RESULTS: The median (interquartile range) of serum folate was 39·7 (28·8-55·3) nmol/l and only four children presented with folate deficiency (<10 nmol/l). Surprisingly, 30·9 % of children presented with serum folate concentrations above the upper limit of detectable values by the commercial kit used for analysis. The frequency of vitamin B12 deficiency (<148 pmol/l) was 15 % and it was inversely associated with the highest tertile of serum folate concentrations (P<0·001). Having high serum folate concentration (≥50·1 nmol/l) and vitamin B12≥148 pmol/l was associated with lower frequency of anaemia in these children (prevalence ratio=0·53; 95% CI 0·30, 0·92). CONCLUSIONS: High frequency of elevated serum concentration of folate was found among young Brazilian children and 15 % of them had vitamin B12 deficiency. The combination of high serum folate and normal vitamin B12 status was associated with a lower frequency of anaemia in these children. Improvements in the current strategies to promote healthy food-based complementary feeding along with prevention and control of micronutrient deficiencies are recommended to improve children's health.

Multiple micronutrients in powder delivered through primary health care reduce iron and vitamin A deficiencies in young Amazonian children.

OBJECTIVE: We evaluated the effect of home fortification with multiple micronutrient powder (MNP) on anaemia and micronutrient status of young Amazonian children. DESIGN: A pragmatic controlled trial was performed. A control group (CG) of children aged 11-14 months was recruited in the routine of primary health-care centres for assessing anaemia and micronutrient status. At the same time, an intervention group (IG) of infants aged 6-8 months was recruited in the same health centres to receive MNP daily in complementary feeding for 2 months. The IG children were assessed 4-6 months after enrolment (n 112) when they had reached the age of the CG participants (n 128) for comparisons. SETTING: Primary health centres in Rio Branco city, Brazilian Amazon. SUBJECTS: A total of 240 children aged<2 years. RESULTS: In the CG, the prevalence of anaemia (Hb8·3 mg/l) and vitamin A deficiency (VAD; serum retinol <0·70 µmol/l) was 20·3 %, 72·4 % and 18·6 %, respectively. Among the IG participants (aged 11-14 months), the prevalence of anaemia, ID and VAD was 15·2 %, 25·2 % and 4·7 %, respectively. The IG had a lower likelihood of ID (prevalence ratio (95 % CI): 0·34 (0·24, 0·49)) and VAD (0·25 (0·09, 0·64)). CONCLUSIONS: Home fortification of complementary feeding delivered through primary health care was effective in reducing iron and vitamin A deficiencies among young Amazonian children.

Factors Associated with Age at Breastfeeding Cessation in Amazonian Infants: Applying a Proximal-Distal Framework.

Introduction Breastfeeding is an important determinant of child survival and normal growth and development, but breastfeeding prevalence is generally low in Brazil. Factors associated with infant feeding practices there are not well understood. This paper examines factors associated with breastfeeding cessation in a township in the western Brazilian Amazon. Methods A cross-sectional, population-based study was conducted among children younger than 25 months and collected information on maternal and child characteristics. Survival analysis based on a proximal-distal framework examined the association between breastfeeding duration and socioeconomic and maternal/child biological factors. Results The median breastfeeding duration among 101 children who were no longer breastfeeding was 120 days. Almost two-thirds (63 %) of these children stopped breastfeeding before 6 months of age. In the larger sample of 209 children, 74.6 % had previously been bottle-fed. Considering the full proximal-distal model, a child who had ever been bottle-fed was expected to cease breastfeeding about 88 % sooner than one who was never bottle-fed (p < 0.001). Children in the second-poorest wealth quartile stopped breastfeeding sooner than children in the poorest quartile (p < 0.05). Discussion Breastfeeding cessation in the study area occurred much earlier than the recommended 2 years of age. Factors associated with ending breastfeeding early included ever-use of a bottle, having a single mother, and belonging to the second-poorest wealth quartile. Further research is needed to better understand these factors and other barriers women face to continuing breastfeeding.

