Reduced Exercise Capacity in Adults Born at Very Low Birth Weight: A Population-based Cohort Study.

Rationale: Population-based data regarding the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult exercise capacity are limited. Objectives: To compare exercise capacity in a national VLBW cohort with term-born controls and explore factors contributing to the differences. Methods: At 26-30 years of age, 228 VLBW survivors and 100 controls underwent lung function tests, cardiopulmonary exercise testing, and assessment of resting cardiac structure and function using echocardiography. Data on self-reported physical activity were collected. Measurements and Main Results: Compared with controls, adults with VLBW demonstrated reduced oxygen uptake, work rate, and oxygen pulse at peak exercise (9.3%, 10.7%, and 10.8% lower, respectively) and earlier anaerobic threshold (all P < 0.0001), with all mean values within normal range. VLBW survivors showed reduced physical activity, impaired lung function (reduced FEV1, FEV1/FVC, and DlCO), altered left ventricular structure and function (reduced mass, size, stroke volume, and cardiac output), and reduced right atrial and ventricular size. Adjustment for the combination of three sets of covariates (physical activity with body mass index, lung function, and cardiac structure and function) explained most of the exercise group differences. Beyond the effects of physical activity and body mass index, lung function and cardiac structure and function contributed approximately equally. BPD with other prematurity-related perinatal factors (ventilation, antenatal steroids, extremely low birth weight, and extreme preterm) were not associated with a reduced exercise capacity. Conclusions: Exercise capacity was significantly reduced in adults with VLBW, which we speculate is from combined effects of impaired lung function, altered heart structure and function, and reduced physical activity. Perinatal factors including BPD were not associated with a reduced exercise capacity.

Biomarkers of ageing in New Zealand VLBW young adults and controls.

BACKGROUND: There is individual variation in physiological ageing. Former very low birthweight (VLBW; birthweight < 1500 g) young adults may have less satisfactory measurements on some physiological parameters than term controls. We hypothesized that a summation score of physiological biomarkers that change with age would show VLBW adults to have a more advanced physiologic age than controls. METHODS: VLBW adults (229; 71% survivors of a national VLBW cohort) and term-born controls (100) were clinically assessed at 26-30 years. Ten measured physiological biomarkers were selected and measurements converted to z-scores using normative reference data. Between-group comparisons were tested for statistical significance for individual biomarker z-scores and a summation score. RESULTS: Nine of 10 biomarkers showed a mean z-score suggestive of older physiological age in the VLBW group versus controls. The observed mean difference in the summation score was highly significant (p < 0.001), representing a mean shift of 0.47 SD in the distribution of test scores for VLBW relative to controls. CONCLUSIONS: Utilizing a 10-biomarker score, VLBW young adults have a score indicative of poorer physiological functioning than term-born controls. Repeating these measures after an interval could provide insights into the comparative pace of ageing between VLBW and term-born adults. IMPACT: A summation score of 10 physiological biomarkers that are known to change with age shows that former very low birthweight adults have significantly poorer physiological functioning by the end of their third decade than term-born controls. This result adds to existing literature showing very preterm and very low birthweight young adults often have physiological and metabolic test results that are less satisfactory than those from term controls, despite mostly being in the normal range for age; for instance, higher systolic blood pressure. Although the pace of ageing in later years is yet to be established, the implications of this study are that preventative measures and lifestyle choices that impact on physiological ageing might have even greater importance for very preterm and very low birthweight graduates.

Cardiovascular Outcomes in Young Adulthood in a Population-Based Very Low Birth Weight Cohort.

