Booster vaccination with SARS-CoV-2 mRNA vaccines and myocarditis in adolescents and young adults: a Nordic cohort study.

BACKGROUND AND AIMS: The SARS-CoV-2 mRNA vaccines are associated with an increased risk of myocarditis. This association appears to be strongest in male adolescents and younger males and after the second dose. The aim was to evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds. METHODS: A multinational cohort study was conducted using nationwide register data in Denmark, Finland, Norway, and Sweden and comprising all 8.9 million individuals residing in each of the four countries. Participants were followed for an inpatient diagnosis of myocarditis. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis comparing vaccination schedules, with associated 95% confidence intervals (CIs). Country-specific results were combined in meta-analyses. RESULTS: A total of 8.9 million residents were followed for 12 271 861 person-years and 1533 cases of myocarditis were identified. In 12-to-39-year-old males, the 28-day acute risk period following the third dose of BNT162b2 or mRNA-1273 was associated with an increased incidence rate of myocarditis compared to the post-acute risk period 28 days or more after the second dose [IRR 2.08 (95% CI 1.31-3.33) and 8.89 (2.26-35.03), respectively]. For females, the corresponding IRR was only estimable for BNT162b2, 3.99 (0.41-38.64). The corresponding absolute risks following the third dose of BNT162b2 and mRNA-1273 in males were 0.86 (95% CI 0.53-1.32) and 1.95 (0.53-4.99) myocarditis events within 28 days per 100 000 individuals vaccinated, respectively. In females, the corresponding absolute risks following the third dose of BNT162b2 were 0.15 (0.04-0.39) events per 100 000 individuals vaccinated. No deaths occurred within 30 days of vaccine-related cases. CONCLUSIONS: The results suggest that a booster dose is associated with increased myocarditis risk in adolescents and young adults. However, the absolute risk of myocarditis following booster vaccination is low.

Cardiometabolic health in adults born with very low birth weight-a sibling study.

BACKGROUND: Preterm survivors have increased risk for impaired cardiometabolic health. We assessed glucose regulation and cardiometabolic biomarkers in adult very low birth weight (VLBW, <1500 g) survivors, using siblings as controls. METHODS: VLBW-participants were matched with term-born, same-sex siblings. At mean age 29.2 years (SD 3.9), 74 VLBW-adults and 70 siblings underwent a 2-h 75 g oral glucose tolerance test and blood tests for assessment of cardiometabolic biomarkers. RESULTS: Of participants, 23 (31%) VLBW and 11 (16%) sibling-controls met World Health Organization criteria for impaired glucose regulation (OR adjusted for age and sex 2.5, 95% CI: 1.1 to 5.8). Adjusting for age and sex, VLBW-participants showed 9.2% higher 2-h glucose (95% CI: 0.4% to 18.8%) than their siblings. Also, fasting (13.4%, -0.3% to 29.0%) and 2-h free fatty acids (15.6%, -2.4% to 36.9%) were higher in VLBW-participants. These differences were statistically significant only after further adjusting for confounders. No statistically significant differences were found regarding other measured biomarkers, including insulin resistance, atherogenic lipid profiles or liver tests. CONCLUSIONS: VLBW-adults showed more impaired fatty acid metabolism and glucose regulation. Differences in cardiometabolic biomarkers were smaller than in previous non-sibling studies. This may partly be explained by shared familial, genetic, or environmental factors. IMPACT: At young adult age, odds for impaired glucose regulation were 3.4-fold in those born at very low birth weight, compared to same-sex term-born siblings. Taking into consideration possible unmeasured, shared familial confounders, we compared cardiometabolic markers in adults born preterm at very low birth weight with term-born siblings. Prematurity increased risk for impaired glucose regulation, unrelated to current participant characteristics, including body mass index. In contrast to previous studies, differences in insulin resistance were not apparent, suggesting that insulin resistance may partially be explained by factors shared between siblings. Also, common cardiometabolic biomarkers were similar within sibling pairs.

Epigenetic signature of very low birth weight in young adult life.

