Diagnostic accuracy of small-for-gestational-age status for infant mortality and school-age outcomes of live births <28 weeks' gestation: a cohort study.

OBJECTIVES: To determine the diagnostic accuracy of small-for-gestational-age (SGA; <10th centile) status for infant mortality and adverse school-age outcomes in infants born extremely preterm (EP; <28 weeks' gestation). DESIGN: Geographical cohort studies. SETTING: The state of Victoria, Australia. PATIENTS: For mortality, live births 22-27 weeks' gestation from 2009 to 2017 offered active care after birth. For school-age outcomes, survivors to 8 years' corrected age born in 1991-1992, 1997 or 2005. EXPOSURES: SGA <10th centile on four commonly used growth references: three derived from neonatal data (Fenton, UK-WHO and Intergrowth Newborn Size) and one from fetal data (Intergrowth Estimated Fetal Weight). MAIN OUTCOME MEASURES: (a) Infant mortality; (b) major neurodevelopmental disability, and poor performance on tests of IQ, academic achievement, motor function, and executive function. RESULTS: Infant mortality data were available for 2040 infants, and neurodevelopmental data for 499 children. Diagnostic accuracy of SGA status was low overall and varied with the growth reference. Positive predictive values for infant mortality ranged from 18% to 21%, only marginally higher than its 18% prevalence. Compared with a prevalence of 17%, positive predictive values for major neurodevelopmental disability ranged from 30% to 38% for the neonatal growth references but was only 20% for Intergrowth Estimated Fetal Weight. SGA status was also associated with lower IQ, poor academic achievement and poor motor performance. CONCLUSIONS: Among infants born EP, the diagnostic accuracy of SGA status was low for both infant mortality and adverse neurodevelopmental outcomes at school age, but importantly varied with the growth reference used to identify SGA status.

Health-related quality of life in adults born extremely preterm or with extremely low birth weight in the postsurfactant era: a longitudinal cohort study.

OBJECTIVES: To compare health-related quality of life (HRQoL) at 25 and 18 years in individuals born extremely preterm (EP, <28 weeks' gestation) or with extremely low birth weight (ELBW, birth weight <1000 g) with term-born (≥37 weeks) controls. Within the EP/ELBW cohort, to determine whether HRQoL differed between those with lower and higher IQs. METHODS: HRQoL was self-reported using the Health Utilities Index Mark 3 (HUI3) at 18 and 25 years by 297 EP/ELBW and 251 controls born in 1991-1992 in Victoria, Australia. Median differences (MDs) between groups were estimated using multiple imputation to handle missing data. RESULTS: Adults born EP/ELBW had lower HRQoL (median utility 0.89) at 25 years than controls (median utility 0.93, MD -0.040), but with substantial uncertainty in the estimate (95% CI -0.088 to 0.008) and a smaller reduction at 18 years (MD -0.016, 95% CI -0.061 to 0.029). On individual HUI3 items, there was suboptimal performance on speech (OR 9.28, 95% CI 3.09 to 27.93) and dexterity (OR 5.44, 95% CI 1.04 to 28.45) in the EP/ELBW cohort. Within the EP/ELBW cohort, individuals with lower IQ had lower HRQoL compared with those with higher IQ at 25 (MD -0.031, 95% CI -0.126 to 0.064) and 18 years (MD -0.034, 95% CI -0.107 to 0.040), but again with substantial uncertainty in the estimates. CONCLUSIONS: Compared with term-born controls, young adults born EP/ELBW reported poorer HRQoL, as did those with lower IQ compared with those with higher IQ in the EP/ELBW cohort. Given the uncertainties, our findings need corroboration.

Relationships between early postnatal cranial ultrasonography linear measures and neurodevelopment at 2 years in infants born at <30 weeks' gestational age without major brain injury.

OBJECTIVE: To explore relationships of early postnatal cranial ultrasonography (cUS) linear measures of brain size and brain growth with neurodevelopment at 2 years in infants born <30 weeks' gestational age (GA) and free of major brain injury. DESIGN: Prospective observational cohort study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: 139 infants born <30 weeks' GA, free of major brain injury on neonatal cUS and without congenital or chromosomal anomalies known to affect neurodevelopment. INTERVENTION: Linear measures of brain tissue and fluid spaces made from cUS at 1-week, 1-month and 2-months' postnatal age. MAIN OUTCOME MEASURES: Cognitive, language and motor scores on the Bayley Scales of Infant and Toddler Development, third edition at 2 years' corrected age. RESULTS: 313 scans were evaluated from the 131 children who were assessed at 2 years. Larger measures of the corpus callosum at 1 week, 1 month and 2 months, cerebellum and vermis at 2 months and faster positive growth of the cerebellum and vermis between 1 month and 2 months, were related to higher cognitive and language scores at 2 years. No relation between tissue measures and motor scores was found. Larger measures, and faster rate of increase, of fluid spaces within the first weeks after birth were related to better cognitive, language and motor outcomes at 2 years. CONCLUSIONS: Early postnatal cUS linear measures of brain tissue were related to cognitive and language development at 2 years in infants born <30 weeks' GA without major brain injury. Relationships between cUS linear measures of fluid spaces in the early postnatal period and later neurodevelopment warrant further exploration.

