Jeroen Douwes

Background: Respiratory syncytial virus (RSV) infection during infancy has been associated with subsequent wheezing and asthma, but the importance of timing of primary RSV exposure remains uncertain. We investigated whether expected timing of primary RSV infection during the COVID-19 pandemic was associated with asthmatic wheezing and respiratory tract infections during the first three years of life. Methods: In this nationwide population-based cohort study, we included children born in Denmark between Oct 1, 2016, and Sept 30, 2021, and followed them until three years of age. Birth cohorts were used as proxies for different expected timings of primary RSV infection, with comparisons between the Pre-COVID, Early-COVID, and Late-COVID cohorts. The primary outcomes were asthmatic wheezing and respiratory tract infections. Population-standardised risks and risk ratios at one and three years were estimated using Cox proportional hazards models with g-computation. Findings: Among 302,724 children, those in the Early-COVID cohort had lower population-standardised risks of asthmatic wheezing and respiratory tract infections by one year of age than those in the Pre-COVID cohort (risk ratio 0·69 [95% CI 0·64–0·74] and 0·62 [0·60–0·63], respectively). By three years, these differences had substantially attenuated. The risk of asthmatic wheezing was similar in the Early-COVID and Late-COVID cohorts (1·00 [0·96–1·05]), whereas the Early-COVID cohort had an intermediate risk of respiratory tract infections between the Pre-COVID and Late-COVID cohorts. Interpretation: Birth cohorts with different expected timings of primary RSV infection differed in respiratory morbidity during early childhood. The substantially lower risks in the Early-COVID cohort during infancy attenuated markedly during follow-up, suggesting that reduced respiratory morbidity during infancy predominantly reflected delayed rather than sustained protection. These findings provide limited support for lasting protection from reduced opportunity for RSV exposure during infancy and are compatible with timing of primary RSV infection being relevant to subsequent respiratory trajectories.

Background: Overuse of antibiotics contributes to antibiotic resistance, and may result in gut microbiome dysbiosis, potentially increasing the risk of chronic childhood conditions. Objectives: To examine patterns of antibiotic dispensing in utero and during the first 5 years of life. Methods: We conducted a retrospective cohort study of all children ( n = 315 786) born in New Zealand from 2005 to 2010 using linked pharmaceutical dispensing data to ascertain antibiotic use during the mother's pregnancy and for the first 5 years of life. Descriptive analyses were conducted as well as negative binomial regression controlled for potential confounders. Results: In total, 96% of children had been dispensed ≥ 1 course of antibiotics by age five; for pregnant women this was 30%. Penicillin, particularly Amoxicillin, was most frequently dispensed during both periods. Postnatal antibiotic dispensing was higher for males (adjusted IRR 1.09, 95% CI 1.08–1.10); Māori (1.16, 1.15–1.17), Pacific peoples (1.32, 1.30–1.33), and Middle East Latin American and African (MELAA) ethnicities (1.07, 1.04–1.10); children in the highest deprivation quintile (1.16, 1.15–1.17) and those born pre‐term (1.05, 1.04–1.05); and urban children (1.21, 1.20–1.22). Low and high birthweight and caesarean deliveries were also associated with higher antibiotic dispensing. Similar patterns were observed for antibiotic dispensing for mothers during pregnancy. Dispensing rates were highest during winter months. Conclusion: Antibiotic dispensing is high in New Zealand children and pregnant women, with significant ethnic and socioeconomic differences, suggesting that current antibiotic stewardship programmes are not fully effective.