BACKGROUND: Globally, one in ten babies is born preterm (<37 weeks), and 1-2% preterm at very low birth weight (VLBW, <1500 g). As adults, they are at increased risk for a plethora of health conditions, e.g., cardiometabolic disease, which may partly be mediated by epigenetic regulation. We compared blood DNA methylation between young adults born at VLBW and controls. METHODS: 157 subjects born at VLBW and 161 controls born at term, from the Helsinki Study of Very Low Birth Weight Adults, were assessed for peripheral venous blood DNA methylation levels at mean age of 22 years. Significant CpG-sites (5'-C-phosphate-G-3') were meta-analyzed against continuous birth weight in four independent cohorts (pooled n = 2235) with cohort mean ages varying from 0 to 31 years. RESULTS: In the discovery cohort, 66 CpG-sites were differentially methylated between VLBW adults and controls. Top hits were located in HIF3A, EBF4, and an intergenic region nearest to GLI2 (distance 57,533 bp). Five CpG-sites, all in proximity to GLI2, were hypermethylated in VLBW and associated with lower birth weight in the meta-analysis. CONCLUSION: We identified differentially methylated CpG-sites suggesting an epigenetic signature of preterm birth at VLBW present in adult life. IMPACT: Being born preterm at very low birth weight has major implications for later health and chronic disease risk factors. The mechanism linking preterm birth to later outcomes remains unknown. Our cohort study of 157 very low birth weight adults and 161 controls found 66 differentially methylated sites at mean age of 22 years. Our findings suggest an epigenetic mark of preterm birth present in adulthood, which opens up opportunities for mechanistic studies.

Mental health, pain and tiredness in adults born very preterm or with very low birthweight.

AIM: Adults born preterm have increased risk of mental health problems and other neurodevelopmental conditions. We aimed to investigate associations of mental health with pain and tiredness in adults born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) and at term, and whether these associations are influenced by physical activity. METHODS: As part of an EU Horizon 2020 project, individual participant data from six prospective cohort studies were harmonised for 617 VP/VLBW and 1122 term-born participants. Mental health was assessed by the Achenbach System of Empirically Based Assessment Adult Self-Report. Pain and tiredness were harmonised based on specific items from self-reported questionnaires. Associations between mental health and pain or tiredness were explored by linear regression. RESULTS: An increase in the mental health scales internalising, externalising and total problems was associated with increased pain and tiredness in the preterm and term group alike. Results were maintained when adjusting for physical activity. CONCLUSION: The findings indicate that associations between mental health, pain and tiredness in adults are independent of gestation or birthweight. Future research should explore other potential mechanisms that may underlie the increased risk of mental health problems in the preterm population.

Romantic and sexual relationships of young adults born very preterm: An individual participant data meta-analysis.

AIM: To compare romantic and sexual relationships between adults born very preterm (VP; <32 weeks of gestation) or with very low birth weight (VLBW; <1500 g) and at term, and to evaluate potential biological and environmental explanatory factors among VP/VLBW participants. METHODS: This individual participant data (IPD) meta-analysis included longitudinal studies assessing romantic and sexual relationships in adults (mean sample age ≥ 18 years) born VP/VLBW compared with term-born controls. Following PRISMA-IPD guidelines, 11 of the 13 identified cohorts provided IPD from 1606 VP/VLBW adults and 1659 term-born controls. IPD meta-analyses were performed using one-stage approach. RESULTS: Individuals born VP/VLBW were less likely to be in a romantic relationship (OR 0.49; 95% CI 0.31-0.76), to be married/cohabiting (OR 0.70, 95% CI 0.53-0.92), or to have had sexual intercourse (OR 0.21, 95% CI 0.09-0.36) than term-born adults. If sexually active, VP/VLBW participants were more likely to experience their first sexual intercourse after the age of 18 years (OR 1.93, 95% CI 1.24-3.01) than term-born adults. Among VP/VLBW adults, males, and those with neurosensory impairment were least likely to experience romantic relationships. CONCLUSIONS: These findings reflect less optimal social functioning and may have implications for socioeconomic and health outcomes of adults born VP/VLBW.

Risk-Taking Behavior of Adolescents and Young Adults Born Preterm.

