Inflammation is increasingly recognized as a cause or consequence of common problems of humanity including obesity, stress, depression, pollution and disease states such as autoimmunity, asthma, and ...infection. Maternal immune activation (MIA), triggered by both acute and systemic chronic inflammation, is hypothesized to be one of the mechanisms implicated in the pathogenesis of neurodevelopmental disorders (NDD). Although there is substantial preclinical evidence to support the MIA hypothesis, the human evidence is disparate. We performed a systematic review on human studies examining associations between maternal inflammatory states and offspring NDDs (autism spectrum disorder- ASD, attention deficit hyperactivity disorder-ADHD, Tourette syndrome-TS). 32 meta-analyses and 26 additional individual studies were identified. Maternal states associated with ASD include obesity, gestational diabetes mellitus, pre-eclampsia, pollution, stress, depression, autoimmune diseases, and infection. Maternal states associated with ADHD include obesity, pre-eclampsia, smoking, low socioeconomic status (SES), stress, autoimmune disease, and asthma. Maternal states associated with TS include low SES, depression, and autoimmune diseases. Diverse maternal inflammatory states in pregnancy are associated with common offspring NDDs. Given the increased prevalence of NDDs, there is urgent need to explore relative and cumulative maternal risk factors and disease mechanisms. Defining preventable risk factors in high-risk pregnancies could mitigate the expression and severity of NDDs.
To determine sex and age differences in the use of medications for diabetes and cardiovascular risk factors in people with diabetes in Australia. Pharmaceutical claims data of participants in the 45 ...and Up Study who self-reported having diabetes before 2013, were alive on 1.sup.st January 2013 and had at least one medication dispensing record between 1.sup.st January 2013 and 31.sup.st December 2019 were analysed. Annual sex and age-specific percentages of participants supplied specific medications were estimated for years 2013 to 2019. Percentages were reported for any glucose lowering medications and by drug class, any lipid modifying agents, and any blood pressure lowering medications. Altogether 25,733 participants (45.2% women) with diabetes were included. The percentage of participants who were supplied with glucose lowering medications was consistently lower in women compared to men. In both sexes, the percentage of participants who were supplied with glucose lowering medications was lowest among those aged greater than or equal to75 years and this decreased over time. Similar findings were observed for lipid modifying agents and blood pressure lowering medications. The use of sodium glucose co-transporter 2 inhibitors increased substantially in participants aged <75 years since it became available in 2013. However, no sex differences were observed in its use among people with hospital-recorded history of cardiovascular disease. Practitioners should be aware of possible sex disparities in the pharmacological treatment of diabetes and cardiovascular risk factors in people with diabetes in Australia. There is a possible time lag between reporting of research findings and uptake of sodium glucose co-transporter 2 inhibitors prescribing in individuals with diabetes and high cardiovascular risk in clinical practice, nevertheless, the result observed was consistent with the management guidelines at the time of the study.
Aims
Public health responses to reduce SARS‐CoV‐2 transmission have profoundly affected the epidemiology and management of other infections. We examined the impact of COVID‐19 restrictions on ...antibiotic dispensing in Australia.
Methods
We used national claims data to investigate antibiotic dispensing trends from November 2015 to October 2020 and whether changes reflected reductions in primary care consultations. We used interrupted time series analysis to quantify changes in monthly antibiotic dispensing and face‐to‐face and telehealth GP consultations and examined changes by recipient age, pharmacy State and prescriber specialty.
Results
Over the study period, an estimated 19 921 370 people had 125 495 137 antibiotic dispensings, 71% prescribed by GPs. Following COVID‐19 restrictions, we observed a sustained 36% (95% CI: 33–40%) reduction in antibiotic dispensings from April 2020. Antibiotics recommended for managing respiratory tract infections showed large reductions (range 51–69%), whereas those recommended for non‐respiratory infections were unchanged. Dispensings prescribed by GPs decreased from 63.5 per 1000 population for April–October 2019 to 37.0 per 1000 for April–October 2020. Total GP consultation rates remained stable, but from April 2020, 31% of consultations were telehealth.
Conclusion
In a setting with a low COVID‐19 incidence, restrictions were associated with a substantial reduction in community dispensings of antibiotics primarily used to treat respiratory infections, coincident with reported reductions in respiratory viral infections. Our findings are informative for post‐pandemic antimicrobial stewardship and highlight the potential to reduce inappropriate prescribing by GPs and specialists for respiratory viral infections.