OBJECTIVES: To assess differences in left heart structure and function, and endothelial function in a national cohort of very low birth weight (VLBW) young adults and term-born controls. STUDY DESIGN: The New Zealand VLBW study is a prospective, population-based, longitudinal cohort study which included all infants born <1500 g in 1986. The VLBW cohort (n = 229; 71% of survivors) and term-born controls (n = 100), were assessed at age 26-30 years. Measures of left heart structure and function were evaluated by echocardiography, vascular function was assessed using blood pressure, reactive hyperemia index, and arterioventricular coupling by calculating left ventricular (LV) and arterial elastance. RESULTS: Compared with controls, those born VLBW had smaller LVs, even when indexed for body surface area (mean LV mass, 89.7 ± 19.3 g/m2 vs 95.0 ± 22.3 g/m2 [P = .03]; LV end-diastolic volume, 58.3 ± 10.9 mL/m2 vs 62.4 ± 12.4 mL/m2 [P = .002]; and LV end-systolic volume, 20.8 ± 4.9 mL/m2 vs 22.6 ± 5.8 mL/m2 [P = .004]). VLBW participants had lower stroke volume (median, 37.2 mL/m2 [IQR, 33-42 mL/m2] vs median, 40.1 mL/m2 [IQR, 34-45 mL/m2]; P = .0059) and cardiac output (mean, 4.8 ± 1.2 L/min vs 5.1 ± 1.4 L/min; P = .03), but there was no difference in ejection fraction. The VLBW group had higher LV elastance (3.37 ± 0.88 mm Hg/mL vs 2.86 ± 0.75 mm Hg/mL; P < .0001) and arterial elastance (1.84 ± 0.4 vs 1.6 ± 0.4; P < .0001) and lower reactive hyperemia index (0.605 ± 0.28 vs 0.688 ± 0.31; P = .041). These measures were influenced by birth weight and sex, but we found limited associations with other perinatal factors. CONCLUSIONS: Being born preterm and VLBW is associated with differences in cardiovascular structure and function in adulthood. This population may be more vulnerable to cardiovascular pathology as they age. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12612000995875.

Psychogenic nonepileptic seizures that remit when the diagnosis is given: Just good luck?

OBJECTIVE: Some patients with psychogenic nonepileptic seizures (PNES) remit when given the diagnosis. It is not realistically possible to test this potential therapeutic effect in an Randomized Controlled Trial (RCT) so we aim to statistically demonstrate it using the temporal relationship between the communication of the diagnosis and the timing of remission. METHOD: Re-analysis of data from a study of PNES, where diagnosis was communicated, and outcomes recorded in 54 patients. Making conservative assumptions and using the binomial distribution, the Poisson distribution and the chi-squared test distribution, we calculated likelihoods of the null hypothesis: that communication of the diagnosis and remission of seizures had occurred in random temporal relationship. RESULTS: Remission occurred in the week following communication of the diagnosis in 15 out of 54 patients. The χ2 test assigned this result a p value of <0.00001. Binomial and Poisson distribution calculations also indicated that remission was highly unlikely to have occurred by chance and that, in a dataset similar to ours, was unlikely to be due to chance if occurring in more than 9 patients (16.7%). CONCLUSIONS: We showed that the observed remissions were highly unlikely to be due to chance. Where an intervention is 'short and sharp' and the outcome can be measured with reasonable temporal acuity, then this type of method may provide an alternative to RCT methodology when the latter is impracticable.

Medically Unexplained Symptoms and Antecedent Sexual Abuse: An Observational Study of a Birth Cohort.

OBJECTIVE: Medically unexplained symptoms (MUS) are common and associated with high consumption of health care resources. Cross-sectional studies in selected and clinical populations show consistent linkages between history of childhood sexual abuse (CSA) and presentation with MUS and somatization. However, there are almost no well-controlled prospective studies in population samples. METHODS: Data were gathered in a longitudinal study of a New Zealand birth cohort born in 1977. Hospital e-record data for the period 2008-2015 (age, 30-38 years) were searched for a subsample of 408 study participants who were resident in one District Health Board region, and details of MUS contacts were recorded. Retrospective reports of CSA (<16 years) were obtained at ages 18 and 21 years. Associations between CSA and MUS were sequentially adjusted using logistic regression methods for both childhood confounders assessed before age 16 years and potential mediating mental health/family context up to age 30 years. RESULTS: Twenty (4.9%) participants were classified as having MUS, of whom 11 had a history of CSA. Severe CSA involving attempted/completed sexual penetration was strongly associated with risk of MUS (odds ratio = 11.6, 95% confidence interval = 4.3-31.7, p < .001). A substantial association remained after statistically adjusting for confounding and mediating mental health/family context (adjusted odds ratio = 5.1, 95% confidence interval = 1.2-21.3, p = .024). This strong association was specific to severe CSA (as opposed to childhood physical abuse) and to MUS rather than medically explained symptoms. CONCLUSIONS: CSA involving attempted/completed penetration was strongly associated with attendance at secondary level care for MUS. Implications for prevention and treatment of MUS are discussed.

