Maternal early pregnancy obesity and related pregnancy and pre-pregnancy disorders: associations with child developmental milestones in the prospective PREDO Study.

BACKGROUND/OBJECTIVES: Previous studies have linked maternal pre-pregnancy obesity (BMI ≥30 kg/m2) with suboptimal neurodevelopment in her offspring; however, the literature is not entirely consistent. Whether these effects are muddled by maternal self-reports of pre-pregnancy weight and height, or are driven or amplified by the well often comorbid hypertensive and diabetic pregnancy and pre-pregnancy disorders, remains unclear. We examined whether maternal early pregnancy obesity is associated with developmental delay in her offspring, and if the associations are driven or amplified by diabetic and hypertensive pregnancy and pre-pregnancy disorders. SUBJECTS/METHODS: A total of 2504 mother-child dyads participated in the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study. Data on maternal early pregnancy obesity, pre-pregnancy, and gestational hypertension, pre-eclampsia, type 1 and gestational diabetes were derived from the Finnish Medical Birth Register. At the child's mean age of 42.1 (SD = 8.2) months the mothers completed the Ages and Stages Questionnaire (ASQ) Third edition for developmental milestones. RESULTS: Children of obese mothers had 1.81-2.74 (p-values <0.02) higher odds of failing to meet the development that is typical for a child's age (developmental domain score ≤-2SD below the child's age) on the communication, fine and gross motor, problem solving and personal/social skills and children of overweight mothers had 2.14 (p = 0.002) higher odds of failing to meet the development that is typical for the child's age on communication skills. Odds of developmental delay were also higher for children of mothers with pre-eclampsia and gestational diabetes. The associations were robust to covariates and confounders, the effects of overweight/obesity and pre-eclampsia were not driven by the other disorders, and overweight/obesity and hypertensive and diabetic disorders did not show additive effects. CONCLUSIONS: Maternal early pregnancy overweight, obesity, and pre-eclampsia are independently associated with neurodevelopmental delay in her offspring. Further studies unraveling the underlying mechanisms are warranted.

Effects of vigorous late-night exercise on sleep quality and cardiac autonomic activity.

Sleep is the most important period for recovery from daily load. Regular physical activity enhances overall sleep quality, but the effects of acute exercise on sleep are not well defined. In sleep hygiene recommendations, intensive exercising is not suggested within the last 3 h before bed time, but this recommendation has not been adequately tested experimentally. Therefore, the effects of vigorous late-night exercise on sleep were examined by measuring polysomnographic, actigraphic and subjective sleep quality, as well as cardiac autonomic activity. Eleven (seven men, four women) physically fit young adults (VO(2max) 54±8 mL·kg(-1)·min(-1) , age 26±3 years) were monitored in a sleep laboratory twice in a counterbalanced order: (1) after vigorous late-night exercise; and (2) after a control day without exercise. The incremental cycle ergometer exercise until voluntary exhaustion started at 21:00±00:28 hours, lasted for 35±3 min, and ended 2:13±00:19 hours before bed time. The proportion of non-rapid eye movement sleep was greater after the exercise day than the control day (P<0.01), while no differences were seen in actigraphic or subjective sleep quality. During the whole sleep, no differences were found in heart rate (HR) variability, whereas HR was higher after the exercise day than the control day (54±7 versus 51±7, P<0.01), and especially during the first three sleeping hours. The results indicate that vigorous late-night exercise does not disturb sleep quality. However, it may have effects on cardiac autonomic control of heart during the first sleeping hours.

The Impact of Early Life Stress on Anxiety Symptoms in Late Adulthood.

Early life stress (ELS) may increase the risk of anxiety throughout the life course. Whether this effect extends to late adulthood is poorly known. In our study comprising 1872 participants from the Helsinki Birth Cohort Study born in 1934-1944, we investigated the association of various forms of ELS and their accumulation with self-reported anxiety symptoms at the age of 65-77 years. Data on childhood socioeconomic status and separation from parents were based on national registers for all participants. Information on self-reported emotional and physical trauma, parental divorce, and death of a family member in childhood was obtained from 1277 participants. We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood [B = 0.44 (95% CI = 0.31-0.58); B = 0.33 (95% CI = 0.20-0.46); B = 0.10 (95% CI = 0.01-0.19), respectively]. These associations remained significant even after controlling for other forms of ELS. Accumulation of early life stress also increased the levels of late-adulthood anxiety symptoms and the risk of anxiety regarded as clinically significant. Screening for potentially stressful childhood experiences in elderly populations may help identifying individuals with increased anxiety symptoms and planning preventive and therapeutic interventions for those exposed to ELS.

Maternal Depressive Symptoms During and After Pregnancy and Psychiatric Problems in Children.

