IMPORTANCE: Maternal antenatal corticosteroid treatment is standard care to accelerate fetal maturation when birth before 34 weeks is imminent. Recently, expansion of the indications beyond 34 ...gestational weeks has been debated. However, data about long-term outcomes remain limited, especially among infants who after treatment exposure are born at term. OBJECTIVE: To study if antenatal corticosteroid treatment is associated with mental and behavioral disorders in children born at term (≥37 weeks 0 days’ gestation) and preterm (<37 weeks 0 days’ gestation) and if unmeasured familial confounding explains these associations. DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort study using nationwide registries of all singleton live births in Finland surviving until 1 year and a within-sibpair comparison among term siblings. Children were born between January 1, 2006, and December 31, 2017, and followed up until December 31, 2017. EXPOSURES: Maternal antenatal corticosteroid treatment. MAIN OUTCOMES AND MEASURES: Primary outcome was any childhood mental and behavioral disorder diagnosed in public specialized medical care settings. RESULTS: Of the 674 877 singleton children born in Finland during the study period, 670 097 were eligible for analysis. The median length of follow-up was 5.8 (interquartile-range, 3.1-8.7) years. Of the 14 868 (2.22%; 46.1% female) corticosteroid treatment–exposed children, 6730 (45.27%) were born at term and 8138 (54.74%) were born preterm; of the 655 229 (97.78%; 48.9% female) nonexposed children, 634 757 (96.88%) were born at term and 20 472 (3.12%) were born preterm. Among the 241 621 eligible term-born maternal sibpairs nested within this population, 4128 (1.71%) pairs were discordant for treatment exposure. Treatment exposure, compared with nonexposure, was significantly associated with higher risk of any mental and behavioral disorder in the entire cohort of children (12.01% vs 6.45%; absolute difference, 5.56% 95% CI, 5.04%-6.19%; adjusted hazard ratio HR, 1.33 95% CI, 1.26-1.41), in term-born children (8.89% vs 6.31%; absolute difference, 2.58% 95% CI, 1.92%-3.29%; HR, 1.47 95% CI, 1.36-1.69), and when sibpairs discordant for treatment exposure were compared with sibpairs concordant for nonexposure (6.56% vs 4.17% for within-sibpair differences; absolute difference, 2.40% 95% CI, 1.67%-3.21%; HR, 1.38 95% CI, 1.21-1.58). In preterm-born children, the cumulative incidence rate of any mental and behavioral disorder was also significantly higher for the treatment-exposed compared with the nonexposed children, but the HR was not significant (14.59% vs 10.71%; absolute difference, 3.38% 95% CI, 2.95%-4.87%; HR, 1.00 95% CI, 0.92-1.09). CONCLUSIONS AND RELEVANCE: In this population-based cohort study, exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children. These findings may help inform decisions about maternal antenatal corticosteroid treatment.
: During the past decade, a considerable body of evidence has emerged showing that circumstances during the fetal period may have lifelong programming effects on different body functions with a ...considerable impact on disease susceptibility
. The purpose of this article is to provide a synopsis of these findings and their role in explaining the development of stress‐related adult disease. In the context of Per Björntorp memorial symposium, stress‐related disease will be interpreted broadly, including cardiovascular disease and components of the metabolic syndrome, for which the evidence of fetal origins is most abundant. It has however become evident that early‐life programming has a much broader potential effect on an individual's health. For example, perinatal variables, such as low birth weight, have been associated with increased prevalence of depressive symptoms. Mechanistic studies in animals and humans have shown that lifelong programming of the hypothalamic‐pituitary‐adrenal axis (HPAA) function by fetal life conditions is likely to be a key factor in mediating associations with these disorders, which frequently are characterized by HPAA overactivity. Preliminary observations suggest a similar important role for early‐life programming of sympathoadrenal function. Reduced HPAA activity is characteristic of a number of stress‐related disorders, including posttraumatic stress disorder; chronic pain; fatigue; and atypical, melancholic depression. It is therefore highly plausible that susceptibility to these disorders originates in a similar manner during early life, although direct evidence is to a great deal lacking. Important targets for future research include distinction between the effects of different pregnancy conditions, such as maternal malnutrition, preeclampsia, and maternal infection, which may have dissimilar late‐life consequences. This will be a crucial step when the associations that are currently emerging will be translated into disease prevention.
Women with psychiatric diagnoses are at increased risk of preterm birth (PTB), with potential life-long impact on offspring health. Less is known about the risk of PTB in offspring of fathers with ...psychiatric diagnoses, and for couples where both parents were diagnosed. In a nationwide birth cohort, we examined the association between psychiatric history in fathers, mothers, and both parents and gestational age.