OBJECTIVES: To study sexually transmitted Chlamydia trachomatis infections (STCTs), teenage pregnancies, and payment defaults in individuals born preterm as proxies for engaging in risk-taking behavior. STUDY DESIGN: Our population-based register-linkage study included all 191 705 children alive at 10 years (8492 preterm [4.4%]) born without malformations in Finland between January 1987 and September 1990 as each mother's first child within the cohort. They were followed until young adulthood. We used Cox regression to assess the hazards of STCTs, teenage pregnancies, payment defaults, criminal offending, and substance abuse by gestational age. Gestational age was considered both as a continuous and categorical (extremely, very, moderately, late preterm, early term, post term, and full term as reference) exposure. RESULTS: A linear dose-response relationship existed between gestational age and STCT and teenage pregnancy; adjusted hazard for STCT decreased by 1.6% (95% CI, 0.7%-2.6%), and for teenage pregnancy by 3.3% (95% CI, 1.9%-4.8%) per each week decrease in gestational age. Those born extremely preterm (23-27 completed weeks) had a 51% (95% CI, 31%-83%) lower risk for criminal offending than their full-term born counterparts, and those born very preterm (range, 28-31 weeks) had a 28% (95% CI, 7%-53%) higher hazard for payment defaults than those born at full term. Gestational age was not associated with substance abuse. CONCLUSIONS: The lower risk-taking that characterizes people born preterm seems to generalize to sexual and to some extent criminal behavior. Those born very preterm are, however, more likely to experience payment defaults.

Body composition in adults born preterm with very low birth weight.

BACKGROUND: Studies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults. METHODS: We studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years. RESULTS: In mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, -1.5% to 3.5%, men 0.8%; -2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3). CONCLUSION: Compared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely explained by their shorter height. This could contribute to lower insulin sensitivity and muscular fitness previously found in VLBW survivors and predispose to functional limitations with increasing age. IMPACT: In mid-adulthood, individuals born preterm with very low birth weight had similar body fat percentage but lower lean body mass than those born at term. This was largely explained by their shorter height. First study to report longitudinal assessments of body size and composition from young to mid-adulthood in very low birth weight adults. Lower lean body mass in very low birth weight adults could contribute to lower insulin sensitivity and muscular fitness and lead to earlier functional limitations with increasing age.

ADHD symptoms and diagnosis in adult preterms: systematic review, IPD meta-analysis, and register-linkage study.

BACKGROUND: This study examined differences in ADHD symptoms and diagnosis between preterm and term-born adults (≥18 years), and tested if ADHD is related to gestational age, birth weight, multiple births, or neonatal complications in preterm borns. METHODS: (1) A systematic review compared ADHD symptom self-reports and diagnosis between preterm and term-born adults published in PubMed, Web of Science, and PROQUEST until April 2021; (2) a one-stage Individual Participant Data(IPD) meta-analysis (n = 1385 preterm, n = 1633 term; born 1978-1995) examined differences in self-reported ADHD symptoms[age 18-36 years]; and (3) a population-based register-linkage study of all live births in Finland (01/01/1987-31/12/1998; n = 37538 preterm, n = 691,616 term) examined ADHD diagnosis risk in adulthood (≥18 years) until 31/12/2016. RESULTS: Systematic review results were conflicting. In the IPD meta-analysis, ADHD symptoms levels were similar across groups (mean z-score difference 0.00;95% confidence interval [95% CI] -0.07, 0.07). Whereas in the register-linkage study, adults born preterm had a higher relative risk (RR) for ADHD diagnosis compared to term controls (RR = 1.26, 95% CI 1.12, 1.41, p < 0.001). Among preterms, as gestation length (RR = 0.93, 95% CI 0.89, 0.97, p < 0.001) and SD birth weight z-score (RR = 0.88, 95% CI 0.80, 0.97, p < 0.001) increased, ADHD risk decreased. CONCLUSIONS: While preterm adults may not report higher levels of ADHD symptoms, their risk of ADHD diagnosis in adulthood is higher. IMPACT: Preterm-born adults do not self-report higher levels of ADHD symptoms, yet are more likely to receive an ADHD diagnosis in adulthood compared to term-borns. Previous evidence has consisted of limited sample sizes of adults and used different methods with inconsistent findings. This study assessed adult self-reported symptoms across 8 harmonized cohorts and contrasted the findings with diagnosed ADHD in a population-based register-linkage study. Preterm-born adults may not self-report increased ADHD symptoms. However, they have a higher risk of ADHD diagnosis, warranting preventive strategies and interventions to reduce the presentation of more severe ADHD symptomatology in adulthood.

