Search

Objectives: Recent discussions in human biology have highlighted how local ecological contexts shape the relationship between social stressors and health across populations. Chronic low‐grade inflammation has been proposed as a pathway linking social stressors to health, with evidence concentrated in high‐income Western contexts. However, it remains unclear whether this is an important pathway in populations where prevalence is lower due to lower adiposity and greater infectious exposures. To investigate this further, we tested associations between multiple types of intimate partner violence (IPV), a highly prevalent stressor and health crisis globally, and C‐reactive protein (CRP), a commonly used measure of chronic low‐grade inflammation, in Cebu, Philippines. For reference, we compared results for CRP to depression, a well‐established and consistently observed health outcome of IPV. Methods: Data came from 1601 currently partnered women (ages 35–69 years) as part of the Cebu Longitudinal Health and Nutrition Survey. IPV exposures included physical, emotional, and controlling behavior. Depression scores were measured using a modified version of the Center for Epidemiologic Studies‐Depression Scale for this population, whereas plasma CRP was measured from overnight‐fasted morning blood samples. Results: All three types of IPV were associated with a higher depression score. However, none of the IPV measures were associated with CRP. In a post hoc interaction test, emotional IPV became positively associated with CRP as waist circumference increased above the mean. Conclusions: Our results suggest a complex relationship between social stressors and chronic low‐grade inflammation, which is likely dependent on the population‐specific context of lifestyle and environmental factors. [ABSTRACT FROM AUTHOR]

• Socioeconomic status (SES) predicts numerous health outcomes. • Chronic inflammation and immunosenescence are implicated pathways. • Studies on SES and immune function outside high income countries are limited. • In Cebu, Philippines, SES was negatively associated with measures of immunosenescence. • SES was positively associated with inflammation and mediated by adiposity. Socioeconomic status (SES) gradients in health are well-documented, and while biological pathways are incompletely understood, chronic inflammation and accelerated immune aging (immunosenescence) among lower SES individuals have been implicated. However, previous findings have come from samples in higher income countries, and it is unclear how generalizable they are to lower- and middle-income countries (LMIC) with different infectious exposures and where adiposity—an important contributor to chronic inflammation—might show different SES patterning. To address this gap, we explored associations between SES and inflammation and immunosenescence in a sample of women in Cebu, Philippines. Data came from the mothers of the Cebu Longitudinal Health and Nutrition Survey birth cohort (mean age: 47.7, range: 35–69 years). SES was measured as a combination of annual household income, education level, and assets. Chronic inflammation was measured using C-reactive protein (CRP) in plasma samples from 1,834 women. Immunosenescence was measured by the abundance of exhausted CD8T (CD8 + CD28-CD45RA-) and naïve CD8T and CD4T cells, estimated from DNA methylation in whole blood in a random subsample of 1,028. Possible mediators included waist circumference and a collection of proxy measures of pathogen exposure. SES was negatively associated with the measures of immunosenescence, with slight evidence for mediation by a proxy measure for pathogen exposure from the household's drinking water source. In contrast, SES was positively associated with CRP, which was explained by the positive association with waist circumference. Similar to higher income populations, in Cebu there is an SES-gradient in pathogen exposures and immunosenescence. However, lifestyle changes occurring more rapidly among higher SES individuals is contributing to a positive association between SES and adiposity and inflammation. Our results suggest more studies are needed to clarify the relationship between SES and inflammation and immunosenescence across LMIC. [ABSTRACT FROM AUTHOR]

Objectives: The drivers of human life expectancy gains over the past 200 years are not well‐established, with a potential role for historical reductions in infectious disease. We investigate whether infectious exposures in infancy predict biological aging using DNA methylation‐based markers that forecast patterns of morbidity and mortality later in life. Methods: N = 1450 participants from the Cebu Longitudinal Health and Nutrition Survey—a prospective birth cohort initiated in 1983—provided complete data for the analyses. Mean chronological age was 20.9 years when venous whole blood samples were drawn for DNA extraction and methylation analysis, with subsequent calculation of three epigenetic age markers: Horvath, GrimAge, and DunedinPACE. Unadjusted and adjusted least squares regression models were evaluated to test the hypothesis that infectious exposures in infancy are associated with epigenetic age. Results: Birth in the dry season, a proxy measure for increased infectious exposure in the first year of life, as well as the number of symptomatic infections in the first year of infancy, predicted lower epigenetic age. Infectious exposures were associated with the distribution of white blood cells in adulthood, which were also associated with measures of epigenetic age. Conclusions: We document negative associations between measures of infectious exposure in infancy and DNA methylation‐based measures of aging. Additional research, across a wider range of epidemiological settings, is needed to clarify the role of infectious disease in shaping immunophenotypes and trajectories of biological aging and human life expectancy. [ABSTRACT FROM AUTHOR]

Objectives: The gut microbiome (GM) connects physical and social environments to infant health. Since the infant GM affects immune system development, there is interest in understanding how infants acquire microbes from mothers and other household members. Materials and Methods: As a part of the Cebu Longitudinal Health and Nutrition Survey (CLHNS), we paired fecal samples (proxy for the GM) collected from infants living in Metro Cebu, Philippines at 2 weeks (N = 39) and 6 months (N = 36) with maternal interviews about prenatal household composition. We hypothesized that relationships between prenatal household size and composition and infant GM bacterial diversity (as measured in fecal samples) would vary by infant age, as well as by household member age and sex. We also hypothesized that infant GM bacterial abundances would differ by prenatal household size and composition. Results: Data from 16 S rRNA bacterial gene sequencing show that prenatal household size was the most precise estimator of infant GM bacterial diversity, and that the direction of the association between this variable and infant GM bacterial diversity changed between the two time points. The abundances of bacterial families in the infant GM varied by prenatal household variables. Conclusions: Results highlight the contributions of various household sources to the bacterial diversity of the infant GM, and suggest that prenatal household size is a useful measure for estimating infant GM bacterial diversity in this cohort. Future research should measure the effect of specific sources of household bacterial exposures, including social interactions with caregivers, on the infant GM. [ABSTRACT FROM AUTHOR]

Epigenetic clocks quantify regular changes in DNA methylation that occur with age, or in relation to biomarkers of ageing, and are strong predictors of morbidity and mortality. Here, we assess whether measures of fetal nutrition and growth that predict adult chronic disease also predict accelerated biological ageing in young adulthood using a suite of commonly used epigenetic clocks. Data come from the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a long-running cohort followed since birth in metropolitan Cebu, Philippines. Past work has shown that birth weight (BW) and the mother's arm fat during pregnancy (a measure of pregnancy energy status) relate inversely to health outcomes in the CLHNS but primarily in males. Genome-wide DNA methylation was assessed in whole blood using the Infinium EPIC array. Participants included males (n=895) and females (n=803) measured in 2005 (20.8–22.5 years). Clocks included the Hannum and Horvath clocks trained on chronological age, the DNAmPhenoAge and DNAmGrimAge clocks trained on clinical biomarkers, the Dunedin pace of ageing (DunedinPACE) clock trained on longitudinal changes in ageing biomarkers, and the DNAmTL clock trained on leukocyte telomere length. In males, lower BW predicted advanced biological ageing using the Hannum, DNAmPhenoAge, DunedinPoAm, and DNAmTL clocks. In contrast, BW did not predict any clock in female participants. Participants' mothers' pregnancy arm fat only predicted DNAmTL in males. These findings suggest that epigenetic clocks are a useful tool for gauging long-term outcomes predicted by fetal growth, and add to existing evidence in the CLHNS for sex differences in these relationships. [ABSTRACT FROM AUTHOR]

