Fernando C. Barros

International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project

BACKGROUND In 2006, WHO published international growth standards for children younger than 5 years, which are now accepted worldwide. In the INTERGROWTH-21(st) Project, our aim was to complement them by developing international standards for fetuses, newborn infants, and the postnatal growth period of preterm infants. METHODS INTERGROWTH-21(st) is a population-based project that assessed fetal growth and newborn size in eight geographically defined urban populations. These groups were selected because most of the health and nutrition needs of mothers were met, adequate antenatal care was provided, and there were no major environmental constraints on growth. As part of the Newborn Cross-Sectional Study (NCSS), a component of INTERGROWTH-21(st) Project, we measured weight, length, and head circumference in all newborn infants, in addition to collecting data prospectively for pregnancy and the perinatal period. To construct the newborn standards, we selected all pregnancies in women meeting (in addition to the underlying population characteristics) strict individual eligibility criteria for a population at low risk of impaired fetal growth (labelled the NCSS prescriptive subpopulation). Women had a reliable ultrasound estimate of gestational age using crown-rump length before 14 weeks of gestation or biparietal diameter if antenatal care started between 14 weeks and 24 weeks or less of gestation. Newborn anthropometric measures were obtained within 12 h of birth by identically trained anthropometric teams using the same equipment at all sites. Fractional polynomials assuming a skewed t distribution were used to estimate the fitted centiles. FINDINGS We identified 20,486 (35%) eligible women from the 59,137 pregnant women enrolled in NCSS between May 14, 2009, and Aug 2, 2013. We calculated sex-specific observed and smoothed centiles for weight, length, and head circumference for gestational age at birth. The observed and smoothed centiles were almost identical. We present the 3rd, 10th, 50th, 90th, and 97th centile curves according to gestational age and sex. INTERPRETATION We have developed, for routine clinical practice, international anthropometric standards to assess newborn size that are intended to complement the WHO Child Growth Standards and allow comparisons across multiethnic populations. FUNDING Bill & Melinda Gates Foundation.

Impact of breast feeding on admission for pneumonia during postneonatal period in Brazil: nested case›control study

Abstract Objective: To determine whether breast feeding protects infants against pneumonia and whether the protection varies with age. Design: Nested case-control study. Setting: Pelotas, southern Brazil. Subjects: Cases were 152 infants aged 28-364 days who had been admitted to hospital for pneumonia. Controls were 2391cases in a population based case-control study. Main outcome measure: Odds ratio of admission for pneumonia according to type of milk consumed (breast milk alone, breast and formula milk, or formula milk and other fluids only), use of fluid supplements apart from formula milk, and use of solid supplements. Results: Infants who were not being breast fed were 17 times more likely than those being breast fed without formula milk to be admitted to hospital for pneumonia (95% confidence interval 7.7 to 36.0). This relative risk was 61 (19.0 to 195.5) for children under 3 months old, decreasing to 10 (2.8 to 36.2) thereafter. Supplementation with solids was associated with a relative risk of 13.4 (7.6 to 23.5) for all infants and 175 (21.8to 1405.1) for those under 3 months old. Conclusion: Breast feeding protects young children against pneumonia, especially in the first months of life. These results may be used for targeting intervention campaigns at the most vulnerable age groups.

The associations of parity and maternal age with small-for-gestational-age preterm and neonatal and infant mortality: a meta-analysis.

BackgroundPrevious studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).MethodsData from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.ResultsNulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.ConclusionsNulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.FundingFunding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis

BACKGROUND Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. METHODS For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2,015,019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. FINDINGS Pooled overall RRs for preterm were 6·82 (95% CI 3·56-13·07) for neonatal mortality and 2·50 (1·48-4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34-2·50) for neonatal mortality and 1·90 (1·32-2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11-26·12). INTERPRETATION Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4--the reduction of child mortality. FUNDING Bill & Melinda Gates Foundation.

International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project

BACKGROUND In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. METHODS The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. FINDINGS We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. INTERPRETATION We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. FUNDING Bill & Melinda Gates Foundation.

Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation

BACKGROUND In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. METHODS We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. FINDINGS Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores -1·54 vs -3·13, difference 1·58 [95% CI 1·45-1·72]); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0·28 [95% CI 0·14-0·56]); and were less likely to have a history of rash during pregnancy (20·7% vs 61·4%, ratio 0·34 [95% CI 0·27-0·42]). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above -2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. INTERPRETATION Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. FUNDING Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust.

