Retrospective assessment of the use of extended-release cabergoline in the management of equine pituitary pars intermedia dysfunction.

Introduction: Dopaminergic agonists are accepted as the most effective treatment for pituitary pars intermedia dysfunction. However, some horses are refractory to daily oral pergolide, the recommended registered treatment. Extended-release cabergoline (ERC) injection may offer an alternative. The objective of this retrospective case series was to describe clinical and endocrinological responses to ERC. Methods: Medical records of horses treated with weekly intramuscular injections of ERC (5 mg/mL, BOVA Aus) at either 0.01 mg/kg (high dose, HD) (n = 10) or 0.005 mg/kg (low dose, LD) (n = 30) were reviewed. Short-term ACTH responses were assessed at 5-8 days using a Wilcoxon signed ranked test. Longer-term ACTH responses (30 to 365 days) were assessed using generalised estimating equations. Results: Five to eight days after the first dose of LDERC, median adrenocorticotropic hormone (ACTH) concentration was lower (p = 0.001), changing from 153 pg/mL (IQR: 78, 331) to 57 pg/mL (IQR: 30, 102). With HDERC, median ACTH concentration was also 153 pg/mL (IQR: 96, 185) before and then 56 pg/mL (IQR: 29, 86) after 5-8 days of treatment (p = 0.047). Over 12 months of treatment, ACTH concentration ranged from 14 to >1,250 pg/mL (median: 51 pg/mL) in horses treated with LDERC and 20 to 472 pg/mL (median: 50 pg/mL) in horses treated with HDERC. Measurements remained above the seasonal reference range in 39.3 and 52.3% of horses treated with LDERC and HDERC, respectively. Clinical improvement was reported by owners in 78.3 and 100% of horses treated with LDERC and HDERC, respectively. Partial, self-limiting inappetence was reported in 30.0% of LDERC and 60% HDERC cases. Seven horses exhibited lethargy (5 LDERC, 2 HDERC). Insulin concentrations measured 30 days post-ERC treatment were no different from baseline. Discussion: Clinical and endocrinological responses were consistent with results of previous reports of oral pergolide treatment. Weekly injection of ERC may be an effective alternative to pergolide; the 0.005 mg/kg dose appeared to be as effective, with less risk of inappetence, than the 0.01 mg/kg dose that has been reported previously.

Medicine utilization studies in Australian individual-level dispensing data: A blinded, multi-center replicated analysis.

PURPOSE: Medicine dispensing data require extensive preparation when used for research and decisions during this process may lead to results that do not replicate between independent studies. We conducted an experiment to examine the impact of these decisions on results of a study measuring discontinuation, intensification, and switching in a cohort of patients initiating metformin. METHODS: Four Australian sites independently developed a HARmonized Protocol template to Enhance Reproducibility (HARPER) protocol and executed their analyses using the Australian Pharmaceutical Benefits Scheme 10% sample dataset. Each site calculated cohort size and demographics and measured treatment events including discontinuation, switch to another diabetes medicine, and intensification (addition of another diabetes medicine). Time to event and hazard ratios for associations between cohort characteristics and each event were also calculated. Concordance was assessed by measuring deviations from the calculated median of each value across the sites. RESULTS: Good agreement was found across sites for the number of initiators (median: 53 127, range: 51 848-55 273), gender (56.9% female, range: 56.8%-57.1%) and age group. Each site employed different methods for estimating days supply and used different operational definitions for the treatment events. Consequently, poor agreement was found for incidence of discontinuation (median 55%, range: 34%-67%), switching (median 3.5%, range: 1%-7%), intensification (median 8%, range: 5%-12%), time to event estimates and hazard ratios. CONCLUSIONS: Differences in analytical decisions when deriving exposure from dispensing data affect replicability. Detailed analytical protocols, such as HARPER, are critical for transparency of operational definitions and interpretations of key study parameters.

Investigating maternal and neonatal health outcomes associated with continuing or ceasing dexamphetamine treatment for women with attention-deficit hyperactivity disorder during pregnancy: a retrospective cohort study.

