Maternal mental distress and cortisol levels in pregnancies with congenital heart disease.

OBJECTIVES: Prenatal maternal stress is associated with adverse offspring outcomes, which may be mediated by maternal stress hormones. However, evidence supporting the association between maternal stress and cortisol levels in high-risk pregnancies is limited. This study aims to determine the relationship between self-reported maternal mental distress and maternal salivary cortisol levels in pregnancies complicated by foetal CHD compared with healthy pregnancies. METHODS: We recruited women with pregnancies complicated by foetal CHD and healthy pregnancies. Maternal saliva was collected between 22 and 40 gestational weeks. Standardized questionnaires measuring stress, depression, and anxiety were completed by patients. Generalized estimating equation was used to evaluate associations between maternal mental distress scales and cortisol levels. RESULTS: We studied 165 women (55 CHD, 110 controls) and collected 504 cortisol samples (160 CHD, 344 controls). Women carrying CHD foetuses had higher stress, anxiety, and depression scores compared to women carrying healthy foetuses. However, maternal cortisol levels did not significantly differ in CHD and controls. Cortisol levels were higher in women carrying foetuses with functionally single-ventricle versus two-ventricle CHD. In both CHD and controls, there was no significant association between maternal stress, depression or anxiety scores and cortisol levels. CONCLUSION: Our data suggest that self-reported maternal stress, anxiety, and depression are not associated with maternal salivary cortisol levels in CHD and healthy pregnancies. The impact of maternal mental distress on foetal health may be through other mediating pathways other than maternal cortisol concentrations.

The role of maternal environment on calibrating "Mini Puberty" in early infant development.

The postnatal period is a time of increased brain development and plasticity which have enduring influences on brain and behavior. Infants demonstrate a transient surge in testosterone (T) during development referred to as "mini puberty". The utility of studying mini puberty in psychobiology has only recently emerged. Life-history theory postulates that infants "use" the maternal environment-pre and postnatally-to calibrate growth and timing of sexual maturity. As such, variability in infant T levels is not arbitrary and can be predicted by theory. We examine the role of maternal pre- and postnatal cortisol. Using saliva samples (n = 193 dyads), we predicted that higher levels of maternal cortisol are associated with higher levels of infant T. We found only maternal postnatal cortisol had a relationship with infants' mini puberty. This relationship was in the predicted direction and remained after controlling for numerous variables. Discussion will include the potential role of mini puberty as an inflection point where systems related to growth, sexual maturation, and psychosexual behavior can be calibrated and coordinated.

Long-Term Associations Between Prenatal Maternal Cortisol and Child Neuroendocrine-Immune Regulation.

BACKGROUND: Advancing understanding of the developmental origins of neuroendocrine-immune (NEI) functioning is key to elucidating the biological mechanisms involved in health and disease risk across the lifespan. This study examined whether prenatal maternal hypothalamic-pituitary-adrenal (HPA) activity moderates child NEI relations and explored the consistency of this moderating effect across gestation. METHODS: Pregnant women participated in five prenatal study visits from 24 to 38 weeks gestation. At each visit, women provided a saliva sample. In a 5-year follow-up study, children (nfemale = 25, nmale=20) provided four saliva samples and participated in behavioral assessments and challenge tasks. Prenatal maternal saliva samples were assayed for cortisol. Child saliva samples were assayed for cortisol and cytokines (IL-1ß, IL-6, IL-8, TNFα) as indices of HPA and inflammatory activity. Multilevel mixed-effects models examined the moderation of child NEI relations by prenatal maternal cortisol. RESULTS: Among males, average prenatal maternal cortisol did not moderate child NEI relations. Among females, average prenatal maternal cortisol moderated some child NEI relations with higher prenatal cortisol associated with more positive cortisol-cytokine relations at age five. When examined by gestational time point, there were more significant NEI moderation effects by maternal cortisol from later gestation (≥ 30 weeks) than earlier. CONCLUSIONS: The findings suggest prenatal maternal HPA activity may moderate child NEI functioning. Additional research conducted with more heterogeneous and larger samples is needed to fully understand these relations. Furthering our knowledge of NEI development has important research and clinical implications, particularly for understanding and addressing conditions with inflammatory pathophysiologies, such as depression and cardiovascular disease.

Maternal Lifetime Trauma and Birthweight: Effect Modification by In Utero Cortisol and Child Sex.

