Trends in survival, perinatal morbidities and two-year neurodevelopmental outcomes in extremely low-birthweight infants over four decades.

BACKGROUND: Although outcomes for infants born extremely low birthweight (ELBW; <1000 g birthweight) have improved over time, it is important to document survival and morbidity changes following the advent of modern neonatal intensive care in the 1990s. OBJECTIVE: To describe trends in survival, perinatal outcomes and neurodevelopment to 2 years' corrected age over time across six discrete geographic cohorts born ELBW between 1979 and 2017. METHODS: Analysis of data from discrete population-based prospective cohort studies of all live births free of lethal anomalies with birthweight 500-999 g in the state of Victoria, Australia, over 6 eras: 1979-80, 1985-87, 1991-92, 1997, 2005 and 2016-17. Perinatal data collected included survival, duration and type of respiratory support, neonatal morbidities and two-year neurodevelopmental outcomes. RESULTS: More ELBW live births were inborn (born in a maternity hospital with a neonatal intensive care unit) over time (1979-80, 70%; 2016-17, 84%), and more were offered active care (1979-80, 58%; 2016-17, 90%). Survival to 2 years rose substantially, from 25% in 1979-80 to 80% in 2016-17. In survivors, rates of any assisted ventilation rose from 75% in 1979-80 to 99% in 2016-17. Cystic periventricular leukomalacia, severe retinopathy of prematurity and blindness improved across eras. Two-year data were available for 95% (1054/1109) of survivors. Rates of cerebral palsy, deafness and major neurodevelopmental disability changed little over time. The annual numbers with major neurodevelopmental disability increased from 12.5 in 1979-80 to 30 in 2016-17, but annual numbers free of major disability increased much more, from 31 in 1979-80 to 147 in 2016-17. CONCLUSIONS: Active care and survival rates in ELBW children have increased dramatically since 1979 without large changes in neonatal morbidities. The numbers of survivors free of major neurodevelopmental disability have increased more over time than those with major disability.

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.

Temporal Trends in Neurodevelopmental Outcomes to 2 Years After Extremely Preterm Birth.

Importance: Survival of infants born extremely preterm (EP) (<28 weeks' gestation) has increased since the early 1990s. It is necessary to know whether increased survival is accompanied by increased neurodevelopmental disability. Objective: To examine changes in major (ie, moderate or severe) neurodevelopmental disability and survival free of major neurodevelopmental disability at 2 years in infants born EP. Design, Setting, and Participants: Four prospective longitudinal cohort studies comprising all EP live births at 22 to 27 weeks' gestation from April 1, 2016, to March 31, 2017, and earlier eras (1991-1992, 1997, and 2005), and contemporaneous term-born controls in the state of Victoria, Australia. Among 1208 live births during the periods studied, data were available for analysis of 2-year outcomes in 1152 children: 422 (1991-1992), 215 (1997), 263 (2005), and 252 (2016-2017). Data analysis was performed from September 17, 2020, to April 15, 2021. Exposures: Extreme preterm live birth. Main Outcomes and Measures: Survival, blindness, deafness, cerebral palsy, developmental delay, and neurodevelopmental disability at 2 years' corrected age. Developmental delay comprised a developmental quotient less than -1 SD relative to the control group means on the Bayley Scales for each era. Major neurodevelopmental disability comprised blindness, deafness, moderate to severe cerebral palsy, or a developmental quotient less than -2 SDs. Individual neurodevelopmental outcomes in each era were contrasted relative to the 2016-2017 cohort using logistic regression adjusted for gestational age, sex, birth weight z score, and sociodemographic variables. Changes in survival free of major neurodevelopmental disability over time were also assessed using logistic regression. Results: Survival to 2 years was highest in 2016-2017 (73% [215 of 293]) compared with earlier eras (1991-1992: 53% [225 of 428]; 1997: 70% [151 of 217]; 2005: 63% [170 of 270]). Blindness and deafness were uncommon (<3%). Cerebral palsy was less common in 2016-2017 (6%) than in earlier eras (1991-1992: 11%; 1997: 12%; 2005: 10%). There were no obvious changes in the rates of developmental quotient less than -2 SDs across eras (1991-1992: 18%; 1997: 22%; 2005: 7%; 2016-2017: 15%) or in rates of major neurodevelopmental disability (1991-1992: 20%; 1997: 26%; 2005: 15%; 2016-2017: 15%). Rates of survival free of major neurodevelopmental disability increased steadily over time: 42% (1991-1992), 51% (1997), 53% (2005), and 62% (2016-2017) (odds ratio, 1.30; 95% CI, 1.15-1.48 per decade; P < .001). Conclusions and Relevance: These findings suggest that survival free of major disability at age 2 years in children born EP has increased by an absolute 20% since the early 1990s. Increased survival has not been associated with increased neurodevelopmental disability.

