Lower Socioeconomic Status Predicts Increased Proinflammatory Signaling in Late Pregnancy: Evidence From a Filipino Cohort.

OBJECTIVES: Maternal socioeconomic status (SES) is an important predictor of adverse birth outcomes and postnatal health across global populations. Chronic inflammation is implicated in cardiometabolic disease risk in high-income contexts and is a potential pathway linking maternal adversity to offspring health trajectories. To clarify how socioeconomic inequality shapes pregnancy inflammation in middle-income settings, we investigated SES as a predictor of inflammatory cytokines in late gestation in a sample from the Cebu Longitudinal Health Nutrition Survey in Cebu, Philippines. METHODS: We used multiple regression to evaluate maternal SES, reflected in household assets, as a predictor of general inflammation (C-reactive protein), inflammatory cytokines (interleukin-6, interleukin-10), and inflammatory balance (n = 407). Inflammatory markers were measured at 29.9 weeks gestation in dried blood spots, and a measure reflecting relative balance of IL6 and IL10 was calculated to capture pro- versus anti-inflammatory skewed immune profiles. RESULTS: Greater household assets significantly predicted lower IL6 concentration (p <  0.001), with a trend toward lower IL6 relative to IL10 (p = 0.084). C-reactive protein and IL10 were not individually related to SES. CONCLUSIONS: The inverse relationship between SES and pregnancy inflammation in Cebu is consistent with results from high-income settings. These findings further highlight the influence of socioeconomic conditions on immune regulation during pregnancy. Given the evidence that gestational inflammation impacts offspring fetal growth, our results suggest that social and economic effects on immune function may be an important pathway for the intergenerational transmission of health disparities.

Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies.

BACKGROUND: Fast weight gain and linear growth in children in low-income and middle-income countries are associated with enhanced survival and improved cognitive development, but might increase risk of obesity and related adult cardiometabolic diseases. We investigated how linear growth and relative weight gain during infancy and childhood are related to health and human capital outcomes in young adults. METHODS: We used data from five prospective birth cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa. We investigated body-mass index, systolic and diastolic blood pressure, plasma glucose concentration, height, years of attained schooling, and related categorical indicators of adverse outcomes in young adults. With linear and logistic regression models, we assessed how these outcomes relate to birthweight and to statistically independent measures representing linear growth and weight gain independent of linear growth (relative weight gain) in three age periods: 0-2 years, 2 years to mid-childhood, and mid-childhood to adulthood. FINDINGS: We obtained data for 8362 participants who had at least one adult outcome of interest. A higher birthweight was consistently associated with an adult body-mass index of greater than 25 kg/m(2) (odds ratio 1·28, 95% CI 1·21-1·35) and a reduced likelihood of short adult stature (0·49, 0·44-0·54) and of not completing secondary school (0·82, 0·78-0·87). Faster linear growth was strongly associated with a reduced risk of short adult stature (age 2 years: 0·23, 0·20-0·52; mid-childhood: 0·39, 0·36-0·43) and of not completing secondary school (age 2 years: 0·74, 0·67-0·78; mid-childhood: 0·87, 0·83-0·92), but did raise the likelihood of overweight (age 2 years: 1·24, 1·17-1·31; mid-childhood: 1·12, 1·06-1·18) and elevated blood pressure (age 2 years: 1·12, 1·06-1·19; mid-childhood: 1·07, 1·01-1·13). Faster relative weight gain was associated with an increased risk of adult overweight (age 2 years: 1·51, 1·43-1·60; mid-childhood: 1·76, 1·69-1·91) and elevated blood pressure (age 2 years: 1·07, 1·01-1·13; mid-childhood: 1·22, 1·15-1·30). Linear growth and relative weight gain were not associated with dysglycaemia, but a higher birthweight was associated with decreased risk of the disorder (0·89, 0·81-0·98). INTERPRETATION: Interventions in countries of low and middle income to increase birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from adult chronic disease risk factors, with few adverse trade-offs. FUNDING: Wellcome Trust and Bill & Melinda Gates Foundation.

Investigating the IGF axis as a pathway for intergenerational effects.