Brain Volumes and Abnormalities in Adults Born Preterm at Very Low Birth Weight.

OBJECTIVES: To assess radiographic brain abnormalities and investigate volumetric differences in adults born preterm at very low birth weight (<1500 g), using siblings as controls. STUDY DESIGN: We recruited 79 adult same-sex sibling pairs with one born preterm at very low birth weight and the sibling at term. We acquired 3-T brain magnetic resonance imaging from 78 preterm participants and 72 siblings. A neuroradiologist, masked to participants' prematurity status, reviewed the images for parenchymal and structural abnormalities, and FreeSurfer software 6.0 was used to conduct volumetric analyses. Data were analyzed by linear mixed models. RESULTS: We found more structural abnormalities in very low birth weight participants than in siblings (37% vs 13%). The most common finding was periventricular leukomalacia, present in 15% of very low birth weight participants and in 3% of siblings. The very low birth weight group had smaller absolute brain volumes (-0.4 SD) and, after adjusting for estimated intracranial volume, less gray matter (-0.2 SD), larger ventricles (1.5 SD), smaller thalami (-0.6 SD), caudate nuclei (-0.4 SD), right hippocampus (-0.4 SD), and left pallidum (-0.3 SD). We saw no volume differences in total white matter (-0.04 SD; 95% CI, -0.13 to 0.09). CONCLUSIONS: Preterm very low birth weight adults had a higher prevalence of brain abnormalities than their term-born siblings. They also had smaller absolute brain volumes, less gray but not white matter, and smaller volumes in several gray matter structures.

Preterm birth and subsequent timing of pubertal growth, menarche, and voice break.

BACKGROUND: We evaluated pubertal growth and pubertal timing of participants born preterm compared to those born at term. METHODS: In the ESTER Preterm Birth Study, we collected growth data and measured final height of men/women born very or moderately preterm (<34 gestational weeks, n = 52/55), late preterm (34-<37 weeks, 94/106), and term (≥37 weeks, 131/151), resulting in median 9 measurements at ≥6 years. Timing of menarche or voice break was self-reported. Peak height velocity (PHV, cm/year) and age at PHV (years) were compared with SuperImposition by Translation And Rotation (SITAR) model (sexes separately). RESULTS: Age at PHV (years) and PHV (cm/year) were similar in all gestational age groups. Compared to term controls, insignificant differences in age at PHV were 0.1 (95% CI: -0.2 to 0.4) years/0.2 (-0.1 to 0.4) for very or moderately/late preterm born men and -0.0 (-0.3 to 0.3)/-0.0 (-0.3 to 0.2) for women, respectively. Being born small for gestational age was not associated with pubertal growth. Age at menarche or voice break was similar in all the gestational age groups. CONCLUSIONS: Timing of pubertal growth and age at menarche or voice break were similar in participants born preterm and at term. IMPACT: Pubertal growth and pubertal timing were similar in preterm and term participants in a relatively large cohort with a wide range of gestational ages. Previous literature indicates that small for gestational age is a risk for early puberty in term born children. This was not shown in preterm children. While our study had limited power for children born very preterm, all children born preterm were not at increased risk for early puberty.

Bone mineral density in very low birthweight adults-A sibling study.