OBJECTIVE: Maternal depressive symptoms during pregnancy are associated with increased risk of psychiatric problems in children. A more precise understanding of the timing of the symptoms during pregnancy and their independence of other prenatal and postnatal factors in predicting child psychopathology risk is needed. We examined whether maternal depressive symptoms during pregnancy predict child psychiatric problems, whether these associations are trimester- or gestational-week-specific and/or independent of pregnancy disorders, and whether maternal depressive symptoms after pregnancy mediate or add to the prenatal effects. METHOD: The study sample comprised 2,296 women and their children born in Finland between 2006-2010, participating in the prospective pregnancy cohort study Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) and followed up from 1.9 to 5.9 years of age. The women completed the Center for Epidemiologic Studies Depression Scale biweekly between gestational weeks+days 12+0/13+6 and 38+0/39+6 or delivery. In the follow-up, they completed the Beck Depression Inventory-II and Child Behavior Checklist 1½-5. RESULTS: Maternal depressive symptoms during pregnancy predicted significantly higher internalizing (0.28 SD unit per SD unit increase [95% CI = 0.24-0.32]), externalizing (0.26 [0.23-0.30]), and total problems (0.31 [0.27-0.35]) in children. These associations were nonspecific to gestational week and hence pregnancy trimester, independent of pregnancy disorders, and independent of, although partially mediated by, maternal depressive symptoms after pregnancy. Psychiatric problems were greatest in children whose mothers reported clinically significant depressive symptoms across pregnancy trimesters and during and after pregnancy. CONCLUSION: Maternal depressive symptoms during pregnancy predict increased psychiatric problems in young children. Preventive interventions from early pregnancy onward may benefit offspring mental health.

Maternal depressive symptoms during and after pregnancy are associated with attention-deficit/hyperactivity disorder symptoms in their 3- to 6-year-old children.

Maternal depressive symptoms during pregnancy have been associated with child behavioural symptoms of attention-deficit/hyperactivity disorder (ADHD) in early childhood. However, it remains unclear if depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain times, and if maternal depressive symptoms after pregnancy add to or mediate any prenatal effects. 1,779 mother-child dyads participated in the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study. Mothers filled in the Center of Epidemiological Studies Depression Scale biweekly from 12+0-13+6 to 38+0-39+6 weeks+days of gestation or delivery, and the Beck Depression Inventory-II and the Conners' Hyperactivity Index at the child's age of 3 to 6 years (mean 3.8 years, standard deviation [SD] 0.5). Maternal depressive symptoms were highly stable throughout pregnancy, and children of mothers with consistently high depressive symptoms showed higher average levels (mean difference = 0.46 SD units, 95% Confidence Interval [CI] 0.36, 0.56, p < 0.001 compared to the low group), and proportion (32.1% vs. 14.7%) and odds (odds ratio = 2.80, 95% CI 2.20, 3.57, p < 0.001) of clinically significant ADHD symptoms. These associations were not explained by the effects of maternal depressive symptoms after pregnancy, which both added to and partially mediated the prenatal effects. Maternal depressive symptoms throughout pregnancy are associated with increased ADHD symptomatology in young children. Maternal depressive symptoms after pregnancy add to, but only partially mediate, the prenatal effects. Preventive interventions suited for the pregnancy period may benefit both maternal and offspring mental health.

Telomere length and hypothalamic-pituitary-adrenal axis response to stress in elderly adults.

OBJECTIVE: Telomere shortening, a biomarker of cellular aging, has been associated with aging-related diseases. While psychological stress has been implicated in the process of telomere shortening, associations with activity of physiological stress systems have remained elusive. We studied whether leukocyte telomere length (LTL) is associated with hypothalamic-pituitary-adrenal (HPA) axis responses to psychosocial stress in elderly adults. METHODS: LTL, measured by qPCR method was available in 1964 women and men from the Helsinki Birth Cohort Study at a mean age of 61.5 (SD=2.9) years. At a mean age of 63.5 (SD=2.7) years a subsample of them took part in the Trier Social Stress Test (TSST) during which salivary cortisol (n=283) and plasma cortisol and ACTH concentrations (n=215) were measured. RESULTS: Mixed model regression analyses showed no linear or non-linear associations between LTL and HPA axis activity during TSST (p-values for LTL main effects >298; p-values for LTL×time interactions >096). Only one non-linear association between LTL and plasma ACTH area under the curve increment was significant after adjustments for covariates and confounders. This association did not survive correction for multiple testing. CONCLUSIONS: Our findings suggest that LTL is not consistently associated with HPA axis activity during a standardized psychosocial stress test in elderly adults.

Associations between the five-factor model of personality and leukocyte telomere length in elderly men and women: The Helsinki Birth Cohort Study (HBCS).