Early nutritional and growth experiences can impact development, metabolic function, and reproductive outcomes in adulthood, influencing health trajectories in the next generation. The insulin-like growth factor (IGF) axis regulates growth, metabolism, and energetic investment, but whether it plays a role in the pathway linking maternal experience with offspring prenatal development is unclear. To test this, we investigated patterns of maternal developmental weight gain (a proxy of early nutrition), young adult energy stores, age, and parity as predictors of biomarkers of the pregnancy IGF axis (n = 36) using data from the Cebu Longitudinal Health and Nutrition Survey in Metro Cebu, Philippines. We analyzed maternal conditional weight measures at 2, 8, and 22 years of age and leptin at age 22 (a marker of body fat/energy stores) in relation to free IGF-1 and IGFBP-3 in mid/late pregnancy (mean age = 27). Maternal IGF axis measures were also assessed as predictors of offspring fetal growth. Maternal age, parity, and age 22 leptin were associated with pregnancy free IGF-1, offspring birth weight, and offspring skinfold thickness. We find that free IGF-1 levels in pregnancy are more closely related to nutritional status in early adulthood than to preadult developmental nutrition and demonstrate significant effects of young adult leptin on offspring fetal fat mass deposition. We suggest that the previously documented finding that maternal developmental nutrition predicts offspring birth size likely operates through pathways other than the maternal IGF axis, which reflects more recent energy status.

Waist circumference and the risk of hypertension and prediabetes among Filipino women.

OBJECTIVES: To examine waist circumference as a risk factor for having hypertension only, impaired fasting glucose only, or both hypertension and impaired fasting glucose, and assess whether the associations vary according to overweight status. Furthermore, optimal cut-offs for waist circumference in overweight women and non-overweight women were explored. DATA AND METHODS: Data from 1,871 women aged 35-68 years in the 2005 Cebu Longitudinal Health and Nutrition Survey were used. Multinomial logistic regressions were used to model how waist circumference influenced the likelihood of having the three illness categories compared to having neither condition. Waist circumference cut-offs were explored using receiver operating characteristic analysis. RESULTS: Adjusted for age and other confounders, each cm increase in waist circumference increased the odds of hypertension by 5 % for non-overweight women and 3 % for overweight women; impaired fasting glucose by 9 and 3 % for non-overweight and overweight women, respectively; and hypertension and impaired fasting glucose by 17 % among non-overweight versus 9 % for overweight women. Waist circumference cut-offs for non-overweight women were lower than overweight women. CONCLUSION: Waist circumference was significantly associated with impaired fasting glucose and both hypertension and impaired fasting glucose, and the associations vary by overweight status.

Early-life stature, preschool cognitive development, schooling attainment, and cognitive functioning in adulthood: a prospective study in four birth cohorts.

BACKGROUND: Nutrition is important for growth and brain development and therefore cognitive ability. Growth faltering in early childhood, an important indicator of early adversity, is associated with poorer developmental outcomes, some into adulthood, but this association probably reflects early-life deprivation. We aimed to investigate the associations between early-life stature, child IQ, and adult IQ. METHODS: In this cohort study, we used prospective longitudinal data collected in four birth cohorts from Brazil (born in 1993), Guatemala (born in 1969-77), the Philippines (born in 1983-84), and South Africa (born in 1990). Using multivariable linear models, we estimated the relative contributions of early-life stature, child IQ, and schooling (highest school year completed) to adult IQ, including interaction effects among the early-childhood measures and schooling. FINDINGS: We included 2614 individuals in the analysis. Early-life stature was associated with adult IQ (range across eight site-by-sex groups -0·14 to 3·17 IQ points) and schooling (-0·05 to 0·77 years) per height-for-age Z-score. These associations were attenuated when controlling for child IQ (-0·86 to 1·72 for adult IQ and -0·5 to 0·60 for schooling). The association of early-life stature with adult IQ was further attenuated when controlling for schooling (-1·86 to 1·21). Child IQ was associated with adult IQ (range 3·91 to 10·02 points) and schooling (0·25 to 1·30 years) per SD of child IQ in all groups; these associations were unattenuated by the addition of early-life stature to the models. The interaction between schooling and child IQ, but not that between schooling and early-life stature, was positively associated with adult IQ across groups. INTERPRETATION: The observed associations of early-life stature with adult IQ and schooling varied across cohorts and sexes and explained little variance in adult IQ beyond that explained by child IQ. These findings suggest that interventions targeted at growth for health and early development are important. Our results are consistent with the inference that improving long-term cognitive outcomes might require interventions that more specifically target early cognitive ability. FUNDING: Bill & Melinda Gates Foundation.