We included all infants live-born to Nordic parents in 1997 to 2016 in Sweden. Psychiatric diagnoses were obtained from the National Patient Register. Data on gestational age were retrieved from the Medical Birth Register. Associations between parental psychiatric history and PTB were quantified by relative risk (RR) and two-sided 95% confidence intervals (CIs) from log-binomial regressions, by psychiatric disorders overall and by diagnostic categories. We extended the analysis beyond PTB by calculating risks over the whole distribution of gestational age, including "early term" (37 to 38 weeks). Among the 1,488,920 infants born throughout the study period, 1,268,507 were born to parents without a psychiatric diagnosis, of whom 73,094 (5.8%) were born preterm. 4,597 of 73,500 (6.3%) infants were born preterm to fathers with a psychiatric diagnosis, 8,917 of 122,611 (7.3%) infants were born preterm to mothers with a pscyhiatric diagnosis, and 2,026 of 24,302 (8.3%) infants were born preterm to both parents with a pscyhiatric diagnosis. We observed a shift towards earlier gestational age in offspring of parents with psychiatric history. The risks of PTB associated with paternal and maternal psychiatric diagnoses were similar for different psychiatric disorders. The risks for PTB were estimated at RR 1.12 (95% CI 1.08, 1.15 p < 0.001) for paternal diagnoses, at RR 1.31 (95% CI 1.28, 1.34 p < 0.001) for maternal diagnoses, and at RR 1.52 (95% CI 1.46, 1.59 p < 0.001) when both parents were diagnosed with any psychiatric disorder, compared to when neither parent had a psychiatric diagnosis. Stress-related disorders were associated with the highest risks of PTB with corresponding RRs estimated at 1.23 (95% CI 1.16, 1.31 p < 0.001) for a psychiatry history in fathers, at 1.47 (95% CI 1.42, 1.53 p < 0.001) for mothers, and at 1.90 (95% CI 1.64, 2.20 p < 0.001) for both parents. The risks for early term were similar to PTB. Co-occurring diagnoses from different diagnostic categories increased risk; for fathers: RR 1.10 (95% CI 1.07, 1.13 p < 0.001), 1.15 (95% CI 1.09, 1.21 p < 0.001), and 1.33 (95% CI 1.23, 1.43 p < 0.001), for diagnoses in 1, 2, and ≥3 categories; for mothers: RR 1.25 (95% CI 1.22, 1.28 p < 0.001), 1.39 (95% CI 1.34, 1.44 p < 0.001) and 1.65 (95% CI 1.56, 1.74 p < 0.001). Despite the large sample size, statistical precision was limited in subgroups, mainly where both parents had specific psychiatric subtypes. Pathophysiology and genetics underlying different psychiatric diagnoses can be heterogeneous.
Paternal and maternal psychiatric history were associated with a shift to earlier gestational age and increased risk of births before full term. The risk consistently increased when fathers had a positive history of different psychiatric disorders, increased further when mothers were diagnosed and was highest when both parents were diagnosed.
According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, several noncommunicable diseases, including hypertension, type 2 diabetes, and coronary heart disease, have their ...origins in early life. Chronic kidney disease (CKD) has traditionally been assumed to develop as the result of an interaction between genetic and environmental factors, although more recently, the importance of factors present early in life has been recognized.
Longitudinal birth cohort study.
20,431 people born in 1924 to 1944 in Helsinki, Finland, who were part of the Helsinki Birth Cohort Study were followed up through their life course from birth until death or age 86 years.
Prenatal growth and socioeconomic factors.
Death or hospitalization for CKD.
Smaller body size at birth was associated with increased risk for developing CKD. Each standard deviation higher birth weight was associated with an HR for CKD of 0.82 (95% CI, 0.74-0.91; P<0.001). Associations with ponderal index at birth, placental weight, and birth length were also statistically significant (P<0.001, P<0.001, and P=0.002, respectively), but only among men. Prematurity also predicted increased risk for CKD.
The study was restricted to people who were born in Helsinki in 1924 to 1944.
Smaller body size at birth was associated with increased risk for developing CKD in men. Prematurity was also associated with increased risk for CKD in women. These findings in the Helsinki Birth Cohort Study support the importance of early life factors in the development of CKD.
