Association between cumulative maternal exposures related to inflammation and child attention-deficit/hyperactivity disorder: A cohort study.

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.

Examination of validity of identifying congenital heart disease from hospital discharge data without a gold standard: Using a data linkage approach.

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.

Outcomes of lowered newborn screening thresholds for congenital hypothyroidism.

BACKGROUND: Newborn screening (NBS) has largely eliminated the physical and neurodevelopmental effects of untreated congenital hypothyroidism (CH). Many countries, including Australia, have progressively lowered NBS bloodspot thyroid-stimulating hormone (b-TSH) thresholds. The impact of these changes is still unclear. OBJECTIVES: To evaluate the performance of CH NBS following the reduction of b-TSH thresholds in New South Wales (NSW) and the Australian Capital Territory (ACT), Australia, from 15 to 8 mIU/L, and to determine the clinical outcomes of cases detected by these thresholds. METHODS: NBS data of 346 849 infants born in NSW/ACT, Australia from 1 November, 2016-1 March, 2020 inclusive were analysed. A clinical audit was conducted on infants with a preliminary diagnosis of CH born between 1 January, 2016-1 December, 2020 inclusive. RESULTS: The lowered b-TSH threshold (≥8 mIU/L, ~99.5th centile) detected 1668 infants (0.48%), representing an eight-fold increase in recall rate, of whom 212 of 1668 (12.7%) commenced thyroxine treatment. Of these 212 infants, 62 (29.2%) (including eight cases with a preliminary diagnosis of thyroid dysgenesis) had an initial b-TSH 8-14.9 mIU/L. The positive predictive value for a preliminary diagnosis of CH decreased from 74.3% to 12.8% with the lowered threshold. Proportionally, more pre-term infants received a preliminary CH diagnosis on screening with the lower threshold (16.1% of 62) than with the higher threshold (8.0% of 150). CONCLUSION: Clinically relevant CH was detected using the lowered threshold, albeit at the cost of an eight-fold increase in recall rate. Further clinical and economic studies are required to determine whether benefits of lowered screening thresholds outweigh potential harms from false-positive results on infants, their families and NBS programs.

A systematic review of the outcomes of false-positive results on newborn screening for congenital hypothyroidism.

OBJECTIVES: The potential of harm to infants or their parents from a false positive (FP) newborn screening (NBS) result for congenital hypothyroidism (CH) is often cited as an argument against lowering of screening thresholds for CH. This systematic review (SR) examines the evidence of harm and factors that possibly contribute. STUDY DESIGN: PRISMA guidelines were followed and the protocol was registered online (Prospero, ID CRD42019123950, 20 August 2019) before the search was conducted. Multiple electronic databases and grey literature were searched. Articles were included/excluded based on predetermined eligibility criteria. Included articles were appraised for quality, using the relevant Critical Appraisal Skills Program (CASP) tool. Data were extracted and results were tabulated and summarised as part of a narrative synthesis. RESULTS: A total of six studies met the inclusion criteria. All were qualitative and three were based on the same cohort. Studies were published between 1983 and 1996. CASP appraisals scored 2/6 studies as moderate quality and 4/6 as low quality. Studies reported that FP results on CH screening may cause initial stress for parents and poorly defined behavioural disturbance in a small number of children, though these effects were generally not long-lasting. Poor screening processes and inadequate communication with parents, increased the risk of harm to parents and children, from FP results. CONCLUSION: This SR found a small number of dated, qualitative studies of low to moderate quality, conducted soon after the initiation of NBS for CH. Conclusive evidence of the risks of harm from FP results and ways to mitigate harm, awaits further, well-designed studies.

Association of elevated neonatal thyroid-stimulating hormone levels with school performance and stimulant prescription for attention deficit hyperactivity disorder in childhood.