Weight Gain in the First Two Years of Life Is an Important Predictor of Schooling Outcomes in Pooled Analyses from Five Birth Cohorts from Low- and Middle-Income Countries

Schooling predicts better reproductive outcomes, better long-term health, and increased lifetime earnings. We used data from 5 cohorts (Brazil, Guatemala, India, the Philippines, and South Africa) to explore the relative importance of birthweight and postnatal weight gain for schooling in pooled analyses (n = 7945) that used appropriate statistical methods [conditional weight (CW) gain measures that are uncorrelated with prior weights] and controlled for confounding. One SD increase in birthweight, ∼0.5 kg, was associated with 0.21 y more schooling and 8% decreased risk of grade failure. One SD increase in CW gain between 0 and 2 y, ∼0.7 kg, was associated with higher estimates, 0.43 y more schooling, and 12% decreased risk of failure. One SD increase of CW gain between 2 and 4 y, ∼0.9 kg, was associated with only 0.07 y more schooling but not with failure. Also, in children born in the lowest tertile of birthweight, 1 SD increase of CW between 0 and 2 y was associated with 0.52 y more schooling compared with 0.30 y in those in the upper tertile. Relationships with age at school entry were inconsistent. In conclusion, weight gain during the first 2 y of life had the strongest associations with schooling followed by birthweight; weight gain between 2 and 4 y had little relationship to schooling. Catch-up growth in smaller babies benefited schooling. Nutrition interventions aimed at women and children under 2 y are among the key strategies for achieving the millennium development goal of universal primary education by 2015.

Prevalência de obesidade em adultos e seus fatores de risco

INTRODUCTION: A population-based cross-sectional study was conducted in Pelotas, Southern Brazil, with the objective of determining the prevalence of obesity and identify associated, variables as this condition increased markedly in the country between 1974 and 1989. MATERIAL AND METHODS: One thousand and thirty-five adults between 20 and 69 years of age were studied. Obesity was defined as a Body Mass Index - BMI - equal to or over 30 Kg/square meter). The multivariate analyses took into account the hierarchical model of the variables associated with obesity for both men and women. RESULTS: The prevalence for the overall population was of 21% (CI 18 - 23). It was higher among women - 25% (CI 22 - 29) than for men - 15% (CI 12 - 18). Socioeconomic status was positively associated with obesity among men, whereas the opposite situation was reported for women, with those belonging to the poorest social strata presenting increased BMI. Reported obesity in their parents was associated with increased BMI in the subjects, and this association remained statistically significant even after compensating for the effect of possible confounding variables. Self-reported diabetes and arterial hypertension doubled the risk of obesity, whereas non-smoking was associated with obesity only among women. Variables which were not associated with obesity after adjusting for confounders were alcohol consumption, marital status and parity. Women having more daily meals were less prone to obesity, even after controlling for confounders, and this association was not quite significant for men (p = 0.07). CONCLUSIONS: The prevalence of obesity was higher among women, and important differences in risk factors were noticed when the population was considered by sex.

Operacionalização do conceito de classe social em estudos epidemiológicos

Procura-se demonstrar que e possivel operacionalizar o conceito de classe social de forma a utiliza-lo em estudos epidemiologicos. Foi adaptado as caracteristicas da formacao social de Pelotas, RS (Brasil), modelo de classificacao desenvolvido para o Mexico e comparado com o desenvolvido para Ribeirao Preto, SP (Brasil). Mediu-se o poder discriminatorio das duas classificacoes em termos do processo saude-doenca, tendo como variavel dependente o crescimento de 5.384 criancas nascidas em 1982. As duas classificacoes estao associadas com diferencas significativas (P<0,001) no crescimento infantil, mas o modelo do Mexico mostra melhor poder discriminatorio do que a classificacao de Ribeirao Preto. Quando ambas foram incluidas em uma analise multivariada do peso e da altura das criancas, o efeito do modelo do Mexico foi altamente significativo (P<0,001), ao contrario do efeito da classificacao, modelo Ribeirao Preto.

Maternal education in relation to early and late child health outcomes: Findings from a Brazilian cohort study

In a population-based cohort of approximately 6000 Brazilian children, the associations between maternal education and a number of child health outcomes were studied while controlling for potentially confounding variables such as family income and education of the husband. In the crude analyses, maternal education was associated with perinatal and infant mortality, hospital admissions in the first 20 months of life and the three nutritional indicators (length-for-age, weight-for-age and weight-for-length) at mean age 20 months. After adjustment for confounding, the apparent associations with outcomes in early infancy--birthweight and perinatal mortality--were no longer present, while that with infant mortality persisted despite being reduced. Strong associations remained with later outcomes including hospital admissions, length-for-age and weight-for-age at mean age 20 months. Among infants born to women with little or no schooling, deaths due to diarrhoea, pneumonia and other infectious diseases were particularly common. These findings support the hypothesis that maternal education has an effect on child health which is partly independent from that of other socioeconomic factors; they also suggest that maternal care is more important than the biological characteristics of the mothers since stronger effects were observed for the late (postneonatal mortality, hospital admissions and nutritional status) than for the early (birthweight, perinatal mortality) outcomes.