Associations between schizophrenia genetic risk, anxiety disorders and manic/hypomanic episode in a longitudinal population cohort study.

BACKGROUND: Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.AimsWe examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia. METHOD: Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and - using linear regression - total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children). RESULTS: Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode. CONCLUSIONS: The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.Declarations of interestNone.

Does adolescent heavier alcohol use predict young adult aggression and delinquency? Parallel analyses from four Australasian cohort studies.

While the association between heavy alcohol consumption and aggression has been well documented, the causal direction of this association, particularly at a population level, is disputed. A number of causal sequences have been proposed. First, that aggression leads to heavy alcohol use. Second, that heavy alcohol use leads to aggression. Third, that the association between alcohol use and aggression is due to confounding by (a) sociodemographic variables or (b) delinquency. We report here data from four Australasian prospective longitudinal studies of adolescents, to assess the temporal sequence of heavy drinking and aggression over the period from adolescence to young adulthood. The four cohort studies provide a total sample of 6,706 persons (Australian Temperament Project, n = 1701; Christchurch Health and Development Study, n = 931; Mater-University of Queensland Study of Pregnancy, n = 2437; Victorian Adolescent Health Cohort Study, n = 1637). We use multinomial logistic regression to determine whether early adolescent aggression predicts subsequent age of onset of heavy episodic drinking (HED), after adjustment for concurrent sociodemographic factors and delinquency. We then consider whether HED predicts subsequent aggression, after adjusting for past aggression, concurrent delinquency, and a range of confounders. There are broadly consistent findings across the four cohort studies. Early aggression strongly predicts subsequent HED. HED predicts later aggression after adjustment for prior aggression and other confounders. Policies that alter population levels of alcohol consumption are likely to impact on levels of aggression in societies where HED linked to aggression is more common.

Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm infants and use in determination of haemodynamic significance of patent ductus arteriosus.

This study aimed to investigate factors affecting N-terminal pro-B-type natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to predict haemodynamically significant patent ductus arteriosus (HsPDA). Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p < 0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen day 3 NTproBNP value of ≥ 287 pmol/L for the prediction of day 3 HsPDA correctly classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only modest ability to predict severe BPD. Chronological but not gestational age affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence NTproBNP but creatinine level was positively correlated. CONCLUSION: Day 3 NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in future trial design. What is Known: • NTproBNP is a cardiac hormone used to diagnose and monitor cardiac dysfunction in adults and has been shown to be higher in premature infants with haemodynamically significant ductus arteriosus (HsPDA). What is new: • NTproBNP is highly predictive of ultrasound-defined HsPDA and may be a useful tool for further triage • Early NTproBNP higher in infants who develop severe BPD and with renal impairment but not affected by gestational age, recent exposure to hypoxia or haemoglobin levels while late levels unexpectedly higher in those without BPD or HsPDA.

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Personality characteristics in childhood and outcomes in adulthood: findings from a 30 year longitudinal study.

