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.

Maternal antenatal depression is associated with metabolic alterations that predict birth outcomes, neurodevelopment and mental health of the child.

BACKGROUND: Evidence regarding metabolic alterations associated with maternal antenatal depression (AD) is limited, and their role as potential biomarkers improving the prediction of AD and adverse child birth, neurodevelopmental, and mental health outcomes remains unexplored. METHODS: In a cohort of 331 mother-child dyads, we studied associations between AD (history of medical register diagnoses and/or Center of Epidemiological Studies Depression Scale score during pregnancy≥20) and 95 metabolic measures analyzed three times during pregnancy. We tested whether the AD-related metabolic measures increased variance explained in AD over its risk factors, and in child birth, neurodevelopmental, and mental health outcomes over AD. We replicated the findings in a cohort of 416 mother-child dyads. RESULTS: Elastic net regression identified 15 metabolic measures that collectively explained 25% (p<0.0001) of variance in AD, including amino and fatty acids, glucose, inflammation, and lipids. These metabolic measures increased the variance explained in AD over its risk factors (32.3%,p<0.0001 vs. 12.6%,p=0.004), and in child gestational age (9.0%,p<0.0001 vs. 0.7%, p=0.34), birth weight(9.0%,p=0.03 vs. 0.7%, p=0.33), developmental milestones at the age of 2.3-5.7 years(21.0%,p=0.002 vs. 11.6%,p<0.001) and any mental or behavioral disorder by the age of 13.1-16.8 years(25.2%,p=0.03 vs. 5.0%,p=0.11) over AD, child sex and age. These findings replicated in the independent cohort. CONCLUSIONS: AD is associated with alterations in 15 metabolic measures, which collectively improve the prediction of AD over its risk factors, and birth, neurodevelopmental and mental health outcomes of the child over AD. These metabolic measures may become biomarkers identifying at-risk mothers and children for personalized interventions.

A Finnish nationwide register-based study shows a further 50% decline in already low child mortality.

AIM: Child mortality declined significantly in Finland in 1969-2004. We investigated whether the already low mortality rate could still decline from 2005 to 2020. METHODS: This was a nationwide register-based study. The subjects were children under 16 years of age who had resided in Finland between 2005 and 2020. The study population was identified from Finland's Population Information System of the Digital and Population Data Services Agency. Causes of death were obtained from Statistics Finland. Changes in annual overall and cause-specific mortality rates were evaluated. RESULTS: 3685 children (55% boys) under 16 years of age died in Finland in 2005-2020 from 325 causes. Overall annual child mortality declined by 50% (95% confidence interval 37 to 64%) during the study period, from 0.31/1000 in 2005 to 0.16/1000 in 2020. The mortality rate in children under one year of age declined from 3.1/1000 in 2005 to 1.8/1000 in 2020. The deaths from sudden infant death syndrome fell by 84%, congenital malformations by 62%, infectious diseases by 60%, external causes by 52%, and perinatal disorders by 41%. CONCLUSION: Finland's low child mortality further declined over the past two decades. Contributing factors likely include achievements in paediatric research, public health, and clinical practice.

Association between risk of infant death and birth-weight z scores according to gestational age: A nationwide study using the Finnish Medical Birth Register.

OBJECTIVE: To investigate the association between infant mortality and birth weight using estimated fetal weight (EFW) versus birth-weight charts, by gestational age (GA). METHODS: This nationwide population-based study used data from the Finnish Medical Birth Register from 2006 to 2016 on non-malformed singleton live births at 24-41+6 weeks of gestation (N = 563 630). The outcome was death in the first year of life. Mortality risks by birth-weight z score, defined as a continuous variable using Marsál's EFW and Sankilampi's birth-weight charts, were assessed using generalized additive models by GA (24-27+6, 28-31+6, 32-36+6, 37-38+6, 39-41+6 weeks). We calculated z score thresholds associated with a two- and three-fold increased risk of infant death compared with newborns with a birth weight between 0 and 0.675 standard deviations. RESULTS: The z score thresholds (with corresponding centiles in parentheses) associated with a two-fold increase in infant mortality were: -3.43 (<0.1) at 24-27+6 weeks, -3.46 (<0.1) at 28-31+6 weeks, -1.29 (9.9) at 32-36+6 weeks, -1.18 (11.9) at 37-38+6 weeks, and - 1.34 (9.0) at 39-41+6 weeks according to the EFW chart. These values were - 2.43 (0.8), -2.62 (0.4), -1.34 (9.0), -1.37 (8.5), and - 1.43 (7.6) according to the birth-weight chart. CONCLUSION: The association between birth weight and infant mortality varies by GA whichever chart is used, suggesting that different thresholds for the screening of growth anomalies could be used across GA to identify high-risk newborns.

