Maternal Cortisol Levels Research Articles

Maternal prenatal licorice consumption alters hypothalamic–pituitary–adrenocortical axis function in children

Overexposure to glucocorticoids has been proposed as a mechanism by which prenatal adversity 'programs' the function of the hypothalamic-pituitary-adrenocortical axis (HPAA), thereby increasing the risk of adult diseases. Glycyrrhizin, a natural constituent of licorice, potently inhibits 11β-hydroxysteroid dehydrogenase type 2, the feto-placental barrier to the higher maternal cortisol levels. We studied if maternal consumption of glycyrrhizin in licorice associates with HPAA function in children. Diurnal salivary cortisol and salivary cortisol during the Trier Social Stress Test for Children (TSST-C) were measured in children (n=321, mean age=8.1, SD=0.3 years) whose mothers consumed varying levels of glycyrrhizin in licorice during pregnancy; exposure-level groups were labeled high (≥500 mg/week), moderate (250-499 mg/week) and zero-low (0-249 mg/week). In comparison to the zero-low exposure group, children in the high exposure group had 19.2% higher salivary cortisol awakening peak, 33.1% higher salivary cortisol awakening slope, 15.4% higher salivary cortisol awakening area under the curve (AUC), 30.8% higher baseline TSST-C salivary cortisol levels, and their salivary cortisol levels remained high throughout the TSST-C protocol (P-values <0.05). These effects appeared dose-related. Our findings lend support to prenatal 'programming' of HPAA function by overexposure to glucocorticoids.

Touch attenuates infants’ physiological reactivity to stress

Animal studies demonstrate that maternal touch and contact regulate infant stress, and handling during periods of maternal deprivation attenuates the stress response. To measure the effects of touch on infant stress reactivity during simulated maternal deprivation, 53 dyads were tested in two paradigms: still-face (SF) and still-face with maternal touch (SF+T). Maternal and infant cortisol levels were sampled at baseline, reactivity, and recovery and mother's and infant's cardiac vagal tone were measured during the free play, still-face, and reunion episodes of the procedure. Cortisol reactivity was higher among infants in the SF condition and while cortisol decreased at recovery for infants in the SF+T, it further increased for those in the SF. Vagal tone showed a greater suppression when SF was not accompanied by maternal touch. Touch synchrony during free play was associated with higher infant vagal tone, whereas touch myssynchrony--maternal tactile stimulation while the infant gaze averts--correlated with higher maternal and infant cortisol. In humans, as in mammals, the provision of touch during moments of maternal unavailability reduces infants' physiological reactivity to stress.

The impact of maternal childhood abuse on maternal and infant HPA axis function in the postpartum period

Early life trauma, particularly child abuse, has been associated with aberrations in hypothalamic-pituitary-adrenal (HPA) axis functioning in adulthood. However, the relationship of early abuse and later adult neuroendocrine changes may be moderated by additional factors such as comorbid psychopathology and recent life stress. Parental exposure to child abuse may have transgenerational effects, with offspring of abuse victims showing similar neuroendocrine profiles as their mothers. The majority of previous studies in this area focus on adult offspring, and the degree to which the effects of parental child abuse can be detected earlier in the development of the offspring remains obscure. The current study utilized a clinical sample of women with a history of MDD (N=126), to examine the effects of maternal early life sexual and physical abuse (Childhood Trauma Questionnaire (CTQ)) on both maternal and infant salivary cortisol levels during a laboratory stress paradigm at 6 months postpartum. Maternal child abuse was associated with steeper declines in cortisol in the mothers and lower baseline cortisol in their infants. Comorbid maternal PTSD, current maternal depressive symptoms, and recent life stressors were significant moderators of maternal cortisol change. Maternal abuse history was associated with increases in cortisol levels in those mothers who experienced these additional stressors. Similarly, a history of early maternal abuse and comorbid PTSD was associated with greater increases in infant cortisol levels. Maternal childhood abuse was associated with HPA axis function in both the mother and the infant during the postpartum period.

