Timing of the luteal-placental shift is delayed with additional fetuses in litter-bearing callitrichid monkeys, Saguinus oedipus and Callithrix jacchus.

The luteal-placental shift is an important milestone of mammalian pregnancy signifying when endocrine control of pregnancy shifts from the corpus luteum of the ovary to the placenta. The corpus luteum is maintained by chorionic gonadotropin (CG). Upon sufficient placental maturation, CG production wanes, the corpus luteum involutes, and control is shifted to the placenta, one consequence of which is a midgestational rise in glucocorticoid production, especially cortisol and cortisone, by both mother and fetus. Glucocorticoids are involved in initiating parturition, prenatal programming of offspring phenotype, and maturing fetal organs. Limited evidence from human pregnancy suggests that the timing of this shift is delayed in twin pregnancies, but little is known about the timing of the luteal-placental shift in litter-bearing monkeys from the primate family Callitrichidae. Here we provide evidence from cotton-top tamarins (Saguinus oedipus) and common marmosets (Callithrix jacchus) of longer duration of elevated CG associated with multiple infant births compared to single births. Urinary profiles from cotton-top tamarins demonstrate that the decline of the extended elevation of CG precedes the onset of the midpregnancy sustained rise in glucocorticoids; this shift occurs later with an increase from one to two fetuses carried to term. In the common marmoset, the onset of the sustained rise of glucocorticoids in maternal urine is also delayed with an increase in infant number. Total urinary glucocorticoid levels during the last half of gestation increase monthly but do not differ by infant number. The significant delay in the luteal-placental shift suggests a longer period of placental maturation is needed to support a greater number of fetuses.

Global Public Health Nursing.

BACKGROUND: An often under addressed and tragic legacy of genocide is the conception of children from rape. While the experience has been documented from their mothers' perspective, the perspectives and needs of individuals born of genocidal rape has been under-studied. METHODS: We conducted an integrative review of all peer-reviewed articles that reported on studies conducted among individuals born of genocidal rape published through 2020. We used an inductive process to identify and describe the themes from those studies. RESULTS: Twelve studies met the inclusion criteria. Ten articles reported on youth born of genocidal rape in Rwanda aged between 16 and 21 years, and two articles represented the perspective of adolescents in the former Yugoslavia aged 1416 years. Four themes were indentified: (1) birth origin stories associated with the crime of the father, (2) fractured sense of belonging to the victim-mother, perpetrator-father, their families, and the community at large, (3) intergenerational legacy of trauma and family identity, and (4) strategies to move forward including knowing the truth about one's origin, mental health, and peer support. CONCLUSION: These findings suggest that understanding increased risk of adverse health outcomes of youth born of genocidal rape could inform the design of evidence-based interventions for these and similar populations.

Maternal weight affects placental DNA methylation of genes involved in metabolic pathways in the common marmoset monkey (Callithrix jacchus).

Accumulating evidence suggests that dysregulation of placental DNA methylation (DNAm) is a mechanism linking maternal weight during pregnancy to metabolic programming outcomes. The common marmoset, Callithrix jaccus, is a platyrrhine primate species that has provided much insight into studies of the primate placenta, maternal condition, and metabolic programming, yet the relationships between maternal weight and placental DNAm are unknown. Here, we report genome-wide DNAm from term marmoset placentas using reduced representation bisulfite sequencing. We identified 74 genes whose DNAm pattern is associated with maternal weight during gestation. These genes are predominantly involved in energy metabolism and homeostasis, including the regulation of glycolytic and lipid metabolic processes pathways.

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

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

The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity.

Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.

The AVPR1A Gene and Its Single Nucleotide Polymorphism rs10877969: A Literature Review of Associations with Health Conditions and Pain.