Overweight in Adolescence and Young Adulthood in Association With Adult Cerebrovascular Disease: The NFBC1966 Study.

BACKGROUND: Risk factors for cerebrovascular disease in adulthood are well known. However, research on individuals' risk factors throughout their life span has been limited. This prospective cohort study aims to determine the effect of body mass index (BMI) and its changes in adolescence and young adulthood on early onset cerebrovascular disease. METHODS: This study includes 10 491 people (5185 women) from the Northern Finland Birth Cohort 1966. Height, weight, and BMI were measured at ages 14 and 31 years. Sex- and age-specific BMI ranges were used to define overweight and obesity. Data on ischemic and hemorrhagic cerebrovascular diseases between ages 14 and 54 years were extracted from national hospital and death registers. Cox proportion hazard models (95% CI) were used to estimate associations between BMI or its changes and cerebrovascular disease, while adjusting for sex, smoking, educational level, BMI at the other time point, and age at menarche for women. Additionally, sex-BMI interactions were calculated. RESULTS: A total of 452 individuals (4.7%) experienced cerebrovascular disease during the follow-up. The risk of ischemic cerebrovascular disease was increased for overweight women at ages 14 years (hazard ratio [HR], 2.49 [95% CI, 1.44-4.31]) and 31 years (HR, 2.13 [95% CI, 1.14-3.97]), as well as for obese women at ages 14 years (HR, 1.87 [95% CI, 0.76-4.58) and 31 years (HR, 2.67 [95% CI, 1.26-5.65]), with normal weight as the reference. These results were independent of earlier or later BMI. Similar associations were not found among men. The risk of hemorrhagic cerebrovascular disease was increased at age 31 years both among obese women (HR, 3.49 [95% CI, 1.13-10.7) and obese men (HR, 5.75 [95% CI, 1.43-23.1). The risk of any cerebrovascular disease related to overweight at age 14 years was 2.09× higher among girls than boys (95% CI, 1.06-4.15). The risk of ischemic cerebrovascular disease related to obesity at age 31 years was 6.96× higher among women than men (95% CI, 1.36-35.7). CONCLUSIONS: Among women, being overweight in adolescence or young adulthood increases the risk of cerebrovascular disease, especially ischemic, independent of their earlier or later BMI.

Fetal cord plasma herpesviruses and preeclampsia: an observational cohort study.

A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) of the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort: 539 from a pregnancy with PE and 737 without. We studied these samples and 30 placentas from PE pregnancies by a multiplex qPCR for the DNAs of all nine human herpesviruses. To assess the population prevalence of iciHHV-6, we studied whole-genome sequencing data from blood-derived DNA of 3421 biobank subjects. Any herpes viral DNA was detected in only two (0.37%) PE and one (0.14%) control sample (OR 2.74, 95% CI 0.25-30.4). One PE sample contained iciHHV-6B and another HHV-7 DNA. The control's DNA was of iciHHV-6B; the fetus having growth restriction and preterm birth without PE diagnosis. Placentas showed no herpesviruses. In the biobank data, 3 of 3421 subjects (0.08%) had low level HHV-6B but no iciHHV-6. While iciHHV-6 proved extremely rare, both fetuses with iciHHV-6B were growth-restricted, preterm, and from a pregnancy with maternal hypertension. Our findings suggest that human herpesviruses are not a significant cause of PE, whereas iciHHV-6 may pose some fetal risk.

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.

Physical Activity, Fitness, and Cardiac Autonomic Function among Adults Born Postterm.