Maternal Cortisol Levels and Behavior Problems in Adolescents and Adults with ASD

Using daily diary methods, mothers of adolescents and adults with ASD (n = 86) were contrasted with a nationally representative comparison group of mothers of similarly-aged unaffected children (n = 171) with respect to the diurnal rhythm of cortisol. Mothers of adolescents and adults with ASD were found to have significantly lower levels of cortisol throughout the day. Within the ASD sample, the son or daughter's history of behavior problems interacted with daily behavior problems to predict the morning rise of the mother's cortisol. A history of elevated behavior problems moderated the effect of behavior problems the day before on maternal cortisol level. Implications for interventions for both the mother and the individual with ASD are suggested.

Maternal cortisol and offspring birthweight: Results from a large prospective cohort study

Maternal psychosocial problems may affect fetal growth through maternal cortisol. This large prospective cohort study examined among 2810 women (1) the association of maternal cortisol levels with offspring birthweight and small for gestational age (SGA) risk and (2) the mediating role of maternal cortisol on the relation between maternal psychosocial problems and fetal growth. Pregnant women in Amsterdam were approached during their first prepartum visit (+/-13 weeks gestation). Total maternal cortisol level was determined in serum and maternal psychosocial indicators were collected through a questionnaire. Maternal cortisol levels were negatively related to offspring birthweight (B=-0.35; p<.001) and positively to SGA (OR=1.00; p=.027); after adjustment (for gestational age at birth, infant gender, ethnicity, maternal age, parity, BMI, and smoking), these effects were statistically insignificant. Post hoc analysis revealed a moderation effect by time of day: only in those women who provided a blood sample < or =09:00h (n=94), higher maternal cortisol levels were independently related to lower birthweights (B=-0.94; p=.025) and a higher SGA risk (OR=1.01; p=.032). Maternal psychosocial problems were not associated with cortisol levels. In conclusion, although an independent association between maternal cortisol levels in early pregnancy and offspring birthweight and SGA risk was not observed, exploratory post hoc analysis suggested that the association was moderated by time of day, such that the association was only present in the early morning. The hypothesis that maternal psychosocial problems affect fetal growth through elevated maternal cortisol levels could not be supported.

Maternal Licorice Consumption and Detrimental Cognitive and Psychiatric Outcomes in Children

Overexposure to glucocorticoids may link prenatal adversity with detrimental outcomes in later life. Glycyrrhiza, a natural constituent of licorice, inhibits placental 11-beta-hydroxysteroid dehydrogenase type 2, the feto-placental "barrier" to higher maternal levels of cortisol. The authors studied whether prenatal exposure to glycyrrhiza in licorice exerts detrimental effects on cognitive performance (subtests of the Wechsler Intelligence Scale for Children III as well as the Children's Developmental Neuropsychological Assessment and the Beery Developmental Test of Visual-Motor Integration) and psychiatric symptoms (Child Behavior Checklist) in 321 Finnish children 8.1 years of age born in 1998 as healthy singletons at 35-42 weeks of gestation. In comparison to the group with zero-low glycyrrhiza exposure (0-249 mg/week), those with high exposure (>or=500 mg/week) had significant decrements in verbal and visuospatial abilities and in narrative memory (range of mean differences in standard deviation units, -0.31 to -0.41; P < 0.05) and significant increases in externalizing symptoms and in attention, rule-breaking, and aggression problems (range of odds ratios, 2.15 to 3.43; P < 0.05). The effects on cognitive performance appeared dose related. Data are compatible with adverse fetal "programming" by overexposure to glucocorticoids and caution against excessive intake of licorice-containing foodstuffs during pregnancy.