Influence of early life factors on body mass index trajectory during childhood: a population-based longitudinal analysis in the Western Brazilian Amazon.

Low- to middle-income countries may experience the occurrence of a dual burden of under and overnutrition. To better understand the overall progression of body mass index (BMI) during childhood, we estimated average BMI-for-age z-score (BAZ) growth curves in a population-based longitudinal study of 255 children living in the Brazilian Amazon. Children were aged 0.1-5.5 years at recruitment (2003). We collected data on socio-economic and maternal characteristics, children's birthweight and infant feeding practices. Child anthropometric measurements were taken in 2003, 2007 and 2009. BAZ differences among categories of exposure variables were calculated at 6 and 12 months, and 2, 7 and 10 years. At baseline, the mean (standard deviation) age was 2.6 (1.4) years; 12.9% were overweight and 3.9% thin. After adjustment, mean BAZ estimates were mostly negative. Boys were close to the median value for BAZ until 12 months, whereas girls were below the median (P=0.05). Children from households above the wealth median were 0.36 z- and 0.49 z-less underweight than poorer children at 7 and 10 years, respectively (P<0.01). Maternal BMI was positively associated with children's BAZ since 12 months old; BAZ in children from overweight mothers was higher by 0.69 compared with their counterparts at 10 years (P<0.01). Birthweight was positively related to BAZ up until 2 years (P=0.01). Socio-economic background and maternal nutritional status are important predictors of BAZ throughout childhood. Although excessive weight gain is a public health concern, it is critical to restrict inequities, while promoting healthier growth in developing countries.

BMI gain and insulin resistance among school-aged children: a population-based longitudinal study in the Brazilian Amazon.

Investigation of the determinants of metabolic outcomes associated with non-communicable diseases is increasingly important in developing countries, but such parameters have not been explored extensively during childhood. The present study assessed the impact of weight gain, measured as BMI-for-age Z-scores, on glucose and insulin concentrations, homeostasis model assessment index of insulin resistance (HOMA-IR) values, and systolic and diastolic blood pressure during school years among Amazonian children. A population-based prospective study of 696 children aged >4 to ≤ 10 years with complete anthropometric information at baseline (51% females and 86% of mixed race) was carried out; 411 children had data on metabolic parameters after a median follow-up period of 2.0 years (range 1.7-2.6 years). During follow-up, there was a significant increase in the proportion of overweight children (BMI-for-age Z-score >1) from 10.1 to 15.8% (P= 0.003). In linear regression models adjusted for the child's sex, age, race/ethnicity, baseline household wealth, birth weight and pubertal development stage, for each unit of BMI-for-age Z-score variation during follow-up, an increase of 8.58 (95% CI 7.68, 9.60) pmol/l in fasting plasma insulin concentrations and 1.47 (95% CI 1.30, 1.66) in HOMA-IR values was observed. There was no significant impact of weight gain on glucose concentrations and systolic and diastolic blood pressure. In conclusion, we found evidence that an increase in BMI during a 2-year period affected insulin resistance during school years. Considering the significant increase in overweight in this age group, special attention should be paid to monitoring increases in BMI in children from the Brazilian Amazon.

Food insecurity and dental caries in schoolchildren: a cross-sectional survey in the western Brazilian Amazon.