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Background Women with hypertensive disorders in pregnancy are at an increased risk of cardiovascular disease and type 2 diabetes later in life. Offspring born from these hypertensive pregnancies have ...increased levels of cardiovascular risk factors; whether they are at an increased risk of type 2 diabetes is not known. Objective The objective of the investigation was to study the risk of type 2 diabetes in the adult offspring exposed to maternal preeclampsia or gestational hypertension in utero. Study Design We studied 5335 members of the Helsinki Birth Cohort Study, who were born between 1934 and 1944 and who lived in Finland in 1995 when the National Medication Purchase Register was initiated. We ascertained gestational hypertension and preeclampsia according to modern criteria by using maternal and birth records. We defined type 2 diabetes through purchases of antidiabetic medication recorded in the comprehensive National Medication Purchase Register, excluding the 31 subjects who had purchased only insulin. We used Cox regression to assess hazard ratios for type 2 diabetes. Results A total of 590 men (21.6%) and 433 women (16.9%) had purchased medication for diabetes. The hazard ratio for type 2 diabetes for offspring exposed to any maternal hypertension in pregnancy was 1.13 (95% confidence interval, 1.00–1.29; n = 1780). For maternal gestational hypertension, it was 1.15 (95% confidence interval, 1.00–1.33; n = 1336) and for preeclampsia 0.98 (95% confidence interval, 0.71–1.34; n = 231). For type 2 diabetes with first medication purchase before 62 years, the corresponding hazard ratios were 1.25 (95% confidence interval, 1.04–1.51); 1.28 (95% confidence interval, 1.05–1.58), and 1.18 (95% confidence interval, 0.75–1.84). The hazard ratios were similar when adjusted for birthweight SD score for gestation, length of gestation, maternal body mass index in late pregnancy, height, age, and parity and for childhood or adult socioeconomic position. An increased risk of type 2 diabetes was also associated with low birthweight SD score, independent of the association with gestational hypertension. Conclusion Offspring exposed to maternal gestational hypertension in utero have an increased risk of type 2 diabetes in late adult life. This finding underlines the role of the whole spectrum of hypertensive disorders of pregnancy as risk factors of offspring disease throughout life. It also reinforces previous suggestions that adult health care providers should incorporate birth histories when evaluating an individual’s risk to develop type 2 diabetes.
Whether one is male or female is one of the most important determinants of human health. While males are more susceptible to cardiovascular and infectious disease, they are outnumbered by women for ...many autoimmune disorders, fibromyalgia and chronic pain. Recently, individual differences in the physiological response to stress have emerged as a potentially important risk factor for these disorders. This raises the possibility that sex differences in prevalence of disease could at least in part be explained by sex differences in the nature of the physiological response to stress.
In a psychophysiological laboratory, the autonomic nervous system response can be provoked by many different stressors including physical, mental and psychosocial tasks, while the hypothalamic–pituitary–adrenal axis (HPAA) response seems to be more specific to a psychosocial challenge incorporating ego involvement. The responses of both systems to different psychosocial challenges have been subject to extensive research, although in respect of sex differences the HPAA response has probably been more systematically studied. In this review, we focus on sex differences in HPAA and autonomic nervous system responses to acute psychosocial stress. Although some differences are dependent on the stressor used, the responses of both systems show marked and consistent differences according to sex, with the phase of the menstrual cycle, menopausal status and pregnancy having marked effects. Between puberty and menopause, adult women usually show lower HPAA and autonomic responses than men of same age. However, the HPAA response is higher in the luteal phase, when for example poststress free cortisol levels approach those of men. After menopause, there is an increase in sympathoadrenal responsiveness, which is attenuated during oral hormone replacement therapy, with most evidence suggesting that HPAA activity shows the same trends. Interestingly, pregnancy is associated with an attenuated response of the sympathoadrenal and HPAA systems at least as assessed by biochemical stimulation.
It is likely that these sex differences in autonomic function are a result of estrogen exposure which attenuates sympathoadrenal responsiveness. The HPAA is however somewhat more complex and evidence now suggests the influence of other modifiers such as arginine vasopressin (AVP) and the regulation of circulating cortisol bioavailability by corticosteroid-binding globulin (CBG).
The pronounced and multi-faceted sex differences in stress responsiveness suggest that they are a product of a strong evolutionary pressure. We hypothesise that this has to a great deal been driven by the need to protect the fetus from the adverse effects of maternal stress responses, in particular excess glucocorticoid exposure. Studying this hypothesis may have a fundamental impact on our understanding about how adult health is set during early life and how adult disease could be prevented in men and women.
Gestational diabetes (GDM) is often accompanied by maternal overweight. Our aim was to evaluate the separate and concomitant effects of GDM and maternal overweight/obesity on perinatal outcomes.