OBJECTIVE: Personality traits have been associated with cardiometabolic diseases and mental disorders as well as with longevity. However, the underlying mechanisms are not fully understood. Accelerated cellular aging may play a role in this process. We studied whether personality traits in late adulthood, as defined in the five-factor model (FFM), were associated with a biomarker of cellular vitality, leukocyte telomere length (LTL). METHODS: At a mean age of 63.4 (SD=2.8) years, 1671 (742 men, 929 women) participants from the Helsinki Birth Cohort Study filled in the Neuroticism, Extraversion and Openness Personality Inventory (NEO-PI). LTL was measured at a mean age of 61.5 (SD=2.9) years by using a real-time quantitative PCR method. RESULTS: None of the FFM personality dimensions were significantly associated with the LTL in the analyses of both sexes combined. We however found interaction between sex and agreeableness (B=0.020, 95% CI=.008, 0.032, p=.001) and in the sex-specific analyses, men who scored higher on agreeableness (B=-0.086, 95% CI=-0.155, -0.016, p=.016) and women who scored lower on agreeableness (B=0.074, 95% CI=0.014, 0.134, p=.016) had shorter LTL. CONCLUSIONS: FFM dimensions of personality were not associated with LTL in a sample of elderly individuals. The counterintuitive and sporadic sex specific finding on agreeableness requires replication. Overall our findings suggest that LTL, a biomarker of cellular aging, may not offer insight into the associations between personality, longevity and health.

The history of sleep apnea is associated with shorter leukocyte telomere length: the Helsinki Birth Cohort Study.

OBJECTIVES: Sleep apnea poses an elevated risk for chronic age-related diseases. Leukocyte telomere length (LTL), a biomarker and factor associated with accelerated cellular aging processes, may serve as a novel mechanism underlying these disease risks. We investigated if a history of clinician-diagnosed sleep apnea or primary snoring was associated with LTL in later adulthood. METHODS: Data on sleep apnea, primary snoring and LTL, were available for 1948 participants from the Helsinki Birth Cohort Study. Patients with sleep apnea (n=44) and primary snoring (n=29) severe enough to be recorded as an inpatient diagnosis for hospitalization were identified by their case records through the Finnish Hospital Discharge Register. The LTL was measured by using the realtime quantitative polymerase chain reaction (PCR) method at a mean age of 61.5 years (standard deviation [SD], 2.9). RESULTS: A history of sleep apnea was associated with shorter LTL (P=.010). Adjustment for a number of covariates did not alter the association. CONCLUSIONS: Accelerated cellular aging reflected in shorter LTL in patients with a history of sleep apnea may partly explain their higher risk for age-related diseases. Future studies elucidating the impacts of long-term or successful treatment history of sleep apnea on the maintenance of LTL are warranted.

Associations between early life stress, self-reported traumatic experiences across the lifespan and leukocyte telomere length in elderly adults.

Early life stress (ELS) poses a risk for mental disorders and aging-related diseases. Accelerated biological aging, reflected in shorter leukocyte telomere length (LTL), may underlie these risks. We examined whether objectively recorded ELS and retrospectively self-reported traumatic experiences across the lifespan are associated with LTL in later adulthood. Of 1486 participants, 215 had been exposed to ELS, namely to temporary separation from both parents in childhood. Participants self-reported emotionally or physically traumatic experiences across the lifespan at a mean age of 63.2 years. LTL was measured using a quantitative PCR method at a mean age of 61.5 years. Separation or self-reported traumatic experiences were not associated with LTL. However, separated participants who self-reported traumatic experiences had shorter LTL. Our results suggest that while ELS or self-reported traumatic experiences are not per se associated with LTL measured decades later, ELS may in combination with self-reported traumatic events be associated with accelerated biological aging.

History of mental disorders and leukocyte telomere length in late adulthood: the Helsinki Birth Cohort Study (HBCS).

Shorter leukocyte telomere length (LTL) has been linked with mental disorders and with other manifestations of chronic non-communicable diseases. Mental disorders are associated with increased morbidity and premature mortality. It remains unclear if shorter LTL characterizes patients who have been diagnosed with mental disorders in the past, and who have survived till late adulthood. 1051 women and 905 men of the Helsinki Birth Cohort Study participated in this study. LTL was measured by using the real-time quantitative PCR method for subjects and patients at the mean age of 61.5 years. Patients with a mental disorder severe enough to warrant hospitalization (n = 116) were identified by their case records in the Finnish Hospital Discharge Register and the use of psychotropic medication by reimbursement entitlements or prescription fills (n = 665) data in the Finnish Social Insurance Register. Participants hospitalized for any mental or substance use disorders had longer LTL than non-hospitalized controls (p-values < 0.042). Moreover, only those any mental disorder patients who had psychotropic medication use had longer LTL than non-hospitalized controls (p = 0.02). Adjustment for a number of covariates did not attenuate the association. Our findings suggest that shorter LTL may not be an intrinsic feature of mental disorders. Future research is needed to elucidate if psychotropic medication is involved in leukocyte telomere length maintenance in subjects with mental disorders.