PURPOSE: Attention-deficit hyperactivity disorder (ADHD) is becoming more commonly diagnosed in women, consequently, more women of reproductive age are taking ADHD medication, such as dexamphetamine. However, the safety associated with continuing or ceasing dexamphetamine during pregnancy is unclear. This study investigates outcomes associated with the continuation of dexamphetamine during pregnancy compared to those who ceased or were unexposed. METHODS: A population-based retrospective cohort of women from Western Australia who had been dispensed dexamphetamine during pregnancy and gave birth between 2003 and 2018. Women had either continued to take dexamphetamine throughout pregnancy (continuers, n = 547) or ceased dexamphetamine before the end of the second trimester (ceasers, n = 297). Additionally, a matched (1:1) comparison group of women who were dispensed an ADHD medication prior to pregnancy but not during pregnancy (unexposed) was included in the study (n = 844). Multivariable generalised linear models were used to compare maternal and neonatal health outcomes. RESULTS: Compared to continuers, ceasers had greater odds of threatened abortion (OR: 2.28; 95%CI: 1.00, 5.15; p = 0.049). The unexposed had some benefits compared to the continuers, which included lower risk of preeclampsia (OR: 0.58; 95%CI: 0.35, 0.97; p = 0.037), hypertension (OR: 0.32; 95%CI: 0.11, 0.93; p = 0.036), postpartum haemorrhage (OR: 0.57; 95%CI: 0.41, 0.80; p = 0.001), neonatal special care unit admittance (OR: 0.16; 95%CI: 0.12, 0.20; p < 0.001) and fetal distress (OR: 0.73; 95%CI: 0.54, 0.99; p = 0.042). CONCLUSION: Continuing dexamphetamine throughout pregnancy was not associated with an increase in adverse neonatal and maternal health outcomes compared to ceasing. Ceasing dexamphetamine during pregnancy was associated with increased odds of threatened abortion compared with continuing dexamphetamine. However, this is something that requires further investigation due to the small sample size, difficulties examining timing, and the inability to examine spontaneous abortions. The unexposed showed some benefits compared to the continuers, suggesting that where possible the cessation of dexamphetamine prior to pregnancy may be advisable.

Prenatal Opioid Exposure and Immune-Related Conditions in Children.

Importance: Prenatal opioid exposure (POE) may alter with fetal development of the immune system, which may influence long-term health and susceptibility to immune-related conditions. Objective: To compare the risk of hospitalization and emergency department presentation for immune-related conditions in children with and without POE. Design, Setting, and Participants: This retrospective, population-based cohort study used linked administrative health records of all children born in Western Australia between January 1, 2003, and December 31, 2018 (N = 401 462). Exposure: Prenatal exposure to prescription opioids (overall and by trimester), neonatal abstinence syndrome diagnosis, and opioid indication (pain or opioid use disorder [OUD]). Main Outcomes and Measures: The main outcome was hospital admissions and emergency department presentations during which a child was diagnosed with an immune-related condition, including infections, conditions associated with an overactive immune system (eg, asthma, eczema, and allergy and anaphylaxis), and autoimmune diseases diagnosed before age 5 years or June 30, 2020. Data were analyzed between August 30, 2022, and February 27, 2023. Results: Neonates with POE (1656 [0.4%]; mean [SD] gestational age, 37.7 [2.1] weeks; 836 females [50.5%]; 820 males [49.5%]) were more likely to be born preterm, have low birth weight for gestational age, and be coexposed to cigarette smoke compared with nonexposed neonates. Perinatal opioid exposure was associated with an increased risk of perinatal infection (adjusted odds ratio [AOR], 1.62; 95% CI, 1.38-1.90) and eczema and dermatitis (AOR, 11.91; 95% CI, 9.84-14.41) compared with nonexposure. Neonatal abstinence syndrome was also associated with both conditions (AOR, 2.91 [95% CI, 2.36-3.57] and 31.11 [95% CI, 24.64-39.28], respectively). Prenatal opioid exposure was also associated with an increased risk of childhood asthma (adjusted hazard ratio [AHR], 1.44; 95% CI, 1.16-1.79), but not allergies and anaphylaxis. It was also associated with an increased risk of childhood eczema and dermatitis, but only in children with POE from opioids used to treat OUD (AHR, 1.47; 95% CI, 1.08-1.99) rather than pain. In contrast, POE from opioids used for pain was associated with an increased risk of infection (AHR, 1.44; 95% CI, 1.32-1.58), but POE to opioids used to treat OUD was not. Autoimmune conditions were rare and were not observed to be associated with POE. Conclusions and Relevance: In this cohort study, POE was associated with an increased risk of infection, eczema and dermatitis, and asthma, but not allergies and anaphylaxis or autoimmune conditions. These findings highlight the importance of further study of opioid-induced immune changes during pregnancy, the potential impact on long-term health in exposed children, and the mechanisms of opioid-induced immune dysregulation.