Recent studies have suggested that adverse outcomes of postterm birth (≥42 completed weeks of gestation), including increased cardiometabolic risk factors, impaired glucose metabolism, and obesity, may extend into adulthood. We studied interconnected determinants of cardiovascular health, including physical activity (based on accelerometry for two weeks), muscular strength (handgrip strength), cardiorespiratory fitness (4-min step test), and cardiac autonomic function (heart rate recovery, heart rate variability, and baroreflex sensitivity) among 46-year-old adults from the Northern Finland Birth Cohort (NFBC) born postterm (n = 805) and at term (n = 2,645). Adults born postterm undertook vigorous-intensity physical activity 2.0 min/day (95% CI 0.4, 3.7) less than term-born adults when adjusted for sex, age, and maternal- and pregnancy-related covariates in multiple linear regression. Postterm birth was associated with reduced cardiorespiratory fitness based on a higher peak heart rate (2.1 bpm, 95% CI 0.9, 3.4) and slower heart rate recovery 30 s after the step test (-0.7 bpm, 95% CI -1.3, -0.1). Postterm birth was associated with lower vigorous-intensity physical activity and cardiorespiratory fitness and slower heart rate recovery in middle age. Our findings reinforce previous suggestions that postterm birth should be included as a perinatal risk factor for adult cardiometabolic disease.

Serum hydroxysteroid (17beta) dehydrogenase 1 concentration in pregnant women correlates with pregnancy-associated plasma protein A but does not serve as an independent marker for preeclampsia†.

Hydroxysteroid (17beta) dehydrogenase 1 (HSD17B1) is a steroid synthetic enzyme expressed in ovarian granulosa cells and placental syncytiotrophoblasts. Here, HSD17B1 serum concentration was measured with a validated immunoassay during pregnancy at three time points (12-14, 18-20 and 26-28 weeks of gestation). The concentration increased 2.5-fold (P < 0.0001) and 1.7-fold (P = 0.0019) during the follow-up period for control women and women who later developed preeclampsia (PE), respectively, and a significant difference was observed at weeks 26-28 (P = 0.0266). HSD17B1 concentration at all the three time points positively correlated with serum PAPPA measured at the first time point (first time point r = 0.38, P = 1.1 × 10-10; second time point r = 0.27, P = 5.9 × 10-6 and third timepoint r = 0.26, P = 2.3 × 10-5). No correlation was observed between HSD17B1 and placental growth factor (PLGF). Serum HSD17B1 negatively correlated with the mother's weight and body mass index (BMI), mirroring the pattern observed for PAPPA. The univariable logistic regression identified a weak association between HSD17B1 at 26-28 weeks and later development of PE (P = 0.04). The best multivariable model obtained using penalized logistic regression with stable iterative variable selection at 26-28 weeks included HSD17B1, together with PLGF, PAPPA and mother's BMI. While the area under the receiver operating characteristic curve of the model was higher than that of the adjusted PLGF, the difference was not statistically significant. In summary, the serum concentration of HSD17B1 correlated with PAPPA, another protein expressed in syncytiotrophoblasts, and with mother's weight and BMI but could not be considered as an independent marker for PE.

Foveal thickness and its association with visual acuity in adults born preterm with very low birth weight: A two-country birth cohort study.

PURPOSE: To explore foveal and parafoveal thickness in adults born preterm with very low birth weight (VLBW) and its association with best-corrected visual acuity (BCVA) and gestational age (GA) compared to adults born at term. METHODS: In a joint study of the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight Life study (Norway), 106 VLBW and 143 term-born controls were examined with spectral-domain optical coherence tomography and BCVA at age 31-43 years. Thickness of retinal layers was segmented in the foveal and parafoveal areas of the macula. RESULTS: The total retinal thickness in the foveal area was thicker in VLBW adults compared with controls; mean (SD): 292.5 µm (28.2) and 272.4 µm (20.2); p < 0.001, and thinner in the parafoveal areas of the macula. These findings could be explained by a thicker inner retinal layer in the foveal area found in VLBW adults compared with controls (mean difference 20.4 µm; CI: 15.0 to 25.9), where a thicker fovea was associated with lower GA, but not BCVA. CONCLUSION: Adults born preterm with VLBW had a thicker retina in the foveal area than controls and this was associated with GA, but not with BCVA. These changes seem to be related to a thicker inner retinal layer in VLBW adults. The findings imply that signs of macular underdevelopment are still present in adulthood, but not necessarily related to reduced visual function.

Accelerometer-Measured Physical Activity, Fitness and Indicators of Cardiometabolic Risk among Rural Adolescents: A Cross-Sectional Study at 15-Year Follow-up of the MINIMat Cohort.

