The influence of natural disasters on violence, mental health, food insecurity, and stunting in the Philippines: Findings from a nationally representative cohort.

BACKGROUND: Climate change is leading to an increased number of natural disasters. Children from low- and middle-income countries are disproportionately affected. The impacts of exposure to multiple natural disasters on the development of children are not well understood. The Philippines had 6.5 million people affected by natural disasters in 2018 and is therefore an ideal country in which to study the cumulative effects of natural disasters on human development. METHODS: We used wave 1 (2016-17) of the Longitudinal Cohort Study on the Filipino Child, a nationally representative cohort study of 4952 10-year-old children, to examine the impact of natural disasters. For caregivers, we examined mental health, family violence, and food insecurity. For children, we examined exposure to violence and stunting. We used random effects models to estimate the associations between natural disasters and children's development outcomes and caregivers' outcomes, after adjusting for neighbourhood, demographic, and geographic variables. Disaster exposure was measured using caregiver-reported measures of cumulative exposure and cumulative impact of disasters, average neighbourhood reports and data linked from the International Disaster Database (EM-DAT), an independent measure of community exposure to disaster. FINDINGS: We found that experiencing natural disasters, as measured by neighbourhood reports, was associated with higher levels of family violence in the previous 12 months, parenting stress, children witnessing physical violence, physical abuse of children, stunting in children, and greater food insecurity. Associations with individual self-reported exposure showed was similar. Associations with natural disasters measured using EM-DAT data showed a similar pattern: exposure to greater numbers of natural disasters was associated with higher levels of family violence, physical abuse of children, stunting in children, and food insecurity. Impacts of disasters was associated with higher levels of family violence, depression and food insecurity. INTERPRETATION: This is the first national study to document that cumulative measures of natural disasters had small, but wide-ranging, impacts on children and their caregivers. Further research is needed to identify factors that will protect populations who are at risk of high levels of natural disasters to ensure the optimal development of children. FUNDING: The Philippines Project, The Australian National University.

Stunting, IQ, and final school attainment in the Cebu Longitudinal Health and Nutrition Survey birth cohort.

School attainment is an important aspect of human capital, and a key determinant of long-term health and well-being. Early life deprivation and poor nutritional status are well known predictors of school entry and progression. We examine the persistence of early life influences and subsequent socioeconomic disadvantage (SED) across the multiple school continuation decisions that lead to final school attainment. Using data from a Philippine birth cohort followed for 35 years, we model 6 continuation decisions: Did not complete elementary school, elementary graduate only (completed grade 6), some secondary schooling, high school graduate, some postsecondary schooling, and college graduate, as well as total years of schooling. We estimate the association of school attainment with early life length for age Z-score (LAZ at 2 years of age) and cognitive development (IQ) as well as underlying indicators of SED and other family influences through early adulthood. The analysis sample includes >1900 participants in the Cebu Longitudinal Health and Nutrition Survey. Females completed, on average, one year more schooling than males, and twice as many females as males were college graduates (29.1 vs 15.0 %). LAZ and one standard deviation of IQ were each independently associated with 0.4 more years of attained schooling. A path model demonstrated strong direct associations of SED with years of schooling as well as indirect associations through LAZ and IQ. Sequential logits used to estimate continuing education decisions show persistent associations of early life LAZ and IQ and schooling even after accounting for changing SED of households over the schooling life course. Filipino parents had high but often unmet educational aspirations for their children because of the child's loss of interest in school and perceived financial barriers. Results further emphasize the importance of early life SED as a key risk factor for suboptimal school attainment.

Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.

Evolutionary life history theory as an organising framework for cohort studies: insights from the Cebu Longitudinal Health and Nutrition Survey.