Across vertebrates, testosterone is an important mediator of reproductive trade-offs, shaping how energy and time are devoted to parenting versus mating/competition. Based on early environments, organisms often calibrate adult hormone production to adjust reproductive strategies. For example, favorable early nutrition predicts higher adult male testosterone in humans, and animal models show that developmental social environments can affect adult testosterone. In humans, fathers' testosterone often declines with caregiving, yet these patterns vary within and across populations. This may partially trace to early social environments, including caregiving styles and family relationships, which could have formative effects on testosterone production and parenting behaviors. Using data from a multidecade study in the Philippines (n = 966), we tested whether sons' developmental experiences with their fathers predicted their adult testosterone profiles, including after they became fathers themselves. Sons had lower testosterone as parents if their own fathers lived with them and were involved in childcare during adolescence. We also found a contributing role for adolescent father--son relationships: sons had lower waking testosterone, before and after becoming fathers, if they credited their own fathers with their upbringing and resided with them as adolescents. These findings were not accounted for by the sons' own parenting and partnering behaviors, which could influence their testosterone. These effects were limited to adolescence: sons' infancy or childhood experiences did not predict their testosterone as fathers. Our findings link adolescent family experiences to adult testosterone, pointing to a potential pathway related to the intergenerational transmission of biological and behavioral components of reproductive strategies. [ABSTRACT FROM AUTHOR]

Alloparental caregiving is key to humans' highly flexible reproductive strategies. Across species and across societies, alloparental care is more common in harsh and/or unpredictable environments (HUEs). Currently, however, it is unclear whether HUEs predict intra-population variation in alloparental care, or whether early life HUEs might predict later alloparental care use in adulthood, consistent with adaptive developmental plasticity. We test whether harshness measures (socioeconomic status (SES), environmental hygiene, crowding) and unpredictability measures (parental unemployment, paternal absence, household moves) predicted how much alloparental assistance families in Cebu, Philippines received, in a multigenerational study with data collected across four decades. Though worse environmental hygiene predicted more concurrent alloparental care in 1994, we found little evidence that HUEs predict within-population variation in alloparental care in this large-scale, industrialized society. Indeed, less-crowded conditions and higher SES predicted more alloparental care, not less, in the 1980s and in 2014 respectively, while paternal absence in middle childhood predicted less reliance on alloparental care in adulthood. In this cultural context, our results generally do not provide support for the translation of interspecific or intersocietal patterns linking HUEs and alloparental care to intra-population variation in alloparental care, nor for the idea that a reproductive strategy emphasizing alloparental care use may be preceded by early life HUEs. [ABSTRACT FROM AUTHOR]

Current evolutionary theory conceptualizes fathers' childcare as highly facultative and likely contingent on a variety of local socioecological predictors. Much of the evolutionarily-motivated work on the predictors of paternal care has focused on smaller-scale societies, while similar, potentially complementary research in larger-scale societies has focused on theoretical frameworks from (e.g.) economics and developmental psychology. Due to the different emphases, relatively few studies have incorporated information on variables known to predict paternal care in one context with those known to predict it in the other. Here, we assess whether paternal care conforms to predictions derived from the facultative fathering hypothesis and life history theory in Cebu, the Philippines. We evaluated which of 6 variables—hours worked outside the home, age and number of children, number of other caregivers, family residence pattern, and fathers' educational attainment—predicted the number of hours fathers reported spending on 12 common caregiving tasks. Consistent with the basic premise of facultative fathering, men who worked more spent less time on childcare. Additionally, the time fathers spent on different types of caregiving reflected changes in demand as children age. However, alloparental care appears to be a complement to, rather than a substitute for, paternal care in this context, in contrast to the predictions of the facultative fathering hypothesis. We also found that men with more education reported spending more time on childcare, consistent with a caregiving strategy that emphasizes heavy investment in embodied capital across generations. Our data illustrate the context-specific nature of 'facultative' caregiving in humans, and highlight the importance of considering locally-relevant predictors when testing predictions derived from evolutionary theory. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives The androgen receptor (AR) mediates expression of androgen-associated somatic traits such as muscle mass and strength. Within the human AR is a highly variable glutamine short-tandem repeat (AR-CAGn), and CAG repeat number has been inversely correlated to AR transcriptional activity in vitro. However, evidence for an attenuating effect of long AR-CAGn on androgen-associated somatic traits has been inconsistent in human populations. One possible explanation for this lack of consistency is that the effect of AR-CAGn on AR bioactivity in target tissues likely varies in relation to circulating androgen levels. Materials and Methods We tested whether relationships between AR-CAGn and several androgen-associated somatic traits (waist circumference, lean mass, arm muscle area, and grip strength) were modified by salivary (waking and pre-bed) and circulating (total) testosterone (T) levels in young adult males living in metropolitan Cebu, Philippines ( n = 675). Results When men's waking T was low, they had a reduction in three out of four androgen-associated somatic traits with lengthening AR-CAGn ( p < .1), consistent with in vitro research. However, when waking T was high, we observed the opposite effect-lengthening AR-CAGn was associated with an increase in these same somatic traits. Discussion Our finding that longer AR-CAGn predicts greater androgen-associated trait expression among high-T men runs counter to in vitro work, but is generally consistent with the few prior studies to evaluate similar interactions in human populations. Collectively, these results raise questions about the applicability of findings derived from in vitro AR-CAGn studies to the receptor's role in maintaining androgen-associated somatic traits in human populations. [ABSTRACT FROM AUTHOR]

Background: Rates of overweight and obesity are on the rise globally, and excess adipose tissue may contribute to elevations in inflammation during pregnancy, leading to pregnancy complications and adverse birth outcomes.Objective: The purpose of this study was to evaluate adiposity and inflammation in young women as predictors of inflammation in the third trimester of pregnancy in a community-based sample of healthy women.Methods: Female participants (24-30 y) in a prospective observational cohort study (Cebu Longitudinal Health and Nutrition Survey) were contacted between 2009 and 2014 to identify new pregnancies. A total of 309 women provided data from 409 pregnancies. An in-home interview was scheduled for the third trimester to collect pregnancy information, anthropometric measurements, and a blood sample. Circulating C-reactive protein (CRP) was measured with a high-sensitivity immunoassay. Data collected from assessments in 2005 and 2009 were used to assess body mass index (BMI) and CRP in young adulthood, before pregnancy. Robust regression models were implemented to evaluate BMI and CRP in young adulthood as predictors of pregnancy CRP.Results: Pre-pregnancy BMI was a stronger predictor of third-trimester circulating CRP than BMI in the third trimester. No association was found between pregnancy weight gain and CRP. Pre-pregnancy CRP was a significant predictor of CRP in pregnancy, independent of BMI.Conclusions: Levels of overweight/obesity and inflammation in young adulthood, before pregnancy, are important predictors of inflammation in the third trimester of pregnancy. These results may have implications for addressing the growing concern about the contribution of obesity to adverse birth outcomes, and they suggest that factors that influence the regulation of inflammation, before pregnancy and independent of adiposity, may be important in shaping the inflammatory response to pregnancy. [ABSTRACT FROM AUTHOR]