OBJECTIVES: To evaluate associations between maternal lifetime traumatic stress and offspring birthweight and examine modifying effects of third trimester cortisol and fetal sex. STUDY DESIGN: Analyses included 314 mother-infant dyads from an ethnically mixed pregnancy cohort. Maternal lifetime trauma was reported via the Life Stressor Checklist-Revised. Fenton birthweight for gestational age z-scores (BWGA-z) were calculated. A 3-cm scalp-nearest maternal hair segment collected at birth was assayed to reflect cumulative third trimester cortisol secretion. Multivariable regression was used to investigate associations between maternal lifetime trauma and BWGA-z and examine 2- and 3-way interactions with cortisol and fetal sex. Because subjects with low or high cortisol levels could represent susceptible populations, varying coefficient models that relax the linearity assumption on cortisol level were used to assess the modification of maternal lifetime trauma associations with BWGA-z as a function of cortisol. RESULTS: Women were primarily minorities (41% Hispanic, 26% black) with ≤12 years education (63%); 63% reported ≥1 traumatic event. Prenatal cortisol modified the association between maternal lifetime trauma and birthweight. Women with higher lifetime trauma and increased cortisol had significantly lower birthweight infants in males; among males exposed to the 90th percentile of cortisol, a 1-unit increase in trauma score was associated with a 0.19-unit decrease in BWGA-z (95% CI, -0.34 to -0.04). Associations among females were nonsignificant, regardless of cortisol level. CONCLUSIONS: These findings underscore the need to consider complex interactions among maternal trauma, disrupted in utero cortisol production, and fetal sex to fully elucidate intergenerational effects of maternal lifetime trauma.

Prenatal Maternal Cortisol Has Sex-Specific Associations with Child Brain Network Properties.

Elevated maternal cortisol concentrations have the potential to alter fetal development in a sex-specific manner. Female brains are known to show adaptive behavioral and anatomical flexibility in response to early-life exposure to cortisol, but it is not known how these sex-specific effects manifest at the whole-brain structural networks. A prospective longitudinal study of 49 mother child dyads was conducted with serial assessments of maternal cortisol levels from 15 to 37 gestational weeks. We modeled the structural network of typically developing children (aged 6-9 years) and examined its global connectome properties, rich-club organization, and modular architecture. Network segregation was susceptible only for girls to variations in exposure to maternal cortisol during pregnancy. Girls generated more connections than boys to maintain topologically capable and efficient neural circuits, and this increase in neural cost was associated with higher levels of internalizing problems. Maternal cortisol concentrations at 31 gestational weeks gestation were most strongly associated with altered neural connectivity in girls, suggesting a sensitive period for the maternal cortisol-offspring brain associations. Our data suggest that girls exhibit an adaptive response by increasing the neural network connectivity necessary for maintaining homeostasis and efficient brain function across the lifespan.

Maternal serum cortisol levels during pregnancy differ by fetal sex.

BACKGROUND: Males and females have different patterns of fetal growth, resulting in different sizes at birth. Increased maternal cortisol levels in pregnancy negatively impact fetal growth. However, it is unknown whether sexual dimorphism displays differences in maternal cortisol levels already during early pregnancy and to what extent it explains sex differences in intra-uterine growth. The present cross-sectional study investigated whether fetal sex was associated with the level of maternal serum total cortisol in first half of pregnancy and its contribution to sex differences in fetal growth. METHOD: The study population comprised 3049 pregnant women from the Amsterdam Born Children and their Development (ABCD)-cohort). Total serum cortisol levels were determined during pregnancy. Multivariable linear regression was used to determine fetal sex differences in maternal cortisol levels and its association with sex differences in fetal growth measured as birth weight standardized for gestational age, parity and sex. RESULTS: Maternal serum total cortisol increased during pregnancy from on average 390 ± 22 nmol/L (at 5th week) to 589 ± 15 nmol/L (at 20th week). Women carrying a female fetus had higher maternal total cortisol levels. This sex difference was not significant before the 11th week; at the 12th week the difference was 15 ± 7 nmol/L which increased to 45 ± 22 nmol/L at the 20th week (p-for-interaction=0.05). Maternal total cortisol levels were associated with birth weight (ß:-0.22;P < 0.001). However, sex differences in birth weight were not explained by related maternal total cortisol levels. CONCLUSION: The sexual dimorphic maternal serum total cortisol levels are apparent after the first trimester but do not explain the different patterns of fetal growth.

Higher Maternal Cortisol Associated With Lower Blood Pressure in Offspring From 3 Months to 5 Years of Age in the Odense Child Cohort.

