Hormonal and experiential predictors of infant survivorship and maternal behavior in a monogamous primate (Callicebus cupreus)

To better understand the roles that hormones and experience play in infant survival and maternal behavior in a biparental primate species, we analyzed urinary estrone (E(1)C) and pregnanediol glucuronide (PdG) from 24 socially housed titi monkey (Callicebus cupreus) females over 54 pregnancies (N = 1,430 samples). Pregnancies were categorized according to whether the infant survived (N = 35) or not (N = 19), and by maternal parity (primiparous: N = 9; multiparous: N = 45). Mothers of infants that survived had a significantly greater drop in PdG from the third trimester to the first week postpartum than mothers of infants that did not survive. Multiparous mothers had a greater increase in PdG from the first to the third trimester as well as greater increases in the E(1)C:PdG ratio from the first to the third trimester and from the third trimester to the first week postpartum. There were positive relationships between third trimester PdG and maternal carrying and nursing during the first week postpartum, and between maternal age and carrying during the infant's first month of life. There was a negative correlation between maternal age and PdG during the third trimester. These results suggest that elevated progesterone during late pregnancy followed by progesterone withdrawal immediately following parturition is associated with greater probability of infant survivorship and maternal behavior in this species, and that older females engage in more postpartum maternal care.     

Economic inequalities in maternal health care: prenatal care and skilled birth attendance in India, 1992-2006

Background

The use of maternal health care is limited in India despite several programmatic efforts for its improvement since the late 1980''s. The use of maternal health care is typically patterned on socioeconomic and cultural contours. However, there is no clear perspective about how socioeconomic differences over time have contributed towards the use of maternal health care in India.

Methodology/Principal Findings

Using data from three rounds of National Family Health Survey (NFHS) conducted during 1992–2006, we analyse the trends and patterns in utilization of prenatal care (PNC) in first trimester with four or more antenatal care visits and skilled birth attendance (SBA) among poor and nonpoor mothers, disaggregated by area of residence in India and three contrasting provinces, namely, Uttar Pradesh, Maharashtra and Tamil Nadu. In addition, we investigate the relative contribution of public and private health facilities in meeting the demand for SBA, especially among poor mothers. We also examine the role of salient socioeconomic, demographic and cultural factors in influencing aforementioned outcomes. Bivariate analyses, concentration curve and concentration index, logistic regression and multinomial logistic regression models are used to understand the trends, patterns and predictors of the two outcome variables. Results indicate sluggish progress in utilization of PNC and SBA in India and selected provinces during 1992–2006. Enormous inequalities in utilization of PNC and SBA were observed largely to the disadvantage of the poor. Multivariate analysis suggests growing inequalities in utilization of the two outcomes across different economic groups.

Conclusions

The use of PNC and SBA remains disproportionately lower among poor mothers in India irrespective of area of residence and province. Despite several governmental efforts to increase access and coverage of delivery services to poor, it is clear that the poor (a) do not use SBA and (b) even if they had SBA, they were more likely to use the private providers.     

Chronic corticosterone during pregnancy and postpartum affects maternal care, cell proliferation and depressive-like behavior in the dam

Stress during pregnancy and the postpartum can influence the well-being of both the mother and her offspring. Prolonged elevated levels of glucocorticoids are associated with depression and we developed an animal model of postpartum depression/stress based on high levels of corticosterone (CORT) during the postpartum. Gestational stress is a risk factor for postpartum depression and prenatal and/or postnatal high levels of CORT may have differential effects on the mother. Thus the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on maternal care, depressive-like behavior and hippocampal cell proliferation in the dam. Only the high dose of CORT administered during the postpartum increased depressive-like behavior in the dam. Furthermore the high dose of CORT altered maternal care (reduced time spent on the nest and nursing) regardless of whether administration of CORT was during gestation or postpartum. Gestational and/or postpartum treatment with high CORT and postpartum low CORT reduced cell proliferation in the dentate gyrus of postpartum dams compared to oil-treated controls. Thus prolonged treatment with high levels of CORT postpartum reduced maternal care, hippocampal cell proliferation and induced depressive-like behavior in the dam and therefore might be considered an animal model of postpartum depression. More research is needed to understand the effects of stress hormones during different phases of reproduction and how they affect the brain and behavior of the mother and her offspring.     

