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Importance: This study introduces how the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) international birth weight standards alter our previous understanding and interpretations of fetal growth restriction as represented by small for gestational age (SGA) status., Objectives: To compare the birth weight distributions of the INTERGROWTH-21st international standard to commonly used US references and examine the differences in the prevalence and neonatal mortality risk of SGA status (below the 10th percentile of a population reference)., Design, Setting, and Participants: We analyzed data from 16 prospective cohorts of newborns on gestational age, birth weight, and systematic mortality follow-up through 28 days from 10 low- and middle-income countries. The studies included were conducted between 1983 and 2008. The analysis was conducted in 2014. Infants were categorized as SGA using the 1991 US birth weight reference, the 1999-2000 US birth weight reference, and the new INTERGROWTH-21st standard. For each study, we compared the SGA prevalence and the risk ratio between SGA status and neonatal mortality, calculated using Poisson regression with robust error variance., Main Outcomes and Measures: We examine neonatal mortality (death within the first 28 days after birth) as the main outcome measure., Results: The pooled SGA prevalence was 23.7% (95% CI, 16.5%-31.0%) using the INTERGROWTH-21st standard compared with 36.0% (95% CI, 27.0%-45.0%) with the US 2000 reference. The relative decrease in prevalence was larger among infants born at 33 to less than 37 weeks' gestation compared with term infants. The pooled neonatal mortality risk did not differ significantly; the adjusted risk ratios were 2.13 (95% CI, 1.78-2.54; P < .001) for the INTERGROWTH-21st standard and 2.12 (95% CI, 1.81-2.48; P < .001) for the US 2000 reference., Conclusions and Relevance: To our knowledge, INTERGROWTH-21st is the first international newborn standard for size for gestational age for healthy fetal growth. We observed a greater-than-one-quarter reduction in SGA prevalence and no significant change in the associated neonatal mortality risk, resulting in a decrease in the percentage of neonatal death attributable to SGA. Our study sheds light on how previously published studies on SGA status may be reinterpreted with the introduction of this new birth weight standard.

Design: Cross-sectional visit to a subsample of a population-based birth cohort., Sample: A total of 1076 adolescents aged 14-16 y; 51% males., Measurements: Weight, height, subscapular and triceps skinfolds were used for assessing overweight and obesity in adolescence, using WHO-recommended criteria. Anthropometric status in early life was measured through birthweight and through weight and length/height at average ages of 20 and 43 months., Results: All analyses were adjusted for socioeconomic and maternal confounding factors. Birthweight and attained size (Z-scores of weight-for-age, height-for-age and weight-for-height) at 20 and 43 months were associated linearly and positively with overweight and obesity in adolescence. Four in each five obese adolescents were not overweight in childhood. Rapid weight gain, both between birth and 20 months, and between 20 and 43 months, was also associated with adolescent overweight and with obesity. Rapid height gain between 20 and 43 months was associated with overweight only. Most associations were stronger for boys., Conclusions: Birth size, attained size in childhood and particularly growth velocity in early life were associated with increased prevalence of obesity and overweight in Brazilian adolescents. On the other hand, the vast majority of overweight or obese adolescents were not overweight children. Early interventions are undoubtedly important, but population-based strategies aimed at improving diets and physical activity appear to have greater long-term potential than measures targeted at overweight children.

The deaths of children aged 1-4 years were studied in a cohort of 5914 Brazilian liveborns. A total of 29 early childhood deaths were recorded (cumulative mortality risk of approximately 6 per 1000), 17 of which (59%) were due to infectious diseases. The death rate was highest in the second year. Deaths were highly concentrated in children from low income (< US $50/month) families, where the cumulative risk of early childhood death was about 10 per 1000; on the other hand, there were no deaths among the 616 children from families with a monthly income of US $300 or more. Birthweight was also associated with mortality: the cumulative risk of children weighing less than 2000 g at birth was 21 per 1000, compared to 4 per 1000 among those with birthweights of 3500 g or more. Simultaneous adjustment for income and birthweight did not substantially change these differentials. These findings confirm the strong association between early childhood mortality and socioeconomic conditions, but also make evident the long-term effects of low birthweight.

The beneficial effects of breast-feeding on infant mortality and morbidity have been demonstrated in many studies. Few of these, however, have taken into account the possible confounding effect of birth weight. Several studies have shown that babies of low birth weight are less likely to be breast-fed. In some circumstances, this alone may account for a more than twofold excess in postperinatal infant mortality rates among non-breast-fed babies, even in the absence of any beneficial effect of breast-feeding. The association between birth weight and breast-feeding and the magnitude of the confounding effect is illustrated using data from a longitudinal study of infant mortality in Pelotas, Southern Brazil, and also using published results from other studies. It is concluded that studies designed or analyzed to relate breast-feeding to infant mortality should take the confounding effect of birth weight into account to avoid overestimating the beneficial effects of human milk.