BACKGROUND: Little is known about the relationship of physical activity (PA) and fitness with cardiometabolic risk among rural adolescents in low- and middle-income countries. Thus, we examined the associations of PA and fitness with selected cardiometabolic indicators along with potential gender-based differences in a birth cohort of rural adolescents from southeast Bangladesh. METHODS: We utilized data from the 15-year follow-up of Maternal and Infant Nutrition Interventions in Matlab (MINIMat) cohort (n = 2253). Wrist-worn ActiGraph wGT3x-BT accelerometers were used to estimate sedentary time (ST) and PA. Fitness was assessed using: handgrip strength, standing long jump, and Chester Step Test. Anthropometric parameters, systolic blood pressure (SBP), and fasting lipid, insulin and glucose levels were measured. We calculated insulin resistance using the Homeostasis Model Assessment equation (HOMA-IR). Linear regression and isotemporal substitution models were fitted. RESULTS: The adolescents spent 64 min/day (inter-quartile range: 50-81) in moderate-to-vigorous physical activity (MVPA). A 10-minute-per-day higher vigorous PA (VPA) was associated with: 4.9% (95% confidence interval (CI): 2.9-6.8%) lower waist circumference (WC), 3.2 mmHg (95% CI: 1.5-4.8) lower SBP, 10.4% (95% CI: 2.9-17.3%) lower TG, and 24.4% (95% CI: 11.3-34.9%) lower HOMA-IR. MVPA showed similar associations of notably smaller magnitude. Except for WC, the associations were more pronounced among the boys. Substituting ST with VPA of equal duration was associated with lower WC, SBP, triglyceride and HOMA-IR. Grip strength was favorably associated with all indicators, displaying considerably large effect sizes. CONCLUSION: Our findings indicated beneficial roles of PA- particularly VPA- and muscular fitness in shaping cardiometabolic profile in mid-adolescence. VPA and grip strength may represent potential targets for preventive strategies tailored to adolescents in resource-limited settings.

Association between parental psychiatric disorders and risk of offspring autism spectrum disorder: a Swedish and Finnish population-based cohort study.

Background: Roughly more than one in six adults worldwide suffer from psychiatric conditions. Sporadic studies have associated parental psychiatric disorders with autism spectrum disorder in offspring. Comprehensively examining the association between parental psychiatric disorders and offspring autism spectrum disorder is needed to guide health policies, and to inform etiologic studies. Methods: We included all children born in Sweden and Finland 1997-2016. Diagnoses were clinically ascertained from National Registers through 2017. We calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for autism spectrum disorder in offspring of fathers and mothers with psychiatric disorders, in both parents jointly and across co-occurring conditions. Findings: Among 2,505,842 children, 33,612 were diagnosed with autism spectrum disorder, of which 20% had a parent with psychiatric disorders. The risk of autism spectrum disorder was increased across all psychiatric disorders in fathers (Sweden: aHR = 2.02, 95% CI = 1.92-2.12; Finland: aHR = 1.63, 95% CI = 1.50-1.77), mothers (Sweden: aHR = 2.34, 95% CI = 2.24-2.43; Finland aHR = 2.12, 95% CI = 1.92-2.28), or both parents (Sweden: aHR = 3.76, 95% CI = 3.48-4.07; Finland aHR = 3.61, 95% CI = 3.20-4.07), compared to neither parents. Co-occurrence of parental psychiatric disorders further increased risk (e.g., Sweden: for one, two or ≥three different diagnostic categories compared to no diagnosis, in fathers aHR = 1.81, 2.07, 2.52; in mothers aHR = 2.05, 2.63, 3.57). Interpretation: Psychiatric disorders in both parents conveyed the highest risk of offspring autism spectrum disorder, followed by mothers and then fathers. The risk increased with number of co-occurring disorders. All parental psychiatric disorders were associated with increased the risk of autism spectrum disorder. To reliably assess the risk of autism spectrum disorder in children, a comprehensive history incorporating the full range of parental psychiatric disorders is needed beyond solely focusing on familial autism spectrum disorder. Funding: Swedish-Research-Council-2021-0214.

Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study.