Untreated severe newborn thyroid deficiency causes neurocognitive impairment; however, the impact of mild thyroid deficiency is not known. This study aimed to examine whether mildly elevated neonatal thyroid-stimulating hormone (TSH) levels are associated with poor school performance or stimulant prescription for attention deficit hyperactivity disorder (ADHD). This record-linkage study included 232,790 term-born infants in Australia with a TSH level below newborn screening threshold (< 15 mIU/L). Among our cohort, as TSH levels increased, the proportion of infants born low birthweight via caesarean section and with disadvantaged socioeconomic status increased. Multivariable logistic regression analysis showed that, compared with infants with 'normal' neonatal TSH level (< 5 mIU/L), those with neonatal TSH 10-15 mIU/L had an increased risk of being exempt from school testing (aOR 1.63 (95% CI 1.06-2.69)) or prescribed a stimulant for ADHD (aOR 1.57 (95% CI 1.10-2.24)), adjusted for perinatal and sociodemographic factors. Among a nested analysis of 460 sibling pairs, siblings with 'mildly elevated' TSH levels were more likely to be exempt from school tests compared with siblings with normal TSH levels (aOR 2.53, 95% CI 1.01-6.33).Conclusion: In this population cohort and sibling analysis, mildly elevated neonatal TSH levels were associated with being exempt from school testing due to significant or complex disability. What is Known: • Newborn screening for severe thyroid hormone deficiency has virtually eliminated congenital hypothyroidism-associated intellectual disability in developed countries. • The impact of mild thyroid hormone deficiency in infants is unclear. What is New: • Children with a mildly elevated neonatal TSH level below current newborn screening cut-offs have an increased likelihood of being exempt from school testing due to significant or complex disability compared with siblings and peers. This study includes a population-based and nested sibling analysis.

Neonatal Thyroxine, Maternal Thyroid Function, and Cognition in Mid-childhood in a US Cohort.

OBJECTIVE: Examine the associations of maternal thyroid hormones, maternal dietary information, and newborn T4 levels with cognitive outcomes in mid-childhood. METHODS: We studied 921 children born 1999-2003 at gestational age ≥ 34 weeks, who were participants in Project Viva, a prospective pre-birth cohort study in Massachusetts. We examined maternal dietary information, maternal thyroid hormone levels, and neonatal levels of T4. Research staff performed cognitive testing in mid-childhood (median age 7.7 years). RESULTS: We included 514 women with measured first trimester thyroid hormone concentrations (mean 10.2 weeks); 15% of women had a thyroid stimulating hormone (TSH) level ≥ 2.5 mU/L, and 71% were college graduates. Newborn T4 was collected from 375 infants (mean 17.6 µg/dl; SD 4.0), on day 2 (mean 1.9 days; SD 0.7) as part of the newborn screening program. Mean (SD) verbal and nonverbal IQ, memory, and motor scores of children were 113.2 (14.3), 107.1 (16.7), 17.1 (4.4), and 92.5 (16.6) points, respectively. In multivariable analysis, first trimester maternal thyroid function (total T3, total T4, free T4, thyroid stimulating hormone (TSH) or total thyroid peroxidase (TPO) antibody levels) or newborn T4 were not associated with any of the cognitive outcomes in mid-childhood after adjustment for sociodemographic and perinatal variables. CONCLUSIONS FOR PRACTICE: Maternal or neonatal thyroid hormone levels were not associated with cognitive outcomes in mid-childhood in this population with generally normal thyroid function. As we studied a highly educated cohort residing in an iodine-sufficient area, findings may not be generalizable.

School-Age Developmental and Educational Outcomes Following Cardiac Procedures in the First Year of Life: A Population-Based Record Linkage Study.