Background Few studies have investigated the longitudinal association between breastfeeding and maternal cardiovascular disease ( CVD ) outcomes. This study examined the association between ...breastfeeding and CVD hospitalization and mortality in a large Australian cohort. Methods and Results Baseline questionnaire data (2006-2009) from a sample of 100 864 parous women aged ≥45 years from New South Wales, Australia, were linked to hospitalization and death data until June 2014 and December 2013, respectively. Analysis was restricted to women without self-reported medically diagnosed CVD at baseline or without past CVD hospitalization 6 years before study entry. Never versus ever breastfeeding and average breastfeeding duration per child, derived from self-reported lifetime breastfeeding duration and number of children, and categorized as never breastfed, <6, >6 to 12, or >12 months/child, were assessed. Cox proportional hazards models were used to explore the association between breastfeeding and CVD outcomes. Covariates included sociodemographic characteristics, lifestyle risk factors, and medical and reproductive history. There were 3428 (3.4%) first CVD -related hospital admissions and 418 (0.4%) deaths during a mean follow-up time of 6.1 years for CVD hospitalization and 5.7 years for CVD mortality. Ever breastfeeding was associated with lower risk of CVD hospitalization (adjusted hazard ratio 95% CI: 0.86 0.78, 0.96; P=0.005) and CVD mortality (adjusted hazard ratio 95% CI: 0.66 0.49, 0.89; P=0.006) compared with never breastfeeding. Breastfeeding ≤12 months/child was significantly associated with lower risk of CVD hospitalization. Conclusions Breastfeeding is associated with lower maternal risk of CVD hospitalization and mortality in middle-aged and older Australian women. Breastfeeding may offer long-term maternal cardiovascular health benefits.
Summary
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.
As well as being highly comorbid conditions, autism spectrum disorders (ASD) and intellectual disability (ID) share a number of clinically-relevant phenomena. This raises questions about similarities ...and overlap in diagnosis and aetiological pathways that may exist for both conditions.
To examine maternal conditions and perinatal factors for children diagnosed with an ASD, with or without ID, and children with ID of unknown cause, compared with unaffected children.
The study population comprised all live singleton births in Western Australia (WA) between January 1984 and December 1999 (N = 383,153). Univariate and multivariate multinomial logistic regression models were applied using a blocked modelling approach to assess the effect of maternal conditions, sociodemographic factors, labour and delivery characteristics and neonatal outcomes.
In univariate analyses mild-moderate ID was associated with pregnancy hypertension, asthma, urinary tract infection, some types of ante-partum haemorrhage, any type of preterm birth, elective C-sections, breech presentation, poor fetal growth and need for resuscitation at birth, with all factors showing an increased risk. Severe ID was positively associated with poor fetal growth and need for resuscitation, as well as any labour or delivery complication. In the multivariate analysis no maternal conditions or perinatal factors were associated with an increased risk of ASD without ID. However, pregnancy hypertension and small head circumference were associated with a reduced risk (OR = 0.64, 95% CI: 0.43, 0.94; OR = 0.58, 95% CI: 0.34, 0.96, respectively). For ASD with ID, threatened abortion before 20 weeks gestation and poor fetal growth were associated with an increased risk.
Findings show that indicators of a poor intrauterine environment are associated with an elevated risk of ID, while for ASD, and particularly ASD without ID, the associations are much weaker. As such, these findings highlight the importance of accounting for the absence or presence of ID when examining ASD, if we are to improve our understanding of the causal pathways associated with these conditions.
Modifications to diagnostic criteria and introduction of genetic testing have likely affected the pattern and timing of Rett syndrome diagnosis. The trends in incidence and prevalence of Rett ...syndrome in Australia were examined; the cumulative risk of a female being diagnosed was determined; and the impact of changes to diagnostic criteria and availability of genetic testing on these frequencies was investigated. The population-based Australian Rett Syndrome Database was used to identify a total of 349 verified Rett syndrome females born 1976-2006 and diagnosed 1982-2008. The proportion of female cases born and diagnosed per year and the cumulative risk of a diagnosis were determined. The median age of Rett syndrome diagnosis decreased from 4.5 y if diagnosed before 2000 to 3.5 y if diagnosed after 1999. The cumulative risk of diagnosis had almost doubled by 32 y of age 1/8,905 or 11.23 per 100,000 person-years (95% CI, 10.03-12.45) in comparison with 5 y of age 1/15,361 or 6.51 per 100,000 person-years (95% CI, 5.65-7.39). Earlier age of diagnosis may result in families experiencing less stress and emotional strain compared with those with delayed diagnosis.
Most evidence for interpregnancy interval (IPI) and adverse birth outcomes come from studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the ...same women can address this issue.