BACKGROUND: Few studies have examined longitudinal changes in lifestyle-related factors and frailty. METHODS: We examined the association between individual lifestyle factors (exercise, diet, sleep, alcohol, smoking and body composition), their sum at baseline, their change over the 17-year follow-up and the rate of change in frailty index values using linear mixed models in a cohort of 2,000 participants aged 57-69 years at baseline. RESULTS: A higher number of healthy lifestyle-related factors at baseline was associated with lower levels of frailty but not with its rate of change from late midlife into old age. Participants who stopped exercising regularly (adjusted ß × Time = 0.19, 95%CI = 0.10, 0.27) and who began experiencing sleeping difficulties (adjusted ß × Time = 0.20, 95%CI = 0.10, 0.31) experienced more rapid increases in frailty from late midlife into old age. Conversely, those whose sleep improved (adjusted ß × Time = -0.10, 95%CI = -0.23, -0.01) showed a slower increase in frailty from late midlife onwards. Participants letting go of lifestyle-related factors (decline by 3+ factors vs. no change) became more frail faster from late midlife into old age (adjusted ß × Time = 0.16, 95% CI = 0.01, 0.30). CONCLUSIONS: Lifestyle-related differences in frailty were already evident in late midlife and persisted into old age. Adopting one new healthy lifestyle-related factor had a small impact on a slightly less steeply increasing level of frailty. Maintaining regular exercise and sleeping habits may help prevent more rapid increases in frailty.

Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden.

AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.

Neonatal outcomes according to different glucose threshold values in gestational diabetes: a register-based study.

BACKGROUND: Mild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using different oral glucose tolerance test (OGTT) thresholds. METHODS: This register-based study included all (n = 4,939) singleton pregnant women participating a 75 g 2-h OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting ≥ 5.3, 1 h ≥ 10.0 or 2-h glucose ≥ 8.6 mmol/L. Women who did not meet these criteria but met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1-5.2 mmol/L and/or 2-h glucose 8.5 mmol/L, n = 509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-h glucose 7.8-8.5 mmol/L, n = 166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups (n = 1292 and n = 612, respectively). Controls were normoglycaemic according to all criteria (fasting glucose < 5.1 mmol/L, 1-h glucose < 10.0 mmol/L and 2-h glucose < 8.5 mmol/L, n = 3031). Untreated mild hyperglycemia groups were compared to controls and treated GDM groups. The primary outcome - a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality - was analysed using multivariate logistic regression. RESULTS: The risk for the adverse neonatal outcome in untreated mild hyperglycemia was not increased compared to controls (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 0.71-1.44, using the IADPSG criteria; aOR: 1.05, 95% CI: 0.60-1.85, using the NICE criteria). The risk was lower compared to the treated IADPSG (aOR 0.38, 95% CI 0.27-0.53) or the treated NICE group (aOR 0.32, 95% CI 0.18-0.57). DISCUSSION: The risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia compared to normoglycaemic controls and was lower than in the treated GDM groups. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 h seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes.

Problems in peer relationships and low engagement in romantic relationships in preterm born adolescents: effects of maternal warmth in early childhood.

This study examined whether maternal warmth in early childhood moderates the association between preterm birth and problems in peer relationships and low engagement in romantic relationships in adolescence. We studied 9193 individuals from the Millennium Cohort Study in the United Kingdom, 99 (1.1%) of whom were born very preterm (VPT; < 32 weeks of gestation) and 629 (6.8%) moderate-to-late preterm (MLPT; 32-36 weeks gestation). Maternal warmth was reported by the mothers when their children were 3 years old. Peer relationship problems were reported by both the participants and their mothers at 14 and 17 years. Further, participants reported their engagement in romantic relationships at 14 and 17 years. All outcome variables were z-standardized, and the moderation effect was examined via hierarchical linear regressions. Compared to full-term birth, both MLPT and VPT birth were associated with lower engagement in romantic relationships at 17 years of age (b = .04, p = .02; b = .11, p = .02, respectively), and VPT birth was associated with increased peer relationship problems at 14 (b = .29, p = .01) and 17 years of age (b = .22, p = .046). Maternal warmth in early childhood was similarly associated with lower peer relationship problems in MLPT, VPT and full-term born adolescents. However, there was no influence of maternal warmth on engagement in romantic relationships at 17 years of age. There is no major modifying effect of maternal warmth in early childhood on the association between PT birth and peer relationship problems and low engagement in romantic relationships at 14 and 17 years of ages.

Motor abilities in adults born with very low birthweight: A study of two birth cohorts from Finland and Norway.