BACKGROUND: Children and adults born very low birthweight (VLBW, <1500 g) at preterm gestations have lower bone mineral density (BMD) and/or bone mineral content (BMC) than those born at term, but causality remains unknown. OBJECTIVES: Our aim was to assess BMD and BMC in adults born at VLBW in a sibling comparison setting to account for shared genetic and environmental confounders. METHODS: We conducted a cohort study of 77 adults born VLBW and 70 same-sex term-born siblings at mean age of 29 years. The primary outcome variables were BMD Z-scores, and BMC, of the femoral neck, lumbar spine, and whole body, measured using dual-energy X-ray absorptiometry. We analysed data by linear mixed models. RESULTS: The VLBW adults had a 0.25 (95% CI 0.02, 0.47) Z-score unit lower femoral neck BMD, and 0.35 (95% CI 0.16, 0.54) grams lower femoral neck BMC than their term-born siblings, after adjustment for sex, age, and maternal smoking. Additional adjustment for adult body size attenuated the results. Lumbar spine, and whole body BMC were also lower in the VLBW group. CONCLUSIONS: Individuals born at VLBW had lower BMC values at all three measurement sites, as well as lower femoral neck BMD Z-scores, compared to term-born siblings, partly explained by their smaller adult body size, but the differences were smaller than those reported previously with unrelated controls. This suggests that genetic or environmental confounders explain partly, but not exclusively, the association between preterm VLBW birth and adult bone mineralisation.

Migraine in children and adults born preterm: A nationwide register linkage study.

OBJECTIVE: Being born preterm is related to adverse health effects later in life. We studied whether preterm birth predicts the risk of migraine. METHODS: In this nationwide register study, we linked data from six administrative registers for all 235,624 children live-born in Finland (January 1987 to September 1990) and recorded in the Finnish Medical Birth Register. n = 228,610 (97.0%) had adequate data and were included. Migraine served as primary outcome variable and was stringently defined as a diagnosis from specialised health care and/or ≥2 reimbursed purchases of triptans. We applied sex- and birth year-stratified Cox proportional hazard regression models to compute hazard ratios and confidence intervals (95% confidence intervals) for the association between preterm categories and migraine. The cohort was followed up until an average age of 25.1 years (range: 23.3-27.0). RESULTS: Among individuals born extremely preterm (23-27 completed weeks of gestation), the adjusted hazard ratios for migraine was 0.55 (0.25-1.24) when compared with the full-term reference group (39-41 weeks). The corresponding adjusted hazard ratios and 95% confidence intervals for the other preterm categories were: Very preterm (28-31 weeks); 0.95 (0.68-1.31), moderately preterm (32-33 weeks); 0.96 (0.73-1.27), late preterm (34-36 weeks); 1.01 (0.91-1.11), early term (37-38 weeks); 0.98 (0.93-1.03), and post term (42 weeks); 0.98 (0.89-1.08). Migraine was predicted by parental migraine, lower socioeconomic position, maternal hypertensive disorder and maternal smoking during pregnancy. CONCLUSION: We found no evidence for a higher risk of migraine among individuals born preterm.

Reaction times, learning, and executive functioning in adults born preterm.

BACKGROUND: This study examines cognitive functioning in adults born across the range of prematurity with appropriate or small for gestational age (SGA) birth weight compared with full-term controls. METHODS: ESTER Preterm Birth Study participants without severe disabilities, comprising 133 early preterm (<34 weeks, 17% SGA), 241 late preterm (34 + 0-36 + 6 weeks, 13% SGA), and 348 full-term subjects, performed the Cogstate® test at a mean age of 23.3 (SD = 1.2) years. Subtests measured paired associate learning, psychomotor function, executive function, spatial memory efficiency, visual memory, attention, working memory, visual learning, and emotional cognition. Data were analyzed with linear regression, full models adjusted for prenatal and postnatal factors and socioeconomic position. RESULTS: Early preterm, late preterm, and full-term participants showed similar abilities in almost all subtests. Early preterm participants had 0.6 fewer moves/10 s (95% CI: -1.0; -0.2, full model) and late preterm and SGA participants had 1.3 fewer moves/10 s (95% CI: -2.1; -0.4) than full-term controls in the Groton Maze Learning Test, indicating weaker spatial memory efficiency. CONCLUSIONS: Adults born across the range of prematurity on average lack major defects in cognitive abilities. Cognitive problems may persist to adulthood only among those born the smallest: very preterm or preterm and SGA. IMPACT: Although preterm birth is a risk for the developing brain, adults born preterm as a group showed similar cognitive performance to their full-term peers. Children born preterm across gestational ages show defects in cognitive domains. With a supportive environment, many of them have the potential to catch up with those born at term. The unfavorable effect of late preterm birth on cognitive functions in childhood may not persist to adulthood; in this study, adults born late preterm showed similar cognitive functioning to adults born full-term. The deficits in cognitive function in adults born preterm detected by earlier studies mainly concern those born the smallest, i.e., very preterm or preterm and small for gestational age.