School-aged neurodevelopmental outcomes for children born extremely preterm.

As survival rates for children born extremely preterm (EP, <28 weeks' gestation) have increased with advances in perinatal and neonatal care, their long-term functioning and quality of life assume more importance. Outcomes in early childhood provide some information, but outcomes at school-age are more informative of life-long functioning. Children born EP at school-age have substantially higher rates of intellectual impairment, poorer executive, academic and motor function, more neurodevelopmental disability, and poorer health-related quality of life than do contemporaneous term-born controls. Because the rates of adverse outcomes remain unacceptably high, and particularly since some outcomes may be deteriorating rather than improving over time, new strategies to ameliorate these problems, targeting periods before, during and after birth, and throughout the lifespan, are a priority.

Early developmental screening and intervention for high-risk neonates - From research to clinical benefits.

With advances in neonatal care there has been an increase in survival rates for infants born very preterm and/or with complex needs, such as those who require major surgery, who may not have survived decades ago. Despite advances in survival, these infants remain at high-risk for a range of neurodevelopmental delays and/or impairments including motor, cognitive and emotional/behavioural challenges. Research has improved our ability to identify which infants are at high-risk of developmental delay and/or impairments, and there is mounting evidence that early interventions can improve outcomes of these infants. However, clinical practice varies throughout the world regarding recommendations for developmental screening. Moreover, intervention, when available, is often not commenced early enough in development. Given limited resources, those infants most at risk of developmental impairments and their families should be targeted, with further research needed on the cost-effectiveness of surveillance and early interventions.

Changes over time in quality of life of school-aged children born extremely preterm: 1991-2005.

OBJECTIVE: To compare health-related quality of life (HRQOL) at 8 years in children born extremely preterm (EP) with contemporaneous term-born controls over three epochs: 1991-92, 1997 and 2005. DESIGN: Prospective recruitment of geographic cohorts across three distinct eras. Utilities were calculated from the parent-completed Health Utilities Index (HUI), version 2 (1991-92 and 1997 cohorts) and version 3 (2005 cohort). Differences in utilities >0.05 are clinically important. SETTING: The state of Victoria, Australia. PATIENTS: 475 EP (<28 weeks' gestation) and 570 term controls. MAIN OUTCOME MEASURES: Utilities of children born EP compared with term controls within each era, and paired differences between an EP and matched controls compared across eras. RESULTS: Overall, 86% of survivors had utility data at 8 years of age; 475 EP and 570 controls. In all eras, parent-reported utilities were lower for children born EP compared with controls (difference in medians (95% CIs); 1991-92, -0.053 (-0.071 to -0.035); 1997, -0.053 (-0.072 to -0.034); 2005, -0.082 (-0.097 to -0.068)). Mean differences (MD) between EP children and matched controls within each era were lower in the 2005 cohort compared with both the 1991-92 cohort (MD -0.054, 95% CI -0.097 to -0.010) and the 1997 cohort (MD -0.053, 95% CI -0.097 to -0.009). CONCLUSION: Children born EP in the postsurfactant era have clinically important reductions in parent-reported HRQOL compared with controls, which may be worsening over time.

Extreme prematurity, growth and neurodevelopment at 8 years: a cohort study.

OBJECTIVE: Infants born extremely preterm (EP, <28 weeks' gestation) exhibit poorer growth and neurodevelopmental impairment in early childhood compared with their term-born peers. Whether poor growth persists and whether associations of growth with neurodevelopmental functioning have changed in the decades since the introduction of surfactant are not well described. This study aims to (1) compare growth from birth to 2 years then 8 years in children born EP between three different eras, and (2) investigate the associations of growth from birth to 2 years then 8 years with cognitive, academic, executive and motor function at 8 years, and if associations have changed over time. DESIGN: Prospective observational cohort studies in the State of Victoria, Australia in three discrete eras: 1991-1992, 1997 and 2005. EP children had weight and head circumference measured at birth, and weight, head circumference and height at 2 and 8 years. Cognitive ability, academic performance, executive function and motor skills were assessed at 8 years, corrected for prematurity. RESULTS: 499/546 (91%) of surviving EP children were fully assessed at 8 years. Growth in children born EP did not differ substantially between eras and associations between growth and neurodevelopment did not change over time. Overall, better weight and head growth from birth to 2 years were associated with improved neurodevelopment at 8 years. CONCLUSIONS: Growth of children born EP has not improved in more recent eras. Better early head and weight growth are associated with improved neurodevelopment in mid-childhood.