Chronic corticosterone during pregnancy and postpartum affects maternal care,cell proliferation and depressive-like behavior in the dam

Stress during pregnancy and the postpartum can influence the well-being of both the mother and her offspring. Prolonged elevated levels of glucocorticoids are associated with depression and we developed an animal model of postpartum depression/stress based on high levels of corticosterone (CORT) during the postpartum. Gestational stress is a risk factor for postpartum depression and prenatal and/or postnatal high levels of CORT may have differential effects on the mother. Thus the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on maternal care, depressive-like behavior and hippocampal cell proliferation in the dam. Only the high dose of CORT administered during the postpartum increased depressive-like behavior in the dam. Furthermore the high dose of CORT altered maternal care (reduced time spent on the nest and nursing) regardless of whether administration of CORT was during gestation or postpartum. Gestational and/or postpartum treatment with high CORT and postpartum low CORT reduced cell proliferation in the dentate gyrus of postpartum dams compared to oil-treated controls. Thus prolonged treatment with high levels of CORT postpartum reduced maternal care, hippocampal cell proliferation and induced depressive-like behavior in the dam and therefore might be considered an animal model of postpartum depression. More research is needed to understand the effects of stress hormones during different phases of reproduction and how they affect the brain and behavior of the mother and her offspring.     

Family networks in prenatal and postnatal health

This paper examines the effects of kin access on prenatal health practices, birth outcome, and postnatal health practice for infants born to black and white mothers ages 21 to 28 in the U.S. during 1984-86. The data used for this research were compiled from three sources: (1) The National Longitudinal Survey of Youth; (2) The Children of the National Longitudinal Survey of Youth; (3) special kin access data files, which were created specifically for this study. Logistic regression procedures are used to assess the effects of kin proximity, maternal grandmother proximity, and presence of the child's father on health practices (N = 1,030) and birth outcome (N = 1,385), controlling for the mother's educational attainment, work experience, poverty, presence of the child's father, and birth order of the child. We find no evidence supporting the notion that kin access positively affects the prenatal and postnatal health practices of young mothers. The results suggest that young mothers who reside with their mothers or other adult kin, and those who are in close proximity to them, are no more likely to seek prenatal care during the first trimester, or to avoid smoking or drinking during pregnancy. Mothers who live with a sexual partner or husband are, however, somewhat more likely to seek prenatal care and to avoid alcohol use during pregnancy. Closer kin access is associated with a lower probability of breastfeeding. These results suggest that it will not be adequate to rely on kin networks or kin assistance to improve the prospect of healthy birth outcomes.     

Effect of serotonin deficit at different stages of prenatal ontogenesis on behavior of adult male and female rats

Effects of maternal parachlorophenilalanine (PCPA) administration on the offspring behavior were studied in the open field, Porsolt forced swimming, and Morris water maze tests. PCPA was administered in two different gestational periods: on gestational days (GD) 8-11 or GD 14-17, at doses 200/100/100/50 mg/kg. It was found that prenatal exposure to PCPA results in fetal serotonin (5-HT) depletion and changes in both open field activity and depression-related behavior, as well as impairments in spatial learning in the adult offspring. The most pronounced effects on behavior were observed in the male and female offspring whose mothers were depleted of serotonin by PCPA during the third trimester of pregnancy. These results provide further evidence that adverse factors have the most severe effects on the development of rat brain function when exposed during the final trimester of pregnancy than during the second trimester.     

Maternal stress during pregnancy and early childhood development

We estimate the impact of prenatal stress on early childhood development outcomes known as “middle years” or intermediate outcomes, which has not been studied previously. Using a unique measure of actual maternal stress induced by a large earthquake, we find that relative to children that were not exposed, in utero maternal stress reduces children’s cognitive skills and socio-emotional problems by age 3, and that the effects are heterogeneous. The negative impacts on cognitive skills occur during the first trimester of pregnancy and are found among both low and high-income children, and boys and girls. The harmful effects on socio-emotional behaviors occur when stress is experienced in the last trimester of pregnancy.     