By tracking a group of individuals through time, cohort studies provide fundamental insights into the developmental time course and causes of health and disease. Evolutionary life history theory seeks to explain patterns of growth, development, reproduction and senescence, and inspires a range of hypotheses that are testable using the longitudinal data from cohort studies. Here we review two decades of life history theory-motivated work conducted in collaboration with the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a birth cohort study that enrolled more than 3000 pregnant women in the Philippines in 1983 and has since followed these women, their offspring and grandoffspring. This work has provided evidence that reproduction carries "costs" to cellular maintenance functions, potentially speeding senescence, and revealed an unusual form of genetic plasticity in which the length of telomeres inherited across generations is influenced by reproductive timing in paternal ancestors. Men in Cebu experience hormonal and behavioural changes in conjunction with changes in relationship and fatherhood status that are consistent with predictions based upon other species that practice bi-parental care. The theoretical expectation that early life cues of mortality or environmental unpredictability will motivate a "fast" life history strategy are confirmed for behavioural components of reproductive decision making, but not for maturational tempo, while our work points to a broader capacity for early life developmental calibration of systems like immunity, reproductive biology and metabolism. Our CLHNS findings illustrate the power of life history theory as an integrative, lifecourse framework to guide longitudinal studies of human populations.

C-reactive protein response to influenza vaccination predicts cardiovascular disease risk in the Philippines.

Inflammation is associated with increased risk for chronic degenerative diseases, as well as age-related functional declines across many systems and tissues. Current understandings of inflammation, aging, and human health are based on studies conducted almost exclusively in high-income nations that rely primarily on baseline measures of chronic inflammation. This analysis investigates the inflammatory response to vaccination as a predictor of cardiovascular disease (CVD) among older women in the Philippines, a lower-middle income nation with rising rates of overweight/obesity and relatively high burdens of infectious disease. Concentrations of C-reactive protein (CRP) were measured at baseline and 72 h following influenza vaccination in 530 women (mean age = 55.2 years). Ankle-brachial index (ABI) - an indicator of peripheral arterial disease and broader CVD risk - was measured approximately three years later. The magnitude of CRP response to vaccination was positively associated with ABI, indicating that a larger inflammatory response predicts lower CVD risk. Baseline CRP was negatively associated with CRP response to vaccination, and was not associated with ABI independently of CRP response. These results suggest that research across ecological settings, and with more dynamic measures of inflammatory response and regulation, may yield important insights into the associations among inflammation, aging, and disease.

Maternal birth weight is associated with milk epidermal growth factor in Filipino women.

OBJECTIVES: Lactational programming, through which milk-borne bioactives influence both neonatal and long-term biological development, is well established. However, almost no research has investigated how developmental stimuli during a mother's early life may influence her milk bioactives in adulthood. Here, we investigated the association between maternal birth weight and milk epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) in later life. We predicted there would be a decrease in both milk EGF and EGF-R in the milk produced by mothers who were themselves born low birth weight. METHODS: Study participants are from the Cebu Longitudinal Health and Nutrition Survey. Mothers (n = 69) were followed longitudinally since birth with prospective data collection. Anthropometrics, health, and dietary recalls were collected with early morning milk samples when mothers were 24 to 25 years of age. Milk samples were analyzed for EGF and its receptor (EGF-R). Analysis of variance was used to test for differences in milk EGF and EGF-R between low and average birthweight mothers after adjustment for parity, age, and maternal dietary energy intake. RESULTS: Mothers who were low birth weight produced milk with significantly less EGF and more EGF-R which resulted in a lower ratio of EGF to EGF-R. These associations persisted after adjustment for infant age, maternal adiposity, and dietary energy. CONCLUSIONS: While this is a small sample size, these preliminary findings suggest that maternal early life characteristics, such as birth weight, may be important contributors to variation in milk bioactives. Future work is necessary to understand how variation in maternal early life may influence milk composition in adulthood.

Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

Profiles of gene expression in maternal blood predict offspring birth weight in normal pregnancy.