We analyzed the association between food insecurity and dental caries in 7- to 9-yr-old schoolchildren. We performed a cross-sectional survey nested in a population-based cohort study of 203 schoolchildren. The participants lived in the urban area of a small town within the western Brazilian Amazon. Dental examinations were performed according to criteria recommended by the World Health Organization. The number of decayed deciduous and permanent teeth as a count variable was the outcome measure. Socio-economic status, food security, behavioral variables, and child nutritional status, measured by Z-score for body mass index (BMI), were investigated, and robust Poisson regression models were used. The results showed a mean (SD) of 3.63 (3.26) teeth affected by untreated caries. Approximately 80% of schoolchildren had at least one untreated decayed tooth, and nearly 60% lived in food-insecure households. Sex, household wealth index, mother's education level, and food-insecurity scores were associated with dental caries in the crude analysis. Dental caries was 1.5 times more likely to be associated with high food-insecurity scores after adjusting for socio-economic status and sex. A significant dose-response relationship was observed. In conclusion, food insecurity is highly associated with dental caries in 7- to 9-yr-old children and may be seen as a risk factor. These findings suggest that food-security policies could reduce dental caries.

Internal consistency of the Strengths and Difficulties Questionnaire in Amazonian children.

OBJECTIVE: To describe the frequency of behavioral problems and the internal consistency of the parent version of the Strengths and Difficulties Questionnaire (SDQ-P) in Amazonian preschool children during the covid-19 pandemic. METHODS: Data from the Maternal and Child Health and Nutrition in Acre (MINA-Brazil) study, a population-based birth cohort in the Western Brazilian Amazon, were used. The SDQ-P was applied in 2021 at the five-year follow-up visit to parents or caregivers of 695 children (49.4% of which were girls). This instrument is a short behavioral screening questionnaire composed of 25 items reorganized into five subscales: emotional symptoms, conduct problems, hyperactivity/inattention, peer relationship problems, and prosocial behavior. Cases of behavioral problems were defined according to the original SDQ cut-offs based on United Kingdom norms. Moreover, cut off points were estimated based on the SDQ-P percentile results of our study sample. Internal consistency was assessed by calculating Cronbach's alpha coefficient and McDonald's omega for each scale. RESULTS: According to the cut-offs based on our studied population distribution, 10% of all children had high or very high total difficulty scores, whereas it was almost twice when the original SDQ cut-offs based on United Kingdom norms, were applied (18%). Differences were also observed in the other scales. Compared to girls, boys showed higher means of externalizing problem and lower means of prosocial behavior. The five-factor model showed a moderate internal consistency of the items for all scales (0.60 ≤ α ≤ 0.40), except for total difficulty scores, which it considered substantial (α > 0.61). CONCLUSIONS: Our results support the usefulness of SDQ in our study population and reinforce the need for strategies and policy development for mental health care in early life in the Amazon.

Maternal depression and offspring mental health at age 5: MINA-Brazil cohort study.

OBJECTIVE: To identify longitudinal patterns of maternal depression between three months and five years after child's birth, to examine predictor variables for these trajectories, and to evaluate whether distinct depression trajectories predict offspring mental health problems at age 5 years. METHODS: We used data from the Maternal and Child Health and Nutrition in Acre (MINA-Brazil) study, a population-based birth cohort in the Western Brazilian Amazon. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at 3 and 6-8 months, and 1 and 2 years after delivery. Mental health problems in 5-year-old children were evaluated with the Strengths and Difficulties Questionnaire (SDQ) reported by parents. Trajectories of maternal depression were calculated using a group-based modelling approach. RESULTS: We identified four trajectories of maternal depressive symptoms: "low" (67.1%), "increasing" (11.5%), "decreasing" (17.4%), and "high-chronic" (4.0%). Women in the "high/chronic" trajectory were the poorest, least educated, and oldest compared with women in the other trajectory groups. Also, they were more frequently multiparous and reported smoking and having attended fewer prenatal consultations during pregnancy. In the adjusted analyses, the odds ratio of any SDQ disorder was 3.23 (95%CI: 2.00-5.22) and 2.87 (95%CI: 1.09-7.57) times higher among children of mothers belonging to the "increasing" and "high-chronic" trajectory groups, respectively, compared with those of mothers in the "low" depressive symptoms group. These differences were not explained by maternal and child characteristics included in multivariate analyses. CONCLUSIONS: We identified poorer mental health outcomes for children of mothers assigned to the "chronic/severe" and "increasing" depressive symptoms trajectories. Prevention and treatment initiatives to avoid the adverse short, medium, and long-term effects of maternal depression on offspring development should focus on women belonging to these groups.