We ...used the Finnish Medical Birth Register to identify all 24,577 women with a singleton pregnancy who delivered in 2009 in Finland and underwent an oral glucose tolerance test (OGTT). Women were divided into groups according to the result of OGTT (GDM/no GDM) and pre-pregnancy body mass index (BMI): normal weight (≤24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). Primary outcomes included macrosomia, caesarean delivery, and treatment at neonatal ward. Normal weight women without GDM constituted the reference group.
Compared to reference group, overweight or obese women without GDM had an increased risk of macrosomia odds ratio adjusted for age, parity, smoking and socio-economic status (aOR)1.18 (95% CI 1.09-1.28) and 1.50 (95% CI 1.19-1.88), and caesarean delivery aORs 1.17 (95% CI 1.07-1.28) and 1.52 (95% CI 1.37-1.69), respectively. In normal weight GDM women the risk of macrosomia aOR 1.17 (95% CI 0.85-1.62) and caesarean delivery aOR 1.10 (95% CI 0.96-1.27) was not significantly increased as compared to normal weight women without GDM. GDM increased the risk of treatment at neonatal ward in all BMI categories and maternal obesity without GDM was also a risk factor for treatment at neonatal ward. Interaction p values between BMI and GDM on these outcomes were <0.001.
Maternal overweight and obesity without GDM increased the risk of macrosomia and caesarean delivery when compared to the reference group. These risks were amplified when overweight/obesity was accompanied by GDM. Obesity without GDM was a risk factor for treatment at neonatal ward; GDM increased this risk in all BMI categories. Our results suggest that especially maternal obesity should be considered as a risk factor for adverse pregnancy outcomes and GDM further amplifies this risk.
...with advances in neonatal care, the survival for very preterm babies has improved, but longer-term risks in this group have not been comprehensively investigated. ASD has a male predominance, and ...size at birth is known to influence ASD risk, with increased risks in children born either small or large for GA 27–29. ...sex and size for GA should be considered in analyses of ASD risk by GA. To adjust for differences in birth weight, sex-specific size for GA was calculated as “small for GA” (below or equal to the 10th percentile), “appropriate for GA” (between the 11th and 90th percentile), and “large for GA” (above the 90th percentile) 36. Cohort characteristics by gestational age (weeks) in 3,526,174 live births. https://doi.org/10.1371/journal.pmed.1003207.t001 Risk of ASD The risk of ASD by GA showed a gradual increase in risk of ASD from GA week 40 to GA week 24, and a small rise between GA week 40 and 44, with statistically significantly higher risk across the range of GA compared to the reference group of infants born week 40.
Preterm birth with very low birth weight (VLBW, birth weight < 1500 g) is associated with health problems later in life. How VLBW individuals perceive their physical and mental health-related quality ...of life (HRQoL) is important to understand their putative burden of disease. Previous studies have shown mixed results, and longitudinal studies into adulthood have been requested. This study aimed to investigate differences in HRQoL between preterm VLBW and term born individuals at 32 years of age, and to study changes in HRQoL from 20 to 32 years.
In a geographically based longitudinal study, 45 VLBW and 68 term born control participants completed the Short Form 36 Health Survey (SF-36) at 32 years of age. Data from three previous timepoints was also available (20, 23 and 28 years of age). The SF-36 yields eight domain scores as well as a physical and a mental component summary. Between-group differences in these variables were investigated. We also performed subgroup analyses excluding individuals with disabilities, i.e., cerebral palsy and/or low estimated intelligence quotient.
At 32 years of age, the physical component summary was 5.1 points lower (95% confidence interval (CI): 8.6 to 1.6), and the mental component summary 4.1 points lower (95% CI: 8.4 to - 0.3) in the VLBW group compared with the control group. For both physical and mental component summaries there was an overall decline in HRQoL from 20 to 32 years of age in the VLBW group. When we excluded individuals with disabilities (n = 10), group differences in domain scores at 32 years were reduced, but physical functioning, bodily pain, general health, and role-emotional scores remained lower in the VLBW subgroup without disabilities compared with the control group.
We found that VLBW individuals reported lower HRQoL than term born controls at 32 years of age, and that HRQoL declined in the VLBW group from 20 to 32 years of age. This was in part, but not exclusively explained by VLBW individuals with disabilities.
Boys live dangerously in the womb Eriksson, Johan G.; Kajantie, Eero; Osmond, Clive ...
American journal of human biology,
May/June 2010, Letnik:
22, Številka:
3
Journal Article
PDF