According to region-specific hospital-based studies, the location of ruptured intracranial aneurysm (RIA) influences the case fatality rate (CFR) of aneurysmal subarachnoid hemorrhage (SAH). However, little is known about whether CFRs vary by RIA location in population-based studies that include prehospital SAH deaths. We assessed whether CFRs and CFR-trends differ by RIA location using whole population data from Finland and New Zealand. We used externally validated administrative databases to identify all nonhospitalized and hospitalized SAH cases in Finland and New Zealand from 2001 to 2017. Using the ICD-10, we categorized RIAs into anterior communicating artery (Acom) (ICD-10 I60.2), internal carotid artery (ICA) (I60.0/I60.3), middle cerebral artery (MCA) (I60.1), and vertebrobasilar artery (VBA) (I60.4/I60.5) locations. To validate the location-specific SAH diagnoses, we used external hospital- and population-based datasets and autopsy data. We calculated sudden death rates (those occurring before admission to a ward) and overall 30-day CFRs, and computed age-, sex, and country-adjusted risk ratios using a Poisson regression model with 95% CIs. Among 13,470 SAH cases (5,056 from New Zealand; median age 58 years; 61.3% women), 26.6% had Acom, 18.4% ICA, 29.5% MCA, 11.5% VBA, and 14.0% other/unspecified RIAs. The overall 30-day CFRs were the greatest for VBA (54.1%), followed by MCA (40.5%), Acom (29.1%), and ICA (28.5%) RIAs. Location-specific sudden death rates were 33.0%, 21.6%, 11.9%, and 9.9%, respectively. Between 2001-2003 and 2015-2017, overall 30-day CFRs declined significantly for VBA (24%, 95% CI 13%-34%) and MCA (15%, 95% CI 5%-24%) RIAs. Location-specific differences in CFRs were similar between countries, but temporal decreases were observed only in Finland. Between 2001-2003 and 2014-2017, the proportion of VBA RIAs increased by 35.9% (from 10.3% to 14.0%). SAH CFRs vary significantly by RIA location, with VBA and MCA RIAs having the greatest CFRs, mainly due to high sudden death rates. It is unclear whether aneurysms with these high-risk locations could benefit from improved primary/secondary prevention or prehospital management strategies. These findings cannot be directly applied to the preventive treatment of unruptured intracranial aneurysms.

Antibiotic use in early life is associated with autoimmune diseases like Type 1 diabetes (T1D), but evidence is inconsistent. We examined associations of prenatal and early-childhood (0–5 years) antibiotic use and T1D in New Zealand, a country with high antibiotic consumption. Using linked data, we identified antibiotic use during pregnancy and the first 5 years for all children born between 2005 and 2010 (n = 315,789), followed until 2021. Associations were assessed using Cox proportional hazard regression, adjusted for parental and perinatal factors. For prenatal exposure, we assessed associations with T1D-diagnosis from birth; for early-childhood exposure, associations were assessed with T1D-diagnosis from age 5. Antibiotic use (≥ 1 course) was 29.2% for pregnant mothers and 96.3% for children aged 0–5 years. T1D was diagnosed in 0.36% (n = 1,131), with 0.28% (n = 906) diagnosed after age 5 years. Antibiotic use during pregnancy was associated with T1D, both expressed as a continuous variable (HR 1.05, 95% CI 1.03–1.08) and as a dichotomous variable (0 vs ≥ 1 course; HR 1.20, 1.05–1.38). When categorised into 0, ≤ 1, ≤ 2, and ≥ 3 courses, a significant (p = 0.0008) positive trend was observed. For postnatal exposure, the HR was 1.02 (1.02–1.03) and 1.62 (1.00–2.63), respectively; when categorised into 0, ≤ 4, ≤ 7, ≤ 12, and ≥ 13 courses, a significant dose-response trend (p = 0.0017) was shown. Strongest associations were found for moderate and broad-spectrum antibiotics in both periods. Prenatal penicillin and cephalosporins/cephamycins-use, and postnatal exposure to all antibiotic classes except tetracyclines were associated with a higher risk of T1D. In conclusion, antibiotic use during both prenatal and early childhood is associated with an increased risk of T1D.