Elevated maternal cortisol levels during pregnancy are associated with reduced childhood IQ

In animal models, there is evidence to suggest a causal link between maternal cortisol levels during pregnancy and offspring outcomes; however, evidence for this relationship in humans is inconclusive. We address important confounders of this association by estimating the relationship between maternal cortisol levels in late pregnancy and childhood IQ in a birth cohort and in a subsample of siblings. This study included 832 children who were members of the Collaborative Perinatal Project. Maternal serum collected between 1959 and 1966 during the third trimester of pregnancy was analysed for free cortisol. We investigated the relationship between maternal cortisol in quintiles and full, verbal and performance scale scores on the Wechsler Intelligence Scale for Children at age 7 years, adjusting for prenatal and family characteristics. We repeated this analysis among 74 discordant sibling pairs using a fixed effects approach, which adjusts for shared family characteristics. Maternal cortisol levels were negatively related to full-scale IQ, an effect driven by verbal IQ scores. Compared with those in the lowest quintile of cortisol exposure, the verbal IQ of children in the highest quintile of exposure was 3.83 points lower [95% confidence interval (CI): -6.44 to -1.22]. Within sibling pairs, being in the highest quintile of exposure was associated with verbal IQ scores 5.5 points lower (95% CI: -11.24 to 0.31) compared with the other quintiles. These findings are consistent with prior human and animal studies, and suggest that exposure to high levels of maternal cortisol during pregnancy may be negatively related to offspring cognitive skills independently of family attributes that characterize the postnatal environment.

Pre-natal stress amplifies the immediate behavioural responses to acute pain in piglets

Pre-natal stress (PNS) or undernutrition can have numerous effects on an individual's biology throughout their lifetime. Some of these effects may be adaptive by allowing individuals to tailor their phenotype to environmental conditions. Here we investigated, in the domestic pig Sus scrofa, whether one possible consequence of a predicted adverse environment could be altered pain perception. The behavioural response of piglets to the surgical amputation ('docking') of their tail or a sham procedure was measured for 1 min in piglets born to mothers who either experienced mid-gestation social stress or were left undisturbed throughout pregnancy. A behavioural pain score was found to predict the docked status of piglets with high discriminant accuracy. Piglets exposed to PNS had a significantly higher pain score than controls, and for each litter of tail-docked piglets, the average pain score was correlated with mid-gestation maternal cortisol levels. The data presented here provide evidence that the experience of stress in utero can result in a heightened acute response to injury in early life. Speculatively, this may represent an adaptive alteration occurring as a consequence of a pre-natal 'early warning' of environmental adversity.

The effect of spinal and general anaesthesia on maternal and fetal cortial levels in effective caeserian section deliveries

Objective: To compare the levels of maternal and fetal cortisol in patients who receive either spinal or general anesthesia in elective caesarian section deliveries. Setting: Tertiary Hospital in Lagos. Methods: Pregnant women were randomly assigned into two groups to receive spinal n=30 (group I) and general n=30 (group II) aneathesia for elective caesarian section. Maternal and cortisol were sampled five minute of ceasarian section of delivery and fetal and blood cortisol levels five minute of delivery and compared statistically. Results: Maternal cortisol concentrations were high in general aneathesia groups (18.25+ 2.9mg/dl) than spinal aneasthesia groups (10.5+3.2mg/dl) (R<0.001.). Fetal and blood cortisol concentration in general aneasthesia groups were higher than (13.6+ 4.2mg/dl) than spinal aneasthesia group (71.+ 3.9mg/dl) (P<0.001). A significant positive correlation between maternal and fetal cortisol concentration were found between general and spinal aneasthesia groups. Conclusion: Our result showed lower matenal and fetal cortial concentrations in spinal aneasthesia than in general aneasthesia. Spinal aneasthesia seem to be less stressful for mothers and fetus.

Hormonal changes and somatopsychologic manifestations in the first trimester of pregnancy and post partum

Objective To investigate links between psychologic distress and levels of maternal hormones and cortisol during pregnancy and post partum. Method The study population of 308 pregnant or recently delivered women was divided into 4 equal groups, 3 representing each pregnancy trimester and the fourth one representing the first week of the postpartum period. The women were screened for psychological distress and had blood drawn to measure serum levels of estradiol, progesterone, and total cortisol on the same day. Results The rates of anxiety and depression were higher in the first trimester and the postpartum groups. Depression was correlated with sharp changes in estradiol and progesterone levels; anxiety was correlated with total cortisol level; and there was a correlation between depression and anxiety. Conclusion Sharp changes in maternal hormone levels were correlated with depression; depression was correlated with anxiety; and anxiety was correlated with elevated cortisol levels, which may adversely affect the health of mother and offspring. Measuring maternal hormones may be a diagnostic tool to evaluate psychologic stress and associated risks.