School-age outcomes following intraventricular haemorrhage in infants born extremely preterm.

OBJECTIVE: To determine the associations of different grades of intraventricular haemorrhage (IVH), particularly grades 1 and 2, with neurodevelopmental outcomes at 8 years of age in children born extremely preterm. DESIGN: Population-based cohort study. SETTING: State of Victoria, Australia. PATIENTS: Survivors born at <28 weeks' gestational age (n=546) and matched term-born controls (n=679) from three distinct eras, namely, those born in 1991-1992, 1997 and 2005. EXPOSURE: Worst grade of IVH detected on serial neonatal cranial ultrasound. OUTCOME MEASURES: Intellectual ability, executive function, academic skills, cerebral palsy and motor function at 8 years. RESULTS: There was a trend for increased motor dysfunction with increasing severity of all grades of IVH, from 24% with no IVH, rising to 92% with grade 4 IVH. Children with grade 1 or 2 IVH were at higher risk of developing cerebral palsy than those without IVH (OR 2.24, 95% CI 1.21 to 4.16). Increased rates of impairment in intellectual ability and academic skills were observed with higher grades of IVH, but not for grade 1 and 2 IVH. Parent-rated executive functioning was not related to IVH. CONCLUSION: While low-grade IVH is generally considered benign, it was associated with higher rates of cerebral palsy in school-aged children born EP, but not with intellectual ability, executive function, academic skills or overall motor function. Higher grades of IVH were associated with higher rates and risks of impairment in motor function, intellectual ability and some academic skills, but not parental ratings of executive function.

Long-term effects of postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia: Balancing the risks and benefits.

Postnatal corticosteroids are effective in preventing or treating bronchopulmonary dysplasia (BPD) in preterm newborns, but their benefits need to exceed their risks. Several types of corticosteroids, and different timing and administration modes have been trialed. Systemic corticosteroids, given either early or late, have proven efficacy for reducing BPD and the combined outcome of death or BPD. Inhaled corticosteroids are less effective. However, systemic dexamethasone given early is associated with more neurosensory disability and cerebral palsy in survivors. The risk of adverse neurodevelopment is highest if dexamethasone is given to preterm infants at low risk of BPD. Current trials focus on corticosteroids, mixed with surfactant, delivered intratracheally directly to the lung, which may avoid some systemic adverse effects of corticosteroids. Early trials of intratracheal corticosteroids are encouraging, but more data are needed to determine whether this method of administration is preferable to systemic corticosteroids for preventing or treating BPD.

Late preterm births: New insights from neonatal neuroimaging and neurobehaviour.

With increasing evidence of neurodevelopmental problems faced by late preterm children, there is a need to explore possible underlying brain structural changes. The use of brain magnetic resonance imaging has provided insights of smaller and less mature brains in infants born late preterm, associated with developmental delay at 2 years. Another useful tool in the newborn period is neurobehavioural assessment, which has also been shown to be suboptimal in late preterm infants compared with tern infants. Suboptimal neurobehaviour is also associated with poorer 2-year neurodevelopment in late preterm infants. More research into these tools will provide a better understanding of the underlying processes of developmental deficits of late preterm children. The value of their role in clinical care remains to be determined.

Early surgery and neurodevelopmental outcomes of children born extremely preterm.

OBJECTIVES: To (1) compare the neurodevelopmental outcomes at 8 years of age of children born extremely preterm (EP) who underwent surgical procedures during the course of their initial hospital admission with those who did not and (2) compare the outcomes across eras, from 1991 to 2005. DESIGN: Prospective observational cohort studies conducted over three different eras (1991-1992, 1997 and 2005). Surviving EP children, who required surgical intervention during the primary hospitalisation, were assessed for general intelligence (IQ) and neurosensory status at 8 years of age. Major neurosensory disability comprised any of moderate/severe cerebral palsy, IQ less than -2 SD relative to term controls, blindness or deafness. RESULTS: Overall, 29% (161/546) of survivors had surgery during the newborn period, with similar rates in each era. Follow-up rates at 8 years were high (91%; 499/546), and 17% (86/499) of survivors assessed had a major neurosensory disability. Rates of major neurosensory disability were substantially higher in the surgical group (33%; 52/158) compared with those who did not have surgery (10%; 34/341) (OR 4.28, 95% CI 2.61 to 7.03). Rates of disability in the surgical group did not improve over time. After adjustment for relevant confounders, no specific surgical procedure was associated with increased risk of disability. IMPLICATIONS AND RELEVANCE: Major neurosensory disability at 8 years was higher in children born EP who underwent surgery during their initial hospital admission compared with those who did not. The rates of major neurosensory disability in the surgical cohort are not improving over time.