The association between lower birth weight and increased disease risk in adulthood has drawn attention to the physiological processes that shape the gestational environment. We implement genome-wide transcriptional profiling of maternal blood samples to identify subsets of genes and associated transcription control pathways that predict offspring birth weight. Female participants (N = 178, mean = 27.0 years) in a prospective observational birth cohort study were contacted between 2009 and 2014 to identify new pregnancies. An in-home interview was scheduled for early in the third trimester (mean = 30.3 weeks) to collect pregnancy-related information and a blood sample, and birth weight was measured shortly after delivery. Transcriptional activity in white blood cells was determined with a whole-genome gene expression direct hybridization assay. Fifty transcripts were differentially expressed in association with offspring birth weight, with 18 up-regulated in relation to lower birth weight, and 32 down-regulated. Examination of transcription control pathways identified increased activity of NF-κB, AP-1, EGR1, EGR4, and Gfi families, and reduced the activity of CEBP, in association with lower birth weight. Transcript origin analyses identified non-classical CD16+ monocytes, CD1c+ myeloid dendritic cells, and neutrophils as the primary cellular mediators of differential gene expression. These results point toward a systematic regulatory shift in maternal white blood cell activity in association with lower offspring birth weight, and they suggest that analyses of gene expression during gestation may provide insight into regulatory and cellular mechanisms that influence birth outcomes.

Regulation of inflammation during gestation and birth outcomes: Inflammatory cytokine balance predicts birth weight and length.

OBJECTIVES: The maternal environment during gestation influences offspring health at birth and throughout the life course. Recent research has demonstrated that endogenous immune processes such as dysregulated inflammation adversely impact birth outcomes, increasing the risk for preterm birth and restricted fetal growth. Prior analyses examining this association suggest a relationship between maternal C-reactive protein (CRP), a summary measure of inflammation, and offspring anthropometric outcomes. This study investigates pro- and anti-inflammatory cytokines, and their ratio, to gain deeper insight into the regulation of inflammation during pregnancy. METHODS: IL6, IL10, TNFɑ, and CRP were quantified in dried blood spots collected in the early third trimester (mean = 29.9 weeks) of 407 pregnancies in Metropolitan Cebu, Philippines. Relationships between these immune markers and offspring anthropometrics (birth weight, length, head circumference, and sum of skinfold thicknesses) were evaluated using multivariate regression analyses. Ratios of pro- to anti-inflammatory cytokines were generated. RESULTS: Higher maternal IL6 relative to IL10 was associated with reduced offspring weight and length at birth. Individual cytokines did not predict birth outcomes. CONCLUSIONS: Consistent with the idea that the relative balance of cytokines with pro- and anti-inflammatory effects is a key regulator of inflammation in pregnancy, the IL6:IL10 ratio, but neither cytokine on its own, predicted offspring birth outcomes. Our findings suggest that prior reports of association between CRP and fetal growth may reflect, in part, the balance between pro- and anti-inflammatory cytokines, and that the gestational environment is significantly shaped by cytokine imbalance.

Ankle brachial index (ABI) in a cohort of older women in the Philippines: Prevalence of peripheral artery disease and predictors of ABI.

OBJECTIVE: Cardiovascular disease (CVD) is rising in low and middle-income countries, but studies of CVD epidemiology in such settings often focus on risk factors rather than measures of disease progression. Here we use the ankle brachial index (ABI) to assess the prevalence of peripheral artery disease (PAD) among older women living in Metropolitan Cebu, Philippines, and relationships between ABI and CVD risk factors and body composition. METHODS: ABI was measured using the Doppler technique in 538 female participants in the 2015 Cebu Longitudinal Health and Nutrition Survey (mean age 58 years, range 47-78 years). ABI was related to a panel of CVD risk factors measured in 2005 and 2012, and to 2012 body composition measures. RESULTS: The prevalence of PAD (1.8%) was among the lowest reported in any comparably-aged sample, and only 9.9% of participants had an ABI indicating borderline PAD risk. Smoking (P < 0.011) and use of CVD medications (P < 0.0001) predicted lower ABI (indicating higher PAD risk), which was also lower in relation to 2012 systolic blood pressure (P < 0.054). ABI was unrelated to other CVD risk factors. An apparent protective relationship between body mass index (BMI) and ABI, noted in previous studies, was found to be confounded by protective relationships between ABI and fat free mass, height, and grip strength (all P < 0.05). CONCLUSIONS: The prevalence of PAD is low in Cebu Longitudinal Health and Nutrition Survey participants, and ABI was related to few CVD risk factors. Past reports of lower PAD risk in relation to BMI may reflect confounding by lean mass, which has protective relationships with ABI.