Effects of Sucking and Skin-to-Skin Contact on Maternal ACTH and Cortisol Levels During the Second Day Postpartum—Influence of Epidural Analgesia and Oxytocin in the Perinatal Period

In this study we made a detailed analysis of the mothers' release pattern of adrenocorticotropic hormone (ACTH) and cortisol during a breastfeeding session during the second day postpartum and related these patterns to maternal oxytocin levels as well to the duration of sucking and the duration of skin-to-skin contact before sucking the breast. Furthermore, we investigated if epidural analgesia and oxytocin administration during and after labor influenced the release pattern of ACTH and cortisol. Sixty-three primiparae were included in the study. Fourteen received oxytocin intramuscularly postpartum, nine received oxytocin infusion, 14 received epidural analgesia combined with oxytocin infusion, and six received epidural analgesia alone. Twenty mothers did not receive any of these medical interventions. Blood samples were analyzed for ACTH and cortisol by enzyme-linked immunoassay. Both ACTH and cortisol levels fell significantly during the breastfeeding session. A significant negative relationship was found between oxytocin and ACTH levels, but not between oxytocin and cortisol levels. A positive and significant relationship was found between ACTH and cortisol levels. The duration of skin-to-skin contact before onset of sucking was significantly and negatively associated with lower cortisol levels, but not with ACTH levels. Cortisol levels differed significantly between mothers having received epidural analgesia with and without oxytocin. Breastfeeding is associated with a decrease of ACTH and cortisol levels. Skin-to-skin contact contributes to this effect. ACTH correlated negatively with the duration of sucking and with median oxytocin levels, whereas cortisol levels correlated inversely with the duration of skin-to-skin contact preceding sucking, suggesting a partial dissociation between the mechanisms regulating ACTH and cortisol release. In addition, medical interventions in connection with birth influence the activity of the hypothalamic-pituitary-adrenal axis 2 days after birth.

Mother–infant interactions in free-ranging rhesus macaques: Relationships between physiological and behavioral variables

Studies of mother–infant relationships in nonhuman primates have increasingly attempted to understand the neuroendocrine bases of interindividual variation in mothering styles and the mechanisms through which early exposure to variable mothering styles affects infant behavioral development. In this study of free-ranging rhesus macaques on Cayo Santiago, Puerto Rico, we aimed to: 1) compare lactating and nonlactating females to investigate whether lactation is associated with changes in plasma cortisol, prolactin and oxytocin, as well as changes in CSF levels of serotonin and dopamine metabolites (5-HIAA and HVA); 2) examine the extent to which interindividual variation in maternal physiology is associated with variation in maternal behavior; 3) examine the extent to which interindividual variation in infant physiology and behavior is accounted for by variation in maternal physiology and behavior. Lactating females had higher plasma concentrations of cortisol, prolactin, and oxytocin but lower CSF concentrations of HVA than nonlactating females. Variation in maternal rejection behavior was positively correlated with variation in maternal plasma cortisol levels and in CSF 5-HIAA levels while variation in the time spent nursing and grooming was associated with maternal plasma oxytocin levels. Infants who were protected more by their mothers had higher cortisol levels than those who were protected less, while infants who were rejected more had lower CSF 5-HIAA than infants who were rejected less. Since exposure to high levels of maternal protectiveness and rejection is known to affect the offspring's behavior and responsiveness to the environment later in life, our results are consistent with the hypothesis that these effects are mediated by long-term changes in the activity of the offspring's HPA axis and brain serotonergic system.