Comparison of oral esomeprazole and oral omeprazole in the treatment of equine squamous gastric disease.

BACKGROUND: Oral omeprazole is the accepted treatment for equine squamous gastric disease (ESGD); however, it is not universally effective. Esomeprazole results in more consistent and pronounced acid suppression in men and is more effective than omeprazole in the treatment of oesophageal and gastric disease. Pharmacodynamic and pilot clinical studies have indicated esomeprazole might also be more effective than omeprazole in horses. OBJECTIVES: To compare the efficacy and safety of oral esomeprazole and omeprazole pastes in the treatment of ESGD and, where present, concurrent equine glandular gastric disease (EGGD). STUDY DESIGN: Randomised, single-blinded controlled trial. METHODS: Horses presenting with grade ≥2 ESGD lesions were randomly allocated to receive 4 mg/kg of either a buffered esomeprazole or omeprazole paste orally once daily for 28 days before gastroscopy being repeated within a further 3 days. Videos and images were anonymised and subsequently graded blind by one researcher. The severity of ESGD (and EGGD) lesions before and after treatment, and thereby treatment responses, were compared using univariable logistic regression. RESULTS: A higher proportion of horses had ESGD healing in response to esomeprazole treatment (63/74, 85%) than with omeprazole treatment (43/73, 59%) (odds ratio [OR]: 4.00, 95% confidence interval [CI]: 1.81, 8.82, p = 0.001). In a subset of horses that had concurrent EGGD, a greater proportion of the horses treated with esomeprazole had lesions ≤grade 1 (esomeprazole 28/51, 55%; omeprazole 6/24, 25%; OR: 3.65, 95% CI: 1.25, 10.71, p = 0.02) Using grade 0 as the benchmark for EGGD healing, the difference remained significant (OR: 4.44, 95% CI: 1.33, 14.85, p = 0.02). MAIN LIMITATIONS: It may not be possible to extrapolate these results to other populations with different signalment or management. CONCLUSIONS: Oral-buffered esomeprazole was a more effective treatment for ESGD (and concurrent EGGD) than oral-buffered omeprazole.

Safety of Alprazolam Use in Pregnancy in Western Australia: A Retrospective Cohort Study Using Linked Health Data.

The use of alprazolam in pregnancy can adversely affect maternal and neonatal health. This study examined neonatal outcomes following exposure to alprazolam in pregnancy. Women prescribed alprazolam during pregnancy (n = 48) between 2014 and 2018 were identified from routinely-collected state administrative prescribing records and perinatal data. Two comparison groups of women; 1) prescribed alprazolam outside of pregnancy (n = 96) and 2) women never prescribed alprazolam (n = 96) were also identified. The health of women and their children was examined using administrative hospital, mortality and perinatal data and compared to the comparison groups using generalized linear models. Prenatal alprazolam exposure was not associated with a reduction in average birth weight or gestational age. However, neonates prenatally exposed to alprazolam were more likely be classified as having low birth weight for gestational age compared with alprazolam comparison group (OR: 4.46, 95% CI: 1.54-12.95) and the non-alprazolam comparison group (OR: 3.27, 95% CI: 1.22-8.79). There were no cases of perinatal mortality or floppy baby syndrome in alprazolam-exposed neonates. While the use of alprazolam during pregnancy was not associated with an increased risk of severe adverse neonatal outcomes (e.g. perinatal mortality), it was associated with neonates being born with a low birth weight for gestational age.