Genome-wide analysis of DNA methylation in relation to socioeconomic status during development and early adulthood.

OBJECTIVES: Socioeconomic status (SES) is a powerful determinant of health, but the underlying biological mechanisms are poorly understood. This study investigates whether levels of DNA methylation at CpG sites across the genome are associated with SES in a cohort of young adults in the Philippines. METHODS: DNA methylation was assayed with the Illumina HumanMethylation450 Bead Chip, in leukocytes from 489 participants in the Cebu Longitudinal Health and Nutrition Survey (mean age = 20.9 years). SES was measured in infancy/childhood and adulthood, and was based on composite measures of income, assets, and education. Genome-wide analysis of variable probes identified CpG sites significantly associated with SES after adjustment for multiple comparisons. Functional enrichment analysis was used to identify biological pathways associated with these sites. RESULTS: A total of 2,546 CpG sites, across 1,537 annotated genes, were differentially methylated in association with SES. In comparison with high SES, low SES was associated with increased methylation at 1,777 sites, and decreased methylation at 769 sites. Functional enrichment analysis identified over-representation of biological pathways related to immune function, skeletal development, and development of the nervous system. CONCLUSIONS: Socioeconomic status predicts DNA methylation at a large number of CpG sites across the genome. The scope of these associations is commensurate with the wide range of biological systems and health outcomes that are shaped by SES, and these findings suggest that DNA methylation may play an important role.

Time-use Profiles, Chronic Role Overload, and Women's Body Weight Trajectories from Middle to Later Life in the Philippines.

Although chronic life strain is often found to be associated with adverse health outcomes, empirical research is lacking on the health implications of persistent role overload that many women around the world are subject to, the so-called double burden of work and family responsibilities. Using data from the Cebu Longitudinal Health and Nutrition Survey (1994-2012), we examined the linkage between time-use profiles and body mass index (BMI) trajectories for Filipino women over an 18-year span. Out of the four classes of women with differential levels of a combination of work and family duties, the group with the heaviest double burden has the highest average BMI. In addition, those who have remained in this class for three or more waves of data not only have higher BMI on average but also have experienced the steepest rate of increase in BMI upon transition from midlife to old age.

How Overweight and Obesity Relate to the Development of Functional Limitations among Filipino Women.

As life expectancy and obesity increase in low and middle-income countries, the relationship of weight status to functional outcomes in older adults in these settings requires attention. We examined how overweight (BMI > 25 kg/m2), obesity (BMI > 30 kg/m2), and high waist circumference (WC > 80 cm) related to grip strength, timed up-and-go, and development of limitations in mobility, activities of daily living (ADL), and instrumental activities of daily living (IADL) among Filipino women. We analyzed data from seven rounds of the Cebu Longitudinal Health and Nutrition Survey (1994, n = 2279 to 2015, n = 1568, age 49-78 years) to examine how women's reports of functional limitations related to their prior WC, and how their grip strength and timed up-and-go related to concurrently measured overweight and obesity, adjusted for age, socioeconomic status, and urbanicity. High WC was associated with higher odds of subsequent mobility and IADL limitations. Chronic disease morbidity (sum of self-reported arthritis, high blood pressure, heart disease, diabetes, and cancer) fully mediated the association of high WC with ADL and IADL limitations, but not physical/mobility limitations. Longer up-and-go times, and higher grip strength were related to overweight and obesity. Results emphasize the need for obesity prevention to reduce chronic diseases and maintain good functional status as women age.

Seventeen-Year Changes in Body Mass Index, Waist Circumference, Elevated Blood Pressure, and Diabetes Phenotypes in a Cohort of Filipino Women.