BACKGROUND: Pain is the quintessential symptom for individuals suffering from sickle cell disease (SCD). Although the degree of suffering and the cost of treatment are staggering, SCD continues to be grossly understudied, including a lack of data for pain-related genes and prevalence of polymorphisms in this population. This lack of data adds to the inadequacy of pain therapy in this population. Pain genetics investigators have recently examined allele frequencies of single-nucleotide polymorphisms from candidate genes in people who have SCD. One of the genes identified was the arginine vasopressin receptor 1A gene (AVPR1A) and its associated single-nucleotide polymorphism (SNP) rs10877969. Progress in explaining pain-related polymorphisms associated with SCD can be facilitated by understanding the literature. Aim/Design: The purpose of this literature review was to describe mechanisms of the polymorphic gene AVPR1A and the phenotypic variations associated with its SNPs relative to health conditions and pain. METHODS: Published studies were included if the research addressed AVPR1A and was a full article in a peer-reviewed journal, in the English language, a human or animal study, and published 2009 to present. Abstracts were included if they were in English and provided information not found in a full article. RESULTS: The results of this review revealed that AVPR1A is associated with behavioral phenotypes, which include pair bonding, autism spectrum disorder, musical aptitude, infidelity, altruism, monogamy, mating, substance abuse, and alcohol preference. In addition, there were associations with pain, stress pain by sex, and sickle cell pain. CONCLUSION: Summary of this literature could provide insights into future pain research of this SNP in people with SCD.

Evolutionary genetics and implications of small size and twinning in callitrichine primates.

New World monkeys (NWMs) are characterized by an extensive size range, with clawed NWMs (subfamily Callitrichinae, or callitrichines) such as the common marmoset manifesting diminutive size and unique reproductive adaptations. Perhaps the most notable of these adaptations is their propensity toward multiple gestations (i.e., dichorionic twins and trichorionic triplets). Indeed, with the exception of Goeldi's monkey (Callimico), callitrichine singleton pregnancies rarely occur. Multiple gestations seem to have coevolved with a suite of reproductive adaptations, including hematopoetic chimerism of siblings, suppression of reproduction in nondominant females, and cooperative alloparenting. The sequencing of the common marmoset (Callithrix jacchus) genome offers the opportunity to explore the genetic basis of these unusual traits within this primate lineage. In this study, we hypothesized that genetic changes arising during callitrichine evolution resulted in multiple ovulated ova with each cycle, and that these changes triggered adaptations that minimized complications common to multiple gestations in other primates, including humans. Callitrichine-specific nonsynonymous substitutions were identified in GDF9, BMP15, BMP4, and WFIKKN1. WFIKKN1, a multidomain protease inhibitor that binds growth factors and bone morphogenetic proteins, has nonsynonymous changes found exclusively in common marmosets and other tested callitrichine species that twin. In the one callitrichine species that does not produce twins (Callimico), this change has reverted back to the ancestral (nontwinning) primate sequence. Polymorphisms in GDF9 occur among human cohorts with a propensity for dizygotic twins, and polymorphisms in GDF9 and BMP15 are associated with twinning in sheep. We postulate that positive selection affected NWM growth patterns, with callitrichine miniaturization coevolving with a series of reproductive adaptations.

Body mass growth in common marmosets: toward a model of pediatric obesity.

While much is known about adult obesity in nonhuman primates, very little is known regarding development of childhood adiposity. As small monkeys that are easy to handle and have a relatively fast life history, common marmoset monkeys (Callithrix jacchus) offer interesting opportunities to examine the question of fat versus lean mass growth in a nonhuman primate. This article provides an overview of our understanding of early life growth in mass in marmoset monkeys, based primarily upon our past 20 years of research, culminating in our recent findings on early life obesity in this species. Common marmosets display variance in early life growth patterns that is related to both pre- and postnatal factors and the marmoset uterine environment is exquisitely designed to reflect resources available for the gestation of multiple offspring, making them an interesting model of developmental programming. We have demonstrated that obesity can be generated in very early life in captive marmosets, with excess adiposity evident by one month of age, making this species a potentially valuable model in which to study pediatric obesity and its sequelae. Birth weight is associated with adiposity in animals vulnerable to obesity. Early life exposure to higher fat diets enhances the chances of postweaning obesity development. However, overall higher food consumption is also associated with obesity development at later ages. One unexpected finding in our studies has been the relatively high body fat percentage of neonatal (12-18%) marmosets suggesting that hypotheses regarding the uniqueness of high human neonatal adiposity merit further examination.

Associations between duration of first trimester intrauterine exposure to genocide against the Tutsi and health outcomes in adulthood.