Background C-reactive protein (CRP) is increasingly measured as a marker of systemic inflammation that predicts elevated risk for cardiovascular disease. Influenza vaccination is a mild pro-inflammatory stimulus, and the CRP response to vaccination may provide additional information on individual differences in inflammatory response and risk for disease. Aim To document the pattern of CRP response to influenza vaccination among a large sample of older women in the Philippines. The Philippines exemplifies current global trends toward increasing rates of overweight/obesity, but also maintains relatively high rates of infectious disease. The secondary aim of the study is to investigate the impact of infectious symptoms on the pattern of response to vaccination. Methods A community-based sample of 934 women (mean age = 55.4 years) received the influenza vaccine. CRP was assessed at baseline and 72 h post-vaccination. Descriptive, non-parametric, and parametric analyses were implemented to assess the magnitude of CRP response, and to investigate whether responses were associated with baseline CRP or the presence of infectious symptoms prior to vaccination. Results Influenza vaccination resulted in a statistically significant CRP response of 0.35 mg/L ( p < 0.001), representing a 30.2% increase from baseline. For individuals with symptoms of infectious disease at baseline, the CRP response was smaller (12.9%) and not statistically significant ( p = 0.77). Lower CRP at baseline was associated with larger CRP response to vaccination in the entire sample, and among participants without recent symptoms of infection. Conclusions Influenza vaccination produces a mild CRP response in the Philippines. This study extends prior research in US and European populations validating influenza vaccination as an in vivo model for investigating the dynamics of inflammation, but also raises potential complications in settings where rates of infectious disease are elevated. [ABSTRACT FROM AUTHOR]

Abstract: Testosterone (T) is thought to help facilitate trade-offs between mating and parenting in humans. Across diverse cultural settings married men and fathers have lower T than other men and couples' sexual activity often declines during the first years of marriage and after having children. It is unknown whether these behavioral and hormonal changes are related. Here we use longitudinal data from a large study in the Philippines (n=433) to test this model. We show that among unmarried non-fathers at baseline (n=153; age: 21.5±0.3years) who became newly married new fathers by follow-up (4.5years later), those who experienced less pronounced longitudinal declines in T reported more frequent intercourse with their partners at follow-up (p<0.01) compared to men with larger declines in T. Controlling for duration of marriage, findings were similar for men transitioning from unmarried to married (without children) (p<0.05). Men who remained unmarried and childless throughout the study period did not show similar T-sexual activity outcomes. Among newly married new fathers, subjects who had frequent intercourse both before and after the transition to married fatherhood had more modest declines in T compared to peers who had less frequent sex (p<0.001). Our findings are generally consistent with theoretical expectations and cross-species empirical observations regarding the role of T in male life history trade-offs, particularly in species with bi-parental care, and add to evidence that T and sexual activity have bidirectional relationships in human males. [Copyright &y& Elsevier]

Abstract: Chronic inflammation is a potentially important pathway through which psychosocial stressors increase risk for cardiovascular disease. However, prior research on stress and inflammation has been conducted almost exclusively in high income, industrialized populations with low levels of infectious disease. In this study we test the hypothesis that psychosocial stressors are associated with elevated concentrations of C-reactive protein (CRP) among young adults in the Philippines (n =1622), who have grown up in an ecological and epidemiological setting that differs substantially from that of the US. In addition, we apply a developmental, ecological perspective to consider whether microbial and nutritional environments in infancy alter patterns of association between stressors and CRP. Data come from the Cebu Longitudinal Health and Nutrition Survey, a prospective cohort study that began collecting data in 1983–1984 when participants were in utero. A series of regression models indicate trends toward significant interactions between perceived stress and environmental factors in infancy, including exposure to animal feces, season of birth, and birth weight. Parental absence in childhood was a significant predictor of CRP in adulthood in interaction with exposure to animal feces in infancy. Positive associations between stressors and CRP were only evident for individuals with lower levels of microbial exposure in infancy, or lower birth weight. These results suggest that early environments influence the development of inflammatory phenotypes in ways that moderate sensitivity to psychosocial stressors in adulthood, and they underscore the value of a comparative, developmental approach to research on social environments, inflammation, and disease. [Copyright &y& Elsevier]

Because cross-species evidence suggests that high testosterone (T) may interfere with paternal investment, the relationships between men's transition to parenting and changes in their T are of growing interest. Studies of human males suggest that fathers who provide childcare often have lower T than uninvolved fathers, but no studies to date have evaluated how nighttime sleep proximity between fathers and their offspring may affect T. Using data collected in 2005 and 2009 from a sample of men (n = 362; age 26.0 ± 0.3 years in 2009) residing in metropolitan Cebu, Philippines, we evaluated fathers' T based on whether they slept on the same surface as their children (same surface cosleepers), slept on a different surface but in the same room (roomsharers), or slept separately from their children (solitary sleepers). A large majority (92%) of fathers in this sample reported practicing same surface cosleeping. Compared to fathers who slept solitarily, same surface cosleeping fathers had significantly lower evening (PM) T and also showed a greater diurnal decline in T from waking to evening (both p<0.05). Among men who were not fathers at baseline (2005), fathers who were cosleepers at follow-up (2009) experienced a significantly greater longitudinal decline in PM T over the 4.5-year study period (p<0.01) compared to solitary sleeping fathers. Among these same men, baseline T did not predict fathers' sleeping arrangements at follow-up (p>0.2). These results are consistent with previous findings indicating that daytime father-child interaction contributes to lower T among fathers. Our findings specifically suggest that close sleep proximity between fathers and their offspring results in greater longitudinal decreases in T as men transition to fatherhood and lower PM T overall compared to solitary sleeping fathers. [ABSTRACT FROM AUTHOR]

Background: Although maternal infection and inflammation during pregnancy can adversely affect offspring birth weight (BW), whether low grade inflammation in the non-pregnant state predicts BW is unknown. Aim: To evaluate relationships between offspring BW and pro- and anti-inflammatory factors measured in parous but non-pregnant women. Subjects and methods: Data come from 234 parous Filipino females (21.5 ± 0.3 years) in the Cebu Longitudinal Health and Nutrition Survey, a population-based birth cohort in Metropolitan Cebu, Philippines. Pro-inflammatory [Interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), tumour necrosis factor alpha (TNFα), C-reactive protein (CRP)] and anti-inflammatory [Interleukin-10 (IL-10)] factors were measured in fasting plasma when the women were not pregnant, and related to recalled offspring BW. Results: BW in female offspring was lower only among women with high IL-1β. Although pro-inflammatory cytokines did not predict BW in male offspring, women with higher anti-inflammatory IL-10 gave birth to larger males. Women with a combination of low inflammatory (IL-6) and high anti-inflammatory (IL-10) factors (interaction p < 0.104) gave birth to the largest males. Conclusion: Immune factors measured outside of pregnancy predict offspring BW in these young women. Stable variation in inflammatory phenotype could impact the gestational environment of offspring, thus pointing to potential inter-generational effects of chronic low-grade inflammation. [ABSTRACT FROM AUTHOR]