The purpose of the study was to evaluate school-age developmental and educational outcomes for children with and without a cardiac procedure in the first year of life to improve understanding of longer-term neurodevelopmental outcomes in children who have had a cardiac procedure for congenital heart disease, the most common serious congenital anomaly. A population-based cohort study using record linkage of state-wide data was undertaken, evaluating children born in New South Wales, Australia, 2001-2007. Those with and without a cardiac procedure in the first year of life with a linked developmental (Australian version Early Development Instrument testing result, age 4-6 years) and/or educational outcome (Australian National Assessment Program result, age 7-9 years) were included. Perinatal, perioperative and sociodemographic factors were examined using multivariable logistic regression models. Of 468,329 eligible children, 768 had a cardiac procedure in the first year of life and 582 were included. For those with a cardiac procedure and developmental outcome (n = 260), 13.1% were classified as having 'special needs' compared to 4.4% without a cardiac procedure. Of those with an educational outcome, after adjusting for perinatal, perioperative and demographic variables, children with a cardiac procedure (n = 396) were twice as likely to score below National Minimum Standard in school literacy and numeracy tests compared to their peers. Significant predictors included low birthweight, parent not completing school and having > 4 re-hospitalisations in their first six years. The developmental and educational trajectory of children who have had a cardiac procedure in their first year remains altered into primary school years. While perioperative factors did not impact outcomes, ongoing health and sociodemographic factors were important in identifying those children at greatest risk.

The impact of general anesthesia on child development and school performance: a population-based study.

BACKGROUND: There has been considerable interest in the possible adverse neurocognitive effects of exposure to general anesthesia and surgery in early childhood. AIMS: The aim of this data linkage study was to investigate developmental and school performance outcomes of children undergoing procedures requiring general anesthesia in early childhood. METHODS: We included children born in New South Wales, Australia of 37+ weeks' gestation without major congenital anomalies or neurodevelopmental disability with either a school entry developmental assessment in 2009, 2012, or Grade-3 school test results in 2008-2014. We compared children exposed to general anesthesia aged <48 months to those without any hospitalization. Children with only 1 hospitalization with general anesthesia and no other hospitalization were assessed separately. Outcomes included being classified developmentally high risk at school entry and scoring below national minimum standard in school numeracy and reading tests. RESULTS: Of 211 978 children included, 82 156 had developmental assessment and 153 025 had school test results, with 12 848 (15.7%) and 25 032 (16.4%) exposed to general anesthesia, respectively. Children exposed to general anesthesia had 17%, 34%, and 23% increased odds of being developmentally high risk (adjusted odds ratio [aOR]: 1.17; 95% CI: 1.07-1.29); or scoring below the national minimum standard in numeracy (aOR: 1.34; 95% CI: 1.21-1.48) and reading (aOR: 1.23; 95% CI: 1.12-1.36), respectively. Although the risk for being developmentally high risk and poor reading attenuated for children with only 1 hospitalization and exposure to general anesthesia, the association with poor numeracy results remained. CONCLUSION: Children exposed to general anesthesia before 4 years have poorer development at school entry and school performance. While the association among children with 1 hospitalization with 1 general anesthesia and no other hospitalization was attenuated, poor numeracy outcome remained. Further investigation of the specific effects of general anesthesia and the impact of the underlying health conditions that prompt the need for surgery or diagnostic procedures is required, particularly among children exposed to long duration of general anesthesia or with repeated hospitalizations.

Survival, Hospitalization, and Acute-Care Costs of Very and Moderate Preterm Infants in the First 6 Years of Life: A Population-Based Study.

OBJECTIVES: To investigate survival, hospitalization, and acute-care costs of very (28-31 weeks' gestation) and moderate preterm (32-33 weeks' gestation) infants in the first 6 years of life and compare outcomes with the more widely studied extremely preterm infants (24-27 weeks' gestation) and to full term (low risk) infants (39-40 weeks' gestation). STUDY DESIGN: Birth data from all women residing in New South Wales, Australia, with gestational ages between 24-33 and 39-40 weeks in 2001-2011 were linked probabilistically to hospitalization and mortality data. Study outcomes were evaluated with the use of descriptive and multivariable analyses at birth (N = 559,532), discharge (N = 540,240), and at 1 (N = 487,447) and 6 years of age (N = 230,498). RESULTS: Mortality was greatest among extremely preterm infants (eg, 31.2% within 6 years) and decreased with increasing gestational age. Likewise, hospitalization within the first year of life increased with decreasing gestational age (aOR 5.5 [95% CI 4.7-6.4], 3.7 [3.4-4.0], and 2.6 [2.5-2.8] for birth at 24-27, 28-31, and 32-33 weeks' gestation, relative to 39-40 weeks' gestation). Hospitalization remained significantly increased with preterm birth at each year of age up to 6 years (aORs 1.3-1.6 at 6 years). Cumulative costs were significantly greater with preterm birth within the first year of life, and also between 1 and 6 years of age. CONCLUSIONS: The risks of adverse health outcomes were significantly greater in very and moderately preterm infants relative to full term infants but lower than extremely preterm infants. Crucially, preterm birth was associated with prolonged increased odds of hospitalization (up to age 6 years), contributing to greater resource use.