We conducted an international longitudinal cohort study of 5,521,211 births to 3,849,193 women from Australia (1980-2016), Finland (1987-2017), Norway (1980-2016) and the United States (California) (1991-2012). IPI was calculated based on the time difference between two dates-the date of birth of the first pregnancy and the date of conception of the next (index) pregnancy. We estimated associations between IPI and preterm birth (PTB), spontaneous PTB, and small-for-gestational age births (SGA) using logistic regression (between-women analyses). We also used conditional logistic regression comparing IPIs and birth outcomes in the same women (within-women analyses). Random effects meta-analysis was used to calculate pooled adjusted odds ratios (aOR).
Compared to an IPI of 18-23 months, there was insufficient evidence for an association between IPI <6 months and overall PTB (aOR 1.08, 95% CI 0.99-1.18) and SGA (aOR 0.99, 95% CI 0.81-1.19), but increased odds of spontaneous PTB (aOR 1.38, 95% CI 1.21-1.57) in the within-women analysis. We observed elevated odds of all birth outcomes associated with IPI ≥60 months. In comparison, between-women analyses showed elevated odds of adverse birth outcomes for <12 month and >24 month IPIs.
We found consistently elevated odds of adverse birth outcomes following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of other adverse birth outcomes. Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries.
Maternity care is a significant contributor to overall healthcare expenditure, and private care is seen as a mechanism to reduce the cost to public funders. However, public funders may still ...contribute to part of the cost of private care. The paper aims to quantify (1) the cost to different funders of maternal and early childhood healthcare over the first 1000 days for both women giving birth in private and public hospitals; (2) any variation in cost to different funders by birth type; and (3) the cost of excess caesarean sections in public and private hospitals in Australia.
This study utilised a whole of population linked administrative dataset, and classified costs by the funding source. The mean cost to different funders for private hospital births, and public hospital births in the Australian state, Queensland are presented by time period and by birth type. The World Health Organization's (WHO's) C-model was used to identify the optimal caesarean section rate based upon demographic and clinical factors, and counterfactual analysis was utilised to identify the cost to different funders if caesarean section had been utilised at this rate across Australia.
We found that for women who gave birth in a public hospital as a public patient, the mean cost was $22 474. For women who gave birth in a private hospital the mean cost was $24 731, and the largest contributor was private health insurers ($11 550), followed by Medicare ($7261) and individuals ($3312). Private hospital births cost government funders $10 050 on average; whereas public hospital public patient births cost government funders $21 723 on average and public hospital private patient births cost government funders $20 899 on average. If caesarean section deliveries were reduced, public hospital funders could save $974 million and private health insurers could save $216 million.
Private hospital births cost government funders less than public hospital births, but government funders still pay for around 40% of the cost of private hospital births. Caesarean sections, which are more frequently performed in private hospitals, are costly to all funders and reducing them could impart significant cost savings to all funders.
Mastitis and accompanying pain have been associated with the cessation of breastfeeding. Mastitis is an inflammatory condition of the breast and may be a result of decreased immunity and a lowered ...resistance to infection. Mastitis affects up to one in five breastfeeding women with most episodes occurring in the first 6-8 weeks postpartum. Antibiotics are often used in the treatment of mastitis, but have not been popular or proven effective as a preventative agent. The WHO has highlighted significant concerns relating to adverse harms of antibiotic use with the production of antibiotic-resistant strains of disease organisms. Increasing research suggests that specific probiotic bacteria possess significant anti-inflammatory properties and supports their potential use as immunomodulatory agents. While animal studies have shown promising results in the use of probiotics for preventing mastitis, their use in human trials has had limited investigation. The aim of this study is to evaluate the effectiveness of oral probiotics for the prevention of mastitis in breastfeeding women.
APProve (CAn Probiotics ImProve Breastfeeding Outcomes?) is a double-blind randomised controlled trial designed to assess outcomes between breastfeeding women ingesting a probiotic versus a placebo daily for 8 weeks following birth. A total of 600 women (300 to each arm) who intend to breastfeed will be randomised after the birth of a term, healthy infant. Daily and weekly surveys for 8 weeks and follow-up surveys at 2, 6 and 12 months after birth will assess the primary outcome of mastitis in the first 8 weeks following birth as well as secondary maternal outcomes of breastfeeding duration (total/partial), antibiotic use, maternal health and well-being, and treatment compliance; and infant outcomes including gastroenteritis, infant health and well-being and growth and development. The acceptability and compliance using a novel mobile phone application system will also be evaluated.
There is an urgent need to explore safe and effective alternatives for preventing mastitis in breastfeeding women. This trial seeks to provide evidence for such an alternative in the form of probiotics, which may also increase breastfeeding duration, providing long-term health, cognitive and developmental benefits for children. Decreased antibiotic usage also benefits the community and health system.
Australian New Zealand Clinical Trials Registry: ACTRN12615000923561 . Date of registration: 4th September, 2015, retrospectively registered.
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