Inflammation is a central part of innate immunity, but its role in anti-pathogen defenses has been overshadowed by recent interest in the contribution of inflammation to a wide range of chronic degenerative diseases. Current research on chronic inflammation is conducted primarily in affluent populations with low levels of infectious disease; comparative research in different ecological settings is needed to advance understandings of the causes and consequences of variation in the regulation of inflammation. This article investigates the levels and predictors of interleukin-6 (IL-6) and interleukin-10 (IL-10)-two cytokines important to the regulation of inflammation-in a large, population-based study in the Philippines. Concentrations of IL-6 and IL-10 were determined in N = 1,569 healthy young adults (20-22 years) in Metro Cebu, Philippines. IL-6 and IL-10 concentrations were positively correlated, and body mass index and symptoms of infectious disease were both associated with higher concentrations of IL-6 and IL-10. Median concentrations of IL-6 (1.0 pg/mL) and IL-10 (7.56 pg/mL) were substantially lower and higher, respectively, than levels reported for other populations based on a systematic review of prior research. This study contributes to a growing body of research in human ecological immunology, and suggests that there may be substantial population differences in the regulation of inflammation that has implications for the association between inflammation and disease. Am J Phys Anthropol, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In species in which males care for young, testosterone (T) is often high during mating periods but then declines to allow for caregiving of resulting offspring. This model may apply to human males, but past human studies of T and fatherhood have been cross-sectional, making it unclear whether fatherhood suppresses T or if men with lower T are more likely to become fathers. Here, we use a large representative study in the Philippines (n = 624) to show that among single nonfathers at baseline (2005) (21.5 ± 0.3 y), men with high waking T were more likely to become partnered fathers by the time of follow-up 4.5 y later (P < 0.05). Men who became partnered fathers then experienced large declines in waking (median: -26%) and evening (median: -34%) T, which were significantly greater than declines in single nonfathers (P < 0.001). Consistent with the hypothesis that child interaction suppresses T, fathers reporting 3 h or more of daily childcare had lower T at follow-up compared with fathers not involved in care (P < 0.05). Using longitudinal data, these findings show that T and reproductive strategy have bidirectional relationships in human males, with high T predicting subsequent mating success but then declining rapidly after men become fathers. Our findings suggest that T mediates tradeoffs between mating and parenting in humans, as seen in other species in which fathers care for young. They also highlight one likely explanation for previously observed health disparities between partnered fathers and single men. [ABSTRACT FROM AUTHOR]

The article presents a study on the risk factors for elevated C-reactive protein (CRP) among women in the Philippines to characterize the changes in waist circumference over 11-year interval. The study evaluates the current circumference and changes using regression analysis to predict the presence of elevated plasma CRP concentration. Results suggest the association of current waist circumference with a higher risk of elevated CRP, however, history of adiposity may be reversible by weight loss.

Cardiovascular disease (CVD) is a leading cause of death in the Philippines, although few studies here have examined the lipid profiles underlying disease risk. The isolated low high density lipoprotein cholesterol/HDL-c) phenotype has been implicated as a CVD risk factor, the prevalence of which exhibits significant variation across populations. To assess population variation in individual lipid components and their associations with diet and anthropometric characteristics, we compare lipid profiles in a population of adult Filipino women (n=1877) to US women participating in the National Health and Nutrition Examination Survey (NHANES, n=477). We conducted multiple regression models to assess the relationship between lipid components, body mass index, and dietary variables in the two populations. We measured the prevalence of lipid phenotypes, and logistic regression models determined the predictors of the isolated low HDL-c phenotype. High density lipoprotein cholesterol was lower in the Philippines (40.8±0.2 mg/dL) than in NHANES (60.7±0.7 mg/dL). The prevalence of the isolated low HDL-c phenotype was 28.8%, compared to 2.10% in NHANES. High prevalence among Filipinos was relatively invariant across all levels of BMI, hut was strongly inversely related to BMI in NHANES and exhibited only at the BMI>25 kg/m2 threshold. Diet did not consistently predict the low-HDL phenotype in Filipinos. Filipino women exhibit a high prevalence of the isolated low HDL-c phenotype, which is largely decoupled from anthropometric factors. The relationship of CVD to population variation in dyslipidemia and body composition needs further study, particularly in populations where the burden of cardiovascular and metabolic disease is rapidly increasing. [ABSTRACT FROM AUTHOR]

Obesity and infectious agents are both sources of inflammatory stimuli that result in increased production of C-reactive protein (CRP). Rates of overweight and obesity are increasing globally, but for many populations, gains in body fat are set against a backdrop of high levels of pathogen exposure. Our primary objective was to evaluate the extent to which adiposity and pathogenicity contribute to a double burden of inflammation in a population currently undergoing the nutrition transition. Measures of adiposity, pathogen exposure, and infectious disease symptoms were evaluated as predictors of high- sensitivity CRP concentration in plasma samples from 1875 women participating in the Cebu Longitudinal Health and Nutrition Survey in the Philippines. Proxy measures of pathogen exposure included household crowding and cleanliness, quality of water source, mode of waste disposal, and fecal exposure. A series of maximum likelihood logistic regression models were used to predict a plasma CRP concentration >3 mg/L. Waist circumference was the strongest anthropometric predictor of elevated CRP [odds ratio (OR) = 2.29; 95% Cl = 2.00, 2.62; P < 0.001]. Presence of infectious~ disease symptoms (OR = 2.51; 95% Cl = 1.84, 3.44; P< 0.001) and level of pathogen exposure (OR = 1.56; 95% Cl = 1.15, 2.12; P< 0.01) were also associated with elevated CRP. These associations were independent of socioeconomic status and other health behaviors. Overweight/obesity and infectious exposures are associated with elevated CRP in the Philippines; it is likely that other populations undergoing the nutrition transition are experiencing comparable double burdens of inflammatory stimuli. These results underscore the need for additional research on the contributions of pathogenicity, adiposity, and inflammation to global epidemics of cardiovascular and metabolic diseases. [ABSTRACT FROM AUTHOR]

Explores the dynamic nature of the urban landscape in the Philippines, using data from the Cebu Longitudinal Health and Nutrition Survey. Conditions that make the area an ideal population for investigating issues related to urbanization and health; Use of factor analysis to identify clusters of household- and community-level variables.

