Growth from infancy to adulthood and associations with cardiometabolic health in individuals born extremely preterm.

Background: Few studies have tracked growth in children born extremely preterm (EP, <28 weeks' gestation) beyond late adolescence. The relationships between growth parameters (including weight and BMI) through childhood and adolescence with later cardiometabolic health, are unclear in those born EP. We aimed to (i) compare growth from 2 to 25 years between EP and controls; and in the EP group (ii) determine the associations of growth parameters with cardiometabolic health. Methods: Prospective state-wide cohort of all EP livebirths in Victoria, Australia, in 1991-1992 and contemporaneous term-born controls. Z-scores for weight (z-weight), height (z-height) and BMI (z-BMI) at 2, 5, 8, 18 and 25 years, and cardiometabolic health at 25 years (body composition, glucose tolerance, lipid profiles, blood pressure, exercise capacity) were measured. Growth trajectories were compared between groups using mixed models. The relationships between z-BMI changes/year, and being overweight at different ages, with cardiometabolic health were explored using linear regression. Findings: Z-weight and z-BMI were lower in EP than controls, but the gap decreased with age due to a more rapid rate of rise in z-weight and a decrease in z-height in the EP group compared with controls. Greater increases in z-BMI/year in the EP group were associated with poorer cardiometabolic health [coefficient (95% CI) per 0.1 z-BMI increase/year: visceral fat volume (cm3) 217.8 (160.9, 274.7), triglycerides (mmol/L) 0.45 (0.20, 0.71), systolic blood pressure (mmHg) 8.9 (5.8, 12.0), and exercise capacity (BEEP test maximum level -1.2 (-1.7, -0.7)), all p < 0.001]. The association between being overweight with poorer cardiometabolic health strengthened with age. Interpretation: The catch-up in weight and BMI by young adulthood in survivors born EP may not be desirable as it is associated with poorer cardiometabolic health. The associations of being overweight from mid-childhood with poorer cardiometabolic health may provide a window for intervention. Funding: National Health and Medical Research Council of Australia.

Mental health in young adults born extremely preterm or extremely low birthweight with contemporary neonatal intensive care.

BACKGROUND: For infants born in the contemporary era of neonatal care, little is known about adult mental health outcomes of extremely preterm birth (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g). This study aimed to compare attention deficit hyperactivity disorder (ADHD), anxiety, mood, and substance use disorder prevalence in young adults born EP/ELBW and normal birthweight (NBW; >2499 g) controls, and to compare change in prevalence of mental health symptoms and disorders from 18 to 25 years. METHODS: Participants were a prospective geographical cohort of 297 consecutive survivors born EP/ELBW during 1991-1992 and 260 NBW controls. At age 25 years, 174 EP/ELBW and 139 NBW participants completed the Adult ADHD Rating Scale, Structured Clinical Interview for DSM-IV Disorders, Beck Anxiety Inventory, and Center for Epidemiologic Studies Depression Scale-Revised. Data from follow-up at 18 years were also utilized. Multiple imputation was used to account for attrition. RESULTS: Mental health outcomes at 25 years were similar between groups: prevalence rates were ADHD 7% v. 5%; anxiety 32% v. 27%; mood 38% v. 35%; substance use 12% v. 14% in the EP/ELBW and NBW groups, respectively. In both groups, ADHD declined between 18 and 25 years [odds ratio (OR) per year = 0.87, 95% confidence interval (CI) 0.79-0.95], and generalized anxiety disorder and major depressive episode became more common (OR 1.22, 95% CI 1.10-1.35 per year; OR 1.20, 95% CI 1.10-1.30 respectively). CONCLUSIONS: This contemporary EP/ELBW cohort has comparable young adult mental health outcomes to controls, and similar patterns of change in mental health from late adolescence.

Exploring the "Preterm Behavioral Phenotype" in Children Born Extremely Preterm.

OBJECTIVE: To examine whether difficulties in emotional, attention, and peer or social functioning (a proposed "preterm behavioral phenotype") co-occur within individual children born extremely preterm (EP; <28 weeks of gestation) and/or extremely low birth weight (ELBW; <1,000 g) and whether different behavioral profiles are related to cognitive and academic outcomes. METHODS: Population-based cohort of all EP/ELBW survivors born in the state of Victoria, Australia, in 2005, and contemporaneous matched controls were recruited at birth. At age 7 to 8 years, parents of 181 EP/ELBW and 185 control children rated their children's behavior on the Strengths and Difficulties Questionnaire problem scales (emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems). Latent profile analysis was used to explore patterns of behavior within individual children. RESULTS: Four behavioral profiles were identified: (1) minimal difficulties in all domains; (2) a profile consistent with the preterm behavioral phenotype; (3) elevations in all domains except peer problems; and (4) marked global elevations in all domains. Most preterm children (55%) had a profile of minimal difficulties. Relative to their risk of being in the minimal difficulties group, EP/ELBW children were overrepresented in the preterm behavioral phenotype (20% vs. 12% controls) and the globally elevated symptom groups (8% vs. 3%). Accounting for birth group and demographic variables, profiles with higher levels of behavior symptoms were associated with poorer cognitive and academic performance. CONCLUSION: Although more EP/ELBW children exhibited the proposed preterm behavioral phenotype than controls, it occurred in only 20% of EP/ELBW children. Greater behavior symptoms were associated with poorer cognitive and academic outcomes.

The cost of long-term follow-up of high-risk infants for research studies.