Association of Gestational Age and Severe Neonatal Morbidity with Mortality in Early Childhood.

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.

Hospitalisations from 1 to 6 years of age: effects of gestational age and severe neonatal morbidity.

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.

Using record linkage to investigate perinatal factors and neonatal thyroid-stimulating hormone.

AIM: Studies examining the relationship between maternal and infant thyroid parameters have shown conflicting results. Record linkage provides an opportunity to examine the association between maternal and infant thyroid-stimulating hormone (TSH) levels. Our aim was to demonstrate the feasibility of record linkage of newborn screening (NBS), laboratory and birth databases for research by investigating the association between maternal and newborn TSH levels. METHODS: The records of 2802 women with first trimester serum TSH concentrations were linked with population-based birth data and NBS data containing infant TSH levels. Association between moderately high neonatal TSH levels (>5 mIU/L) and maternal and infant characteristics was evaluated. The correlation and association between maternal and infant TSH levels were assessed using Pearson's correlation coefficient and multivariable linear regression, respectively. RESULTS: Of maternal and birth records, 99.3% linked with an NBS record. Mother's country of birth, gestational age (>41 weeks) and lower birthweight were associated with neonatal TSH levels >5 mIU/L. Neonatal and maternal first trimester TSH levels were not correlated, although statistically significant (r = 0.05, P = 0.008). The association between neonatal TSH and maternal TSH, after adjusting for maternal age, gestational age and age at NBS testing, was also small (b = 0.039, P = 0.009). CONCLUSIONS: Record linkage is a feasible and cost-efficient way to investigate the association between maternal factors and neonatal hormone levels. First trimester maternal thyroid levels are not correlated with neonatal TSH levels. This method of outcome assessment can be used for future research examining long-term outcomes for infants with different NBS results.

Trends in New South Wales infant hospital readmission rates in the first year of life: a population-based study.

OBJECTIVE: To examine the trends in hospital readmissions in the first year of life and identify whether changes in maternal and infant risk factors explain any changes. DESIGN: Population-based study using de-identified linked health data. PARTICIPANTS: All 788 798 live-born infants delivered in New South Wales from 1 January 2001 to 31 December 2009 with a linked birth and hospital record. MAIN OUTCOME MEASURES: The number of infants readmitted to hospital at least once after discharge home from the birth admission to 1 year of age, per 100 live births each year, and changes in maternal and infant risk factors assessed by logistic regression. RESULTS: The number of infants readmitted to hospital up to age 1 year decreased by 10.5% (average annual reduction, 1.8%; 95% CI, - 1.7% to - 0.01%, P = 0.001), from 18.4 per 100 births in 2001 to 16.5 in 2009. Fifty-five per cent of this decrease could be explained by changes in factors that are associated with likelihood of hospitalisation; length of stay during the birth admission, maternal age and maternal smoking. The rate of readmissions for jaundice and feeding difficulties increased significantly over the study period, while readmissions for infections decreased. CONCLUSIONS: There has been a decrease in the rate of infants readmitted to hospital in the first year of life, which can be partly explained by increasing maternal age, decreasing maternal smoking and a shift to shorter length of hospital stay at birth. Improved maternal and neonatal care in hospital and increased postnatal support at home may have contributed to reduced risk of readmission.

Estimating the Prevalence of Autism Spectrum Disorder in New South Wales, Australia: A Data Linkage Study of Three Routinely Collected Datasets.