Common Core Assessments in follow-up studies of adults born preterm-Recommendation of the Adults Born Preterm International Collaboration.

BACKGROUND: Of all newborns, 1%-2% are born very preterm (VP; <32 weeks) or with very low birthweight (VLBW; ≤1500 g). Advances in prenatal and neonatal care have substantially improved their survival, and the first generations who have benefited from these advances are now entering middle age. While most lead healthy lives, on average these adults are characterised by a number of adversities. These include cardiometabolic risk factors, airway obstruction, less physical activity, poorer visual function, lower cognitive performance, and a behavioural phenotype that includes inattention and internalising and socially withdrawn behaviour that may affect life chances and quality of life. Outcomes in later adulthood are largely unknown, and identifying trajectories of risk or resilience is essential in developing targeted interventions. Joint analyses of data and maintenance of follow-up of cohorts entering adulthood are essential. Such analyses are ongoing within the Adults Born Preterm International Collaboration (APIC; www.apic-preterm.org). Joint analyses require data harmonisation, highlighting the importance of consistent assessment methodologies. OBJECTIVE: To present an expert recommendation on Common Core Assessments to be used in follow-up assessments of adults born preterm. METHODS: Principles of Common Core Assessments were discussed at APIC meetings. Experts for each specific outcome domain wrote the first draft on assessments pertaining to that outcome. These drafts were combined and reviewed by all authors. Consensus was reached by discussion at APIC meetings. RESULTS: We present a recommendation by APIC experts on consistent measures to be used in adult follow-up assessments. CONCLUSIONS: The recommendation encompasses both "core" measures which we recommend to use in all assessments of adults born preterm that include the particular outcome. This will allow comparability between time and location. The recommendation also lists optional measures, focusing on current gaps in knowledge. It includes sections on study design, cardiometabolic and related biomarkers, biological samples, life style, respiratory, ophthalmic, cognitive, mental health, personality, quality of life, sociodemographics, social relationships, and reproduction.

Intrapartum zigzag pattern of fetal heart rate is an early sign of fetal hypoxia: A large obstetric retrospective cohort study.

INTRODUCTION: The aim of the present study was to identify possible associations of fetal heart rate (FHR) patterns during the last 2 hours of labor with fetal asphyxia expressed by umbilical artery acidemia at birth and with neonatal complications in a large obstetric cohort. MATERIAL AND METHODS: Cardiotocographic recordings from 4988 singleton term childbirths over 1 year were evaluated retrospectively and blinded to the pregnancy and neonatal outcomes in a university teaching hospital in Helsinki, Finland. Umbilical artery pH, base excess and pO2 , low Apgar scores at 5 minutes, need for intubation and resuscitation, early neonatal hypoglycemia, and neonatal encephalopathy were used as outcome variables. According to the severity of the neonatal complications at birth, the cohort was divided into three groups: no complications (Group 1), moderate complications (Group 2) and severe complications (Group 3). RESULTS: Of the 4988 deliveries, the ZigZag pattern (FHR baseline amplitude changes of >25 bpm with a duration of 2-30 minutes) occurred in 11.7%, late decelerations in 41.0%, bradycardia episodes in 52.9%, reduced variability in 36.7%, tachycardia episodes in 13.9% and uterine tachysystole in 4.6%. No case of saltatory pattern (baseline amplitude changes of >25 bpm with a duration of >30 minutes) was observed. The presence of the ZigZag pattern or late decelerations, or both, was associated with cord blood acidemia (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.3-4.7) and severe neonatal complications (Group 3) (OR 3.3, 95% CI 2.4-4.9). In contrast, no significant associations existed between the other FHR patterns and severe neonatal complications. ZigZag pattern preceded late decelerations in 88.7% of the cases. A normal FHR preceded the ZigZag pattern in 90.4% of the cases, whereas after ZigZag episodes, a normal FHR pattern was observed in only 0.9%. CONCLUSIONS: ZigZag pattern and late decelerations during the last 2 hours of labor are significantly associated with cord blood acidemia at birth and neonatal complications. The ZigZag pattern precedes late decelerations, and the fact that normal FHR pattern precedes the ZigZag pattern in the majority of the cases suggests that the ZigZag pattern is an early sign of fetal hypoxia, which emphasizes its clinical importance.

