The Prospective Association of the Diurnal Cortisol Rhythm With Sleep Duration and Perceived Sleeping Problems in Preschoolers: The Generation R Study.

OBJECTIVE: Cortisol, the end product of the hypothalamic-pituitary-adrenal axis, plays an important role in modulating sleep. Yet, studies investigating the association between diurnal cortisol rhythm and sleep patterns in young children are scarce. We tested the hypothesis that the diurnal cortisol rhythm is associated with shorter sleep duration and more sleep problems across early childhood. METHODS: This study was embedded in Generation R, a population-based cohort from fetal life onward. Parents collected saliva samples from their infant at five moments during day 1. In 322 infants aged 12 to 20 months, we determined the diurnal cortisol rhythm by calculating the area under the curve (AUC), the cortisol awakening response (CAR), and the diurnal slope. Sleep duration and sleep behavior were repeatedly assessed across ages of 14 months to 5 years. Generalized estimating equation models were used to assess related cortisol measures to sleep duration and sleep behavior. RESULTS: The diurnal cortisol slope and the CAR, but not the AUC, were associated with sleep duration across childhood. Children with flatter slopes and children with a more positive CAR were more likely to have shorter nighttime sleep duration (ß per nmol/L/h slope = -0.12, 95% confidence interval = -0.19 to -0.05, p = .001; ß per nmol/L CAR = -0.01, 95% confidence interval = -0.02 to 0.00, p = .04). Cortisol measures did not predict sleep problems. CONCLUSIONS: The present study suggests that a flatter diurnal cortisol slope and a more marked morning rise, which can indicate stress (or hypothalamic-pituitary-adrenal dysregulation), have a long-term association with sleep regulation.

The longitudinal association of the diurnal cortisol rhythm with internalizing and externalizing problems in pre-schoolers. The Generation R Study.

BACKGROUND: Studies investigating the association between diurnal cortisol rhythm and behavioural problems in young children have yielded inconsistent results. We tested the hypothesis that variations in diurnal cortisol rhythm in pre-schoolers are already related to problem behaviour early in life with a cross-sectional and longitudinal design. METHODS: This study was embedded in Generation R, a population-based cohort from foetal life onwards. Parents collected saliva samples from their infant at 5 moments during 1 day. In 322 infants aged 12-20 months, we determined the diurnal cortisol rhythm by calculating the area under the curve (AUC), the cortisol awakening response (CAR), and the diurnal slope. Problem behaviour was assessed at ages 1.5 and 3 years with the Child Behavior Checklist/1.5-5 years. RESULTS: No cross-sectional associations between the cortisol composite measures and problem behaviour were found at 1.5 years. However, cortisol predicted change in internalizing problems as assessed from 1.5 to 3 years, but not change in externalizing problems. Children with higher AUC levels, flatter slopes and a more positive CAR at baseline were more likely to score higher on the Internalizing Problems scale (ß per nmol/L AUC: 0.08, 95% CI: 0.00; 0.17, p=0.04; ß per nmol/L/h slope: 0.57, 95% CI: 0.17; 0.98, p=0.006; ß per nmol/L CAR: 0.04, 95% CI: 0.01; 0.08, p=0.02) at follow-up. CONCLUSIONS: Variations in diurnal cortisol rhythm are associated with change in internalizing problems in pre-schoolers. The results suggest that variations in diurnal cortisol patterns early in life precede internalizing problems.

Diurnal cortisol rhythm and cognitive functioning in toddlers: the Generation R Study.

Little is known about the relationship between diurnal cortisol secretion patterns and cognitive function early in life. This population-based study examined whether diurnal cortisol rhythms and cognitive functioning in toddlers are related. Within the Generation R Study, parents of 364 infants (median age: 14.2 months) collected saliva samples at five moments during one day. We assessed the diurnal cortisol rhythm by calculating the area under the curve (AUC), the cortisol awakening response (CAR), and the diurnal slope. Verbal cognitive functioning and fine motor development was determined at age 18 months. Nonverbal cognitive functioning was assessed at age 30 months. A more positive CAR was associated with a lower risk of delay in language comprehension (OR per 1-SD CAR: 0.62, 95%CI: 0.40-0.98, p = .04), a lower risk of nonoptimal fine motor development (OR per 1-SD slope: 0.74, 95%CI: 0.57-0.96, p = .03), and a lower risk of delay in nonverbal cognitive development (OR per 1-SD CAR: 0.58, 95%CI: 0.38-0.90, p = .02). Also, children with flatter slopes had a lower risk of delay in nonverbal cognitive development (OR per 1-SD slope: 0.51, 95%CI: 0.34-0.76, p = .001). Higher AUC levels were associated with a higher risk of delay in language production. These results show that variations in diurnal cortisol rhythms are already associated with variations in cognitive functioning at a young age. Infants with a diurnal cortisol pattern indicative of less stress and more cortisol reactivity, that is, lower AUC levels and a more positive CAR, show a lower risk of delay in cognitive functioning as toddlers.