Routinely collected data help estimate the prevalence of autism spectrum disorder (ASD) in jurisdictions without active autism surveillance. We created a population-based cohort of 1,211,834 children born in 2002-2015 in New South Wales, Australia using data linkage. Children with ASD were identified in three datasets - disability services, hospital admissions, and ambulatory mental health data. The prevalence of ASD in the cohort was 1.3% by age 12 and prevalence at age 6 increased an average of 4.1% per year (95% Confidence Interval, 3.3%, 4.8%). Most children with ASD were identified in disability services data (87%), although data linkage identified 1,711 additional cases that were more likely female, older at first contact, and living in major cities and less disadvantaged areas.

Risk factors and costs of hospital admissions in first year of life: a population-based study.

OBJECTIVE: To identify the maternal and infant risk factors associated with hospital admission in the first year and estimate the associated costs of infant hospitalization. STUDY DESIGN: Data from the Perinatal Data Collection for 599753 liveborn infants born in New South Wales, Australia, 2001-2007 were linked to hospital admission data. Logistic regression models were used to investigate the association between maternal and infant characteristics and admission to hospital once, and more than once in the first year; and average costs for total hospital admissions were calculated. RESULTS: Almost 15% of infants were admitted to hospital once and 4.6% had multiple admissions. Gestational age <37 weeks was most strongly associated with admission to hospital once, and severe neonatal morbidity was most strongly associated with multiple admissions (aOR 2.60; 95% CI 2.47-2.75). Infants born <39 weeks gestational age, to adolescent mothers, mothers who smoke, are not married, or had a planned delivery also have an increased risk of multiple admissions. Infants with severe neonatal morbidity contributed 27% of total infant hospital costs. With each increasing week of gestational age the mean annual cost decreased on average 10% and 27% for infants with and without neonatal morbidity respectively. CONCLUSIONS: Infants born with severe neonatal morbidity have increased hospitalizations in the first year; however, the majority of burden on health system is by infants without severe neonatal morbidity. Hospitalizations, and associated costs, increased with decreasing gestational age, even for infants born at 37-38 weeks. Targeted public health strategies may reduce the burden of infant hospitalizations.

Child characteristics and health conditions associated with paediatric hospitalisations and length of stay: a population-based study.

Background: Paediatric hospital length of stay (LoS) is often used as a benchmark for resource use of hospitalisations. Previous studies have mostly focused on LoS of admissions for specific conditions or medical specialties. We aimed to conduct an evaluation of LoS of all paediatric hospitalisations exploring the frequency and characteristics; and associated childhood conditions. Methods: This population-based cross-sectional study included all hospital admissions in children aged <16 years between January 2017 and December 2019 in New South Wales, Australia. LoS was categorised into: day or overnight stay, 2-7, 8-21 and ≥ 22 days. Socio-demographic and health service characteristics of each individual admission by LoS and age groups were evaluated. Findings: A total of 324,083 children had 518,768 admissions comprising 1,064,032 bed days. Most admissions wereday/overnight stays (71.9%) or 2-7 days (25.3%). While LoS >7 days represented 2.8% of total admissions, they accounted for 27% of total bed days. Children aged 1-4 years had the highest proportion of admissions (35%), with a majority lasting ≤7 days, whereas 45.6% of admissions ≥22 days were for children aged ≥12 years. Respiratory conditions, diseases of the digestive system and traumatic injuries were the most common reasons for hospitalization. LoS >7 days were more common in children from most disadvantaged backgrounds, residing further from hospital and those aged ≥12 years with mental health conditions. Interpretation: The majority of paediatric hospitalizations are for short stay and require programs that target acute conditions that can be managed in primary care. Interventions such as care coordination, tailored models of care and enhanced outpatient/community treatment programs for high-risk groups will help reduce extended LoS and improving child health and well-being. Funding: Australian National Health and Medical Research Council.

Using novel data linkage of congenital heart disease biobank data with administrative health data to identify cardiovascular outcomes to inform genomic analysis.