Coregulation in Salivary Cortisol During Maternal Holding of Premature Infants

The purpose of this study was to examine coregulation between mothers and preterm infants in hypothalamic-pituitary-adrenocortical (HPA) system activity, as indicated by salivary cortisol levels, while mothers held their infants. The research questions were (a) does mother-infant coregulation in HPA activity occur during holding? and (b) if mother- infant coregulation in HPA activity exists during holding, do type of holding, antenatal steroids, sound level, and maternal touch influence this coregulation? The sample consisted of 20 mother- infant dyads with infants at a mean postconceptional age of 34.7 weeks (+0.7) and average postnatal age of 15 days (+9) at the time of cortisol sampling. The design was exploratory using convenience sampling. Maternal and infant cortisol levels were obtained at Time 1 (baseline) and Time 2 (end of holding); at each time, the absolute differences in levels between mother and infant were determined. Coregulation was operationalized as less difference between maternal-infant cortisol levels immediately after holding (Time 2) as compared to before holding (Time 1). The two variables with the highest correlation with the Time 1/Time 2 difference score included antenatal steroids and ambient sound level, which were entered into a linear regression equation as predictor variables. A coregulatory relationship in cortisol levels existed between mothers and infants during holding, which was moderated by sound levels. Nurses in the neonatal intensive care unit (NICU) can facilitate the mother-infant relationship, as reflected in coregulatory measures, by promoting a quiet environment, particularly around mothers who are holding their infants.

Transmission and Treatment of Depression

Transmission and Treatment of Depression

Prenatal depression restricts fetal growth

Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18–20 weeks GA) estimated fetal weight and urine cortisol and birthweight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels ( p = .006) and fetuses who were smaller ( p = .001) and who showed slower fetal growth rates ( p = .011) and lower birthweights ( p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes.

OC057: Maternal distress and evening salivary cortisol levels in ongoing pregnancies with fetal anomaly

OC057: Maternal distress and evening salivary cortisol levels in ongoing pregnancies with fetal anomaly

The effect of Ramadan fasting on maternal serum lipids, cortisol levels and fetal development

To determine the effects of fasting during the month of Ramadan on fetal development and maternal serum cortisol and lipid profile. This study was performed in Obstetrics and Gynecology Department of Gaziantep University Hospital, between 23 September 2006 and 23 October 2006 (during the month of Ramadan). Thirty-six consecutive healthy women with uncomplicated pregnancies of 20 weeks or more, who were fasting during Ramadan, were included in the study group (group 1). The control group (group 2) consisted of 29 healthy pregnant women, who were not fasting during the study period. For evaluating Ramadan's effect on fetus, Doppler ultrasonography was performed on all subjects in the beginning and then once a week until the end of Ramadan for the following measurements: increase of fetal biparietal diameter (BPD), increase of fetal femur length (FL), increase of estimated fetal body weight (EFBW), fetal biophysical profile (BPP), amniotic fluid index (AFI), and umbilical artery systole/diastole (S/D) ratio. Maternal serum cortisol, triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low density lipoprotein (VLDL), and LDL/HDL ratio were also evaluated before and after Ramadan. No significant difference was found between the two groups for the fetal age, maternal weight gain (kilogram), estimated fetal weight gain (EFWG), fetal BPP, AFI, and umbilical artery S/D ratio. In the fasting group, the maternal serum cortisol levels on day 20 were significantly higher than the initial levels obtained 1 week prior to Ramadan (p < 0.05). Although no significant increases were observed in total cholesterol and triglyceride levels in the fasting group, these increases were significantly higher than those in the control group (p < 0.05). LDL and VLDL levels showed a non-significant decrease at the end of the Ramadan. HDL levels showed a slight increase, but LDL/HDL ratios were significantly decreased in fasting group (p < 0.05). The results of this study showed that maternal serum cortisol level was elevated while LDL/HDL ratio were decreased in healthy women with uncomplicated pregnancies of 20 weeks or more, who were fasting during Ramadan. No untoward effect of Ramadan was observed on intrauterine fetal development.