OBJECTIVES: Hundreds of thousands of Rwandans were conceived during the 1994 genocide against the Tutsi, including thousands conceived by genocidal rape. We explore whether the duration of first trimester exposure to the genocide is associated with variation in adult mental health outcomes in individuals exposed to varying degrees of genocide-related stress in utero. MATERIALS AND METHODS: We recruited 30 Rwandans conceived via genocidal rape, 31 Rwandans conceived by genocide survivors not raped, and 30 individuals of Rwandan-descent who were conceived outside of Rwanda at the time of the genocide (control group). Individuals were age- and sex-matched across groups. Adult mental health was assessed through standardized questionnaires for vitality, anxiety, and depression. RESULTS: Among the genocide only group, a longer duration of first trimester prenatal exposure was associated with higher anxiety scores and lower vitality (both p < 0.010), and higher depression scores (p = 0.051). Duration of first trimester exposure was not associated with any measures of mental health among the genocidal rape or control group. DISCUSSION: Duration of exposure to genocide in the first trimester of gestation was associated with variation in adult mental health among the genocide only group. The lack of association between duration of first trimester exposure to genocide and adult mental health in the genocidal rape group may reflect the fact that stress associated with conception through rape persisted beyond the genocide period itself, encompassing all of gestation and likely beyond. Geopolitical and community interventions are needed in the context of extreme events during pregnancy to mitigate adverse intergenerational outcomes.

Obstetric experiences of young black mothers: An intersectional perspective.

BACKGROUND: In Chicago, maternal morbidity and mortality is six times more likely among Black birthing people than white, despite policy initiatives to promote maternal health equity. Disparities in maternal morbidity and mortality reflect experiences of structural inequities - including limited quality obstetric care, implicit bias, and racism resulting patient mistrust in the health care system, inadequate social support, and financial insecurity. Although there is published literature on Black women's experiences with obstetric care, including experiences with individual and structural racism, little is known about the intersection of age and race and experiences with health care. The purpose of this study was to explore the maternal health and pregnancy experiences of young Black women utilizing an intersectional theoretical lens. METHODS: In this study, we conducted two focus groups in a sample of 11 young Black pregnant people. We conducted a thematic analysis to identify codes, themes, and subthemes of the data. RESULTS: We developed two overarching themes: obstetric racism and obstetric resistance. To elucidate how obstetric racism framed our participants' healthcare experiences, we identified sub-themes: intersectional identities as young Black women, medical mistrust, and pregnancy trauma. The second major theme describes ways in which participants protected themselves against obstetric racism to engender positive health experiences. These methods of resistance included identifying advocates and relying on trusted providers. CONCLUSIONS: The current standard of obstetric care in the US is suboptimal due to individual and structural racism. This study provides unique data on the experiences with health care for young, Black pregnant individuals and delivers valuable insight into how individual and structural racism impacts obstetric care for young Black women.

Structural Violence and Stress Experiences of Young Pregnant Black People.

INTRODUCTION: Approximately 10-20% of individuals suffer from mental health concerns during the prenatal period due to their vulnerability and emotional responses to stressful events. Mental health disorders are more likely to be disabling and persistent for people of color, and they are less likely to seek treatment due to stigma. Young pregnant Black people report experiencing stress due to isolation, feelings of conflict, lack of material and emotional resources, and support from significant others. Although many studies have reported the types of stressors experienced, personal resources, emotional stress responses on pregnancy, and mental health outcomes, there is limited data on young Black women's perceptions of these factors. METHODS: This study utilizes the Health Disparities Research Framework to conceptualize drivers of stress related to maternal health outcomes for young Black women. We conducted a thematic analysis to identify stressors for young Black women. RESULTS: Findings revealed the following overarching themes: Societal stress of being young, Black, and pregnant; Community level systems that perpetuate stress and structural violence; Interpersonal level stressors; Individual level effects of stress on mom and baby; and Coping with stress. DISCUSSION: Acknowledging and naming structural violence and addressing structures that create and fuel stress for young pregnant Black people are important first steps to interrogating systems that allow for nuanced power dynamics and for recognizing the full humanity of young pregnant Black people.