OBJECTIVE: Personality has been associated with a variety of outcomes in adulthood. Most of the literature related to mental state disorder and personality is cross sectional. METHODS: Data from more than 900 participants of the Christchurch Health and Development Study (CHDS) were examined. Extroversion and neuroticism were measured at 14 years old and social outcomes at age 30. The presence of mental state disorder between 18-30 years old was identified. Multiple potential confounders in childhood were included in the analysis. RESULTS: Neuroticism at fourteen was significantly correlated with multiple environmental exposures whereas extroversion had relatively few associations. Regression analysis found that neuroticism at 14 predicted depression, anxiety, suicidality and overall mental health problems at 30 as well as poor self-esteem but not relationship quality or wellbeing. Extroversion at 14 predicted alcohol and drug dependence and overall mental health problems, but also predicted improved social wellbeing, self-esteem and relationship quality at 30. CONCLUSIONS: In this analysis extroversion interacts with significantly fewer environmental factors than neuroticism in predicting adult outcomes. Neuroticism at 14 years predicts poorer mental health outcomes in adulthood. Extroversion in childhood may be a protective factor in the development of mental disorder other than alcohol use disorders. Extroverted adolescents have more positive social outcomes at 30 years.

Diagnostic transitions from childhood to adolescence to early adulthood.

BACKGROUND: Quantifying diagnostic transitions across development is needed to estimate the long-term burden of mental illness. This study estimated patterns of diagnostic transitions from childhood to adolescence and from adolescence to early adulthood. METHODS: Patterns of diagnostic transitions were estimated using data from three prospective, longitudinal studies involving close to 20,000 observations of 3,722 participants followed across multiple developmental periods covering ages 9-30. Common DSM psychiatric disorders were assessed in childhood (ages 9-12; two samples), adolescence (ages 13-18; three samples), and early adulthood (ages 19 to age 32; three samples) with structured psychiatric interviews and questionnaires. RESULTS: Having a disorder at an early period was associated with at least a threefold increase in odds for having a disorder at a later period. Homotypic and heterotypic transitions were observed for every disorder category. The strongest evidence of continuity was seen for behavioral disorders (particularly ADHD) with less evidence for emotional disorders such as depression and anxiety. Limited evidence was found in adjusted models for behavioral disorders predicting later emotional disorders. Adult substance disorders were preceded by behavioral disorders, but not anxiety or depression. CONCLUSIONS: Having a disorder in childhood or adolescence is a potent risk factor for a range of psychiatric problems later in development. These findings provide further support for prevention and early life intervention efforts and suggest that treatment at younger ages, while justified in its own right, may also have potential to reduce the risk for disorders later in development.

Post-traumatic stress disorder symptoms form a traumatic and non-traumatic stress response dimension.

OBJECTIVE: This study aims to determine whether symptoms of post-traumatic stress disorder (PTSD) form a latent dimension reflecting responsivity to life events and whether PTSD symptoms are specific to traumatic life events. METHOD: A 30-year longitudinal study of a general population sample of 987 individuals were assessed for PTSD symptoms, exposure to adverse life events, and a variety of psychosocial measures. PTSD symptoms were tested using a confirmatory factor model and a range of fitted models were used to identify significant predictors of latent PTSD symptoms. RESULTS: The rate of DSM IV PTSD was 1.9%. However, subjects reported high rates of at least one significant traumatic or negative life event and PTSD symptoms. The PTSD symptoms conformed well to a single latent factor. There were strong linear associations between severity of PTSD symptoms and exposure to traumatic and non-traumatic life events. Factors contributing to latent PTSD symptoms were gender, childhood anxiety, neuroticism, self-esteem, and quality of parental care. CONCLUSION: Criteria for PTSD form an underlying dimension reflecting the individual's level of responsivity to traumatic and non-traumatic stressful life events. PTSD symptoms form a continuum of severity with minor stress symptoms at one end and severe PTSD at the other.

Is childhood oral health the 'canary in the coal mine' for poor adult general health? Findings from two New Zealand birth cohort studies.