AIMS: Neonatal intensive care is expensive, and thus it is essential that its long-term outcomes are measured. The costs of follow-up studies for high-risk children who survive are unknown. This study aims to determine current costs for the assessment of health and development of children followed up in our research programme. METHODS: Costs were determined for children involved in the research follow-up programme at the Royal Women's Hospital, Melbourne, over the 6-month period between 1st January 2012 and 30th June 2012. The time required for health professionals involved in assessments in early and later childhood was estimated, and converted into dollar costs. Costs for equipment and data management were added. Estimated costs were compared with actual costs of running the research follow-up programme. RESULTS: A total of 134 children were assessed over the 6-month period. The estimated average cost per child assessed was $1184, much higher than was expected. The estimated cost to assess a toddler was $1149, whereas for an 11-year-old it was $1443, the difference attributable to the longer psychological and paediatric assessments. The actual average cost per child assessed was $1623. The shortfall of $439 between the actual and estimated average costs per child arose chiefly because of the need to pay staff even when participants were late or failed to attend. CONCLUSIONS: The average costs of assessing children at each age for research studies are much higher than expected. These data are useful for planning similar long-term follow-up assessments for high-risk children.

Abnormalities in orbitofrontal cortex gyrification and mental health outcomes in adolescents born extremely preterm and/or at an extremely low birth weight.

Extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) infants are at high risk of aberrant neurodevelopment. Sulcogyral folding patterns of the orbitofrontal cortex (OFC) are determined during the third trimester, however little is known about OFC patterning in EP/ELBW cohorts, for whom this gestational period is disturbed. This study investigated whether the distribution of OFC pattern types and frequency of intermediate and/or posterior orbital sulci (IOS/POS) differed between EP/ELBW and control adolescents. This study also investigated whether OFC pattern type was associated with mental illness or executive function outcome in adolescence. Magnetic resonance images of 194 EP/ELBW and 147 full term (>37 completed weeks) and/or normal birth weight (> 2500 g) adolescents were acquired, from which the OFC pattern of each hemisphere was classified as Type I, II, or III. Compared with controls, more EP/ELBW adolescents possessed a Type II in the left hemisphere (P = 0.019). The EP/ELBW group had fewer IOS (P = 0.024) and more POS (P = 0.021) in the left hemisphere compared with controls. OFC pattern type was not associated with mental illness, however in terms of executive functioning, Type III in the left hemisphere was associated with better parent-reported metacognition scores overall (P = 0.008) and better self-reported behavioral regulation scores in the control group (P = 0.001) compared with Type I. We show, for the first time that EP/ELBW birth is associated with changes in orbitofrontal development, and that specific patterns of OFC folding are associated with executive function at age 18 years in both EP/ELBW and control subjects.

Growth of extremely preterm survivors from birth to 18 years of age compared with term controls.

OBJECTIVES: To determine changes in height, weight, and BMI of extremely preterm (EPT; gestational age <28 completed weeks) survivors from birth to 18 years of age, compared with term controls. METHODS: Birth, discharge, and follow-up at ages 2, 5, 8, and 18 years of consecutive EPT survivors and contemporaneous term controls born in 1991-1992 in Victoria, Australia. Weight, height, and BMI were converted to z scores and compared between groups. Height z scores at age 2 and midparental height z scores were examined as predictors of height z score at age 18 years. RESULTS: Follow-up rates were >90% until 18 years, when 166 (74%) of 225 EPT subjects and 153 (60%) of 253 controls were assessed. EPT subjects had lower weight z scores than controls at birth, with a much greater difference at discharge, which reduced progressively until age 18 years. EPT children were shorter than controls at all ages, and this difference did not alter greatly over time. BMI z scores were lower in EPT children at younger ages, but by age 18 were similar between groups. Height at age 2 was a better predictor of height at age 18 in EPT participants, compared with midparental height. CONCLUSIONS: EPT survivors were substantially lighter than term controls from birth to late adolescence, although the gap in weight steadily decreased over time from a peak at the time of discharge. The height disadvantage in EPT children compared with controls remained constant over time and BMI scores were similar at age 18 years.

Postnatal corticosteroids and neurodevelopmental outcomes in extremely low birthweight or extremely preterm infants: 15-year experience in Victoria, Australia.

OBJECTIVE: Postnatal corticosteroids (PCS) are used to prevent or treat bronchopulmonary dysplasia (BPD) in extremely low birthweight (ELBW; <1000 g) or extremely preterm (EPT; <28 weeks) infants. In the early 2000s, concerns were raised about increased risks of cerebral palsy (CP) in association with PCS, which may have affected prescribing of PCS, and influenced rates of BPD, mortality or long-term neurosensory morbidity. Our aim was to determine the changes over time in the rates of PCS use and 2-year outcomes in ELBW/EPT infants in Victoria, Australia. DESIGN: All ELBW or EPT infants born in Victoria, Australia in three distinct eras (1991-92, 1997 and 2005) who were alive at 7 days were included. Rates of PCS use, rates of BPD (oxygen dependency at 36 weeks' corrected age), death before 2 years of age, CP and major disability (any of moderate/severe CP, developmental quotient <-2 SD, blindness or deafness) were contrasted between cohorts. RESULTS: The rate of PCS use and the dose prescribed diminished significantly in 2005 compared with earlier eras, but the rate of BPD rose. Non-significant changes in the rates of mortality over time were mirrored by non-significant changes in the rates of CP or major disability. Combined outcomes of mortality with either major disability or CP were similar over the three eras. CONCLUSIONS: PCS use decreased in 2005 compared with earlier eras, and was accompanied by a rise in BPD, with no significant changes in mortality or neurological morbidity.