Lex W. Doyle

JAMA pediatrics • February 24, 2025

Lex Doyle, Rheanna Mainzer, Jeanie L Cheong

In Reply We thank Groenendaal and Raghuveer and Zackula for their interest in our article.1 We agree with Groenendaal that the different types of cerebral palsy (CP) have different pathologies, and we support his call that the types of CP should be reported in more detail in future publications of neonatal neurodevelopment. It was not possible to consider the different types of CP in this article1 because such details had not been reported in all of the 26 studies that we included. Groenendaal also suggests that dexamethasone is unlikely to be associated with unilateral CP caused by severe intraventricular hemorrhage (IVH) and unilateral venous infarction because such pathology occurs shortly after birth. However, it should be noted that 6 of the 26 studies included in our article started treatment within 24 hours after birth, and 10 by 48 hours after birth, which would precede the occurrence of some cases of severe IVH. Even if treatment started after the main pathology that might ultimately cause CP, corticosteroids could still alter the natural progression to ultimate motor deficit through their anti-inflammatory effects, and prevent the later diagnosis of CP in some cases. Alternatively, through their neurotoxic effects, corticosteroids could accelerate the path to CP in those with severe IVH.

Annals Of The American Thoracic Society • January 21, 2025

Cassidy Du Berry, Rheanna Mainzer, Nicole Westrupp, Tara Fitzgerald, Sarath Ranganathan, Lex Doyle, Liam Welsh, Jeanie L Cheong

Rationale: The effect of moderate to late preterm (MLP) birth (32-36 completed weeks' gestation) on childhood respiratory health is unclear. Objectives: To assess the effect of being born MLP, compared with being born at term (≥37 completed weeks' gestation), on lung function and respiratory morbidity at 9-10 years of age. Methods: A prospective cohort study was conducted among children born MLP or at term at the Royal Women's Hospital (Victoria, Australia). Participants completed pre and postbronchodilator spirometry, measurement of diffusing capacity of the lung for carbon monoxide, plethysmography, and multiple-breath washout at 9-10 years of age. Parents completed the ISAAC (International Study of Asthma and Allergies in Childhood) questionnaire. Mean differences in z-scores of lung function outcomes and risk ratio for ISAAC outcomes between those born MLP and those born at term were estimated using regression models with adjustment for potential confounding. Multiple imputation was used to handle missing data. Results: A total of 148 of 201 children born MLP and 120 of 201 term-born control subjects were assessed at 9-10 years. Compared with control subjects, children born MLP had lower mean z-scores for forced expiratory volume in 1 second (mean difference, -0.35 [95% confidence interval (CI), -0.61 to -0.08]), ratio of forced expiratory volume in 1 second to forced vital capacity (mean difference, -0.29 [95% CI, -0.58 to -0.01]), forced expiratory flow at 25-75% of forced vital capacity (-0.33 [95% CI, -0.62 to -0.04]), and diffusing capacity of the lung for carbon monoxide (-0.24 [95% CI, -0.45 to -0.03]). Participants born MLP had higher risk of experiencing asthma symptoms (risk ratio, 1.52 [95% CI, 1.08-2.14]). Conclusions: Children born MLP have lower lung function and increased risk of exhibiting asthma symptoms compared with term-born peers at 9-10 years. Such findings at the end of the first decade of life may portend adverse consequences for respiratory health in adulthood.

Pediatric Research • December 21, 2024

Background: Very preterm (VPT; <32 weeks) or very low birth weight (VLBW; <1500 g) birth is associated with socioeconomic disadvantages in adulthood; however, the predictors of these outcomes remain underexplored. This study examined socioeconomic disparities and identified neonatal and sociodemographic risk factors among VPT/VLBW individuals. Methods: A one-stage individual participant data meta-analysis was conducted using 11 birth cohorts from eight countries, comprising 1695 VPT/VLBW and 1620 term-born adults aged 18-30 years. Results: VPT/VLBW adults had lower odds of higher educational attainment (0.40[0.26-0.59]), remaining in education (0.63[0.47-0.84]) or paid work (0.76[0.59-0.97]), and higher odds of receiving social benefits (3.93[2.63-5.68]) than term-borns. Disparities in education and social benefits persisted after adjusting for age, sex, and maternal education, even among those without neurosensory impairments (NSI). Among VPT/VLBW adults, NSI significantly impacted all socioeconomic outcomes, increasing the odds of receiving social benefits 6.7-fold. Additional risk factors included medical complications, lower gestational age and birth weight, lower maternal education, younger maternal age, and non-white ethnicity. Conclusions: NSI is the strongest risk factor for adulthood socioeconomic challenges in the VPT/VLBW population. Mitigating these disparities may require improved neonatal care to reduce NSI prevalence and targeted social and educational support for VPT/VLBW individuals. Conclusions: Very preterm or very low birth weight (VPT/VLBW) birth is associated with socioeconomic disadvantages in adulthood, including lower educational attainment, lower employment rates, and a higher need for social benefits compared with individuals born at term. Neurosensory impairments are strongly associated with adverse socioeconomic outcomes among VPT/VLBW adults, while lower gestational age, lower birth weight, and sociodemographic disadvantages serve as additional risk factors. Early interventions in the NICU that reduce medical complications, along with enhanced educational support throughout childhood, may help mitigate long-term socioeconomic disparities for individuals born VPT/VLBW.