OBJECTIVES: This study aimed to investigate whether childhood dental caries was associated with self-reported general health in midlife. METHODS: We used data on childhood oral health (caries experience) and adult self-reported general health from two New Zealand longitudinal birth cohorts, the Dunedin Multidisciplinary Health and Development Study (n = 922 and n = 931 at ages 5 and 45 years, respectively), and the Christchurch Health and Development Study (n = 1048 and n = 904 at ages 5 and 40 years, respectively). We used generalized estimating equations to examine associations between age-5 dental caries and self-rated general health and the number of self-reported physical health conditions at ages 45/40 (diagnosed by a doctor or health professional, n = 14 conditions among both cohorts). Covariates included known risk factors for poor health (SES, IQ, perinatal complications), and personality style, which is known to affect subjective health ratings. RESULTS: Incidence rate ratios for 'Excellent' self-rated health were lower among those who had high experience of dental caries as children than those who had not in both, the Dunedin (IRR, 0.76; 95% CI, 0.50, 1.14) and Christchurch studies (IRR, 0.69; 95% CI, 0.47, 1.00). Childhood dental caries was not associated with the number of self-reported physical health conditions in midlife, in either cohort. Dunedin Study members who at age 5 were not caries-free or whose parents rated their own or their child's oral health as poor were less likely to report 'Excellent' self-rated general health at age 45 than those who were caries-free and whose parents did not give a 'poor' rating (IRR, 0.69; 95% CI, 0.49, 0.97). CONCLUSIONS: Five-year-olds with greater caries experience were more likely to have poorer self-rated general health by midlife. Beyond this longitudinal association, future research should examine whether childhood dental caries is associated with objective/biological markers of physical health and whether it may have utility as an early indicator for poor general health in adulthood.

Health-Related Quality-of-Life Outcomes of Very Preterm or Very Low Birth Weight Adults: Evidence From an Individual Participant Data Meta-Analysis.

BACKGROUND AND OBJECTIVE: Assessment of health-related quality of life for individuals born very preterm and/or low birthweight (VP/VLBW) offers valuable complementary information alongside biomedical assessments. However, the impact of VP/VLBW status on health-related quality of life in adulthood is inconclusive. The objective of this study was to examine associations between VP/VLBW status and preference-based health-related quality-of-life outcomes in early adulthood. METHODS: Individual participant data were obtained from five prospective cohorts of individuals born VP/VLBW and controls contributing to the 'Research on European Children and Adults Born Preterm' Consortium. The combined dataset included over 2100 adult VP/VLBW survivors with an age range of 18-29 years. The main exposure was defined as birth before 32 weeks' gestation (VP) and/or birth weight below 1500 g (VLBW). Outcome measures included multi-attribute utility scores generated by the Health Utilities Index Mark 3 and the Short Form 6D. Data were analysed using generalised linear mixed models in a one-step approach using fixed-effects and random-effects models. RESULTS: VP/VLBW status was associated with a significant difference in the Health Utilities Index Mark 3 multi-attribute utility score of - 0.06 (95% confidence interval - 0.08, - 0.04) in comparison to birth at term or at normal birthweight; this was not replicated for the Short Form 6D. Impacted functional domains included vision, ambulation, dexterity and cognition. VP/VLBW status was not associated with poorer emotional or social functioning, or increased pain. CONCLUSIONS: VP/VLBW status is associated with lower overall health-related quality of life in early adulthood, particularly in terms of physical and cognitive functioning. Further studies that estimate the effects of VP/VLBW status on health-related quality-of-life outcomes in mid and late adulthood are needed.

Parental use of physical punishment in a birth cohort.

AIM: To document the prevalence of child physical punishment by parents and associated predictors in the Christchurch Health and Development Study (CHDS) birth cohort over a 15-year period. METHOD: A cohort of 1,265 CHDS individuals were followed from birth (1977) to age 40 years. At ages 25 (n=155), 30 (n=337), 35 (n=585) and 40 years (n=636), the cohort members with dependent children (<16 years of age) were interviewed about their use of child physical punishment in the past 12 months using the Parent-Child Conflict Tactics Scale. Parent, child and family predictors were also examined. RESULTS: The most common forms of physical punishment were smacking on bottom and slapping on hand, arm or leg. Rates of all forms of physical punishment declined with age, ranging from 77% reporting any physical punishment at age 25 to 42% at age 40. In multivariable models, significant predictors included parental age, numbers/ages of children in the household, childhood family socioeconomic status, parental history of adolescent mental health problems and concurrent intimate partner violence. CONCLUSION: Use of physical punishment remains a relatively common form of child discipline despite the 2007 anti-smacking legislation and reduced public tolerance for physical violence towards children. Implications for prevention/intervention are discussed.