Access to health: women's status and utilization of maternal health services in Nepal

With the objective of reducing maternal and neonatal mortality, the Safe Motherhood Program was implemented in Nepal in 1997. It was launched as a priority programme during the ninth five-year plan period, 1997-2002, with the aim of increasing women's access to health care and raising their status. This paper examines the association of access to health services and women's status with utilization of prenatal, delivery, and postnatal care during the plan period. The 1996 Nepal Family Health Survey and the 2001 Nepal Demographic and Health Survey data were pooled and the likelihood of women's using maternal health care was examined in 2001 in comparison with 1996. Multiple logistic regression analysis indicates that the utilization of maternal health services increased over the period. Programme interventions such as outreach worker's visits, radio programmes on maternal health, maternal health information disseminated through various mass media sources and raising women's status through education were able to explain the observed change in utilization. Health worker visits and educational status of women showed a large association, but radio programmes and other mass media information were only partially successful in increasing use of maternal health services. Socioeconomic and demographic variables such as household economic status, number of living children and place of residence showed stronger association with use of maternal health services then did intervention programmes.     

Family networks in prenatal and postnatal health

Abstract

This paper examines the effects of kin access on prenatal health practices, birth outcome, and postnatal health practice for infants born to black and white mothers ages 21 to 28 in the U.S. during 1984–86. The data used for this research were compiled from three sources: (1) The National Longitudinal Survey of Youth; (2) The Children of the National Longitudinal Survey of Youth; (3) special kin access data files, which were created specifically for this study. Logistic regression procedures are used to assess the effects of kin proximity, maternal grandmother proximity, and presence of the child's father on health practices (N = 1,030) and birth outcome (N = 1,385), controlling for the mother's educational attainment, work experience, poverty, presence of the child's father, and birth order of the child. We find no evidence supporting the notion that kin access positively affects the prenatal and postnatal health practices of young mothers. The results suggest that young mothers who reside with their mothers or other adult kin, and those who are in close proximity to them, are no more likely to seek prenatal care during the first trimester, or to avoid smoking or drinking during pregnancy. Mothers who live with a sexual partner or husband are, however, somewhat more likely to seek prenatal care and to avoid alcohol use during pregnancy. Closer kin access is associated with a lower probability of breastfeeding. These results suggest that it will not be adequate to rely on kin networks or kin assistance to improve the prospect of healthy birth outcomes.     

Prenatal exposure to maternal depression,neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses

Background: In animal models, variations in early maternal care are associated with differences in hypothalamic-pituitary-adrenal (HPA) stress response in the offspring, mediated via changes in the epigenetic regulation of glucocorticoid receptor (GR) gene (Nr3c1) expression. Objective: To study this in humans, relationships between prenatal exposure to maternal mood and the methylation status of a CpG-rich region in the promoter and exon 1F of the human GR gene (NR3C1) in newborns and HPA stress reactivity at age 3 months were examined. Methods: The methylation status of a CpG-rich region of the NR3C1 gene, including exon 1F, in genomic DNA from cord blood mononuclear cells was quantified by bisulfite pyrosequencing in infants of depressed mothers treated with a serotonin reuptake inhibitor antidepressant (SRI) (n=33), infants of depressed non treated mothers (n=13) and infants of non depressed/non treated mothers (n=36). To study the functional implications of the newborn methylation status of NR3C1 in newborns, HPA function was assessed at 3 months using salivary cortisol obtained before and following a non noxious stressor and at a late afternoon basal time. Results: Prenatal exposure to increased third trimester maternal depressed/anxious mood was associated with increased methylation of NR3C1 at a predicted NGFI-A binding site. Increased NR3C1 methylation at this site was also associated with increased salivary cortisol stress responses at 3 months, controlling for prenatal SRI exposure, postnatal age, and pre and postnatal maternal mood. Conclusions: Methylation status of the human NR3C1 gene in newborns is sensitive to prenatal maternal mood and may offer a potential epigenetic process that links antenatal maternal mood and altered HPA stress reactivity during infancy.     