The fetal and early infant origins of a number of adult cardiovascular and metabolic diseases have received considerable attention, but the long-term consequences of early environments for human immune function have not been reported. We investigated the effects of pre- and postnatal environments on thymic hormone production in adolescents participating in an ongoing longitudinal study in the Philippines. Prospective data collected at birth, during y 1 of life, in childhood and in adolescence were used to predict plasma thymopoietin concentration in 14- to 15-y-old adolescents (n = 103). Thymopoietin concentration was compared for small-for-gestational-age and appropriate-for-gestational-age individuals while controlling for a range of postnatal exposures. Prenatal undernutrition was significantly associated with reduced thymopoietin production in interaction with the duration of exclusive breast-feeding (P = 0.006). Growth in length during y 1 of life was positively associated with adolescent thymopoietin production (P = 0.002). These associations remained significant after adjusting for a range of potentially confounding variables. These findings provide support for the importance of fetal and early infant programming of thymic function, and suggest that early environments may have long-term implications for immunocompetence and adult disease risk. [ABSTRACT FROM AUTHOR]

With modernization, the Philippines has experienced increasing rates of obesity and related cardiometabolic diseases. Studying how risk factors cluster in individuals may offer insight into cardiometabolic disease etiology. We used cluster analysis to group women who share the following cardiometabolic biomarkers: fasting triglycerides, HDL-C and LDL-C, C-reactive protein, systolic and diastolic blood pressure, homeostasis model assessment of insulin resistance, and fasting glucose. Participants included 1,768 women (36-69 years) in the Cebu Longitudinal Health and Nutrition Survey. We identified five distinct clusters characterized by: 1) low levels of all risk factors (except HDL-C and LDL-C) or "healthy"; 2) low HDL-C in the absence of other risk factors; 3) elevated blood pressure; 4) insulin resistance; and 5) high C-reactive protein. We identified predictors of cluster membership using multinomial logistic regression. Clusters differed by age, menopausal status, socioeconomic status, saturated fat intake, and combinations of overweight (BMI >23) and high waist circumference (>80 cm). In comparison to the healthy cluster, overweight women without high waist circumference were more likely to be in the high CRP cluster (OR=2.26, 95% CI=1.24-4.11), while women with high waist circumference and not overweight were more likely to be in the elevated blood pressure (OR=2.56, 95% CI=1.20-5.46) or insulin resistant clusters (OR=4.05, 95% CI=1.39-11.8). In addition, a diet lower in saturated fat uniquely increased the likelihood of membership to the low HDL-C cluster. Cluster analysis identified biologically meaningful groups, predicted by modifiable risk factors; this may have implications for the prevention of cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

In Euro-American societies, married people typically have lower overall risks for total mortality and for certain chronic conditions compared to non-married people. However, people becoming partnered and parents also tend to gain weight in Euro-American settings. Few studies have tested whether links between physical health and life history status translate to other cultural contexts where the socio-ecological dynamics of family life may differ. This limits the application of these insights to men's well-being in global public health. To help address this gap, we drew on a large, long-running birth cohort study of Filipino men, using data collected at three waves between 2005 and 2014 when men were 21.5–30.5 years old (N = 607, obs. = 1760). We tested for the effects of the transition to partnering (marriage/cohabitation) and fatherhood on men's physical health (waist circumference, fat-free mass index, and grip strength). Men becoming partnered or partnered fathers (P/PF) had comparable longitudinal physical health trajectories to men remaining single non-fathers. However, men who became P/PF by their mid 20s had higher fat-free mass index values than single non-fathers at each wave, with the largest effect observed when all men were single non-fathers at baseline. Men who became P/PF by their early 30s were also stronger than the reference group at baseline. Thus, men who were more muscular and stronger at baseline were more likely to transition to P/PF status, consistent with a 'marital selection' model. In complementary analyses, men did not exhibit adverse health effects when they became partnered fathers as young adults or parents to infants, respectively. These findings suggest that links between health and life history transitions in this setting differ from those commonly observed in Euro-American societies. While transitions to marriage and fatherhood are promising windows for interventions to improve men's health, our results highlight the importance of tailoring such approaches to local dynamics. • Married men have lower mortality risks than single men in many societies. • Men's health and partnering/parenting links are poorly studied across cultures. • Filipino men's physical health did not differ across life history transitions. • Men who were stronger and more muscular were more likely to become partnered. • Links between men's health and life history transitions differ across contexts. [ABSTRACT FROM AUTHOR]

Abstract: Testosterone (T) is lower among fathers and men in committed relationships, suggesting that the hormone mediates the trade-off between mating and parenting effort. The function of T in women and responses of the hormone to relationships or motherhood are less well understood. Here we report relationships between T and pairbonding and motherhood in a random sample of 67 women (20.9 to 22.4 years old) participating in a population-based birth cohort study in the Philippines. Testosterone was measured in saliva collected at bedtime and at waking the following morning to capture circadian dynamics. Compared to non-mothers and non-pairbonded women, mothers and pairbonded women had 32% (p <0.0001) and 23% (p <0.004) lower waking T, respectively, but similar evening T. The lower waking T in mothers largely reflected reduced T in mothers of young offspring (<2 years), with mothers of older offspring (2+ years) having intermediate T. These differences were independent of measures of breastfeeding, contraceptive pill use, menstrual cycle, sleep quality, education, employment, and socioeconomic status. Our findings highlight a similar relationship between parenting and committed relationships and T in women as documented in men and suggest that caregiving of dependent young may modulate female T. Future research should clarify whether this cross-sectional association reflects a suppressive effect of motherhood on T, whether these relationships vary across cultures, and the role of T within the endocrine architecture regulating female reproductive and caregiving strategies. [Copyright &y& Elsevier]

Abstract: In species with a high level of paternal care, including humans, testosterone (T) is believed to help mediate the trade-off between parenting and mating effort. This hypothesis is supported by the observation of lower T in pairbonded men or fathers compared to single, non-fathers; however, prior work has highlighted population variation in the association between T and pairbonding or fatherhood status. Here we evaluate this hypothesis in a large (n =890), representative birth cohort of young men (age range 20.5–22.5 years) living in Cebu City, the Philippines. Bioavailable T was measured in saliva collected prior to bed and immediately upon waking the following morning. Plasma T and luteinizing hormone (LH) were measured in morning plasma samples. In this sample, 20% of men were pairbonded, defined as living with a partner or married, 13% were fathers, and roughly half of fathers reported involvement in childcare. Pairbonded men had significantly lower T at both times of day. Unlike in other populations, this relationship was accounted for entirely by fatherhood status: among the large sub-sample of non-fathers, mean T was nearly identical among pairbonded and single men. There was a strong association between self-reported involvement in childcare and lower evening T, supporting the idea that the evening nadir in T is related to social interactions across the day. Similar relationships were found for total plasma T and LH, suggesting that these relationships are coordinated by centrally-mediated changes in LH secretion. The relatively modest T difference in relation to fatherhood at Cebu, in comparison to other studies, may reflect a lower level of paternal involvement in childcare activities in this population. Our findings using a large, well-characterized birth cohort support the hypothesized role of T as a mediator of mating and parenting effort in humans, while contributing evidence for cultural variation in the relative importance of pairbonding and fathering to these relationships. [Copyright &y& Elsevier]

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., (© 2024 The Author(s). American Journal of Human Biology published by Wiley Periodicals LLC.)