Textbook typologies: Challenging the myth of the perfect obstetric pelvis.

Medical education's treatment of obstetric-related anatomy exemplifies historical sex bias in medical curricula. Foundational obstetric and midwifery textbooks teach that clinical pelvimetry and the Caldwell-Moloy classification system are used to assess the pelvic capacity of a pregnant patient. We describe the history of these techniques-ostensibly developed to manage arrested labors-and offer the following criticisms. The sample on which these techniques were developed betrays the bias of the authors and does not represent the sample needed to address their interest in obstetric outcomes. Caldwell and Moloy wrote as though the size and shape of the bony pelvis are the primary causes of "difficult birth"; today we know differently, yet books still present their work as relevant. The human obstetric pelvis varies in complex ways that are healthy and normal such that neither individual clinical pelvimetric dimensions nor the artificial typologies developed from these measurements can be clearly correlated with obstetric outcomes. We critique the continued inclusion of clinical pelvimetry and the Caldwell-Moloy classification system in biomedical curricula for the racism that was inherent in the development of these techniques and that has clinical consequences today. We call for textbooks, curricula, and clinical practices to abandon these outdated, racist techniques. In their place, we call for a truly evidence-based practice of obstetrics and midwifery, one based on an understanding of the complexity and variability of the physiology of pregnancy and birth. Instead of using false typologies that lack evidence, this change would empower both pregnant people and practitioners.

Efficacy of an inactivated Zika vaccine against virus infection during pregnancy in mice and marmosets.

Zika virus (ZIKV) is a mosquito-borne arbovirus that can cause severe congenital birth defects. The utmost goal of ZIKV vaccines is to prevent both maternal-fetal infection and congenital Zika syndrome. A Zika purified inactivated virus (ZPIV) was previously shown to be protective in non-pregnant mice and rhesus macaques. In this study, we further examined the efficacy of ZPIV against ZIKV infection during pregnancy in immunocompetent C57BL6 mice and common marmoset monkeys (Callithrix jacchus). We showed that, in C57BL/6 mice, ZPIV significantly reduced ZIKV-induced fetal malformations. Protection of fetuses was positively correlated with virus-neutralizing antibody levels. In marmosets, the vaccine prevented vertical transmission of ZIKV and elicited neutralizing antibodies that remained above a previously determined threshold of protection for up to 18 months. These proof-of-concept studies demonstrate ZPIV's protective efficacy is both potent and durable and has the potential to prevent the harmful consequence of ZIKV infection during pregnancy.

Womb to womb: Maternal litter size and birth weight but not adult characteristics predict early neonatal death of offspring in the common marmoset monkey.

A singular focus on maternal health at the time of a pregnancy leaves much about perinatal mortality unexplained, especially when there is growing evidence for maternal early life effects. Further, lumping stillbirth and early neonatal death into a single category of perinatal mortality may obscure different causes and thus different avenues of screening and prevention. The common marmoset monkey (Callithrix jacchus), a litter-bearing nonhuman primate, is an ideal species in which to study the independent effects of a mother's early life and adult phenotypes on pregnancy outcomes. We tested two hypotheses in 59 marmoset pregnancies at the Southwest National Primate Research Center and the Barshop Institute for Longevity and Aging Studies. We explored 1) whether pregnancy outcomes were predicted independently by maternal adult weight versus maternal litter size and birth weight, and 2) whether stillbirth and early neonatal death were differentially predicted by maternal variables. No maternal characteristics predicted stillbirth and no maternal adult characteristics predicted early neonatal death. In univariate Poisson models, triplet-born females had a significantly increased rate of early neonatal death (IRR[se] = 3.00[1.29], p = 0.011), while higher birth weight females had a decreased rate (IRR[se] = 0.89[0.05], p = 0.039). In multivariate Poisson models, maternal litter size remained an independent predictor, explaining 13% of the variance in early neonatal death. We found that the later in the first week those neonates died, the more weight they lost. Together these findings suggest that triplet-born and low birth weight females have distinct developmental trajectories underlying greater rates of infant loss, losses that we suggest may be attributable to developmental disruption of infant feeding and carrying. Our findings of early life contributions to adult pregnancy outcomes in the common marmoset disrupt mother-blaming narratives of pregnancy outcomes in humans. These narratives hold that the pregnant person is solely responsible for pregnancy outcomes and the health of their children, independent of socioecological factors, a moralistic framing that has shaped clinical pregnancy management. It is necessary to differentiate temporal trajectories and causes of perinatal loss and view them as embedded in external processes to develop screening, diagnostic, and treatment tools that consider the full arc of a mother's lived experience, from womb to womb and beyond.