Prevalence and predictors of breastfeeding in the MINA-Brazil cohort.

OBJECTIVE: To describe the prevalence and factors associated with exclusive (EBF) and continued breastfeeding (BF) practices among Amazonian children. METHODS: Data from 1,143 mother-child pairs recorded on the Maternal and Child Health and Nutrition in Acre (MINA-Brazil) birth cohort were used. Information on EBF and BF was collected after childbirth (July 2015-June 2016) and during the follow-up visits at 1 and 6 months postpartum, 1, 2, and 5 years of age. For longitudinal analysis, the outcomes were EBF and BF duration. Probability of breastfeeding practices were estimated by Kaplan-Meier survival analysis. Associations between baseline predictors variables and outcomes among children born at term were assessed by extended Cox regression models. RESULTS: EBF frequencies (95% confidence interval [95%CI]) at 3 and 6 months of age were 33% (95%CI: 30.2-36.0) and 10.8% (95%CI: 8.9-12.9), respectively. Adjusted hazard ratio for predictors of early EBF cessation were: being a first-time mother = 1.47 (95%CI: 1.19-1.80), feeding newborns with prelacteals = 1.70 (95%CI: 1.23-2.36), pacifier use in the first week of life = 1.79 (95%CI: 1.44-2.23) or diarrhea in the first two weeks of life = 1.70 (95%CI: 1.15-2.52). Continued BF frequency was 67.9% (95%CI: 64.9-70.8), 29.3% (95%CI: 26.4-32.4), and 1.7% (95%CI: 0.9-2.8) at 1, 2 and 5 years of age, respectively. Adjusted hazard ratio for predictors of early BF cessation were: male sex = 1.23 (95%CI: 1.01-1.49), pacifier use in the first week of life = 4.66 (95%CI: 2.99-7.26), and EBF less than 3 months = 2.76 (95%CI: 1.64-4.66). CONCLUSIONS: EBF and continued BF duration among Amazonian children is considerably shorter than recommendations from the World Health Organization. Significant predictors of breastfeeding practices should be considered for evaluating local strategies to achieve optimal breastfeeding practices.

Prevalence and correlates of childhood anemia in the MINA-Brazil birth cohort study.

OBJECTIVE: This study aimed to describe the prevalence and predictors of childhood anemia in an Amazonian population-based birth cohort study. METHODS: Prevalence of maternal anemia was estimated at delivery (hemoglobin [Hb] concentration < 110 g/L) in women participating in the MINA-Brazil birth cohort study and in their children, examined at ages one, two (Hb < 110 g/L), and five (Hb < 115 g/L). Moreover, ferritin, soluble transferrin receptor, and C-reactive protein concentrations were measured in mothers at delivery and in their 1- and 2-year-old children to estimate the prevalence of iron deficiency and its contribution to anemia, while adjusting for potential confounders by multiple Poisson regression analysis (adjusted relative risk [RRa]). RESULTS: The prevalence 95% confidence interval (CI) of maternal anemia, iron deficiency, and iron-deficiency anemia at delivery were 17.3% (14.0-21.0%), 42.6% (38.0-47.2%), and 8.7% (6.3-11.6)%, respectively (n = 462). At one year of age (n = 646), 42.2% (38.7-45.8%) of the study children were anemic, 38.4% (34.6-42.3%) were iron-deficient, and 26.3 (23.0-29.9) had iron-deficiency anemia. At two years of age (n = 761), these values decreased to 12.8% (10.6-15.2%), 18.1% (15.5-21.1%), and 4.1% (2.8-5.7%), respectively; at five years of age (n = 655), 5.2% (3.6-7.2%) were anemic. Iron deficiency (RRa = 2.19; 95%CI: 1.84-2.60) and consumption of ultra-processed foods (UPF) (RRa = 1.56; 95%CI: 1.14-2.13) were significant contributors to anemia at 1 year, after adjusting for maternal schooling. At 2 years, anemia was significantly associated with maternal anemia at delivery (RRa: 1.67; 95%CI: 1.17-2.39), malaria since birth (2.25; 1.30-3.87), and iron deficiency (2.15; 1.47-3.15), after adjusting for children's age and household wealth index. CONCLUSIONS: Anemia continues to be highly prevalent during pregnancy and early childhood in the Amazon. Public health policies should address iron deficiency, UPF intake, maternal anemia, and malaria to prevent and treat anemia in Amazonian children.