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.

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., (© 2019 Wiley Periodicals, Inc.)

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., (© 2019 Wiley Periodicals, Inc.)

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., (© 2019 Wiley Periodicals, Inc.)

Objective: Cross-culturally, men's T declines in response to pairbonding and fatherhood, but less is known about what happens to T during and after life history transitions that theoretically lead to renewed mating effort. We tested whether men's T rises (or declines less with age) as their children age, or when pairbonds end, independent of changes in fatherhood-related variables such as co-residence with children., Methods: We used demographic, behavioral, and salivary hormone data (waking and pre-bed T) collected in 2009 and 2014 for the Cebu Longitudinal Health and Nutrition Survey (n = 571 men)., Results: Fathers with older children tended to have attenuated decline in pre-bedtime T between 2009 and 2014 compared to men with younger children, after controlling for pairbonding (ß = 1.58, SE = 0.88, P = 0.074). Separated men had higher pre-bedtime T than pairbonded men, controlling for fatherhood-related variables (ß = 11.74, SE = 4.33, P = 0.007). Change in T did not significantly differ for men who separated between the two surveys, relative to men who remained pairbonded throughout., Conclusion: We found modest support for the prediction that men experience less of an age-related drop in T as their youngest child ages, a trend that might strengthen as children age further. We also replicate the finding that separated men have higher T, although longitudinal changes in the hormone were not significantly different in these men. Our data suggest that, of two life history transitions that may predict renewed mating effort, pair bond loss is more strongly endocrine mediated than potential mating effort shifts related to the aging of children., (© 2018 Wiley Periodicals, Inc.)

Aim: To determine if field-typical storage and collection conditions are related to salivary testosterone (T), cortisol (cort) and secretory immunoglobulin A (sIgA) as measured using commercially available kits., Subjects and Methods: This study assessed whether storage time (∼6 months to 1.5 years) at -35 °C impacted levels of the measured biomarkers (n = 10,247 samples). For a sub-set of T samples (n = 2954), we also evaluated the impact of collection conditions, such as time spent at room temperature in participants' homes (0-39 hours) and time spent in coolers (0.3-10 hours) in transit., Results: T was unrelated to storage and collection variables and there was no evidence of reduced sample fidelity at longer storage times. Cort samples stored at -35 °C for longer had significantly lower values, but the effect was small (β = -0.003 nmol/L/day, SE <0.001, p = 0.005). sIgA trended higher with longer storage at -35 °C (β = 0.84 µg/mL/day, SE = 0.45, p = 0.063). Collection and storage time variables did not improve the fit of any of the models except the one that evaluated cortisol., Conclusions: Salivary T was unaffected by extended storage at -35 °C and only a weak relationship was found between storage time and salivary cort or sIgA. Findings underscore the robustness of these biomarkers under field-typical freezer storage conditions.

Objectives: We used detailed saliva sampling procedures to test for diurnal changes in men's salivary estradiol (E2) and testosterone (T) and assessed whether greater adiposity predicted higher E2 and T., Methods: We drew on a subsample of young adults enrolled in a long-running birth cohort study in Metro Cebu, Philippines. Subjects provided saliva samples at four time points during the day (waking, waking +40 min, early evening, and bedtime), which were assayed for E2 and T. Using these detailed hormonal data, we calculated E2 (n = 29) and T (n = 44) area-under-the-curve values, which provide insights on hormonal production over the study period., Results: While T declined immediately after waking and reached a nadir in the early evening, E2 did not show significant diurnal change (P ≥ 0.1) but was positively correlated to T at multiple time points (P ≤ 0.05). Subjects with higher adiposity (BMI, waist circumference, skinfolds) had elevated E2 secretion throughout the day (P ≤ 0.01), but adiposity was not related to salivary T., Conclusions: Consistent with past research, our results indicate that adipose tissue is a significant site of E2 production in males but differ from a limited number of prior studies of young men in that we did not find lower T with increasing adiposity. Given E2's role in male hypothalamic-pituitary-gonadal function and complex interfaces with the immune system, these results have important implications for models of male life history as rates of overweight and obesity rise in populations around the world., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: With modernization, cardiometabolic disease risk has increased in low and middle-income countries. To better understand cardiometabolic disease etiology, we evaluated the patterning risk factors in a susceptible young adult population., Methods and Results: Participants included 1,621 individuals from the 2005 Cebu Longitudinal Health and Nutrition Survey. Using cluster analysis, we grouped individuals by the following biomarkers: triglycerides, HDL and LDL cholesterol, C-reactive protein, blood pressure, homeostasis model assessment of insulin resistance, and fasting glucose. Using multinomial logistic regression models we assessed how diet, adiposity, and environment predicted cardiometabolic clusters. We identified 5 distinct sexspecific clusters: 1) Healthy/High HDL cholesterol (with the addition of high LDL cholesterol in women); 2) Healthy/Low blood pressure; 3) High blood pressure; 4) Insulin resistant/High triglycerides; and 5) High Creactive protein. Low HDL cholesterol was the most prevalent risk factor (63%). In men and women, a higher intake of saturated fat increased the likelihood of being in the healthy clusters. In men, poorer environmental hygiene increased the likelihood of being in the High C-reactive protein cluster, compared to the healthy clusters (OR 0.74 [95% CI 0.60-0.90] and 0.83 [0.70-0.99]). Adiposity most strongly associated with membership to the Insulin resistant/high triglyceride cluster., Conclusions: Despite the population's youth and leanness, cluster analysis found patterns of cardiometabolic risk. While adiposity measures predicted clustering, diet and environment also independently predicted clustering, emphasizing the importance of screening lean and overweight individuals for cardiometabolic risk. Finding predictors of risk in early adulthood could help inform prevention efforts for future disease.

Objectives: Pregnancy and lactation involve adaptations in immune regulation, but little is known about cross-cultural variation in inflammatory changes during pregnancy or lactation. Here we report concentrations of C-reactive protein (CRP) in a large cross-sectional sample of healthy Filipino women who vary in parity, gestational, and lactational status, and who come from a population previously described as having low CRP., Methods: Fasting plasma CRP was measured among female participants (ages 20.8-22.4 years) in the Cebu Longitudinal Health and Nutrition Survey (n = 822)., Results: Median CRP was 0.2 mg/l in nulliparous women and peaked at 2.0 mg/l in women in their 3rd trimester of pregnancy. Parous but post-partum women had higher CRP compared to nulliparous women, which was largely explained by body composition differences as reflected in waist circumference and skinfold measures. Among post-partum women with infants, CRP was similar in women who were currently breastfeeding compared to those who were not., Conclusions: At Cebu, women late in gestation have 10-fold higher C-reactive protein compared to nulliparous women, with no evidence that lactation is inflammatory. These population-based findings are similar with findings from prior clinic-based studies and are consistent with the maternal immunological adaptations initiated during pregnancy. The tendency of human females to spend more time than females of other great apes in gestation rather than lactation suggests that the human life history strategy involved increased time spent by reproductively aged females in a pro-inflammatory state., (Copyright © 2012 Wiley Periodicals, Inc.)