The association between birth weight and infant mortality from infectious diseases was investigated in a population-based case-control study in two urban areas in southern Brazil. All deaths of children, seven to 364 days of age, occurring in a year were studied and the parents of the 357 infants dying of an infectious cause were interviewed, as were the parents of two neighborhood control infants for each case. Low birth weight infants (less than 2,500 g) were found, after allowing for confounding factors, to be 2.3 (90% confidence interval = 1.6 to 3.4) times more likely to die of an infection than those of higher birth weight. The odds ratios were 2.0 (1.1 to 3.6) for deaths due to diarrhea, 1.9 (1.0 to 3.6) for respiratory infections, and 5.0 (1.3 to 18.6) for other infections. These estimates of the risks associated with low birth weight are considerably lower than those from studies in developed countries.

A population-based cohort of 1458 Brazilian infants was followed from birth to 9-15 months of age to investigate the effects of birthweight and family income on subsequent growth. There was a strong association between birthweight and attained weight and length, while virtually no malnutrition among children who weighed more than 3000 g at birth; Children with lower birthweights tended to put on less weight during the first year, but these differences were no longer significant after controlling for family income. As a result, infants of lower birthweights tended to remain behind those of higher birthweights. Children from the wealthiest families gained 20% more weight than low-income infants, irrespective of birthweight. Low birthweight infants from high-income families were therefore likely to approach the standard weight at one year old while those from poor families lagged behind.

Objectives: To identify risk factors for antepartum stillbirth, including fetal growth restriction, among women with well-dated pregnancies and access to antenatal care.Design: Population-based, prospective, observational study.Setting: Eight international urban populations.Population: Pregnant women and their babies enrolled in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project.Methods: Cox proportional hazard models were used to compare risks among antepartum stillborn and liveborn babies.Main Outcome Measures: Antepartum stillbirth was defined as any fetal death after 16 weeks' gestation before the onset of labour.Results: Of 60 121 babies, 553 were stillborn (9.2 per 1000 births), of which 445 were antepartum deaths (7.4 per 1000 births). After adjustment for site, risk factors were low socio-economic status, hazard ratio (HR): 1.6 (95% CI, 1.2-2.1); single marital status, HR 2.0 (95% CI, 1.4-2.8); age ≥40 years, HR 2.2 (95% CI, 1.4-3.7); essential hypertension, HR 4.0 (95% CI, 2.7-5.9); HIV/AIDS, HR 4.3 (95% CI, 2.0-9.1); pre-eclampsia, HR 1.6 (95% CI, 1.1-3.8); multiple pregnancy, HR 3.3 (95% CI, 2.0-5.6); and antepartum haemorrhage, HR 3.3 (95% CI, 2.5-4.5). Birth weight <3rd centile was associated with antepartum stillbirth [HR, 4.6 (95% CI, 3.4-6.2)]. The greatest risk was seen in babies not suspected to have been growth restricted antenatally, with an HR of 5.0 (95% CI, 3.6-7.0). The population-attributable risk of antepartum death associated with small-for-gestational-age neonates diagnosed at birth was 11%.Conclusions: Antepartum stillbirth is a complex syndrome associated with several risk factors. Although small babies are at higher risk, current growth restriction detection strategies only modestly reduced the rate of stillbirth.Tweetable Abstract: International stillbirth study finds individual risks poor predictors of death but combinations promising. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Estimated fetal weight ( EFW) and fetal biometry are complementary measures used to screen for fetal growth disturbances. Our aim was to provide international EFW standards to complement the INTERGROWTH-21st Fetal Growth Standards that are available for use worldwide. Methods Women with an accurate gestational-age assessment, who were enrolled in the prospective, international, multicenter, population-based Fetal Growth Longitudinal Study ( FGLS) and INTERBIO-21st Fetal Study ( FS), two components of the INTERGROWTH-21st Project, had ultrasound scans every 5 weeks from 9-14 weeks' until 40 weeks' gestation. At each visit, measurements of fetal head circumference ( HC), biparietal diameter, occipitofrontal diameter, abdominal circumference ( AC) and femur length ( FL) were obtained blindly by dedicated research sonographers using standardized methods and identical ultrasound machines. Birth weight was measured within 12 h of delivery by dedicated research anthropometrists using standardized methods and identical electronic scales. Live babies without any congenital abnormality, who were born within 14 days of the last ultrasound scan, were selected for inclusion. As most births occurred at around 40 weeks' gestation, we constructed a bootstrap model selection and estimation procedure based on resampling of the complete dataset under an approximately uniform distribution of birth weight, thus enriching the sample size at extremes of fetal sizes, to achieve consistent estimates across the full range of fetal weight. We constructed reference centiles using second-degree fractional polynomial models. Results Of the overall population, 2404 babies were born within 14 days of the last ultrasound scan. Mean time between the last scan and birth was 7.7 (range, 0-14) days and was uniformly distributed. Birth weight was best estimated as a function of AC and HC (without FL) as log( EFW) = 5.084820 − 54.06633 × ( AC/100)3 − 95.80076 × ( AC/100)3 × log( AC/100) + 3.136370 × ( HC/100), where EFW is in g and AC and HC are in cm. All other measures, gestational age, symphysis-fundus height, amniotic fluid indices and interactions between biometric measures and gestational age, were not retained in the selection process because they did not improve the prediction of EFW. Applying the formula to FGLS biometric data ( n = 4231) enabled gestational age-specific EFW tables to be constructed. At term, the EFW centiles matched those of the INTERGROWTH-21st Newborn Size Standards but, at < 37 weeks' gestation, the EFW centiles were, as expected, higher than those of babies born preterm. Comparing EFW cross-sectional values with the INTERGROWTH-21st Preterm Postnatal Growth Standards confirmed that preterm postnatal growth is a different biological process from intrauterine growth. Conclusions We provide an assessment of EFW, as an adjunct to routine ultrasound biometry, from 22 to 40 weeks' gestation. However, we strongly encourage clinicians to evaluate fetal growth using separate biometric measures such as HC and AC, as well as EFW, to avoid the minimalist approach of focusing on a single value. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Birth interval is an important and potentially modifiable factor that is associated with child health. Whether an association exists with longer-term outcomes in adults is less well known. Methods: Using the 1982 Pelotas (Brazil) Birth Cohort Study, the association of birth interval with markers of cardiovascular health at 30 years of age was examined. Multivariable linear regression was used with birth interval as a continuous variable and categorical variable, and effect modification by gender was explored. Results: Birth interval and cardiovascular data were present for 2,239 individuals. With birth interval as a continuous variable, no association was found but stratification by gender tended to show stronger associations for girls. When compared to birth intervals of <18 months, as binary variable, longer intervals were associated with increases in height (1.6 cm; 95% CI: 0.5, 2.8) and lean mass (1.7 kg; 95% CI: 0.2, 3.2). No difference was seen with other cardiovascular outcomes. Conclusions: An association was generally not found between birth interval and cardiovascular outcomes at 30 years of age, though some evidence existed for differences between males and females and for an association with height and lean mass for birth intervals of 18 months and longer. [ABSTRACT FROM AUTHOR]