Polymorphisms in genes involved in folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia.

High folate intake has been suggested as an important factor in cancer prevention; however, previous studies on the relation among folate intake, serum folate, and plasma homocysteine (hcy) are controversial. We conducted a hospital-based, case-control study in Brazil investigating associations between dietary and circulating vitamins B-6 and B-12 and folate, hcy, genotypes of folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), methionine synthase reductase (MTRR A66G), and reduced folate carrier (RFC1 G80A) and risk of cervical intraepithelial neoplasia (CIN) grades 1 (CIN1), 2 (CIN2), and 3 (CIN3). The study was composed by 453 controls, 140 CIN1, 126 CIN2, and 231 CIN3. We investigated the joint effects of genetic variants of folate-related genes using genetic risk scores (GRSs) by summing the number of risk alleles for CIN1 and CIN2+ (CIN2 and CIN3 cases). The OR (95% CI) for CIN1 and CIN2+ per each risk allele were 1.29 (1.01, 1.65) and 1.22 (1.01, 1.46), respectively. An association between folate intake and CIN2+ was observed only after stratification according to GRS: crude OR (95% CI) for lower folate intake and GRS ≥ 4 was 1.67 (0.92, 3.04) (P-trend < 0.001) compared with higher folate intake (above the median) and GRS ≤ 3. The CIN2+ risk of lower serum vitamin B-6 and GRS ≥ 4 was 2.14 (0.92, 5.02) (P-trend = 0.05) and lower serum folate (below the median) and GRS ≥ 4 was 0.49 (0.20, 1.17) (P-trend = 0.05) after adjustment for confounding variables and human papillomavirus infection. Our data suggest that polymorphisms in genes related to folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia.

Improved estimates of foetal growth are associated with perinatal outcomes: A latent modelling approach in a population-based birth cohort.

Background: We aimed to estimate latent foetal growth conditions and explore their determinants among maternal characteristics and ultrasound biometric parameters. We additionally investigated the influence of foetal growth conditions on perinatal variables. Methods: We used data from live-born singletons in the Maternal and Child Health and Nutrition in Acre, Brazil (MINA-Brazil Study) population-based birth cohort. Maternal and perinatal characteristics were assessed in medical records from the maternity hospital and interviews with participants from July 2015 to June 2016. A sub-sample went through ultrasound examinations during the antenatal period, with assessment of foetal head and abdominal circumferences, and femur length. We estimated latent foetal growth conditions with a structural equation modelling framework, informed by the child's birth weight z-scores (BWZ) and birth length z-scores (BLZ) according to gestational age. Odds ratios and 95% confidence intervals (CIs) for the occurrence of perinatal events were estimated according to linear predictions of the latent variable. Results: We included 1253 participants. Latent foetal growth conditions explained 88.3% of BWZ and 53.7% of BLZ variation. Maternal elevated blood pressure, primiparity, smoking, malaria, and insufficient gestational weight gain negatively impacted foetal growth conditions. In the subsample (n = 499), ultrasound biometric parameters assessed at 28 weeks were positively associated with the latent variable, with the largest contribution from foetal abdominal circumference. Each standardised unit of predicted foetal growth conditions halved the chance for preterm birth (95% CI = 0.26, 0.74) and longer hospital stay (>3 days) (95% CI = 0.28, 0.88). Conversely, BWZ and BLZ were not independently associated with these perinatal variables in separate logistic regression models. Conclusions: Latent foetal growth conditions jointly encompassing weight gain and linear growth during gestation were negatively influenced by a scenario of dual burden of maternal morbidities, with perinatal implications.