JAMA Pediatrics • November 18, 2024

Lex Doyle, Rheanna Mainzer, Jeanie L Cheong

Systemic postnatal corticosteroids have been shown to reduce rates of bronchopulmonary dysplasia (BPD) in infants born preterm, but both corticosteroids and BPD are associated with cerebral palsy. To describe how the association between systemic postnatal corticosteroids and survival free of cerebral palsy varies with the risk of BPD in infants born preterm, and if the association differs between dexamethasone and hydrocortisone, or with age at starting treatment. This comparative effectiveness research used weighted meta-regression analysis of eligible randomized clinical trials (RCTs) of systemic postnatal corticosteroids reported from June 1989 through March 2022 that included rates of all of BPD, mortality, and cerebral palsy in neonatal intensive care units in 10 countries. Infants born preterm at risk of BPD were included. Data were analyzed from April and July 2024. Systemic dexamethasone or hydrocortisone. Type and timing of corticosteroid, control group rate of BPD, and risk difference in survival free of cerebral palsy between corticosteroid and control arms. Twenty-six RCTs with data on 3700 randomized infants were eligible; 18 (69%) investigated dexamethasone and 8 (31%) hydrocortisone; 12 (46%) started treatment in the first week after birth. There was evidence for a differential association of the type of corticosteroid with the effect of systemic dexamethasone on survival free of cerebral palsy and the risk of BPD in control groups (interaction coefficient, 0.54; 95% CI, 0.25-0.82; P = .001). For dexamethasone, for every 10-percentage point increase in the risk of BPD, the risk difference for survival free of cerebral palsy increased by 3.74% (95% CI, 1.54 to 5.93; P = .002). Dexamethasone was associated with improved survival free of cerebral palsy at a risk of BPD greater than 70%. Conversely, dexamethasone was associated with harm at a risk of BPD less than 30%. There was some evidence for a negative association with hydrocortisone, with possible benefit with risk of BPD less than 30%. There was no strong evidence for a differential effect of timing among those treated with dexamethasone (interaction coefficient, 0.13; 95% CI, -0.04 to 0.30; P = .14). The findings suggest that dexamethasone (compared with control) was associated with improved rates of survival free of cerebral palsy in infants at high risk of BPD but should be avoided in those at low risk. A role for hydrocortisone is uncertain.

JAMA Network Open • November 18, 2024

Jeanie L Cheong, Rheanna Mainzer, Lex Doyle, Joy Olsen, Rachel Ellis, Tara Fitzgerald, Kate Cameron, Lauren Rossetti, Peter Anderson, Alicia Spittle

Although children born moderate to late preterm (MLP; 32-36 weeks' gestation) have more neurodevelopmental problems compared with children born early term or later (≥37 weeks' gestation), detailed understanding of affected domains at school age is lacking. Little is known of risk factors for poorer development. To examine whether being born MLP compared with being born early term or later is associated with neurodevelopmental outcomes at age 9 years and to describe factors associated with poorer neurodevelopment in children born MLP. This prospective, longitudinal cohort study recruited children born MLP and children born early term or later with healthy birth weight (≥2500 g) at a single tertiary hospital in Melbourne, Victoria, Australia, between December 7, 2009, and March 26, 2014. Nine-year follow-up occurred between June 20, 2019, and February 27, 2024. Moderate to late preterm birth. Cognitive ability, academic performance, motor function, behavior, and social communication skills, assessed at 9-year follow-up. Group differences were estimated using linear, logistic, or quantile regression adjusted for multiple birth and socioeconomic risk. Multiple imputation was used to account for missing data. Associations of antenatal and neonatal factors and developmental delay at 2 years with poorer 9-year neurodevelopment were explored using univariable regression. Of 201 recruited children born MLP and 201 born early term or later, 159 born MLP (79.1%; 72 [45.3%] male) and 137 born early term or later (68.2%; 75 [54.7%] male) were assessed. Compared with children born early term or later, children born MLP had lower mean (SD) full-scale IQ scores (105.2 [13.6] vs 110.1 [13.0]; adjusted mean difference, -4.4 [95% CI, -7.7 to -1.0]) and poorer performance for cognitive domains, including verbal comprehension, visuospatial, and working memory. They also had poorer academic performance: pseudoword decoding (mean [SD] score, 103.0 [11.3] vs 107.3 [10.5]; adjusted mean difference, -4.0 [95% CI, -7.0 to -1.1]) and mathematics (mean [SD] score, 96.6 [14.7] vs 101.5 [14.5]; adjusted mean difference, -5.0 [95% CI, -8.8 to -1.2]). Children born MLP had similar manual dexterity to those born early term or later (mean [SD] score, 8.4 [3.5] vs 9.1 [3.4]; adjusted mean difference, -0.9 [95% CI, -1.8 to 0.04]) but more behavioral difficulties (50 of 158 [31.7%] vs 29 of 135 [21.5%]; adjusted risk ratio, 1.57 [95% CI, 1.06-2.33]). Developmental delay at 2 years was associated with poorer 9-year neurodevelopment across multiple domains. In this longitudinal cohort study of children born MLP, neurodevelopmental challenges persisted into school age. An assessment at age 2 years may assist in identifying children born MLP who are at risk of school-age impairments.