Right Ventricular Structure and Function in Young Adults Born Preterm at Very Low Birth Weight.

Being born preterm (PT, <37 weeks gestation) or at very low birth weight (VLBW, <1500 g) is associated with increased rates of cardiopulmonary disorders in childhood. As survivors age, late cardiac effects, including right ventricular (RV) remodelling and occult pulmonary hypertension are emerging. In this population-based study, we aimed to investigate right heart structure and function in young adults born PT at VLBW compared to normal-weight term-born controls. The New Zealand VLBW Study has followed all infants born in 1986 with birth weight <1500 g. All were born preterm from 24 to 37 weeks. A total of 229 (71% of survivors) had echocardiograms aged 26-30 years which were compared to age-matched, term-born, normal-weight controls (n = 100). Young adults born preterm at very low birth weight exhibited smaller RV dimensions compared to term-born peers. Standard echocardiographic measures of RV function did not differ, but mildly reduced function was detected by RV longitudinal strain. This difference was related to birth weight and gestational age but not lung function or left ventricular function. Echocardiographic strain imaging may be an important tool to detect differences in RV function preterm and VLBW.

Association of Very Preterm Birth or Very Low Birth Weight With Intelligence in Adulthood: An Individual Participant Data Meta-analysis.

Importance: Birth before 32 weeks' gestation (very preterm [VPT]) and birth weight below 1500 g (very low birth weight [VLBW]) have been associated with lower cognitive performance in childhood. However, there are few investigations of the association of neonatal morbidities and maternal educational levels with the adult cognitive performance of individuals born VPT or VLBW (VPT/VLBW). Objective: To assess differences in adult IQ between VPT/VLBW and term-born individuals and to examine the association of adult IQ with cohort factors, neonatal morbidities, and maternal educational level among VPT/VLBW participants. Data Sources: Systematic review of published data from PubMed and meta-analysis of individual participant data (IPD) of cohorts from 2 consortia (Research on European Children and Adults Born Preterm [RECAP] and Adults Born Preterm International Collaboration [APIC]). Study Selection: The meta-analysis included prospective longitudinal cohort studies that assessed the full-scale IQ of adults born VPT or VLBW and respective control groups comprising term-born adults. Data Extraction and Synthesis: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for analyses of individual participant data and identified 8 studies that provided data from 2135 adults (1068 VPT/VLBW and 1067 term-born participants) born between 1978 and 1995. Meta-analyses of IPD were performed using a 1-stage approach, treating VPT birth or VLBW and cohort as random effects. Main Outcomes and Measures: Full-scale IQ scores were converted to z scores within each cohort using the combined SD of VPT/VLBW participants and a control group of term-born participants, with scores centered on the mean of the control group. Results: A total of 426 records were identified and screened. After exclusions, 13 studies were included in the aggregate meta-analysis. The IPD meta-analysis included 8 of the 9 RECAP and APIC cohorts with adult IQ data. The mean (SD) age among the 8 IPD cohorts was 24.6 (4.3) years, and 1163 participants (54.5%) were women. In unadjusted analyses, VPT/VLBW participants had mean adult IQ scores that were 0.78 SD (95% CI, -0.90 to -0.66 SD) lower than term-born participants, equivalent to a difference of 12 IQ points. Among VPT/VLBW participants, lower gestational age (score difference per week of gestation, 0.11; 95% CI, 0.07-0.14), lower birth weight z scores (score difference per 1.0 SD, 0.21; 95% CI, 0.14-0.28), the presence of neonatal bronchopulmonary dysplasia (score difference, -0.16; 95% CI, -0.30 to -0.02) or any grade of intraventricular hemorrhage (score difference, -0.19; 95% CI, -0.33 to -0.05), and lower maternal educational level (score difference, 0.26; 95% CI, 0.17-0.35) were all significantly associated with lower IQ scores in adulthood. Conclusions and Relevance: In this IPD meta-analysis, lower gestational age, lower weight for gestational age, neonatal morbidities, and lower maternal educational levels were all important risk factors associated with lower IQ among young adults born VPT or VLBW.

