Hair cortisol in the perinatal period mediates associations between maternal adversity and disrupted maternal interaction in early infancy

Existing literature points to the possibility that cortisol could be one link between maternal adversity and poorer parenting quality, but most studies have examined salivary cortisol concentrations rather than hair cortisol concentrations. The current study examined hair cortisol concentration (HCC) during the third trimester of pregnancy as a mediator between maternal adversity indicators (childhood abuse, severe mental illness, symptomatic functioning) and maternal caregiving behavior at 4 months postpartum. Forty-four women participated in the study: 30 with severe mental disorders, and 14 nonclinical controls. HCC was assessed during the third trimester of pregnancy (HCC-P) and at 4 months postpartum (HCC-4M). Sexual, physical, and emotional abuse were assessed by the Adverse Childhood Experiences Study Questionnaire. Maternal disrupted interaction was reliably coded from mother–infant video interactions during a Still-Face Procedure. Mediation models indicated that maternal HCC-P and HCC-4M mediated associations between maternal psychopathology (severe mental illness, symptomatic functioning) and maternal disrupted interaction at 4 months. Maternal HCC at 4 months also mediated associations between experienced childhood abuse and overall disrupted interaction. Our findings indicate that HCC may be a potential early biomarker for future caregiving challenges among mothers with severe mental illness and histories of childhood abuse.     

Effects of prenatal depressive symptoms on maternal and infant cortisol reactivity

Prenatal depression is associated with adverse offspring outcomes, and the prevailing mechanistic theory to account for mood-associated effects implicates alterations of the maternal and foetal hypothalamic-pituitary adrenal (HPA) axes. Recent research suggests that depression may be associated with a failure to attenuate cortisol reactivity during early pregnancy. The aim of the current study is to investigate whether this effect continues into mid and late gestation. A further aim is to test whether maternal prenatal cortisol reactivity directly predicts infant cortisol reactivity. One hundred three pregnant women were recruited during either the second or third trimester. Depressive symptoms were assessed by self-report, and maternal salivary cortisol responses to a stressor (infant distress film) were measured. Approximately 2 months after birth, mothers (n?=?88) reported postnatal depression and infant salivary cortisol responses to inoculation were measured. Prenatal depression was not associated with cortisol reactivity to acute stress in mid and late pregnancy. Similarly, neither prenatal depression nor maternal prenatal cortisol reactivity predicted infant cortisol reactivity to inoculation at 2 months. If the effects of prenatal depression on foetal and infant development are mediated by alterations of the maternal and foetal HPA axes, then early pregnancy may be a particularly vulnerable period. Alternatively, changes to HPA reactivity may not be as central to this association as previously thought.     

Altered stress patterns and increased risk for postpartum depression among low-income pregnant women

Postpartum depression (PPD) has been associated with a number of negative maternal and infant health outcomes. Despite these adverse health effects, few studies have prospectively examined patterns of pre- and postnatal stress that may increase a woman’s risk for PPD. The current study examined whether the timing of altered salivary cortisol patterns and perceived stress levels during pregnancy and at 3 months postpartum was associated with PPD symptoms among 100 low-income mothers. Higher levels of PPD were found among women with a lower cortisol awakening response (first and second trimester), lower average daily cortisol (second trimester), a flatter diurnal cortisol pattern (second and third trimester and at 3 months postpartum), and a less abrupt drop in both cortisol and perceived stress from the third trimester to 3 months postpartum. These results support the need for early screening and regulation of stress levels to promote depression prevention efforts in at-risk populations.     