Changing consumption of resources for respiratory support and short-term outcomes in four consecutive geographical cohorts of infants born extremely preterm over 25 years since the early 1990s.

OBJECTIVES: It is unclear how newer methods of respiratory support for infants born extremely preterm (EP; 22-27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. DESIGN: Prospective longitudinal cohort study. SETTING: The State of Victoria, Australia. PARTICIPANTS: All EP births offered intensive care in four discrete eras (1991-1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016-March 2017 (12 months): n=250). OUTCOME MEASURES: Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. RESULTS: Median duration of any respiratory support increased from 22 days (1991-1992) to 66 days (2016-2017). The increase occurred in non-invasive respiratory support (2 days (1991-1992) to 51 days (2016-2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016-2017. Survival to discharge home increased (68% (1991-1992) to 87% (2016-2017)). Cystic periventricular leukomalacia decreased (6.3% (1991-1992) to 1.2% (2016-2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991-1992) to 10.0% (2016-2017)). The average additional costs associated with one additional infant surviving in 2016-2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991-1992, 1997 and 2005, respectively. CONCLUSIONS: Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function 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.

Changes in long-term prognosis with increasing postnatal survival and the occurrence of postnatal morbidities in extremely preterm infants offered intensive care: a prospective observational study.

BACKGROUND: Decisions regarding provision of intensive care and post-discharge follow-up for infants born extremely preterm (<28 weeks' gestation) are based on the risks of mortality and neurodevelopmental disability. We aimed to elucidate the changes in probability of three outcomes (death, survival with major disability, and survival without major disability) with postnatal age in extremely preterm infants offered intensive care, and the effect of postnatal events on the probability of survival without major disability. METHODS: In this prospective observational study, we used data from three geographical cohorts composed of all extremely preterm livebirths offered intensive care at birth during three distinct periods (1991-92, 1997, and 2005) in Victoria, Australia. Participants were assessed at 8 years' corrected age for major neurodevelopmental disability, defined as moderate or severe cerebral palsy, general intelligence more than 2 SDs below term-born control means, blindness, or deafness. Probabilities of outcomes conditional on survival to different postnatal ages were calculated by logistic regression. Multivariable logistic regression was used to assess factors predictive of survival with major disability. FINDINGS: 751 (82%) of 915 extremely preterm livebirths free of lethal anomalies were offered intensive care, of whom 546 (73%) survived to age 8 years. Of the 499 survivors assessed, 86 (17%) had a major disability. With increasing gestational age at birth or days of postnatal survival, the probability of death decreased and of survival without major disability increased. By contrast, the probability of survival with major disability varied little with gestational age or postnatal survival. In survivors, major disability was associated with the occurrence of four important postnatal events: grade 3 or 4 intraventricular haemorrhage (odds ratio 2·61 [95% CI 1·11-6·15]), cystic periventricular leukomalacia (9·17 [3·57-23·53]), postnatal corticosteroid use (1·99 [1·03-3·85]), and surgery (2·78 [1·51-5·13]). 241 survivors (48%) had no major postnatal events during the newborn period, and had the lowest prevalence of major disability (17 participants [7%]). The probability of survival without major disability decreased with increasing number of major events (0·93 [0·89-0·96] for no events vs 0·31 [0·11-0·59] for three or more events). INTERPRETATION: Long-term prognosis in terms of death and major neurodevelopmental disability changes rapidly after birth for extremely preterm infants. Counselling of families and post-discharge planning should be individualised to changing circumstances following birth. FUNDING: National Health and Medical Research Council of Australia.