Objectives: Despite ample evidence of variation in timing of menopause, little is known about the extent or underlying causes of individual variation in ovarian reserve and age-related follicular decline. Anti-Müllerian hormone (AMH), a hormonal marker of ovarian reserve, may be a useful tool to clarify these questions. We describe AMH in a cohort of Filipino young adult women, and evaluate whether ovarian reserve in early adulthood relates to measures of life history scheduling (menarcheal age) and reproductive effort (parity)., Methods: Data and samples are obtained from 294 nonpregnant participants (21.5 years ± 0.3) in the Cebu Longitudinal Health and Nutrition Survey. Plasma AMH was assayed using an enzyme immunoassay and relationships between AMH, menarcheal age, and parity were examined., Results: Mean AMH was 4.3 ng/mL. In multiple regression models, women who experienced menarche earlier had significantly higher AMH as young adults (P < 0.05). Women with two (P < 0.05) and three or more (P < 0.01) children had significantly lower AMH than those with no children. These associations were independent of age, smoking, and body mass index., Conclusions: These findings suggest that individual variation in life history scheduling and reproductive history could contribute to variation in ovarian reserve. Moreover, they demonstrate the utility of AMH as a tool for human reproductive ecology, and highlight the need for further research clarifying the extent of human population variation in ovarian reserve and the behavioral and ecological influences underlying this variation., (Copyright © 2012 Wiley Periodicals, Inc.)

Recent research has implicated inflammatory processes in the pathophysiology of a wide range of chronic degenerative diseases, although inflammation has long been recognized as a critical line of defense against infectious disease. However, current scientific understandings of the links between chronic low-grade inflammation and diseases of aging are based primarily on research in high-income nations with low levels of infectious disease and high levels of overweight/obesity. From a comparative and historical point of view, this epidemiological situation is relatively unique, and it may not capture the full range of ecological variation necessary to understand the processes that shape the development of inflammatory phenotypes. The human immune system is characterized by substantial developmental plasticity, and a comparative, developmental, ecological framework is proposed to cast light on the complex associations among early environments, regulation of inflammation, and disease. Recent studies in the Philippines and lowland Ecuador reveal low levels of chronic inflammation, despite higher burdens of infectious disease, and point to nutritional and microbial exposures in infancy as important determinants of inflammation in adulthood. By shaping the regulation of inflammation, early environments moderate responses to inflammatory stimuli later in life, with implications for the association between inflammation and chronic diseases. Attention to the eco-logics of inflammation may point to promising directions for future research, enriching our understanding of this important physiological system and informing approaches to the prevention and treatment of disease.

Objectives: Infancy represents a window of development during which long-term immunological functioning can be influenced. In this study, we evaluate proxies of microbial exposures in infancy as predictors of interleukin-4 (IL-4) in young adulthood. IL-4 is an immunoregulatory cytokine that plays a role in the pathogenesis of atopic and allergic diseases., Methods: Data were obtained from 1,403 participants in the Cebu Longitudinal Health and Nutrition Survey, an ongoing population-based study in the Philippines. Relationships between microbial and nutritional environments in infancy and plasma IL-4 concentrations in adulthood were evaluated using tobit regression models., Results: Having older siblings and more episodes of respiratory illness in infancy significantly predicted lower concentrations of plasma IL-4 in adulthood. Unexpectedly, more episodes of diarrheal illness in infancy were associated with higher IL-4 in adulthood. Interactions between a composite household pathogen exposure score and the duration of exclusive breastfeeding approached significance. This interaction showed that the negative association between household pathogen exposure in infancy and adult IL-4 was only significant for individuals who had been exclusively breastfed for a short duration of time. Finally, currently living in an urban household was unexpectedly, negatively associated with adult IL-4. Associations were independent of early nutrition, socioeconomic status (SES), and urbanicity, as well as current measures of infection, body fat, SES, and smoking., Conclusions: This study builds on a growing body of literature demonstrating that early ecological conditions have long-term effects on human biology by providing evidence that multiple proxies of microbial exposures in infancy are associated with adult IL-4., (Copyright © 2012 Wiley Periodicals, Inc.)

Although humans are considered unusual among mammals for the intensity of care that fathers often provide offspring, little is known about the hormonal architecture regulating human paternal investment. Prolactin has important reproductive functions in both female and male mammals and other taxa, making it a candidate regulator of human paternal behavior. Notably, prolactin is higher during periods of offspring care in some species, but it is unknown if this pattern occurs in human fathers. We draw on a sample of men (n = 289; age 21-23 at baseline) from Metropolitan Cebu City, Philippines to evaluate relationships between prolactin, assayed from dried blood spots, and components of reproductive behavior and relationship status. In this sample, fathers had higher prolactin than nonfathers (P = 0.006), and fathers of infants had borderline higher prolactin than fathers of older children (P = 0.054). Among single nonfathers at baseline (2005), baseline prolactin did not predict who transitioned to fatherhood by follow-up 4.5 years later. Among nonfathers, men with greater prolactin reported more lifetime sexual partners (P = 0.050) as well as more sexual activity in the month before sampling (P = 0.060). Our results suggest that fathers in Cebu have higher prolactin than nonfathers, with hormone levels highest among fathers of young infants. Although these findings are generally consistent with evidence from other species for pronurturing effects of prolactin, evidence for positive relationships between the hormone and measures of sexual behavior at Cebu point to likely complexities in the hormone's involvement in male reproductive strategy., (Copyright © 2012 Wiley Periodicals, Inc.)

Recent genome-wide association studies have related several genetic loci, including C-reactive protein (CRP), hepatocyte nuclear factor 1 homeobox (HNF1A), and genetic variations in the leptin receptor (LEPR), to circulating CRP levels in populations of European ancestry. The genetic effects in other populations and across varying levels of exposure to a pathogenic environment, an important environmental factor associated with CRP, remain to be determined. We tested 2,073,674 single-nucleotide polymorphisms (SNPs) for association with plasma CRP (limited to ≤10 mg/L) in 1,709 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey. The strongest evidence of association was observed with variants at CRP (rs876537, P = 1.4 × 10(-9)) and HNF1A (rs7305618, P = 1.0 × 10(-8)). Among other previously reported CRP-associated loci, the apolipoprotein E ε4 haplotype was associated with decreased CRP level (P = 7.1 × 10(-4)), and modest association was observed with LEPR (rs1892534, P = 0.076), with direction of effects consistent with previous studies. The strongest signal at a locus not previously reported mapped to a gene desert region on chromosome 6q16.1 (rs1408282, P = 2.9 × 10(-6)). Finally, we observed nominal evidence of interaction with exposure to a pathogenic environment for top main effect SNPs at HNF1A (rs7305618, P = 0.031), LEPR (rs1892535, P = 0.030) and 6q16.1 (rs1408282, P = 0.046). Our findings demonstrate convincing evidence that genetic variants in CRP and HNF1A contribute to plasma CRP in Filipino women and provide the first evidence that exposure to a pathogenic environment may modify the genetic influence at the HNF1A, LEPR, and 6q16.1 loci on plasma CRP level.