Out-of-home care placements of children and adolescents born preterm: A register-based cohort study.

BACKGROUND: Preterm birth predisposes to child protection action in the form out-of-home care. The impact of the degree of preterm birth on the likelihood for OHC placement(s) and their timing is unknown. METHODS: This population-based register-linkage study assessed the likelihood of OHC placement in different gestational age groups using multivariable Cox regression models. All 193 033 traceable singleton (8324 preterm, 4.3%) liveborn in Finland (January 1987-September 1990), as the first index child of each mother within the cohort period, were followed up until their 18th birthday. RESULTS: A total of 6562 children (3.4%) experienced OHC. In comparison with full-term children (39-41 weeks), those born at 23-33 completed weeks were predisposed to OHC (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.74, 2.56). For those born late preterm (34-36 weeks) and early term (37-38 weeks), the HR were 1.54 (95% CI 1.37, 1.73) and 1.19 (95% CI 1.12, 1.26), respectively. Adjustment for parental and child characteristics attenuated the HRs: 23-33 weeks: 1.31 (95% CI 1.07, 1.59), 34-36 weeks: 1.17 (95% CI 1.04, 1.31), and 37-38 weeks: 1.08 (95% CI 1.02, 1.16). However, the adjusted HRs for first OHC entries at 0-5 years of age were higher: 23-33 weeks 2.29 (95% CI 1.72, 3.05), 34-36 weeks 1.76 (95% CI 1.46, 2.13), and 37-38 weeks 1.40 (95% CI 1.25, 1.56). Among those born preterm or early term, in comparison with their term born peers, no excess risk for OHC was seen after 5 years. CONCLUSIONS: A dose-response relationship exists between the level of preterm birth and OHC placement risk. OHC placements are more common among early and late preterm, and early term children, compared with those born full term, and occur at younger age. Perinatal and postnatal adverse circumstances appear to explain the phenomenon only partly.

Short Sleep Duration and Later Overweight in Infants.

OBJECTIVE: To provide further knowledge about the longitudinal association between sleep duration and overweight in infants. STUDY DESIGN: The data for this study are from the CHILD-SLEEP birth cohort (n = 1679). The sleep data are based on parent-reported total sleep duration collected at 3, 8, 18, and 24 months. For a subgroup of 8-month old participants (n = 350), an actigraph recording was also made. Growth data were derived from the child health clinic records. A logistic regression model was used to study the association between sleep duration and later weight development. RESULTS: Shorter sleep duration in 3-month-old infants was cross-sectionally associated with lower weight-for-length/height (all P values ≤ .026) and body mass index (all P values ≤ .038). Moreover, short sleep duration at the age of 3 months was associated with greater weight-for-length/height z score at the age of 24 months (aOR 1.56; 95% CI 1.02-2.38) as well as with a predisposition to gain excess weight between 3 and 24 months of age (aOR 2.61; 95% CI 1.75-3.91). No significant associations were found between sleep duration at 8, 18, or 24 months and concurrent or later weight status. Actigraph-measured short night-time sleep duration at the age of 8 months was associated with greater weight-for-length at the age of 24 months (aOR 1.51; 95% CI 1.02-2.23). CONCLUSIONS: Short total sleep duration at the age of 3 months and short night-time sleep duration at the age of 8 months are associated with the risk of gaining excess weight at 24 months of age.

Cardiometabolic risk factors in young adults who were born preterm.