Recent advances in the treatment and prevention of equine peripheral caries.

Equine peripheral caries is a common condition characterized by demineralization and degradation of the clinical crown of equine cheek teeth. The condition can cause significant pain and morbidity, particularly in severe cases. Recent studies indicate that the condition is driven by environmental conditions within the mouth, as only the clinical crown of the tooth is affected (the reserve crown below the gingival margin remains unaffected). It is hypothesized that peripheral caries is driven by changes in oral pH, with risk factors for the condition including the intake of high-sugar feeds (oaten hay and feeding moderate levels of concentrate feed) and access to drinking water with an acidic pH. However, other identified risk factors include breed (Thoroughbred), limited pasture access, and concurrent dental or periodontal disease. Further studies have been able to show that affected teeth can recover from the condition if the inciting cause is removed and the unaffected reserve crown is allowed to replace the damaged clinical crown. Improvements in the condition can be observed within a few months. Signs of inactive (recovering) caries include a darker color and a smooth, hard, and reflective surface, and there is a new layer of unaffected cementum at the gingival margin, indicating that the newly erupted tooth is unaffected. Peripheral caries is a common and often overlooked condition in horses, which can often be treated with simple changes to equine management.

Trends in smoking during pregnancy stratified by the use of opioid agonist therapy and the contribution of smoking to poor outcome in neonates prenatally exposed to opioid agonist treatment.

High rates of cigarette smoking have been observed in pregnant women on opioid agonist therapy (OAT). However, it is unclear if these rates have changed overtime in line with the general population and the degree to which smoking contributes to poor outcomes in neonates born to women on OAT. Women who gave birth in Western Australia (WA) between 2003 and 2018 were identified from whole-population midwives records. Linked records were used to identify women who had been dispensed OAT during pregnancy and those who had smoking during pregnancy. Temporal changes in smoking during pregnancy were examined for women on OAT (n = 1059) and women not on OAT (n = 397,175) using Joinpoint regression. In women treated with OAT during pregnancy, neonatal outcomes were compared between smoking and non-smoking women using generalised linear models. During the study period, 76.3% of women on OAT smoked during pregnancy compared with 12.0% of the general population. There was a decrease in the prevalence of smoking during pregnancy among women not on OAT (APC: - 5.7, 95%CI: - 6.3, - 5.2), but not in women on OAT (APC: 0.8, 95%CI: - 0.4, 2.1). For women receiving OAT, smoking was associated with an increased odds of low birth weight (OR: 1.57, 95%CI: 1.06, 2.32) and neonatal abstinence syndrome (OR: 1.34, 95%CI: 1.01, 1.78) compared with non-smoking. Despite reductions in the prevalence of smoking during pregnancy in the general population, similar reductions have not occurred in pregnant women on OAT. The high prevalence of smoking in pregnant women on OAT is contributing to poor neonatal outcomes.

Trends in prenatal diagnosis of congenital anomalies in Western Australia between 1980 and 2020: A population-based study.

BACKGROUND: Advances in screening and diagnostics have changed the way in which we identify and diagnose congenital anomalies. OBJECTIVE: To examine changes in rates of prenatal diagnosis of congenital anomalies over time and by demographic characteristics. METHODS: We undertook a population-based retrospective cohort study of all children born in Western Australia between 1980 and 2020 and diagnosed with a congenital anomaly. Age at diagnosis (prenatal, neonatal, infancy, early childhood or childhood) prevalence (all-type and type-specific), and prevalence ratios (PR) were calculated. We fit joinpoint regression models to describe the average annual percentage change (APC) in prenatal diagnosis over time, and log-binomial regression models to estimate the association between prenatal diagnosis and demographic characteristics. RESULTS: Prenatal diagnosis prevalence between the first (1980-1989: 28.3 per 10,000 births) and last (2005-2014: 156.1 per 10,000 births) decades of the study increased 5.5-fold (95% confidence interval [CI] 5.0, 5.9). Substantial increases were observed for cardiovascular (PR 10.7, 95% CI 8.0, 14.6), urogenital (PR 10.5, 95% CI: 8.7, 12.6) and chromosomal anomalies (PR 7.0, 95% CI 5.9, 8.3). Prenatal diagnosis was positively associated with the birth year (adjusted risk ratio [RR] 1.04, 95% CI 1.03, 1.04), advanced maternal age (RR 1.14, 95% CI 1.11, 1.18), multiple anomalies (RR 2.86, 95% CI 2.77, 2.96) and major anomalies (RR 3.75, 95% CI 3.36, 4.19), and inversely associated with remoteness (RR 0.89, 95% CI: 0.83, 0.95) and Aboriginality (RR 0.90, 95% CI 0.83, 0.97). CONCLUSIONS: Increases in prenatal diagnosis of congenital anomalies were observed in Western Australia from 1980 to 2020, reflecting advances in screening. Prenatal diagnosis was less common in remote regions and in Aboriginal children, strengthening calls for increased provision of antenatal care services for these populations.