Growth patterns in early childhood and final attained stature: data from five birth cohorts from low- and middle-income countries.

Growth failure is cumulative, and short stature is associated with multiple indices of reduced human capital. Few studies have been able to address in a single analysis both consideration of the timing of growth failure and comparison across populations. We analyzed data from birth cohorts in Brazil, Guatemala, India, the Philippines, and South Africa (n = 4,659). We used data on length at birth (available for three of the five cohorts), 12 mo, 24 mo, and mid-childhood to construct cohort- and sex- specific conditional length measures. We modeled adult height as a function of conditional length in childhood. The five cohorts experienced varying degrees of growth failure. As adults, the Brazil sample was 0.35 +/- 0.89 standard deviations (SD) below the World Health Organization reference, while adult Guatemalans were 1.91 +/- 0.87 SD below the reference. All five cohorts experienced a nadir in height for age Z-score at 24 mo. Birth length (in the three cohorts with this variable), and conditional length at 12 mo (in all five cohorts) were the most strongly associated with adult height. Growth in the periods 12-24 mo and 24 mo to mid-childhood showed inconsistent patterns across tertiles of adult height. Despite variation in the magnitude of cumulative growth failure across cohorts, the five cohorts show highly consistent age-specific associations with adult stature. Growth failure prior to age 12 mo was most strongly associated with adult stature. These consistencies speak to the importance of interventions to address intrauterine growth failure and growth failure in the first 12 mo of life.

Association between maternal age at childbirth and child and adult outcomes in the offspring: a prospective study in five low-income and middle-income countries (COHORTS collaboration).

BACKGROUND: Both young and advanced maternal age is associated with adverse birth and child outcomes. Few studies have examined these associations in low-income and middle-income countries (LMICs) and none have studied adult outcomes in the offspring. We aimed to examine both child and adult outcomes in five LMICs. METHODS: In this prospective study, we pooled data from COHORTS (Consortium for Health Orientated Research in Transitioning Societies)-a collaboration of five birth cohorts from LMICs (Brazil, Guatemala, India, the Philippines, and South Africa), in which mothers were recruited before or during pregnancy, and the children followed up to adulthood. We examined associations between maternal age and offspring birthweight, gestational age at birth, height-for-age and weight-for-height Z scores in childhood, attained schooling, and adult height, body composition (body-mass index, waist circumference, fat, and lean mass), and cardiometabolic risk factors (blood pressure and fasting plasma glucose concentration), along with binary variables derived from these. Analyses were unadjusted and adjusted for maternal socioeconomic status, height and parity, and breastfeeding duration. FINDINGS: We obtained data for 22 188 mothers from the five cohorts, enrolment into which took place at various times between 1969 and 1989. Data for maternal age and at least one outcome were available for 19 403 offspring (87%). In unadjusted analyses, younger (≤19 years) and older (≥35 years) maternal age were associated with lower birthweight, gestational age, child nutritional status, and schooling. After adjustment, associations with younger maternal age remained for low birthweight (odds ratio [OR] 1·18 (95% CI 1·02-1·36)], preterm birth (1·26 [1·03-1·53]), 2-year stunting (1·46 [1·25-1·70]), and failure to complete secondary schooling (1·38 [1·18-1·62]) compared with mothers aged 20-24 years. After adjustment, older maternal age remained associated with increased risk of preterm birth (OR 1·33 [95% CI 1·05-1·67]), but children of older mothers had less 2-year stunting (0·64 [0·54-0·77]) and failure to complete secondary schooling (0·59 [0·48-0·71]) than did those with mothers aged 20-24 years. Offspring of both younger and older mothers had higher adult fasting glucose concentrations (roughly 0·05 mmol/L). INTERPRETATION: Children of young mothers in LMICs are disadvantaged at birth and in childhood nutrition and schooling. Efforts to prevent early childbearing should be strengthened. After adjustment for confounders, children of older mothers have advantages in nutritional status and schooling. Extremes of maternal age could be associated with disturbed offspring glucose metabolism. FUNDING: Wellcome Trust and the Bill & Melinda Gates Foundation.