Prolonged breastfeeding, sugar consumption and dental caries at 2 years of age: A birth cohort study.

OBJECTIVES: Previous cohort studies have found a positive association between prolonged breastfeeding (≥12 months) on dental caries, but few of them analysed the mediated effect of sugar consumption on this association. This study investigated whether prolonged breastfeeding is a risk factor for caries at 2-year follow-up assessment (21-27 months of age) and whether this effect is mediated by sugar consumption. METHODS: A birth cohort study was performed in the Brazilian Amazon (n = 800). Dental caries was assessed using the dmf-t index. Prolonged breastfeeding was the main exposure. Data on baseline covariables and sugar consumption at follow-up visits were analysed. We estimated the OR for total causal effect (TCE) and natural indirect effect (NIE) of prolonged breastfeeding on dental caries using the G-formula. RESULTS: The prevalence of caries was 22.8% (95% CI: 19.8%-25.8%). Children who were breastfed for 12-23 months (TCE = 1.13, 95% CI: 1.05-1.20) and for ≥24 months (TCE = 1.27, 95% CI: 1.14-1.40) presented a higher risk of caries at age of 2 years than those breastfed <12 months. However, this risk was slightly mediated by a decreased frequency of sugar consumption at age of 2 years only for breastfeeding from 12 to 23 months (NIE; OR = 0.95, 95% CI: 0.91-0.97). CONCLUSIONS: In this study, the effect of prolonged breastfeeding on the increased risk of dental caries was slightly mediated by sugar consumption. Early feeding practices for caries prevention and promoting breastfeeding while avoiding sugar consumption should be targeted in the first 2 years of life.

Determinants of linear growth from infancy to school-aged years: a population-based follow-up study in urban Amazonian children.

BACKGROUND: Although linear growth during childhood may be affected by early-life exposures, few studies have examined whether the effects of these exposures linger on during school age, particularly in low- and middle-income countries. METHODS: We conducted a population-based longitudinal study of 256 children living in the Brazilian Amazon, aged 0.1 y to 5.5 y in 2003. Data regarding socioeconomic and maternal characteristics, infant feeding practices, morbidities, and birth weight and length were collected at baseline of the study (2003). Child body length/height was measured at baseline and at follow-up visits (in 2007 and 2009). Restricted cubic splines were used to construct average height-for-age Z score (HAZ) growth curves, yielding estimated HAZ differences among exposure categories at ages 0.5 y, 1 y, 2 y, 5 y, 7 y, and 10 y. RESULTS: At baseline, median age was 2.6 y (interquartile range, 1.4 y-3.8 y), and mean HAZ was -0.53 (standard deviation, 1.15); 10.2% of children were stunted. In multivariable analysis, children in households above the household wealth index median were 0.30 Z taller at age 5 y (P = 0.017), and children whose families owned land were 0.34 Z taller by age 10 y (P = 0.023), when compared with poorer children. Mothers in the highest tertile for height had children whose HAZ were significantly higher compared with those of children from mothers in the lowest height tertile at all ages. Birth weight and length were positively related to linear growth throughout childhood; by age 10 y, children weighing >3500 g at birth were 0.31 Z taller than those weighing 2501 g to 3500 g (P = 0.022) at birth, and children measuring ≥51 cm at birth were 0.51 Z taller than those measuring ≤48 cm (P = 0.005). CONCLUSIONS: Results suggest socioeconomic background is a potentially modifiable predictor of linear growth during the school-aged years. Maternal height and child's anthropometric characteristics at birth are positively associated with HAZ up until child age 10 y.

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.