Obesity, hypertension, and diabetes have risen dramatically in Asia, but few cohort studies track age and secular trends in these conditions. We use Cebu (The Philippines) Longitudinal Health and Nutrition survey data to document 1998 to 2015 prevalence and co-occurrence of body mass index (BMI; >25 kg/m2), high waist circumference (WC; >80 cm), elevated blood pressure (EBP; systolic ⩾130 or diastolic ⩾85 mm Hg), and type 2 diabetes among ~2000 women aged 29 to 62 years in 1998; and identify their relationship to community, household, and individual factors using longitudinal logistic regression. Prevalence (1998-2015) rates were 35% to 49%, BMI >25 kg/m2; 32% to 58% high WC; 21% to 59% EBP; and 2% to 14% diabetes. Only 20% of women had none of these conditions in 2015. Diabetes was strongly driven by age and secular trends in high WC related to higher socioeconomic status and urbanization. Hypertension increased with age in lower socioeconomic status rural and more affluent urban women. Results underscore the continuing need for public health measures to prevent obesity and to identify and treat hypertension and diabetes.

Double burden for women in mid- and later life: evidence from time-use profiles in Cebu, the Philippines.

Using data from the Cebu Longitudinal Health and Nutrition Survey (CLHNS, 1994, 1998, 2002, 2005, 2007, 2012), we utilize latent class analysis (LCA) to develop time use class membership to characterize the degree to which women in Cebu are subject to the double burden of work and family responsibilities in mid and later life. Results suggest that close to a third of the sample are engaged in high intensity work for pay (either outside or home-based) over eighteen years, while combining it with a substantial amount of household chores and with low level of personal time in a span of eighteen years. Our latent transition analysis (LTA) also shows that, with the addition of grandchildren into the household, some women experience a shift in time use class membership by becoming high intensity caregivers or by completely transitioning out of work arena, while others remain double-burdened with active involvement in both work and family responsibilities.

Adolescent reserve capacity, socioeconomic status and school achievement as predictors of mortality in Finland - a longitudinal study.

BACKGROUND: Despite robust evidence on the inverse relationship between socioeconomic status (SES) and mortality, deviations from expected results have been observed likely due to school achievement and psychosocial resources, termed as "reserve capacity." Since adolescence is a critical period in developing sound psychological and behavioural patterns and adolescent markers of SES were seldom used, we determine if family SES in adolescence predicts later mortality. We also study how reserve capacity (perceived health, health-promoting behaviour and social support) and school achievement modify this relationship and reduce the negative effects of low SES. METHODS: A longitudinal study was designed by linking baseline data on 12 to 18 year-old Finns in 1985-95 (N = 41,833) from the Adolescent Health and Lifestyle Surveys with register data on mortality and SES from Statistics Finland. Average follow-up time was 18.4 years with a total of 770,161 person-years. Cox regression models, stratified by sex, were fitted to determine the effects of variables measured during adolescence: family SES, reserve capacity and school achievement on mortality risk. RESULTS: All reserve capacity dimensions significantly predicted mortality in boys. Perceived health and social support predicted that in girls. Adolescents with the lowest school achievement were more than twice at risk of dying compared to those with better school performance. Low SES increased the risk of death in boys (Hazard ratios: 1.6, 95% CI 1.1-2.4) but not in girls. Reserve capacity and school achievement weakened the effects of low SES on boys' risk of death. CONCLUSIONS: High reserve capacity and good school achievement in adolescence significantly reduce the risk of mortality. In boys, these also mitigate the negative effect of low SES on mortality. These findings underscore the roles of reserve capacity and school achievement during adolescence as likely causal or modifying factors in SES-health inequalities.

Is early postnatal growth velocity, a proxy of minipubertal androgen action, related to adult second-to-fourth digit (2D:4D) ratios in men? A test in Cebu, Philippines.