Hair cortisol in pregnancy interacts with maternal depressive symptoms to predict maternal disrupted interaction with her infant at 4 months

Disrupted maternal interaction in early infancy is associated with maladaptive child outcomes. Thus, identifying early risk factors for disrupted interaction is an important challenge. Research suggests that maternal depressive symptoms and maternal cortisol dysregulation are associated with disrupted maternal interaction, but both factors have rarely been considered together as independent or interactive predictors of disrupted interaction. In a sample of 51 women, hair cortisol concentrations (HCC) and depressive symptoms were assessed during pregnancy, and depressive symptoms were assessed again at 4-month postpartum. Maternal disrupted interaction was assessed during the Still-Face Paradigm at 4 months. Results indicated that HCC and depressive symptoms interacted to predict both maternal withdrawing and inappropriate/intrusive interaction. Withdrawing interaction was associated with high levels of HCC in pregnancy in the context of high depressive symptoms at 4 months; inappropriate/intrusive interaction was associated with high levels of HCC in the context of low depressive symptoms. Thus, high HCC potentiated both forms of disrupted interaction. Results raised questions about the meaning of very low reported depressive symptoms, and underscored the importance of chronic stress physiology and maternal depressed mood as risk factors for distinct forms of maternal disrupted interaction, both of which are deleterious for infant development.     

Maternal expressive suppression moderates the relations between maternal and child hair cortisol

Self-reports and physiological indicators of stress such as cortisol levels are correlated in maternal and child samples. This relationship is likely to be influenced by maternal emotion regulation. Herein, we investigate the moderating role of maternal regulation strategies on the association between maternal and child hair cortisol levels. Mother–child dyads (N = 63, child mean age = 49.74 months) participated in the study. Hair samples were collected from mother and child, and cortisol was assayed. Mothers reported on their own emotion regulation strategies, namely expressive suppression and cognitive reappraisal. As expected, mother and child hair cortisol levels were significantly correlated. Interestingly, the relation between maternal and child hair cortisol was moderated by maternal suppression of emotion. Mother and child hair cortisol levels were related at low levels of maternal suppression, but not at higher levels of suppression. Maternal cognitive reappraisal of emotion was not associated with cortisol levels.     

Cortisol levels in pregnancy as a psychobiological predictor for birth weight

Antenatal maternal stress is thought to negatively affect fetal development, birth outcomes, and infant’s development. Glucocorticoids are suggested to be a common link between prenatal stressors and infant’s health. However, data on these mechanisms are rare and sometimes conflicting. The objective of this study was to examine the effects of maternal distress during pregnancy on fetal development and birth weight in humans prospectively. This study focuses on cortisol as one mediating the mechanism of the association between maternal distress and birth outcomes. Pregnancy-related and general distress was measured in 81 women with uncomplicated, singleton pregnancies. The rise of salivary cortisol on awakening (CAR) was assessed in weeks 13–18 and 35–37 postmenstrual age of pregnancy. Mothers completed a structured interview, the perceived stress scale, a widely used psychological instrument that provided a global measure of perceived stress, as well as the Prenatal Distress Questionnaire, a self-report questionnaire designed to assess worries and anxiety in pregnancy. Pre-, peri-, and postnatal medical risk factors as well as birth characteristics were extracted from medical records routinely kept by the attending obstetricians. Hierarchical multiple regressions indicate that maternal cortisol levels explained 19.8% of the variance in birth weight and 9% of the variance in body length at birth, even after controlling for gestational age, parity, pre-pregnancy BMI, smoking, and infant’s sex. Newborns of mothers with higher cortisol levels in pregnancy had lower birth weights and were shorter at birth. An ANCOVA for repeated measures indicated that, after controlling for covariates, pregnancy-related as well as general distress in pregnancy did not influence cortisol levels after awakening (area under the curve). No significant associations between perceived stress and anthrometric measures at birth were found. In conclusion, maternal cortisol levels in pregnancy influence intrauterine growth and may be a better predictor for birth outcome than perceived stress.     

Effects of maternal prenatal stress on offspring development: a commentary

Pregnancy is associated with major physiological changes and adaptation to these changes is crucial for normal fetal development. Heightened emotional stress during pregnancy may interfere with the necessary adaptation and lead to dysregulation of the two major stress response systems: the Hypothalamic-Pituitary-Adrenal (HPA) Axis and the Autonomic Nervous System (ANS). Negative effects on the fetus of such maladaptation have been documented in both animals and humans and range from poor birth outcomes to negative impacts on neurodevelopment, as well as long term emotional and behavioural disturbances. Conversely, it has been hypothesized that low levels of maternal prenatal stress may actually have an adaptive value for the offspring. Investigation of these associations employing physiological markers and repeated measures throughout pregnancy and postpartum of both the mother and the offspring, is required in order to understand the various effects of prenatal stress on the development of the offspring. It is also crucial to explore the possibility of variable periods of vulnerability throughout gestation. The aim of this commentary is to reexamine the current literature on the ill-effects of maternal stress during pregnancy on the offspring and to explore avenues for future treatment and prevention.     

Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: comparison to salivary cortisol

Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair cortisol provides a simple way to monitor total cortisol release over an extended period of time. Hair cortisol levels were determined from each trimester (15, 26 and 36 weeks gestation) and 3 months postpartum. Hair cortisol levels were compared to diurnal salivary cortisol collected over 3 days (3 times/day) at 14, 18, 23, 29, and 34 weeks gestational age and 6 weeks postpartum from 21 pregnant women. Both salivary and hair cortisol levels rose during pregnancy as expected. Hair cortisol and diurnal salivary cortisol area under the curve with respect to ground (AUCg) were also correlated throughout pregnancy. Levels of cortisol in hair are a valid and useful tool to measure long-term cortisol activity. Hair cortisol avoids methodological problems associated with collection other cortisol measures such as plasma, urine, or saliva and is a reliable metric of HPA activity throughout pregnancy reflecting total cortisol release over an extended period.     

Parental care and control during childhood: associations with maternal perinatal mood disturbance and parenting stress

This study examined the associations between perceived parental care and control in childhood and maternal anxiety, depression and parenting stress during the transition to parenthood. Eighty-eight women completed the Parental Bonding Instrument, self-report measures of anxiety and depression and a structured diagnostic interview (Mini-plus International Neuropsychiatric Interview) during the third trimester of pregnancy. The MINI-Plus and anxiety and depression measures were re-administered at 7 months postpartum. The Parenting Stress Index was also administered at this time. Significant associations were found between maternal 'affectionless control' and prenatal and postnatal symptom measures of anxiety and depression, p values <0.005. Compared to women who reported optimal parenting, women who recalled maternal 'affectionless control' were also six times more likely to be diagnosed with an anxiety disorder during pregnancy (OR = 6.1, 95% CI = 2.17-30.11) and seven times more likely to be diagnosed with postnatal major depression (OR = 6.8, 95% CI = 1.80-25.37). Paternal 'affectionless control' was associated with significantly higher scores on symptom measures of prenatal and postnatal anxiety, p values <0.005. This study suggests that assessing a woman's own parenting history is important in identifying and managing the risk of prenatal and postnatal affective disorders and parenting stress.     

Maternal prenatal cortisol and the interaction of income and pre-pregnancy body mass index are independently associated with newborn cortisol

While extensive research has supported the developmental programming hypothesis regarding contributions of prenatal psychosocial or nutritional adversity to offspring stress physiology, fewer studies consider both exposures together with maternal stress physiology. This study examined newborn cortisol output during a stressor as a function of maternal pre-pregnancy health status and nutritional history (pre-pregnancy body mass index [PPBMI]), economic resources (household income), and maternal cortisol awakening response (mCAR) in late pregnancy. Participants were 102 mother-infant pairs from an economically and racial/ethnically diverse sample. Offspring salivary cortisol response to a neurobehavioral exam was assessed at 1 month. Income and maternal PPBMI were positively associated with mCAR in late pregnancy. mCAR was positively related to 1-month newborn cortisol response. The interaction of income and PPBMI was positively associated with newborn cortisol output during an exam at 1-month. Mothers with the highest PPBMI and lowest income had offspring with higher cortisol responses than offspring of mothers with higher income and lower PPBMI. There was no evidence of indirect mediation effects of predictors (PPBMI, income, and interaction) on infant cortisol via mCAR. The differential effects of the interaction of PPBMI and income suggest that these exposures influence infant cortisol output in the context of one another, independent of maternal pregnancy cortisol.     

Elevated second trimester maternal serum beta-HCG concentrations and subsequent adverse pregnancy outcome.