Double Jeopardy: Young adult mental and physical health outcomes following conception via genocidal rape during the 1994 genocide against the Tutsi in Rwanda.

Rwandans conceived by rape during the 1994 genocide against the Tutsi have endured a violent beginning and a troubled childhood. Given compelling evidence of the influence of prenatal environments and adverse childhood experiences (ACEs) on future health, these individuals are at high risk of poor mental and physical health outcomes. The purpose of the study was to characterize mental and physical health outcomes in young adults who were exposed prenatally to maternal stress due to the genocide in general and those conceived by genocidal rape, and to determine whether ACEs compound these effects. Ninety-one 24-year-old Rwandans - 30 conceived by genocidal rape, 31 born of genocide survivors not raped, and a control group of 30 born of women with neither exposure - completed the Adverse Childhood Experiences International Questionnaire and measures of multiple physical and mental health characteristics. Data were collected from March 7 to April 6, 2019. Findings demonstrated that 1) individuals conceived during the genocide had poorer mental function (p = 0.002) and higher scores in post-traumatic stress disorder (PTSD), anxiety, depression, physical function, pain intensity, and sleep disturbance compared to young adults who were not exposed to genocide (all p < 0.033); 2) individuals conceived by genocidal rape reported more depression, PTSD, and pain interference compared to those prenatally exposed to maternal genocide stress only (all p < 0.008); and 3) among the group conceived via genocidal rape, the effects of prenatal exposures on depression, physical function, pain intensity and pain interference were exacerbated by ACEs (all p < 0.041). Being conceived during genocide, especially through genocidal rape, is associated with poor adult physical and mental health. The role of ACEs in exacerbating prenatal genocide exposure highlights opportunities for interventions to reduce these effects.

Change in waist circumference over 11 years and current waist circumference independently predict elevated CRP in Filipino women.

C-reactive protein, a marker of chronic, low-grade inflammation, is strongly associated with current central adiposity, and has been linked to elevated risk of cardiovascular disease. Less is known about the contribution of longitudinal change in waist circumference to current inflammation. We evaluated the extent to which current waist circumference and change over an 11-year interval contribute independently to low-grade systemic inflammation measured in a group of 1,294 women, 35-69 years, participating in the Cebu Longitudinal Nutrition and Health Survey in the Philippines. Waist circumference was measured at the time of blood draw for CRP analysis in 2005 and during an earlier survey in 1994. A waist circumference delta variable was constructed by subtracting current circumference from past circumference. We used logistic regression models to predict having an elevated plasma CRP concentration (3 mg L(-1) < CRP < 10 mg L(-1)). Waist circumference in 2005 was a strong predictor of elevated CRP (OR 1.10, 95% CI = 1.08, 1.12, P < 0.001). In combined models, increase in circumference over 11 years was a significant and independent predictor of elevated CRP risk (OR = 1.023, 95% CI = 1.00, 1.05, P < 0.05). Considering the average increase over time, the cumulative risk of elevated CRP due to increased central adiposity was 25.7%. However, women who reduced their waist circumference between 1994 and 2005 had greatly reduced risk (6.2%), suggesting that even long-term inflammatory burden can be reversed by weight loss. Although current waist circumference is an important contributor to risk of elevated systemic inflammation in this as in other populations, history of central adiposity may be an independent phenomenon.

Fetal signaling through placental structure and endocrine function: illustrations and implications from a nonhuman primate model.