Introduction: Contemporary care of congenital heart disease (CHD) is largely standardised, however there is heterogeneity in post-surgical outcomes that may be explained by genetic variation. Data linkage between a CHD biobank and routinely collected administrative datasets is a novel method to identify outcomes to explore the impact of genetic variation. Objective: Use data linkage to identify and validate patient outcomes following surgical treatment for CHD. Methods: Data linkage between clinical and biobank data of children born from 2001-2014 that had a procedure for CHD in New South Wales, Australia, with hospital discharge data, education and death data. The children were grouped according to CHD lesion type and age at first cardiac surgery. Children in each 'lesion/age at surgery group' were classified into 'favourable' and 'unfavourable' cardiovascular outcome groups based on variables identified in linked administrative data including; total time in intensive care, total length of stay in hospital, and mechanical ventilation time up to 5 years following the date of the first cardiac surgery. A blind medical record audit of 200 randomly chosen children from 'favourable' and 'unfavourable' outcome groups was performed to validate the outcome groups. Results: Of the 1872 children in the dataset that linked to hospital or death data, 483 were identified with a 'favourable' cardiovascular outcome and 484 were identified as having a 'unfavourable' cardiovascular outcome. The medical record audit found concordant outcome groups for 182/192 records (95%) compared to the outcome groups categorized using the linked data. Conclusions: The linkage of a curated biobank dataset with routinely collected administrative data is a reliable method to identify outcomes to facilitate a large-scale study to examine genetic variance. These genetic hallmarks could be used to identify patients who are at risk of unfavourable cardiovascular outcomes, to inform strategies for prevention and changes in clinical care.

Quality of data in perinatal population health databases: a systematic review.

BACKGROUND: Administrative or population health datasets (PHDS) are increasingly being used for research related to maternal and infant health. However, the accuracy and completeness of the information in the PHDS is important to ensure validity of the results of this research. OBJECTIVE: To compile and review studies that validate the reporting of conditions and procedures related to pregnancy, childbirth, and newborns and provide a tool of reference for researchers. METHODS: A systematic search was conducted of Medline and EMBASE databases to find studies that validated routinely collected datasets containing diagnoses and procedures related to pregnancy, childbirth, and newborns. To be included datasets had to be validated against a gold standard, such as review of medical records, maternal interview or survey, specialized register, or laboratory data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and/or κ statistic for each diagnosis or procedure code were calculated. RESULTS: Forty-three validation studies were included. Under-enumeration was common, with the level of ascertainment increasing as time from diagnosis/procedure to birth decreased. Most conditions and procedures had high specificities indicating few false positives, and procedures were more accurately reported than diagnoses. Hospital discharge data were generally more accurate than birth data, however identifying cases from more than 1 dataset further increased ascertainment. CONCLUSIONS: This comprehensive collection of validation studies summarizing the quality of perinatal population data will be an invaluable resource to all researchers working with PHDS.

Incidence of severe adverse neonatal outcomes: use of a composite indicator in a population cohort.

The aim was to develop a composite outcome indicator to identify infants with severe adverse outcomes in routinely collected population health datasets, and assess the indicator's association with readmission and infant mortality rates. A comprehensive list of diagnoses and procedures indicative of serious neonatal morbidity was compiled based on literature review, validation studies and expert consultation. Relevant diagnoses and procedures indicative of severe morbidity that are reliably reported were analysed and reviewed, and the neonatal adverse outcome indicator (NAOI) was refined. Data were obtained from linked birth and hospital data for 516,843 liveborn infants ≥24 weeks gestation, in New South Wales, Australia from 2001 to 2006. Face validity of the indicator was examined by calculating the relative risks (and 95% CI) of hospital readmission or death in the first year of life of those infants identified by the NAOI. Overall 4.6% of all infants had one or more conditions included in the NAOI; 35.4% of preterm infants and 2.4% of term infants. Infants identified by the composite indicator were 10 times more likely to die in the first year of life and twice as likely to be readmitted to hospital in the first year of life compared to infants not identified by the NAOI. The NAOI can reliably identify infants with a severe adverse neonatal outcome and can be used to monitor trends, assess obstetric and neonatal interventions and the quality of perinatal care in a uniform and cost-effective way.