C-reactive protein (CRP) is a component of nonspecific immune defense and is a reliable marker of low-grade inflammation involved in obesity, type 2 diabetes and cardiovascular disease. Genome-wide association studies in middle-aged and elderly populations, predominantly of European descent, demonstrated associations of CRP levels with single-nucleotide polymorphisms (SNPs) at several loci. To examine whether the variants identified are replicated in Filipino young adults, we applied Tobit regression models to study the association of plasma CRP with 12 SNPs at seven loci in a cohort of 1691 Filipino young adults (aged 21.5±0.3 years) from the Cebu Longitudinal Health and Nutrition Survey. SNPs in or near CRP (P=3.2 × 10(-11)), HNF1A, IL6R, APOE-APOC1 and LEPR showed significant associations (P<0.05) and together explained 4.8% of the total variation in CRP. Modest interactions were observed between LEPR-rs1892534 and waist circumference (uncorrected P(interaction)=0.020) and between APOE-rs769449 and pathogen exposure (uncorrected P(interaction)=0.0073) in models predicting CRP. Our results demonstrated that variants in several loci are significantly associated with plasma CRP in Filipino young adults, suggesting shared genetic influences on circulating CRP across populations and age groups.

Objectives: Although cortisol (CORT) may suppress testosterone (T) production under stress, in many species males' T and CORT are co-elevated during mate acquisition or conspecific competition. It is presently unknown how CORT co-varies with T in relation to fatherhood/relationship status in men. Here we evaluate associations between waking (AM) and pre-bed (PM) salivary CORT and T, and with plasma total T and luteinizing hormone. We also test whether co-elevationor co-downregulation of CORT and T are present in men who are mating-oriented (non-pairbonded, non-fathers) and parenting-oriented (pairbonded and/or fathers), respectively., Methods: Data come from 630 of young adult Filipino males (21-23 years) enrolled in the Cebu Longitudinal Health and Nutrition Survey, a population-based birth cohort study in Cebu City, Philippines., Results: T and CORT were positively related in AM (r = 0.37) and PM (r = 0.30) saliva samples (both P < 0.001). The positive relationship between AM measures was strengthened as caloric intake improved (interaction P < 0.05). Mating-oriented men were more likely to have co-elevated PM CORT and T (P < 0.05), defined as being in the highest tertile for both hormones, while parenting-oriented men were more likely to have co-downregulated (lowest tertile for both hormones) AM (P < 0.05) and PM (P < 0.001) CORT and T., Conclusions: CORT and T are positively related upon waking and before bed and are more likely to be co-elevated in mating-oriented men and co-downregulated in parenting-oriented men. Our findings support the interpretation that CORT and T serve complementary roles in facilitating men's mating effort., (Copyright © 2011 Wiley-Liss, Inc.)

Objectives: Inflammation has been associated with a wide range of chronic degenerative diseases, but the developmental factors contributing to the regulation of inflammation are poorly understood. This study investigates the within-individual association between antibody response to vaccination in adolescence and C-reactive protein (CRP) concentration in young adulthood., Methods: In 1998-99, at age 14-15 years, a subset of participants (N = 96) in the Cebu Longitudinal Health and Nutrition Survey were administered a typhoid vaccine, and baseline and follow-up blood samples were drawn to assess the strength of the antibody response to vaccination. In 2005, at age 20-21 years, blood samples were drawn from the full cohort for measurement of CRP. N = 74 individuals had complete data at both time points. Bivariate associations and multivariate logistic regression models were evaluated to test the hypothesis that vaccine responsiveness in adolescence was significantly associated with CRP level in young adulthood., Results: There was a strong and statistically significant association between antibody response to vaccination in adolescence and CRP in young adulthood. Median CRP was more than four times higher among nonresponders than responders, and nonresponders were 2.3 to 3.6 times more likely to have CRP in the top tertile of the sample distribution., Conclusions: This study provides evidence for a prospective, within-individual link between more effective antibody-mediated immune defenses and lower levels of inflammation. In the context of prior research in this population, these results suggest that early environments are important determinants of multiple aspects of an individual's immuno-phenotype., (Copyright © 2010 Wiley-Liss, Inc.)

Adiponectin is an adipocyte-secreted protein involved in a variety of metabolic processes, including glucose regulation and fatty acid catabolism. We conducted a genome-wide association study to investigate the genetic loci associated with plasma adiponectin in 1776 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). Our strongest signal for adiponectin mapped to the gene CDH13 (rs3865188, P ≤ 7.2 × 10(-16)), which encodes a receptor for high-molecular-weight forms of adiponectin. Strong association was also detected near the ADIPOQ gene (rs864265, P = 3.8 × 10(-9)) and at a novel signal 100 kb upstream near KNG1 (rs11924390, P = 7.6 × 10(-7)). All three signals were also observed in 1774 young adult CLHNS offspring and in combined analysis including all 3550 mothers and offspring samples (all P ≤ 1.6 × 10(-9)). An uncommon haplotype of rs11924390 and rs864265 (haplotype frequency = 0.050) was strongly associated with lower adiponectin compared with the most common C-G haplotype in both CLHNS mothers (P = 1.8 × 10(-25)) and offspring (P = 8.7 × 10(-32)). Comprehensive imputation of 2653 SNPs in a 2 Mb region using as reference combined CHB, JPT and CEU haplotypes from the 1000 Genomes Project revealed no variants that perfectly tagged this haplotype. Our findings provide the first genome-wide significant evidence of association with plasma adiponectin at the CDH13 locus and identify a novel uncommon KNG1-ADIPOQ haplotype strongly associated with adiponectin levels in Filipinos.

Plasma homocysteine (Hcy) level is associated with cardiovascular disease and may play an etiologic role in vascular damage, a precursor for atherosclerosis. We performed a genome-wide association study for Hcy in 1786 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The most strongly associated single-nucleotide polymorphism (SNP) (rs7422339, P = 4.7 x 10(-13)) encodes Thr1405Asn in the gene CPS1 and explained 3.0% of variation in the Hcy level. The widely studied MTHFR C677T SNP (rs1801133) was also highly significant (P = 8.7 x 10(-10)) and explained 1.6% of the trait variation. We also genotyped these two SNPs in 1679 CLHNS young adult offspring. The MTHFR C677T SNP was strongly associated with Hcy (P = 1.9 x 10(-26)) and explained approximately 5.1% of the variation in the offspring. In contrast, the CPS1 variant was significant only in females (P = 0.11 in all; P = 0.0087 in females). Combined analysis of all samples confirmed that the MTHFR variant was more strongly associated with Hcy in the offspring (interaction P = 1.2 x 10(-5)). Furthermore, although there was evidence for a positive synergistic effect between the CPS1 and MTHFR SNPs in the offspring (interaction P = 0.0046), there was no significant evidence for an interaction in the mothers (P = 0.55). These data confirm a recent finding that CPS1 is a locus influencing Hcy levels in women and suggest that genetic effects on Hcy may differ across developmental stages.