Lung Function of Adults Born at Very Low Birth Weight.

BACKGROUND: Much remains unknown about the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult lungs. We hypothesized that VLBW adults would have impaired lung function compared with controls, and those with a history of BPD would have worse lung function than those without. METHODS: At age 26 to 30 years, 226 VLBW survivors of the New Zealand VLBW cohort and 100 term controls born in 1986 underwent lung function tests including spirometry, plethysmographic lung volumes, diffusing capacity of the lung for carbon monoxide, and single-breath nitrogen washout (SBN2). RESULTS: An obstructive spirometry pattern was identified in 35% VLBW subjects versus 14% controls, with the majority showing mild obstruction. Compared with controls, VLBW survivors demonstrated significantly lower forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), forced expiratory flow at 25% to 75% of FVC and higher residual volume (RV), RV/total lung capacity (TLC) ratio (RV/TLC), decreased diffusing capacity of the lung for carbon monoxide, and increased phase III slope for SBN2. The differences persisted after adjustment for sex and smoking status. Within the VLBW group, subjects with BPD showed significant reduction in FEV1, FEV1/FVC, and forced expiratory flow at 25% to 75% of FVC, and increase in RV, RV/TLC, and phase III slope for SBN2, versus subjects without. The differences remained after adjustment for confounders. CONCLUSIONS: Adult VLBW survivors showed a higher incidence of airflow obstruction, gas trapping, reduced gas exchange, and increased ventilatory inhomogeneity versus controls. The findings suggest pulmonary effects due to VLBW persist into adulthood, and BPD is a further insult on small airway function.

Adolescent Alcohol Use Trajectories: Risk Factors and Adult Outcomes.

OBJECTIVES: Adolescents often display heterogenous trajectories of alcohol use. Initiation and escalation of drinking may be important predictors of later harms, including alcohol use disorder (AUD). Previous conceptualizations of these trajectories lacked adjustment for known confounders of adolescent drinking, which we aimed to address by modeling dynamic changes in drinking throughout adolescence while adjusting for covariates. METHODS: Survey data from a longitudinal cohort of Australian adolescents (n = 1813) were used to model latent class alcohol use trajectories over 5 annual follow-ups (mean age = 13.9 until 17.8 years). Regression models were used to determine whether child, parent, and peer factors at baseline (mean age = 12.9 years) predicted trajectory membership and whether trajectories predicted self-reported symptoms of AUD at the final follow-up (mean age = 18.8 years). RESULTS: We identified 4 classes: abstaining (n = 352); late-onset moderate drinking (n = 503); early-onset moderate drinking (n = 663); and early-onset heavy drinking (n = 295). Having more alcohol-specific household rules reduced risk of early-onset heavy drinking compared with late-onset moderate drinking (relative risk ratio: 0.31; 99.5% confidence interval [CI]: 0.11-0.83), whereas having more substance-using peers increased this risk (relative risk ratio: 3.43; 99.5% CI: 2.10-5.62). Early-onset heavy drinking increased odds of meeting criteria for AUD in early adulthood (odds ratio: 7.68; 99.5% CI: 2.41-24.47). CONCLUSIONS: Our study provides evidence that parenting factors and peer influences in early adolescence should be considered to reduce risk of later alcohol-related harm. Early initiation and heavy alcohol use throughout adolescence are associated with increased risk of alcohol-related harm compared with recommended maximum levels of consumption (late-onset, moderate drinking).