Effects of In utero environment and maternal behavior on neuroendocrine and behavioral alterations in a mouse model of prenatal trauma

Maternal posttraumatic stress disorder (PTSD) following trauma exposure during pregnancy is associated with an increased risk of affective disorders in children. To investigate the mechanisms by which prenatal trauma and/or maternal PTSD affect brain development and behavior we established a mouse model of prenatal traumatic (PT) experience based on the application of an electric foot shock to C57Bl/6N female mice on the gestational day 12 during their pregnancy. The model is based on a previously validated animal model of PTSD. We found high anxiety levels and poor maternal care along with reduced serum prolactin and increased corticosterone levels in dams following maternal trauma (MT). PT‐pups were born smaller and stayed smaller throughout their life. We show increased time and frequency of ultrasonic calls in PT‐pups when separated from the mothers on the postnatal day (PND) 9. Cross‐fostering experiments reveal lower anxiety levels in PT pups raised by healthy mothers as compared to trauma‐naive pups raised by MT‐dams. Importantly, the combination of prenatal trauma and being raised by a traumatized mother leads to: (1) the highest corticosterone levels in pups, (2) longest USV‐call time and (3) highest anxiety levels in comparison to other experimental groups. Our data indicates a distinct change in maternal care following MT which is possibly associated with trauma‐induced decrease in prolactin levels. Furthermore, we show that maternal behavior is crucial for the development of the offspring anxiety and specific aspects in maternal care overwrite to a significant extend the effects of in utero and postnatal environment. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1254–1265, 2016     

Prenatal Adversity Modulates the Quality of Maternal Care Via the Exposed Offspring

Adversities in pregnancy, including poor diet and stress, are associated with increased risk of developing both metabolic and mental health disorders later in life, a phenomenon described as fetal programming or developmental origins of disease. Predominant hypotheses proposed to explain this relationship suggest that the adversity imposes direct changes to the developing fetus which are maintained after birth resulting in an increased susceptibility to ill health. However, during pregnancy the mother, the developing fetus, and the placenta are all exposed to the adversity. The same adversities linked to altered offspring outcome can also result in suboptimal maternal care, which is considered an independent adverse exposure for the offspring. Recent key experiments in mice reveal the potential of prenatal adversity to drive alterations in maternal care through abnormal maternal–pup interactions and via alterations in placental signaling. Together, these data highlight the critical importance of viewing fetal programming holistically paying attention to the intimate, bidirectional, and reiterative relationship between mothers and their offspring.     

Prenatal Care Utilization for Mothers from Low-Income Areas of New Mexico, 1989–1999

Background

Prenatal care is considered to be an important component of primary health care. Our study compared prenatal care utilization and rates of adverse birth outcomes for mothers from low- and higher-income areas of New Mexico between 1989 and 1999.

Methodology/Principal Findings

Prenatal care indicators included the number of prenatal care visits and the first month of prenatal care. Birth outcome indicators included low birth weight, premature birth, and births linked with death certificates. The results of our study indicated that mothers from low-income areas started their prenatal care significantly later in their pregnancies between 1989 and 1999, and had significantly fewer prenatal visits between 1989 and 1997. For the most part, there were not significant differences in birth outcome indicators between income groupings.

Conclusions/Significance

These findings suggest that while mothers from low-income areas received lower levels of prenatal care, they did not experience a higher level of adverse birth outcomes.     