Maternal adrenocorticotropin, cortisol, and thyroid hormone responses to all three-trimester equivalent repeated binge alcohol exposure: ovine model

Alcohol-mediated alterations in hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid axis function are two proposed mechanisms by which alcohol causes neurodevelopmental injury to the fetus. We previously reported that third-trimester equivalent only alcohol exposure in sheep results in increases in the maternal and fetal adrenocorticotropin and cortisol levels, and decreases in the fetal thyroid hormones T 3 and T 4 and maternal T 3 levels. In this study, we wished to characterize the maternal HPA and hypothalamic-pituitary-thyroid hormone responses to repeated binge alcohol exposure during all three-trimester equivalents of pregnancy in sheep. Pregnant ewes received intravenous infusions of alcohol at doses of 0.75, 1.25, or 1.75 g/kg over 1 h with mean peak blood alcohol concentrations of 90, 126, or 183 mg/dl, respectively, on 3 consecutive days each week beginning on gestational day (GD) 4. Maternal blood samples were collected on GDs 6, 40, 90, and 132. Maternal plasma concentrations of adrenocorticotropin and cortisol increased in response to the high alcohol dose, and the magnitude of these elevations was not different across gestation. Thyroid hormone levels were not different when comparing among treatment groups at any time point during gestation. However, there was an ontogenetic decrease in the maternal T 3 concentration beginning between GDs 6 and 40 and a decrease in maternal T 4 and free T 4 beginning between GDs 40 and 90. The current findings suggest that (1) maternal alcohol consumption at any time during gestation stimulates the HPA axis, (2) maternal HPA responsiveness to alcohol does not change across gestation, (3) binge alcohol exposure at these doses lasting all three-trimester equivalent of human brain development does not reduce maternal thyroid hormone concentration, (4) alterations in fetal thyroid function in response to alcohol exposure do not occur as a result of diminished maternal thyroid hormone contribution, and (5) there is an ontogenetic decrease in ovine maternal thyroid hormones over gestation.

Timing of fetal exposure to stress hormones: Effects on newborn physical and neuromuscular maturation

The purpose of the study was to determine the specific periods during pregnancy in which human fetal exposure to stress hormones affects newborn physical and neuromuscular maturation. Blood was collected from 158 women at 15, 19, 25, and 31 weeks' gestation. Levels of placental corticotropin-releasing hormone (CRH) and maternal cortisol were determined from plasma. Newborns were evaluated with the New Ballard Maturation Score. Results indicated that increases in maternal cortisol at 15, 19, and 25 weeks and increases in placental CRH at 31 weeks were significantly associated with decreases in infant maturation among males (even after controlling for length of gestation). Results also suggested that increases in maternal cortisol at 31 weeks were associated with increases in infant maturation among females, although these results were not significant after controlling for length of gestation. Findings suggest that stress hormones have effects on human fetal neurodevelopment that are independent of birth outcome.

Placental 11β-Hydroxysteroid Dehydrogenase Type 2 is Reduced in Pregnancies Complicated with Idiopathic Intrauterine Growth Restriction: Evidence That This is Associated With an Attenuated Ratio of Cortisone to Cortisol in the Umbilical Artery

The placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) serves as a functional barrier to protect the fetus from excessive exposure to high levels of maternal cortisol. There is evidence that placental 11β-HSD2 is reduced in pregnancies complicated with intrauterine growth restriction (IUGR), but the relationship between the two is uncertain owing to other maternal complications often associated with this pathological condition of pregnancy. To gain insight into the role of placental 11β-HSD2 in the pathogenesis of IUGR, we studied variations in the activity and expression of this important enzyme as well as its functional indicator, the ratio of cortisone to cortisol in umbilical cord blood, in a cohort of 12 term deliveries complicated with idiopathic IUGR and 12 term controls. We showed that both placental 11β-HSD2 activity and mRNA were reduced in IUGR. This was accompanied by a decrease in the ratio of cortisone to cortisol in the umbilical artery, suggesting that not only placental but also fetal 11β-HSD2 activity may be compromised in idiopathic IUGR. Given that we previously identified the nuclear receptor PPARδ as a potent suppressor of placental 11β-HSD2, we also tested but found no evidence to support the hypothesis that placental PPARδ expression is increased in IUGR thereby contributing to the molecular mechanisms that underlie the attenuated placental 11β-HSD2. Taken together, our present findings provide evidence suggesting a role for an attenuated placental as well as fetal 11β-HSD2 in the pathogenesis of IUGR.