Cortisol diurnal rhythm and stress reactivity in constipation and abdominal pain: the Generation R Study.

OBJECTIVES: The aim of this study was to assess whether diurnal cortisol rhythm and cortisol stress reactivity were associated with functional constipation and abdominal pain in infancy. PATIENTS AND METHODS: This study was embedded in a subset of the Generation R Study, a prospective cohort study from fetal life onward in Rotterdam, the Netherlands. Data of infants between 14 and 24 months of age (N =483) were used. Salivary cortisol diurnal rhythm and salivary cortisol stress reactivity after a Strange Situation Procedure were assessed at age 14 months. Data on functional constipation were available according to the Rome II criteria, and data on abdominal pain on the basis of the Abdominal Pain Index were available from questionnaire data at 24 months. RESULTS: In the second year of life, 13% of the infants had functional constipation and 17% had abdominal pain. Only 4% had symptoms of both functional constipation and abdominal pain. Diurnal cortisol rhythm did not differ significantly between children with and children without functional constipation and abdominal pain. Cortisol stress reactivity was slightly higher in infants with abdominal pain than in those without it, but this was not statistically significant (odds ratio 1.41; 95% confidence interval 0.46-4.31). No association was found between the cortisol stress reactivity and functional constipation. CONCLUSIONS: Our results suggest that cortisol as a marker for stress does not play a major role in functional constipation or abdominal pain in infancy.

Does disturbed sleeping precede symptoms of anxiety or depression in toddlers? The generation R study.

OBJECTIVE: To examine whether sleep problems in infancy and early toddlerhood precede symptoms of anxiety or depression at 3 years. METHODS: Data on specific sleep problems at 2 months and 24 months were available for 4,782 children participating in a population-based cohort in The Netherlands. The Child Behavior Checklist for toddlers containing the Anxious/Depressed syndrome scale was assessed at 36 months. We adjusted the logistic regression analyses for several confounding factors; the analyses with sleep problems at 24 months were additionally adjusted for preexisting anxiety or depressive symptoms (at 18 months). RESULTS: Dyssomnia and parental presence during sleep onset at 2 months and 24 months were associated with anxiety or depressive symptoms at 3 years (e.g., parental presence: odds ratio(2 months), 1.22; 95% confidence interval, 1.04-1.44; odds ratio(24 months), 1.58; 95% confidence interval, 1.30-1.92). Parasomnia, short sleep duration, and absence of set bedtime at 24 months, but not at 2 months, also preceded anxiety or depressive symptoms. These significant associations were not due to children's anxiety or depressive symptoms at 18 months. Rhythmicity and co-sleeping were not associated with later anxiety or depressive symptoms. Additional analyses provided little evidence for a bidirectional association with anxiety or depressive symptoms preceding later sleep problems. CONCLUSIONS: Our findings highlight the importance of sleep problems early in life, because different sleep problems are associated with the frequency of anxiety or depressive symptoms. Therefore, healthcare practitioners must be particularly attentive to these problems in young children. Future research should address possible mechanisms underlying the association between disturbed sleeping and anxiety or depressive symptoms.

Do social disadvantage and early family adversity affect the diurnal cortisol rhythm in infants? The Generation R Study.

Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic-pituitary-adrenal (HPA) axis early in life. In 366 infants aged 12-20 months from the Generation R Study, a population-based cohort from fetal life onwards, parents collected saliva samples from their infant at 5 moments over the course of 1 day. The area under the curve (AUC), the cortisol awakening response (CAR) and the diurnal cortisol slope were calculated as different composite measures of the diurnal cortisol rhythm. Information about social disadvantage and early adversity was collected using prenatal and postnatal questionnaires. We found that older infants showed lower AUC levels; moreover, infants with a positive CAR were significantly older. Both the AUC and the CAR were related to indicators of social disadvantage and early adversity. Infants of low income families, in comparison to high income families, showed higher AUC levels and a positive CAR. Infants of mothers who smoked during pregnancy were also significantly more likely to show a positive CAR. Furthermore, infants of mothers experiencing parenting stress showed higher AUC levels. The results of our study show that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in infants. This may reflect the influence of early negative life events on early maturation of the HPA axis.