Previous studies have found an association between elevated second trimester maternal serum alpha-fetoprotein (MS-AFP), in the absence of fetal anomalies, and adverse pregnancy outcome. We studied the association between elevated second trimester maternal serum beta-HCG, now also routinely measured by prenatal screening programs, and adverse pregnancy outcome by reviewing retrospectively the pregnancy outcomes among women with markedly elevated midtrimester beta-HCG in our prenatal screening program. Seven (0.23%) of 3,000 consecutively screened women had a serum beta-HCG above 5 MOM. Four (57%) of these 7 women had an adverse pregnancy outcome including severe preeclampsia (n = 2), abruptio placentae (n = 1), or preterm labor (n = 1). A concurrently elevated MS-AFP was found in only one of these 4 patients. Elevated mid-trimester maternal serum beta-HCG may be an independent risk factor for subsequent adverse pregnancy outcomes.     

Age,reproductive history,seasonality, and maternal body composition during pregnancy for nomadic Turkana of Kenya

To evaluate the potential differences in maternal nutritional investment in pregnancy, data collected from nomadic Ngisonyoka Turkana women during a July 1993–July 1994 field season were utilized. The roles maternal age, parity, duration of the previous nonpregnant interval, overlap between pregnancy and lactation on trimester changes in weight and summed skinfolds during pregnancy were examined. Because seasonality is an important aspect of the Turkana environment, the effects of seasonality were also assessed. First trimester weight gain is positively associated with overlap in pregnancy and lactation. Second trimester maternal weight gain is negatively influenced by higher parity and by overlap between lactation and early pregnancy. Third trimester weight gain is influenced only by seasonally induced morbidity. First trimester changes in maternal skinfolds are negatively influenced by older maternal age and parity, and positively influenced by a longer nonpregnant interval, and overlap between pregnancy and lactation. Second and third trimester skinfolds are significantly associated only with overlap between lactation and pregnancy (negatively in the second, positively in the third). Seasonality does not influence maternal skinfolds. Differences in age- and parity-related patterns of maternal nutritional investment in pregnancy are not supported by the data. The possibility that Turkana cultural beliefs may influence nutritional status during pregnancy is discussed. Am. J. Hum. Biol. 11:658–672, 1999. © 1999 Wiley-Liss, Inc.     

Negative emotionality and cortisol during adolescent pregnancy and its effects on infant health and autonomic nervous system reactivity

This research examined the relations among maternal emotionality, biology, and infant outcome and autonomic nervous system reactivity (cardiac vagal tone). The sample consisted of 27 pregnant adolescents and their 3-week-old infants. Measures of anxiety, depression, anger, and saliva cortisol were obtained from the adolescents both pre- and postnatally. Infant outcome measures consisted of gestational age at delivery, birth weight, number of risk factors at birth and at 24 hr, Apgar score at 1 and 5 min, abnormalities on newborn physical exam, number of resuscitation measures used on the infant, and cardiac vagal tone. Significant relations were found among the adolescent's emotionality, infant physical outcomes, and cardiac vagal tone. Higher concentrations of adolescent cortisol were associated with lower infant Apgar scores and an increased need for resuscitation measures performed on the infant. The positive association between negative emotions and better infant outcomes also was found and may reflect the sensitivity of the adolescents to their feelings and needs during pregnancy. Social support during pregnancy mediated the effects of maternal negative emotionality and infant cardiac vagal tone. © 1998 John Wiley & Sons, Inc. Dev Psychobiol 33: 163–174, 1998     

Prenatal maternal C-reactive protein prospectively predicts child executive functioning at ages 4–6 years