Objective: Estimated fetal weight (EFW) and fetal biometry are complementary measures used to screen for fetal growth disturbances. Our aim was to provide international EFW standards to complement the INTERGROWTH-21st Fetal Growth Standards that are available for use worldwide.Methods: Women with an accurate gestational-age assessment, who were enrolled in the prospective, international, multicenter, population-based Fetal Growth Longitudinal Study (FGLS) and INTERBIO-21st Fetal Study (FS), two components of the INTERGROWTH-21st Project, had ultrasound scans every 5 weeks from 9-14 weeks' until 40 weeks' gestation. At each visit, measurements of fetal head circumference (HC), biparietal diameter, occipitofrontal diameter, abdominal circumference (AC) and femur length (FL) were obtained blindly by dedicated research sonographers using standardized methods and identical ultrasound machines. Birth weight was measured within 12 h of delivery by dedicated research anthropometrists using standardized methods and identical electronic scales. Live babies without any congenital abnormality, who were born within 14 days of the last ultrasound scan, were selected for inclusion. As most births occurred at around 40 weeks' gestation, we constructed a bootstrap model selection and estimation procedure based on resampling of the complete dataset under an approximately uniform distribution of birth weight, thus enriching the sample size at extremes of fetal sizes, to achieve consistent estimates across the full range of fetal weight. We constructed reference centiles using second-degree fractional polynomial models.Results: Of the overall population, 2404 babies were born within 14 days of the last ultrasound scan. Mean time between the last scan and birth was 7.7 (range, 0-14) days and was uniformly distributed. Birth weight was best estimated as a function of AC and HC (without FL) as log(EFW) = 5.084820 - 54.06633 × (AC/100)3  - 95.80076 × (AC/100)3  × log(AC/100) + 3.136370 × (HC/100), where EFW is in g and AC and HC are in cm. All other measures, gestational age, symphysis-fundus height, amniotic fluid indices and interactions between biometric measures and gestational age, were not retained in the selection process because they did not improve the prediction of EFW. Applying the formula to FGLS biometric data (n = 4231) enabled gestational age-specific EFW tables to be constructed. At term, the EFW centiles matched those of the INTERGROWTH-21st Newborn Size Standards but, at < 37 weeks' gestation, the EFW centiles were, as expected, higher than those of babies born preterm. Comparing EFW cross-sectional values with the INTERGROWTH-21st Preterm Postnatal Growth Standards confirmed that preterm postnatal growth is a different biological process from intrauterine growth.Conclusions: We provide an assessment of EFW, as an adjunct to routine ultrasound biometry, from 22 to 40 weeks' gestation. However, we strongly encourage clinicians to evaluate fetal growth using separate biometric measures such as HC and AC, as well as EFW, to avoid the minimalist approach of focusing on a single value. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]