Postpartum depression: Etiology,treatment and consequences for maternal care

This article is part of a Special Issue “Parental Care”. Pregnancy and postpartum are associated with dramatic alterations in steroid and peptide hormones which alter the mothers' hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes. Dysregulations in these endocrine axes are related to mood disorders and as such it should not come as a major surprise that pregnancy and the postpartum period can have profound effects on maternal mood. Indeed, pregnancy and postpartum are associated with an increased risk for developing depressive symptoms in women. Postpartum depression affects approximately 10–15% of women and impairs mother–infant interactions that in turn are important for child development. Maternal attachment, sensitivity and parenting style are essential for a healthy maturation of an infant's social, cognitive and behavioral skills and depressed mothers often display less attachment, sensitivity and more harsh or disrupted parenting behaviors, which may contribute to reports of adverse child outcomes in children of depressed mothers. Here we review, in honor of the “father of motherhood”, Jay Rosenblatt, the literature on postnatal depression in the mother and its effect on mother–infant interactions. We will cover clinical and pre-clinical findings highlighting putative neurobiological mechanisms underlying postpartum depression and how they relate to maternal behaviors and infant outcome. We also review animal models that investigate the neurobiology of maternal mood and disrupted maternal care. In particular, we discuss the implications of endogenous and exogenous manipulations of glucocorticoids on maternal care and mood. Lastly we discuss interventions during gestation and postpartum that may improve maternal symptoms and behavior and thus may alter developmental outcome of the offspring.     

Serum concentrations of androstenediol and androstenediol sulfate, and their relation to cytokine production during and after normal pregnancy

Since it is known that androstenediol (ADIOL) has potent immunoregulatory effects, changes in ADIOL levels during and after pregnancy might affect the maternal immune system. We examined serum concentrations of ADIOL and androstenediol 3-sulfate (ADIOLS) together with IFN-gamma and IL-4 production levels during pregnancy and after delivery up to 10-11 months postpartum. The subjects were 73 normal pregnant, 76 normal postpartum, and 28 normal non-pregnant women. ADIOL and ADIOLS were measured using EIA and GC/MS, respectively. The cytokine levels in the supernatant of whole-blood cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin were measured using ELISA. ADIOL levels significantly decreased compared to non-pregnant levels in the first trimester (P < 0.05) and were reversed in the third trimester (P < 0.05). After pregnancy, ADIOL levels gradually declined, and a significant decrease was observed at 10-11 months postpartum (P < 0.05). ADIOLS levels were significantly lower in the third trimester (P < 0.05) and significantly higher at the first month postpartum (P < 0.001) compared to non-pregnant women. IFN-gamma and IL-4 levels decreased during pregnancy and subsequently increased postpartum. On the other hand, we found significant negative correlations between ADIOL concentrations and production levels of IFN-gamma (P < 0.05) or IL-4 (P < 0.05). These findings suggest that ADIOL may be involved in modifying the maternal immune response during and after pregnancy.     

A Cross-Sectional Analytic Study of Postpartum Health Care Service Utilization in the Philippines

Background

The maternal mortality ratio in the Philippines remains high; thus, it will be difficult to achieve the Millennium Development Goals 5 by 2015. Approximately two-thirds of all maternal deaths occur during the postpartum period. Therefore, we conducted the present study to examine the current state of postpartum health care service utilization in the Philippines, and identify challenges to accessing postpartum care.

Methods

A questionnaire and knowledge test were distributed to postpartum women in the Philippines. The questionnaire collected demographical characteristics and information about their utilization of health care services during pregnancy and the postpartum period. The knowledge test consisted of 11 questions regarding 6 topics related to possible physical and mental symptoms after delivery. Sixty-four questionnaires and knowledge tests were analyzed.

Results

The mean time of first postpartum health care visit was 5.1±5.2 days after delivery. Postpartum utilization of health care services was significantly correlated with delivery location (P<0.01). Women who delivered at home had a lower rate of postpartum health care service utilization than women who delivered at medical facilities. The majority of participants scored low on the knowledge test.

Conclusion

We found inadequate postpartum health care service utilization, especially for women who delivered at home. Our results also suggest that postpartum women lack knowledge about postpartum health concerns. In the Philippines, Barangay health workers may play a role in educating postpartum women regarding health care service utilization to improve their knowledge of possible concerns and their overall utilization of health care services.     