This prospective longitudinal study evaluated multiple maternal biomarkers from the preconception and prenatal periods as time-sensitive predictors of child executive functioning (EF) in 100 mother–child dyads. Maternal glycated hemoglobin (HbA_1C), C-reactive protein (CRP), and blood pressure (BP) were assayed before pregnancy and during the second and third trimesters. Subsequently, children were followed from birth and assessed for EF (i.e. cognitive flexibility, response inhibition) at ages 4–6 years. Perinatal data were also extracted from neonatal records. Higher maternal CRP, but not maternal HbA_1C or BP, uniquely predicted poorer child cognitive flexibility, even with control of maternal HbA_1C and BP, relevant demographic factors, and multiple prenatal/perinatal covariates (i.e. preconception maternal body mass index, maternal depression, maternal age at birth, child birth weight, child birth order, child gestational age, and child birth/neonatal complications). Predictions from maternal CRP were specific to the third trimester, and third trimester maternal CRP robustly predicted child cognitive flexibility independently of preconception and second trimester CRP. Child response inhibition was unrelated to maternal biomarkers from all time points. These findings provide novel, prospective evidence that maternal inflammation uniquely predicts child cognitive flexibility deficits, and that these associations depend on the timing of exposure before or during pregnancy.     

Pattern and predictors of weight gain during pregnancy among HIV-1-infected women from Tanzania

Progression of HIV disease is often accompanied by weight loss and wasting. Gestational weight gain is a strong determinant of maternal and neonatal outcomes; however, the pattern and predictors of weight gain during pregnancy among HIV-positive women are unknown. We obtained monthly anthropometric measurements in a cohort of 957 pregnant women from Tanzania who were HIV infected. We estimated the weekly rate of weight gain at various points during the second and third trimesters of pregnancy and computed rate differences between levels of sociodemographic, nutritional, immunologic, and parasitic variables at the first prenatal visit. The change in mid-upper arm circumference (MUAC) from baseline to delivery was also examined. The rate of weight gain decreased progressively during pregnancy. There was an average decline of 1 cm in MUAC between weeks 12 and 38. Lower level of education and helminthic infections at first visit were associated with decreased adjusted rates of weight gain during the third trimester. High baseline MUAC, not contributing to household income, lower serum retinol and selenium concentrations, advanced clinical stage of HIV disease, and malaria infection were related to decreased rates of weight gain during the second trimester. Low baseline CD4 T-cell counts were related to a poorer pattern of weight gain throughout pregnancy. Prevention and treatment of parasitic infections and improvement of nutritional status are likely to enhance the pattern of gestational weight gain among HIV-infected women.     

Elevated second trimester maternal serum β-HCG concentrations and subsequent adverse pregnancy outcome

Previous studies have found an association between elevated second trimester maternal serum α-fetoprotein (MS-AFP), in the absence of fetal anomalies, and adverse pregnancy outcome. We studied the association between elevated second trimester maternal serum β-HCG, now also routinely measured by prenatal screening programs, and adverse pregnancy outcome by reviewing retrospectively the pregnancy outcomes among women with markedly elevated midtrimester β-HCG in our prenatal screening program. Seven (0.23%) of 3,000 consecutively screened women had a serum β-HCG above 5 MOM. Four (57%) of these 7 women had an adverse pregnancy outcome including severe preeclampsia (n = 2), abruptio placentae (n = 1), or preterm labor (n = 1). A concurrently elevated MS-AFP was found in only one of these 4 patients. Elevated midtrimester maternal serum β-HCG may be an independent risk factor for subsequent adverse pregnancy outcomes.     

Effects of maternal stress on puberty, fertility and aggressive behavior of female mice from different intrauterine positions

We examined the effects of maternal stress (bright light and heat) during the last third of pregnancy on subsequent reproductive and behavioral characteristics of female mice from different intrauterine positions. Female mice that develop in utero between two male fetuses (2M females) differ from females that develop between two female fetuses (0M females) in their serum concentrations of both testosterone and estradiol during the fetal period of sexual differentiation. After birth, 0M and 2M females differ in a wide range of reproductive characteristics. We examined the effects of maternal stress on the response to social cues regulating the timing of first vaginal estrus and the length of the first postpubertal estrous cycle when 4 0M or 4 2M females were housed together next to an adult male. Maternal stress decreased the inhibitory effect of being housed with other females in terms of the length of the first postpubertal estrous cycle, but this only occurred in 0M females. We found no effect of maternal stress or intrauterine position on the capacity to mate and remain pregnant, regardless of whether 0M or 2M females were stressed or not stressed during early pregnancy prior to implantation. While there was no effect of prior intrauterine position on interfemale aggression or behavior toward young, maternal stress did tend to reduce the likelihood that females (in diestrus) would exhibit aggression toward other females.     