Lithium Dispensed for Adults Aged ≥ 50 Years Between 2012 and 2021: Analyses of a 10% Sample of the Australian Pharmaceutical Benefits Scheme.

BACKGROUND: Lithium use seems to be declining in clinical practice. We examined the proportion of adults aged ≥ 50 years dispensed lithium between 2012 and 2021, and investigated the proportion of lithium users dispensed other medications. METHODS: We used a 10% random sample data of the Australian Pharmaceutical Benefits Scheme from 2012 to 2021, and limited our analyses to adults aged ≥ 50 years. We retrieved data on lithium, other mood stabilisers, antipsychotics, antidepressants, anxiolytics and hypnotics, and medications for the treatment of other health systems. RESULTS: We received 7081939 person-years records (53.2% women). The proportion of participants dispensed lithium decreased with age: 0.4% for those aged 50-59 years to < 0.1% for people aged ≥ 90 years. The dispensing of lithium increased over 10 years for those aged 50-69 and decreased in those older than 80 years. Among people dispensed lithium, nearly 1 in 5 were dispensed another mood stabiliser. Antipsychotics and antidepressants were dispensed to about 60% of participants dispensed lithium, with antidepressants dispensed more frequently to women than men. About 20% of people dispensed lithium were dispensed anxiolytics/hypnotics, more frequently for women than men. Medications to treat diseases of the alimentary, cardiovascular, endocrine and nervous systems were commonly dispensed to those dispensed lithium, as were antibiotics. CONCLUSIONS: While the dispensing of lithium increased among young older adults since 2015 when guidelines for the management of mood disorders were published, our findings suggest that lithium may be under-utilised for the management of bipolar disorder in later life.

Reproductive and sexual health of Australian adolescents exposed to family and domestic violence.

BACKGROUND: There is a dearth of research investigating sexually transmitted infections (STIs) in children exposed to family and domestic violence (FDV). Further, there is no research on terminations of pregnancy in children exposed to FDV. METHODS: This retrospective cohort study used linked administrative data from Western Australia to investigate whether exposure to FDV is associated with a risk of hospitalisations for STIs and terminations of pregnancy in adolescents. This study involved children born from 1987 to 2010 whose mother was a victim of FDV. Identification of family and domestic violence was from two sources: police and hospital records. This approach provided an exposed cohort of 16 356 and a non-exposed cohort of 41 996. Dependant variables were hospitalisations for pregnancy terminations and STIs in children aged from 13 up to 18 years of age. The primary explanatory variable was exposure to FDV. Multivariable Cox regression was used to investigate the association of FDV exposure and the outcomes. RESULTS: Following adjustment for sociodemographic and clinical factors, children exposed to FDV had an increased risk of hospitalisations for STIs (HR 1.49, 95% CI 1.15 to 1.92) and terminations of pregnancy (HR 1.34, 95% CI 1.09 to 1.63) as an adolescent than non-exposed peers. CONCLUSION: Children exposed to FDV are at an increased risk of hospitalisation for STI and termination of pregnancy as an adolescent. Effective interventions are needed to support children exposed to FDV.

Systemic juvenile idiopathic arthritis: frequency and long-term outcome in Western Australia.