Adults who were born preterm with a very low birth weight have higher blood pressure and impaired glucose regulation later in life compared with those born at term. We investigated cardiometabolic risk factors in young adults who were born at any degree of prematurity in the Preterm Birth and Early Life Programming of Adult Health and Disease (ESTER) Study, a population-based cohort study of individuals born in 1985-1989 in Northern Finland. In 2009-2011, 3 groups underwent clinical examination: 134 participants born at less than 34 gestational weeks (early preterm), 242 born at 34-36 weeks (late preterm), and 344 born at 37 weeks or later (controls). Compared with controls, adults who were born preterm had higher body fat percentages (after adjustment for sex, age, and cohort (1985-1986 or 1987-1989), for those born early preterm, difference = 6.2%, 95% confidence interval (CI): 0.4, 13.2; for those born late preterm, difference = 8.0%, 95% CI: 2.4, 13.8), waist circumferences, blood pressure (for those born early preterm, difference = 3.0 mm Hg, 95% CI: 0.9, 5.1; for those born late preterm, difference = 1.7, 95% CI: -0.1, 3.4), plasma uric acid levels (for those born early preterm, difference = 20.1%, 95% CI: 7.9, 32.3; for those born late preterm, difference = 20.2%, 95% CI: 10.7, 30.5), alanine aminotransferase levels, and aspartate transaminase levels. They were also more likely to have metabolic syndrome (for those born early preterm, odds ratio = 3.7, 95% CI: 1.6, 8.2; for those born late preterm, odds ratio = 2.5, 95% CI: 1.2, 5.3). Elevated levels of conventional and emerging risk factors suggest a higher risk of cardiometabolic disease later in life. These risk factors are also present in the large group of adults born late preterm.

Objectively measured physical activity in young adults born preterm at very low birth weight.

Unimpaired adults born preterm at very low birth weight (<1500 g) consistently have lower conditioning physical activity than those born at term. We used wrist-worn accelerometers to measure objectively physical activity in 57 very low birth weight and 47 control subjects aged 25 years. We found no difference in any physical activity measures.

Early Protein Intake Is Associated with Body Composition and Resting Energy Expenditure in Young Adults Born with Very Low Birth Weight.

BACKGROUND: Suboptimal nutrition during fetal life and early childhood may be important in early programming of health and disease. Preterm infants born with very low birth weight (VLBW; <1500 g) frequently receive inadequate neonatal nutrition; the long-term consequences are poorly known. OBJECTIVE: We evaluated the association between early macronutrient intake and body composition in young adults born with VLBW. METHODS: We collected comprehensive information on daily nutritional intake during the initial hospital stay for 127 participants of the Helsinki Study of Very Low Birth Weight Adults. We calculated mean daily intakes of energy, protein, fat, and carbohydrate during the first 9 wk of life. At the mean age of 22.5 y, the subjects underwent measurements of weight, height, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure. The associations were examined by linear regression. RESULTS: We found that energy, protein, and fat intakes during the first 3 wk of life, all below current recommendations, predicted adult body composition. When adjusted for sex, age, birth weight SD score, and gestational age, a 1 g · kg(-1) · d(-1) higher protein intake predicted 11.1% higher lean body mass (LBM) (95% CI: 3.7%, 18.9%) and 8.5% higher resting energy expenditure (REE) (95% CI: 0.2%, 17.0%). Among those born before 28 wk of gestation, the numbers were 22.5% (95% CI: 1.9%, 47.4%) for LBM and 22.1% (95% CI: 3.6%, 44.0%) for REE. Similar associations were seen with energy (P = 0.01, P = 0.05) and fat (P < 0.01, P = 0.03) but not with carbohydrate. Energy intake was also associated with BMI (P = 0.01) and fat intake with BMI (P < 0.01) and percentage body fat (P = 0.05). The results were little changed when adjusted for prenatal and postnatal characteristics. CONCLUSIONS: At relatively low neonatal protein intake levels, additional protein intake is reflected in a healthier body composition, accompanied by a higher metabolic rate, in young adults born with VLBW 20 y earlier.