Brief communication: Fecal androgen excretion and fetal sex effects during gestation in wild Assamese macaques (Macaca assamensis)

In placental mammals, pregnancy usually is associated with an increase in maternal androgens, which may significantly impact fetal growth and differentiation, and affect postnatal development and behavior. Owing to their slow life histories and challenging social conditions, determination of maternal androgens and potential interference effects of fetal androgen production are of particular interest in wild primates. However, androgen production has been rarely investigated in wild female primates, and studies on maternal androgens during gestation in particular often do not span the entire pregnancy. Here, we characterize fecal androgen production throughout gestation in wild Assamese macaques (Macaca assamensis) using noninvasive hormone analysis and, furthermore, examine fetal sex effects on maternal androgen excretion. A total of 207 fecal samples were analyzed from seven females for concentrations of immunoreactive epiandrosterone (iEA). Fecal iEA concentrations, as predicted based on cercopithecine blood-serum patterns, increased during early gestation and were significantly higher during the first trimester compared with preconception concentrations and those recorded during later stages of gestation. Further, during the third trimester, male-carrying mothers showed significantly higher iEA concentrations compared with female-carrying mothers. This first characterization of fecal androgen excretion during gestation in Assamese macaques indicates both a maternal and fetal effect on androgen production. Although our sample size is small, our results, nevertheless, provide the basis for assessing potential influences of maternal androgens on postnatal offspring development and behavior.     

Long commutes to work during pregnancy and infant health at birth

We conduct the first empirical study to examine the health impact of long commutes to work during pregnancy on fetuses and infants at birth, using unique data that contain information on not only a woman's home address but also her employer's address during pregnancy, which allows us to calculate the maternal travel distance during pregnancy. Our study contributes to the literature on the relationship between maternal stress during pregnancy and adverse birth outcomes by focusing on the understudied chronic stress induced by long commutes, rather than the stress triggered by a one-time significant event, such as a natural disaster. We find that among long-distance commuters, increasing the maternal travel distance during pregnancy by 10 miles is associated with increases in the probabilities of low birth weight and intrauterine growth restriction by 0.9 and 0.6 percentage points, respectively. In addition to the maternal stress induced by long commutes being one potential biological mechanism, we find suggestive evidence showing that maternal long commutes during pregnancy are also associated with under-utilization of prenatal care.     

Prenatal exposure to bereavement and type-2 diabetes: a danish longitudinal population based study

Background

The etiology of type-2 diabetes is only partly known, and a possible role of prenatal stress in programming offspring for insulin resistance has been suggested by animal models. Previously, we found an association between prenatal stress and type-1 diabetes. Here we examine the association between prenatal exposure to maternal bereavement during preconception and pregnancy and development of type-2 diabetes in the off-spring.

Methods

We utilized data from the Danish Civil Registration System to identify singleton births in Denmark born January 1^st 1979 through December 31^st 2008 (N = 1,878,246), and linked them to their parents, grandparents, and siblings. We categorized children as exposed to bereavement during prenatal life if their mothers lost an elder child, husband or parent during the period from one year before conception to the child’s birth. We identified 45,302 children exposed to maternal bereavement; the remaining children were included in the unexposed cohort. The outcome of interest was diagnosis of type-2 diabetes. We estimated incidence rate ratios (IRRs) from birth using log-linear poisson regression models and used person-years as the offset variable. All models were adjusted for maternal residence, income, education, marital status, sibling order, calendar year, sex, and parents’ history of diabetes at the time of pregnancy.

Results

We found children exposed to bereavement during their prenatal life were more likely to have a type-2 diabetes diagnosis later in life (aIRR: 1.31, 1.01–1.69). These findings were most pronounced when bereavement was caused by death of an elder child (aIRR: 1.51, 0.94–2.44). Results also indicated the second trimester of pregnancy to be the most sensitive period of bereavement exposure (aIRR:2.08, 1.15–3.76).

Conclusions

Our data suggests that fetal exposure to maternal bereavement during preconception and the prenatal period may increase the risk for developing type-2 diabetes in childhood and young adulthood.