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Background: Preclinical studies suggest synergistic effects of maternal inflammatory exposures on offspring neurodevelopment, but human studies have been limited., Objectives: To examine the cumulative association and potential interactions between seven maternal exposures related to inflammation and child attention-deficit/hyperactivity disorder (ADHD)., Methods: We conducted a population-based cohort study of children born from July 2001 to December 2011 in New South Wales, Australia, and followed up until December 2014. Seven maternal exposures were identified from birth data and hospital admissions during pregnancy: autoimmune disease, asthma, hospitalization for infection, mood or anxiety disorder, smoking, hypertension, and diabetes. Child ADHD was identified from stimulant prescription records. Multivariable Cox regression assessed the association between individual and cumulative exposures and ADHD and potential interaction between exposures, controlling for potential confounders., Results: The cohort included 908,770 children, one-third (281,724) with one or more maternal exposures. ADHD was identified in 16,297 children (incidence 3.5 per 1000 person-years) with median age of 7 (interquartile range 2) years at first treatment. Each exposure was independently associated with ADHD, and risk increased with additional exposures: one exposure (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.54, 1.65), two exposures (HR 2.25, 95% CI 2.13, 2.37), and three or more exposures (HR 3.28, 95% CI 2.95, 3.64). Positive interaction was found between smoking and infection. The largest effect size was found for cumulative exposure of asthma, infection, mood or anxiety disorder, and smoking (HR 6.12, 95% CI 3.47, 10.70)., Conclusions: This study identifies cumulative effects of multiple maternal exposures related to inflammation on ADHD, most potentially preventable or modifiable. Future studies should incorporate biomarkers of maternal inflammation and consider gene-environment interactions., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Background: Administrative health data has been used extensively to examine congenital heart disease (CHD). However, the accuracy and completeness of these data must be assessed., Objectives: To use data linkage of multiple administrative data sources to examine the validity of identifying CHD cases recorded in hospital discharge data., Methods: We identified all liveborn infants born 2013-2017 in New South Wales, Australia with a CHD diagnosis up to age one, recorded in hospital discharge data. Using record linkage to multiple data sources, the diagnosis of CHD was compared with five reference standards: (i) multiple hospital admissions containing CHD diagnosis; (ii) receiving a cardiac procedure; (iii) CHD diagnosis in the Register of Congenital Conditions; (iv) cardiac-related outpatient health service recorded; and/or (v) cardiac-related cause of death. Positive predictive values (PPV) comparing CHD diagnosis with the reference standards were estimated by CHD severity and for specific phenotypes., Results: Of 485,239 liveborn infants, there were 4043 infants with a CHD diagnosis identified in hospital discharge data (8.3 per 1000 live births). The PPV for any CHD identified in any of the five methods was 62.8% (95% confidence interval [CI] 60.9, 64.8), with PPV higher for severe CHD at 94.1% (95% CI 88.2, 100). Infant characteristics associated with higher PPVs included lower birthweight, presence of a syndrome or non-cardiac congenital anomaly, born to mothers aged <20 years and residing in disadvantaged areas., Conclusion: Using data linkage of multiple datasets is a novel and cost-effective method to examine the validity of CHD diagnoses recorded in one dataset. These results can be incorporated into bias analyses in future studies of CHD., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Background: Although infant and child mortality rates have decreased substantially worldwide over the past two decades, efforts continue in many nations to further these declines. The identification of pertinent perinatal factors that are associated with early childhood mortality would help with these efforts. We investigated the association of two crucial perinatal factors, gestational age and severe neonatal morbidity at birth, with mortality during infancy (29-364 days) and early childhood (1-5 years)., Methods: The study population included all singleton livebirths, ≥32 weeks' gestation in New South Wales, Australia in 2001-11. Birth data were linked to hospitalisation morbidity data and deaths data (linked birth cohort n = 871 916), and multivariable Cox regression models were used to assess mortality., Results: The median follow-up time per child was 4.95 years (range 0.00-5.92 years; 3 614 738 total person-years), with 984 deaths observed. Gestational age was associated with increased mortality, and specifically from deaths attributable to infections, respiratory conditions, and injuries during infancy, but not during early childhood. Severe neonatal morbidity strongly mediated the effects of gestational age during infancy, but not during early childhood, and was associated with increased mortality from circulatory, nervous, and respiratory system causes., Conclusions: The direct effects of gestational age on mortality extended up to 1 year of age, whereas severe neonatal morbidity remained associated with heightened mortality into early childhood. Efforts to maximise the health and well-being of vulnerable infants, with emphasis on preventing infections and injuries, may help further reduce early childhood mortality., (© 2016 John Wiley & Sons Ltd.)

Background: To investigate whether the adverse infant health outcomes associated with early birth and severe neonatal morbidity (SNM) persist beyond the first year of life and impact on paediatric hospitalisations for children up to 6 years of age., Methods: The study population included all singleton live births, >32 weeks gestation in New South Wales, Australia, in 2001-2005, with follow-up to 6 years of age. Birth data were probabilistically linked to hospitalisation data (n = 392 964). The odds of hospitalisation, mean hospital length of stay (LOS) and costs, and cumulative LOS were evaluated by gestational age and SNM using multivariable analyses., Results: A total of 74 341 (18.9%) and 41 404 (10.5%) infants were hospitalised once and more than once, respectively. SNM was associated with increased odds of hospitalisation once (adjusted odds ratio [aOR] 1.16 [95% confidence interval 1.10, 1.22]) and more than once [aOR 1.51 (1.43, 1.61)]. Decreasing gestational age was associated with increasing odds of hospitalisation more than once from aOR 1.19 at 37-38 weeks to 1.49 at 33-34 weeks. Average LOS and costs per hospital admission were increased with SNM but not with decreasing gestational age. Cumulative LOS was significantly increased with SNM and decreasing gestational age., Conclusions: Adverse effects of SNM and early birth persist between 1 and 6 years of age. Strategies to prevent early birth and reduce SNM, and to increase health monitoring of vulnerable infants throughout childhood may help reduce paediatric hospitalisations., (© 2015 John Wiley & Sons Ltd.)