AIM: To compare overall, fine, and gross motor abilities in adults born preterm with very low birthweight (VLBW) and a control group of term-born individuals. METHOD: In a joint assessment of the Helsinki Study of Very Low Birth Weight Adults and NTNU Low Birth Weight in a Lifetime Perspective study, data were collected with harmonized methods for 118 adults born preterm (gestational age < 37 weeks) with VLBW (≤1500 g) and 147 control individuals. The primary outcome was overall motor abilities; secondary outcomes were fine and gross motor abilities. RESULTS: The Bruininks Motor Ability Test Short Form total score was 4.1 (95% confidence interval 2.7-6.0) points lower in adults born with VLBW than in the control group, adjusted for cohort, age, and sex. This was partly mediated by their shorter height. They also had lower scores for other fine and gross motor tests. Results were similar when participants with neurosensory impairment were excluded, and when we adjusted for additional covariates. INTERPRETATION: Adults born preterm with VLBW had poorer overall, fine, and gross motor abilities than adults born at term. This indicates that substantial difficulties in motor function among individuals born preterm with VLBW persist into mid-adulthood.

Physical activity and cognitive function in adults born very preterm or with very low birth weight-an individual participant data meta-analysis.

OBJECTIVE: Individuals born very preterm (<32 weeks of gestation) or with very low birthweight (<1500g) have lower cognitive function compared with term-born peers. Furthermore, some studies suggest that they are less physically active as young adults than controls, but the relationship between physical activity and cognitive function remains unclear. We performed an individual participant data meta-analysis to examine whether being born preterm/with very low birth weight is associated with physical activity in adulthood and examined if cognitive function mediates this association. STUDY DESIGN: Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase. RESULTS: Five cohorts with 1644 participants aged 22-28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments. CONCLUSION: Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention.

Risk of immune-related diseases in childhood after intrapartum antibiotic exposure.

BACKGROUND: Intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease in newborn infants, but it influences gut microbiota development. Gut microbiota composition is, in turn, associated with immune-related diseases in childhood. OBJECTIVE: This study hypothesized that intrapartum antibiotic exposure is associated with immune-related diseases in childhood. STUDY DESIGN: We conducted a population-based cohort study of vaginally delivered children. We retrieved data on intrapartum antibiotic exposure from structured electronic medical records and obtained outcome data on childhood autoimmune, allergic, and obstructive airway diseases from comprehensive national registers. We used Cox regression analysis with adjustment for maternal and neonatal covariates and regarded death as a competing risk in the analyses. RESULTS: The study population comprised 45,575 vaginally born children of whom 9733 (21%) had been exposed to intrapartum antibiotics. Intrapartum antibiotic exposure was associated with an autoimmune disease diagnosis (adjusted hazard ratio, 1.28; 95% confidence interval, 1.02-1.62), which corresponds to 22% (95% confidence interval, 6-39) as a theoretical population-attributable fraction. Intrapartum antibiotic exposure was not associated with diagnoses of allergic (adjusted hazard ratio, 1.08; 95% confidence interval, 0.97-1.20) or obstructive airway diseases (adjusted hazard ratio, 1.04; 95% confidence interval, 0.96-1.14). CONCLUSION: Intrapartum antibiotic exposure may be associated with an increased risk for autoimmune diseases in childhood. This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future.

Cognition, mental health and quality of life amongst siblings of preterm born children: A systematic review.

AIM: Globally, 1 in 10 babies are born preterm. Families with preterm born infants may suffer strains related to the presence of a preterm child. To date, most evidence focuses on the outcome of children born preterm and of their parents. Our objective was to investigate the evidence on the impact of having a preterm born sibling on cognitive function, mental health and quality of life of term-born siblings and critically appraise the evidence. METHODS: We searched five electronic databases, Google Scholar and reference lists. Two reviewers independently conducted screening, data extraction and critical appraisal. RESULTS: We retrieved 9121 articles. After duplicates, titles, abstract and full text review, seven studies met the inclusion criteria. One study reported higher anxiety and depression scores on index cases in the term born comparison group, compared to the index cases in the preterm born sibling group. Another study reported more feelings of reduced parental attention, and more interpersonal problems in the preterm born sibling group, than the comparison group. CONCLUSIONS: Although two studies reported a difference in outcomes between index cases in preterm born sibling groups and comparison groups, the scarce evidence did not allow us to delineate an effect or lack of it.