Systemic juvenile idiopathic arthritis (S-JIA) is a rare but potentially life threatening autoinflammatory condition of childhood. Given the limited data on S-JIA from the Australasian region, we investigated the epidemiological characteristics and long-term disease outcome in S-JIA. All hospitalised patients under the age of 16 years registered with ICD-10-AM code M08.2 in in the period 1999-2014 were identified in longitudinally linked administrative health data across all Western Australian (WA) hospitals. Incidence and point prevalence estimate were per 100,000 population with Poisson regression to analyse the incidence trend. Readmissions with S-JIA as primary diagnosis were considered flares with rates for flare and other complication reported per 100 person years with 95% confidence intervals (CI). Annual S-JIA incidence was 0.61/100,000 (CI 0.28-1.25) (46 incident cases, 71.7% girls, median age 6.5 years) and stable over time as S-JIA point prevalence reached 7.15/100,000 (CI 5.29-7.45) at the end of study. Most incident cases were diagnosed in winter and spring, but documented preceding infections were rare. During a median follow-up of 8 years, disease flares occurred in 24% of patients with higher flares rate in boys (58.3; CI 44.5-74.9) than girls (14.7; CI 9.9-20.9). No deaths occurred and arthroplasty was the main, but uncommon S-JIA complication (4%). However, readmission (86.3; CI 76.4-97.2) and ED visit (73.3; CI 64.2-83.4) rates for illnesses other than S-JIA were substantial. S-JIA is as rare in WA as in other regions and while s-JIA incurred no deaths in the era of biologics, it associated with a significant long-term burden of (co-) morbidity.

The effect of TNF treatment uptake on incident hospital admission in Western Australia.

OBJECTIVE: Treatment strategies for juvenile idiopathic arthritis (JIA) have shifted significantly over the last 20 years. We examined the effect of the introduction of government-subsidised TNF inhibitor (TNFi) treatment on incident hospitalisation for JIA. METHODS: Western Australian (WA) hospital data were used to identify patients < 16 years hospitalised with JIA between 1990 and 2012. Changes in the number of patients with an incident hospitalisation, overall admissions and admissions for joint aspiration were examined using join-point regression TNFi dispensing data from 2002-2012 was used to describe defined daily doses (DDD)/1000 population/day. RESULTS: We included 786 patients (59.2% girls, median age 8 years) with a first-time admission with JIA. The annual incident admission rate was 7.9 per 100,000 person-years (95%CI: 7.3, 8.4) which did not change significantly between 1990 and 2012 (annual percentage change (APC): 1.3, 95%CI: -0.3, 2.8). Annual hospital-based prevalence of JIA reached 0.72/1000 in 2012. DDD for TNFi usage rose steadily from 2003 indicating TNFi usage by 1/2700 children in 2012, while overall admission rates (APC 3.7; 95%CI: 2.3, 5.1) and admission rates for joint injections (APC 4.9%; 95%CI: 3.8, 6.0) also increased significantly in that period. CONCLUSION: Incident inpatient admission rates for JIA were stable over a 22-year period. The uptake of TNFi was not associated with lower admission rates for JIA, due mainly to an increase in admissions for joint injection. These results indicate a notable but unexpected change in hospital-based management of JIA since the introduction of TNFi therapy in WA, where hospital-based prevalence of JIA is slightly higher than in North America.

The effects of acamprosate on maternal and neonatal outcomes in a mouse model of alcohol use disorders.

