Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

Fetal cranial growth trajectories are associated with growth and neurodevelopment at 2 years of age: INTERBIO-21st Fetal Study.

Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections)1 and preventive interventions (for example, multiple-micronutrient supplementation)2 that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood3. In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites worldwide4, we studied the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks' gestation, against international standards5,6, and growth and neurodevelopment up to 2 years of age7,8. We identified five trajectories associated with specific neurodevelopmental, behavioral, visual and growth outcomes, independent of fetal abdominal growth, postnatal morbidity and anthropometric measures at birth and age 2. The trajectories, which changed within a 20-25-week gestational age window, were associated with brain development at 2 years of age according to a mirror (positive/negative) pattern, mostly focused on maturation of cognitive, language and visual skills. Further research should explore the potential for preventive interventions in pregnancy to improve infant neurodevelopmental outcomes before the critical window of opportunity that precedes the divergence of growth at 20-25 weeks' gestation.

Association Between Preterm-Birth Phenotypes and Differential Morbidity, Growth, and Neurodevelopment at Age 2 Years: Results From the INTERBIO-21st Newborn Study.

Importance: The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures. Objective: To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years. Design, Setting, and Participants: The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020. Exposures/Interventions: Preterm-birth phenotypes. Main Outcomes and Measures: Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool. Results: A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype. Conclusions and Relevance: Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.

Estimating family planning coverage from contraceptive prevalence using national household surveys.

BACKGROUND: Contraception is one of the most important health interventions currently available and yet, many women and couples still do not have reliable access to modern contraceptives. The best indicator for monitoring family planning is the proportion of women using contraception among those who need it. This indicator is frequently called demand for family planning satisfied and we argue that it should be called family planning coverage (FPC). This indicator is complex to calculate and requires a considerable number of questions to be included in a household survey. OBJECTIVES: We propose a model that can predict FPC from a much simpler indicator - contraceptive use prevalence - for situations where it cannot be derived directly. DESIGN: Using 197 Multiple Indicator Cluster Surveys and Demographic and Health Surveys from 82 countries, we explored least-squares regression models that could be used to predict FPC. Non-linearity was expected in this situation and we used a fractional polynomial approach to find the best fitting model. We also explored the effect of calendar time and of wealth on the models explored. RESULTS: Given the high correlation between the variables involved in FPC, we managed to derive a relatively simple model that depends only on contraceptive use prevalence but explains 95% of the variability of the outcome, with high precision for the estimated regression line. We also show that the relationship between the two variables has not changed with time. A concordance analysis showed agreement between observed and fitted results within a range of ±9 percentage points. CONCLUSIONS: We show that it is possible to obtain fairly good estimates of FPC using only contraceptive prevalence as a predictor, a strategy that is useful in situations where it is not possible to estimate FPC directly.

Childbearing during adolescence and offspring mortality: findings from three population-based cohorts in southern Brazil.

BACKGROUND: The role of young maternal age as a determinant of adverse child health outcomes is controversial, with existing studies providing conflicting results. This work assessed the association between adolescent childbearing and early offspring mortality in three birth cohort studies from the city of Pelotas in Southern Brazil. METHODS: All hospital births from 1982 (6,011), 1993 (5,304), and 2004 (4,287) were identified and these infants were followed up. Deaths were monitored through vital registration, visits to hospitals and cemeteries. The analyses were restricted to women younger than 30 years who delivered singletons (72%, 70% and 67% of the original cohorts, respectively). Maternal age was categorized into three groups (< 16, 16-19, and 20-29 years). Further analyses compared mothers aged 12-19 and 20-29 years. The outcome variables included fetal, perinatal, neonatal, postneonatal and infant mortality. Crude and adjusted odds ratios (ORs) were estimated with logistic regression models. RESULTS: There were no interactions between maternal age and cohort year. After adjustment for confounding, pooled ORs for mothers aged 12-19 years were 0.6 (95% CI = 0.4; 1.0) for fetal death, 0.9 (0.6; 1.3) for perinatal death, 1.0 (0.7; 1.6) for early neonatal death, 1.6 (0.7; 3.4) for late neonatal death, 1.8 (1.1; 2.9) for postneonatal death, and 1.6 (1.2; 2.1) for infant death, when compared to mothers aged 20-29 years. Further adjustment for mediating variables led to the disappearance of the excess of postneonatal mortality. The number of mothers younger than 16 years was not sufficient for most analyses. CONCLUSION: The slightly increased odds of postneonatal mortality among children of adolescent mothers suggest that social and environmental factors may be more important than maternal biologic immaturity.