The placenta is a transmitter of fetal need and fetal quality, interfacing directly with maternal physiology and ecology. Plasticity of placental structure and function across the developmental timeframe of gestation may serve as an important tool by which a fetus calibrates its growth to shifting maternal ecology and resource availability, and thereby signals its quality and adaptability to a changing environment. Signals of this quality may be conveyed by the size of the placental interface, an important marker of fetal access to maternal resources, or by production of placental insulin-like growth factor-II, a driver of fetoplacental growth. Litter size variation in the common marmoset monkey offers the opportunity to explore intrauterine resource allocation and placental plasticity in an important nonhuman primate model. Triplet marmosets are born at lower birth weights and have poorer postnatal outcomes and survivorship than do twins; triplet placentas differ in placental efficiency, microscopic morphology, and endocrine function. Through placental plasticity, triplet fetuses are able to adjust functional access to maternal resources in a way that allows pregnancy to proceed. However, the costs of such mechanisms may relate to reduced fetal growth and altered postnatal outcomes, with the potential to lead to adverse adult health consequences, suggesting an important link between the placenta itself and the developmental origins of health and disease.

Placental insulin-like growth factor II (IGF-II) and its relation to litter size in the common marmoset monkey (Callithrix jacchus).

The primate placenta produces a wide variety of hormones throughout gestation that regulate placental function and fetal growth. One such hormone is insulin-like growth factor-II (IGF-II), a peptide implicated in cell division, differentiation, and amino acid transport. IGF-II concentrations were measured in 23 common marmoset (Callithrix jacchus) term placentas from twin and triplet litters in order to determine whether previously described differences in fetoplacental phenotype such as placental and litter mass and placental surface area were related to differences in endocrine function. IGF-II was extracted from frozen tissue samples and measured using an enzyme-linked immunosorbent assay kit designed for human tissue, which was validated for marmoset placenta. IGF-II concentrations were not related to placental or litter mass, and twin and triplet placentas did not differ in total concentration. However, per individual fetus, triplets were associated with a significant 42% reduction in IGF-II concentration (P = 0.03), and IGF-II concentration per gram of fetal mass was a third lower in triplet litters. The triplet placenta exhibits a global expansion of the surface area which was contrasted by a per unit area reduction in IGF-II concentration (r = -0.75, P = 0.01), a pattern that explains why twin and triplet placentas overall did not differ in concentration. Per fetus, triplet pregnancies are associated with relatively less maternal mass, placental mass and microscopic surface area suggesting that the intrauterine growth of triplets is supported by systems that increase the efficiency of nutrient transfer. The finding that individual triplet fetuses are also associated with significantly lower IGF-II concentrations is consistent with the view that the marmoset fetoplacental unit exhibits a flexible pattern of placental allocation and metabolism. Plasticity in placental endocrine and metabolic function is likely to play an important role in the ability of the fetus to sense and accommodate the intrauterine environment and, by extension, the external ecology.

Global population variation in placental size and structure: Evidence from Cebu, Philippines.

INTRODUCTION: Placental morphology influences the intrauterine environment and fetal growth, which help set life-course health trajectories across generations. Little is known about placental characteristics in populations with chronic nutritional insufficiency where birth weights tend to be lower, and how these relationships between birth and placental weights vary across populations. METHODS: We collected weights and stereologically-determined villous mass and surface area of 21 placentas from offspring of women enrolled in a birth cohort study in metropolitan Cebu, Philippines, a low-income population. We identified 15 samples from other global populations ranging from low to high income that had similar data to ours to assess patterns of variation between birth and placental weights and microscopic characteristics. We ranked the population samples in order for each characteristic. RESULTS: Mean birth weight in Cebu was 3162 ±â€¯80 g (ranked 9/16) and placental weight was 454 ±â€¯32 g (ranked 12/16). Birth:placental weight ratio was 7.0 (ranked 3/16). Average villous surface area for Cebu placentas was 6.5 m2 (ranked 9/12); Birth weight:villous surface area was 0.048 g/m2 (ranked 4/12). DISCUSSION: Placentas from Cebu produced heavier neonates per units of placental weight and villous surface area than most other populations, despite lower villous surface areas and less complex surface-to-volume topography. This range of placental efficiency spurs questions about the mechanisms by which placental morphology optimizes efficiency in different environmental contexts during gestation. Placental variation both within and across populations is likely due to many intersecting environmental, metabolic, and (epi)genetic factors that will require additional research to clarify.