Background: The incidence of many common chronic childhood conditions has increased globally in the past few decades, which has been suggested to be potentially attributed to antibiotic overuse leading to dysbiosis in the gut microbiome. Objective: This linkage study will assess the role of antibiotic use in utero and in early life in the development of type 1 diabetes (T1D), attention-deficit/hyperactive disorder (ADHD), and inflammatory bowel disease. Methods: The study design involves several retrospective cohort studies using linked administrative health and social data from Statistics New Zealand’s Integrated Data Infrastructure. It uses data from all children who were born in New Zealand between October 2005 and December 2010 (N=334,204) and their mothers. Children’s antibiotic use is identified for 4 time periods (at pregnancy, at ≤1 year, at ≤2 years, and at ≤5 years), and the development of T1D, ADHD, and inflammatory bowel disease is measured from the end of the antibiotic use periods until death, emigration, or the end of the follow-up period (2021), whichever came first. Children who emigrated or died before the end of the antibiotic use period are excluded. Cox proportional hazards regression models are used while adjusting for a range of potential confounders. Results: As of September 2024, data linkage has been completed, involving the integration of antibiotic exposure and outcome variables for 315,789 children. Preliminary analyses show that both prenatal and early life antibiotic consumption is associated with T1D. Full analyses for all 3 outcomes will be completed by the end of 2025. Conclusions: This series of linked cohort studies using detailed, complete, and systematically collected antibiotic prescription data will provide critical new knowledge regarding the role of antibiotics in the development of common chronic childhood conditions. Thus, this study has the potential to contribute to the development of primary prevention strategies through, for example, targeted changes in antibiotic use. International Registered Report Identifier (IRRID): DERR1-10.2196/66184

Background/Objectives: To assess associations between dietary fibre intake, adiposity, and odds of metabolic syndrome in Pacific and New Zealand European women. Methods: Pacific (n = 126) and New Zealand European (NZ European; n = 161) women (18–45 years) were recruited based on normal (18–24.9 kg/m²) and obese (≥30 kg/m²) BMIs. Body fat percentage (BF%), measured using whole body DXA, was subsequently used to stratify participants into low (p < 0.001). The main source of fibre was discretionary fast foods for Pacific women and whole grain breads and cereals for NZ European women. A regression analysis controlling for age, socioeconomic deprivation, ethnicity, energy intake, protein, fat, and total carbohydrate intake showed an inverse association between higher fibre intake and BF% (β= −0.47, 95% CI = −0.62, −0.31, p < 0.001), and odds of metabolic syndrome (OR = 0.91, 95% CI = 0.84, 0.98, p = 0.010) among both Pacific and NZ European women (results shown for both groups combined). Conclusions: Low dietary fibre intake was associated with increased metabolic disease risk. Pacific women had lower fibre intakes than NZ European women.

BACKGROUND The incidence of many common chronic childhood conditions has increased globally in the past few decades, which has been suggested to be potentially attributed to antibiotic overuse leading to dysbiosis in the gut microbiome. OBJECTIVE This linkage study will assess the role of antibiotic use in utero and in early life in the development of type 1 diabetes (T1D), attention-deficit/hyperactive disorder (ADHD), and inflammatory bowel disease. METHODS The study design involves several retrospective cohort studies using linked administrative health and social data from Statistics New Zealand’s Integrated Data Infrastructure. It uses data from all children who were born in New Zealand between October 2005 and December 2010 (N=334,204) and their mothers. Children’s antibiotic use is identified for 4 time periods (at pregnancy, at ≤1 year, at ≤2 years, and at ≤5 years), and the development of T1D, ADHD, and inflammatory bowel disease is measured from the end of the antibiotic use periods until death, emigration, or the end of the follow-up period (2021), whichever came first. Children who emigrated or died before the end of the antibiotic use period are excluded. Cox proportional hazards regression models are used while adjusting for a range of potential confounders. RESULTS As of September 2024, data linkage has been completed, involving the integration of antibiotic exposure and outcome variables for 315,789 children. Preliminary analyses show that both prenatal and early life antibiotic consumption is associated with T1D. Full analyses for all 3 outcomes will be completed by the end of 2025. CONCLUSIONS This series of linked cohort studies using detailed, complete, and systematically collected antibiotic prescription data will provide critical new knowledge regarding the role of antibiotics in the development of common chronic childhood conditions. Thus, this study has the potential to contribute to the development of primary prevention strategies through, for example, targeted changes in antibiotic use. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/66184