Hair cortisol as a measure of the stress response to social adversity in young children

Hair cortisol has the potential to provide insight into young children's long-term stress response to social adversity. This study investigated associations between children's exposure to adversity from pregnancy to 2 years of age and their hair cortisol at 2 years, using a longitudinal cohort of children enriched for adversity risk, whose mothers were recruited during pregnancy through the “right@home” trial. Exposures were 18 maternal socioeconomic and psychosocial indicators of adversity, examined as concurrent, cumulative, and longitudinal exposure from pregnancy to 2 years. Hair samples were analyzed from 319/603 (53%) children participating at 2 years. Multivariable regression analyses for concurrent exposure showed three indicators of adversity were associated with higher hair cortisol (housing tenure of public rental, paying board or living rent free; not living in a safe place; higher maternal stress symptoms), one with lower hair cortisol (housing problems), and 14 indicators with no evidence of association. There was no evidence of association for the cumulative adversity count. Longitudinal exposure showed “intermittent” and “persistent” high maternal stress symptoms were associated with higher hair cortisol. The small number of associations identified suggests that hair cortisol is limited as a measure of stress response to social adversity in children at 2 years.     

The course and interrelationship of maternal and paternal perinatal depression

The aims of the study were to describe course of depression in both mothers and fathers from the third trimester of pregnancy through 6 months postpartum and to examine the relationship between maternal and paternal depression. Hypotheses were as follows: (a) Depressive symptoms would be correlated between parents and (b) earlier depressive symptoms in one parent would predict later increases in depression in the other. Eighty cohabitating primiparous couples were recruited from prenatal OBGYN visits and community agencies and enrolled during pregnancy, between 28-week gestation and delivery. Participants completed measures of depression on four occasions: baseline and 1, 3, and 6 months postpartum. Ninety-eight percent of the enrolled couples (78; 156 individuals) completed the study. For both mothers and fathers, symptom severity ratings and classification as a probable case were stable across time, with prenatal depression persisting through 6 months in 75 % of mothers and 86 % of fathers. Prenatal depression in fathers predicted worsening depressive symptom severity in mothers across the first six postpartum months but not vice versa. In both expecting/new mothers and fathers, depression demonstrates a stable pattern of occurrence and symptom severity between 28-month gestation and 6 months postpartum. Although prenatal maternal depression is not predictive of symptom change in fathers, mothers with prenatally depressed partners showed significant worsening in overall symptom severity during the first six postpartum months.     

Neuroendocrine and immune markers of maternal stress during pregnancy and infant cognitive development

Antenatal exposure to maternal stress is a factor that may impact on offspring cognitive development. While some evidence exists of an association between maternal antenatal depressive or anxiety symptoms and infants' cognitive outcomes, less is known about the role of biological indices of maternal antenatal stress in relation to infant cognitive development. The current study investigated the association between maternal depressive and anxiety symptoms, stress and inflammatory markers during pregnancy and infant's cognitive development in a sample of 104 healthy pregnant women (mean gestational age = 34.76; SD = 1.12) and their 12-week-old infants (mean postnatal weeks = 11.96; SD = 1.85). Maternal depressive and anxiety symptoms were evaluated during pregnancy, alongside measurements of serum Interleukin-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol, and alpha amylase (sAA) concentrations. Infant cognitive development, maternal caregiving and concurrent anxiety or depressive symptoms were assessed 12 weeks after delivery. Hierarchical linear regressions indicated that higher maternal diurnal cortisol and CRP levels were independently associated with lower infant cognitive development scores, while adjusting for infant gender and gestational age, maternal IQ, caregiving, depressive, or anxiety symptoms. Though correlational, findings seem suggestive of a role for variation in maternal biological stress signals during pregnancy in influencing infants' early cognitive development.