OBJECTIVES: The ratio of the length of the second to the fourth digit (2D:4D) of the hand is often used as an index of prenatal androgen exposure but it might also be affected by androgens during "minipuberty," a period of temporarily high testosterone (T) production in the first few months of life. To examine this, we tested the prediction that men with lower 2D:4D ratios had greater weight growth velocities during the first months of life-a metric recently shown to correlate with concurrent T levels. METHODS: We related early growth data to 2D:4D ratios of both hands measured in 756 men (25-26 years) from Cebu, The Philippines. RESULTS: Birth-to-fourth-month (B4M) weight gain velocity (a proxy of early postnatal androgen action) was not associated with adult 2D:4D ratios of either hand, when the latter was measured continuously. When comparing men with more male-typical digit ratios (<1.0) to those with more female-typical ratios (≥ 1.0), the group of men with more male-typical ratios had greater B4M weight velocity, but this was only the case for the left hand. CONCLUSIONS: We found modest evidence that adult digit ratios relate to an anthropometric correlate of androgen exposure during minipuberty. Definitive assessment of the role of postnatal T in shaping digit ratios will require direct measures of perinatal T related to longitudinally assessed digit ratios.

Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood.

Chronic inflammation contributes to a wide range of human diseases, and environments in infancy and childhood are important determinants of inflammatory phenotypes. The underlying biological mechanisms connecting early environments with the regulation of inflammation in adulthood are not known, but epigenetic processes are plausible candidates. We tested the hypothesis that patterns of DNA methylation (DNAm) in inflammatory genes in young adulthood would be predicted by early life nutritional, microbial, and psychosocial exposures previously associated with levels of inflammation. Data come from a population-based longitudinal birth cohort study in metropolitan Cebu, the Philippines, and DNAm was characterized in whole blood samples from 494 participants (age 20-22 y). Analyses focused on probes in 114 target genes involved in the regulation of inflammation, and we identified 10 sites across nine genes where the level of DNAm was significantly predicted by the following variables: household socioeconomic status in childhood, extended absence of a parent in childhood, exposure to animal feces in infancy, birth in the dry season, or duration of exclusive breastfeeding. To evaluate the biological significance of these sites, we tested for associations with a panel of inflammatory biomarkers measured in plasma obtained at the same age as DNAm assessment. Three sites predicted elevated inflammation, and one site predicted lower inflammation, consistent with the interpretation that levels of DNAm at these sites are functionally relevant. This pattern of results points toward DNAm as a potentially important biological mechanism through which developmental environments shape inflammatory phenotypes across the life course.

Prenatal care and child growth and schooling in four low- and medium-income countries.

BACKGROUND: The effectiveness of prenatal care for improving birth and subsequent child outcomes in low-income countries remains controversial, with much of the evidence to date coming from high-income countries and focused on early-life outcomes. We examined associations between prenatal care visits and birth weight, height-for-age at 24 months and attained schooling in four low- and middle-income countries. METHODS: We pooled data from prospective birth-cohort studies from Brazil, Guatemala, Philippines and South Africa. We created a prenatal care utilization index based on the number and timing of prenatal visits. Associations were examined between this index and birth weight, height-for-age at 24 months, and highest attained schooling grade until adulthood. RESULTS: Among 7203 individuals in the analysis, 68.9% (Philippines) to 96.7% (South Africa) had at least one prenatal care visit, with most having at least four visits. Over 40% of Brazilians and Guatemalans had their first prenatal visit in the first trimester, but fewer Filipinos (13.9%) and South Africans (19.8%) did so. Prenatal care utilization was not significantly associated with birth weight (p>0.05 in pooled data). Each unit increase in the prenatal care utilization index was associated with 0.09 (95% CI 0.04 to 0.15) higher height-for-age z-score at 24 months and with 0.26 (95% CI 0.17 to 0.35) higher schooling grades attained. Although there was some heterogeneity and greater imprecision across sites, the results were qualitatively similar among the four different populations. CONCLUSIONS: While not related to birth weight, prenatal care utilization was associated with important outcomes later in life, specifically higher height-for-age at 24 months and higher attained school grades. These results suggest the relevance of prenatal care visits for human capital outcomes important over the lifecycle.