BACKGROUND: Synthetic glucocorticoid exposure in late pregnancy may be associated with higher blood pressure in offspring. We hypothesized that endogenous cortisol in pregnancy relates to offspring blood pressure (OBP). OBJECTIVE: To investigate associations between maternal cortisol status in third trimester pregnancy and OBP. METHODS: We included 1317 mother-child pairs from Odense Child Cohort, an observational prospective cohort. Serum (s-) cortisol and 24-hour urine (u-) cortisol and cortisone were assessed in gestational week 28. Offspring systolic blood pressure and diastolic blood pressure were measured at age 3, 18 months, and 3 and 5 years. Associations between maternal cortisol and OBP were examined by mixed effects linear models. RESULTS: All significant associations between maternal cortisol and OBP were negative. In boys in pooled analyses, 1 nmol/L increase in maternal s-cortisol was associated with average decrease in systolic blood pressure (ß=-0.003 mmHg [95% CI, -0.005 to -0.0003]) and diastolic blood pressure (ß=-0.002 mmHg [95% CI, -0.004 to -0.0004]) after adjusting for confounders. At 3 months of age, higher maternal s-cortisol was significantly associated with lower systolic blood pressure (ß=-0.01 mmHg [95% CI, -0.01 to -0.004]) and diastolic blood pressure (ß=-0.010 mmHg [95% CI, -0.012 to -0.011]) in boys after adjusting for confounders, which remained significant after adjusting for potential intermediate factors. CONCLUSIONS: We found temporal sex dimorphic negative associations between maternal s-cortisol levels and OBP, with significant findings in boys. We conclude that physiological maternal cortisol is not a risk factor for higher blood pressure in offspring up to 5 years of age.

A biopsychosocial perspective on maternal parenting in the first two years of infant life.

Guided by a biopsychosocial perspective of mothering, this study investigated the interplay among biological (maternal cortisol reactivity), psychological (maternal depressive symptoms), and social (infant emotion and regulation) factors in contributing to early changes in maternal parenting. Participants were 1292 low-income, mother-infant pairs, assessed when the infants were 6-months (T1), 15-months (T2), and 24-months old (T3). Maternal parenting was observed at all assessment points. At T1, infant emotion expression and orienting towards mothers were observed, when maternal cortisol reactivity was assessed. Mothers reported their depressive symptoms at T1. Exploratory factor analysis revealed two parenting factors across time points: positive engagement and negative intrusiveness. Second-order latent growth curve models revealed interactions among maternal cortisol reactivity, depressive symptoms, and child negative emotion/orienting at T1 in predicting intercepts and slopes of two parenting factors. T1 maternal cortisol reactivity was associated with a higher positive engagement intercept for infants having high negative emotion at T1, but a lower positive engagement intercept for infants with low negative emotion at T1, under low T1 maternal depressive symptoms. T1 maternal cortisol reactivity was also related to a lower negative intrusiveness intercept for infants showing high orienting at T1. Longitudinally, maternal cortisol reactivity at T1 predicted a faster decline in positive engagement when infants showed high negative emotion at T1, but a slower decline when infants were less negative at T1. This study reveals a bivalent adaptation process in maternal sensitivity and enhances the current understanding of how biopsychosocial factors contribute to maternal parenting in low-income families.

Associations between maternal psychological distress and salivary cortisol during pregnancy: A mixed-models approach.

BACKGROUND: Maternal psychological distress during pregnancy is related to adverse child behavioral and emotional outcomes later in life, such as ADHD and anxiety/depression. The underlying mechanisms for this, however, are still largely unknown. The hypothalamic-pituitary-adrenal (HPA)-axis, with its most important effector hormone cortisol, has been proposed as a mechanism, but results have been inconsistent. The current study investigated the association between maternal psychological distress (i.e. anxiety and depressive symptoms) and maternal cortisol levels during pregnancy using a mixed models approach. METHOD: During three pregnancy trimesters, mothers (N = 170) collected four salivary samples for two consecutive days. Mothers reported symptoms of anxiety and depression three times during pregnancy (at 13.3 ±â€¯1.1, 20.2 ±â€¯1.5, and 33.8 ±â€¯1.5 weeks of pregnancy, respectively) using the anxiety subscale of the Symptom Checklist (SCL-90), the Spielberger State and Trait Anxiety Inventory (STAI), and the Edinburgh Postnatal Depression Scale (EPDS). Specific fears and worries during pregnancy were measured with the short version of the Pregnancy Related Anxiety Questionnaire (PRAQ-R). RESULTS: We found a significant effect of SCL-90 anxiety subscale on cortisol levels at awakening (p = .008), indicating that mothers with higher anxiety showed lower cortisol at awakening. Maternal psychological variables explained 10.5% of the variance at the person level in awakening cortisol level, but none in the overall diurnal cortisol model. CONCLUSION: More research is necessary to unravel the underlying mechanisms of the association between maternal psychological distress and cortisol and the search for mechanisms other than the HPA-axis should be continued and extended.