BACKGROUND: Despite the teratogenic effects of alcohol, little is known about the safety of pharmacotherapies such as acamprosate for the treatment of alcohol use disorders in pregnancy. The aims of this study were to investigate, in a mouse model, the effects of maternally administered acamprosate on maternal and neonatal health, offspring neurodevelopment and behaviour, as well as examine whether acamprosate reduces the neurological harm associated with alcohol consumption in pregnancy. METHODS: Dams were randomly allocated to one of four treatment groups: (i) control (water), (ii) acamprosate (1.6 g/L), (iii) alcohol (5% v/v) or (iv) acamprosate and alcohol (1.6 g/L; 5% v/v ethanol) and exposed from 2-weeks pre-pregnancy until postpartum day 7. Gestational outcomes including litter size and sex ratio were assessed, in addition to early-life markers of neurodevelopment. At 8 weeks of age, motor coordination, anxiety, locomotion, and memory of the adult offspring were also examined. RESULTS: Exposure to acamprosate did not affect maternal and birth outcomes (mating success, gestational weight gain, litter size, sex ratio), neonatal outcomes (head and body length, postnatal weight) or neurodevelopmental markers (righting reflex and negative geotaxis). Acamprosate exposure did not affect offspring motor control, locomotion or anxiety, however the effects on short-term memory remain uncertain. Prenatal alcohol exposed offspring exhibited various alterations, such as lower postnatal weight, smaller head (p = 0.04) and body lengths (p = 0.046) at postnatal day 70 (males only), increased negative geotaxis speed (p = 0.03), an increased time spent in the inner zone of the open field (p = 0.02). Acamprosate mitigated the effects of alcohol for negative geotaxis at postnatal day 7 (p = 0.01) and female offspring weight at postnatal day 70 (p = 0.03). CONCLUSIONS: Overall, we show that prenatal acamprosate exposure was not associated with poor maternal or neonatal health outcomes or impaired neurodevelopment and behaviour. However, acamprosate's effects on short-term memory remain uncertain. We present preliminary evidence to suggest acamprosate displayed some neuroprotective effects against damage caused by in utero alcohol exposure.

Neonatal Outcomes Associated With in Utero Exposure to Oxycodone, Overall and by Trimester of Exposure: A Retrospective Cohort Study.

Oxycodone is commonly used by pregnant women for the treatment of pain. However, the potential risk associated with its use in pregnancy have not been robustly evaluated. The objective of this study was to examine neonatal outcomes associated with prenatal oxycodone exposure. State dispensing records were matched with midwives records to identify women who had been dispensed oxycodone during pregnancy (n=302). A matched comparison group of women who had been prescribed oxycodone prior to pregnancy was also identified (n=604). Hospital, mortality and congenital abnormality data were obtained for each mother-child dyad. Neonatal outcomes were examined for association with any exposure during pregnancy and trimester specific exposure, using generalized linear models. First trimester exposure was not associated with a significant increased risk of congenital anomalies (OR: 1.74 95%CI: 0.78, 3.87). Second trimester exposure to oxycodone was associated with reduction in average length of gestation (aCoef:-0.83, 95%CI: -1.26, -0.41) and birth weight (aCoef:-188, 95%CI: -299, -76). Second trimester exposure was also associated with an increased risk of very preterm birth (<32 weeks) (OR: 5.03, 95%CI: 1.95, 12.98) and admission to the special care nursery (aOR:1.99, 95%CI: 1.30, 3.03). Third trimester exposure to oxycodone was associated with a reduction in average length of gestation (aCoef:-0.33, 95%CI: -0.63, -0.02) compared with the comparison group. The use of oxycodone in pregnancy was not associated with an increased risk of congenital anomalies. However, oxycodone exposure was associated with a short period of gestation, preterm birth, and NAS, which likely contributed to a longer period of hospitalization following birth. PERSPECTIVE: This article assesses the neonatal risks associated with prenatal exposure to oxycodone, providing clinicians and patients with important information on the safety of oxycodone in the treatment of pain in pregnancy.

The lasting impact of family and domestic violence on neonatal health outcomes.

OBJECTIVES: To compare the health of neonates born to women who experienced family and domestic violence (FDV) 12 months prior to birth, with the health of neonates born to women with an earlier history of FDV and women with no history of FDV. METHODS: A retrospective cohort of women who experienced FDV within 12 months of birth (antenatal FDV [AFDV]) (n = 1230) was identified using data from the Western Australia (WA) Police Force Incident Management System and WA Hospital Morbidity Data Collection. Two comparison cohorts were used, the first including women with a history of FDV (HFDV) 12-60 months prior to birth (n = 1549) and the second with no history of FDV (NFDV) recorded (n = 3690). Hospital, birth, mortality, and congenital anomaly data were used in generalized linear models to examine and compare neonatal health outcomes. RESULTS: Women in the AFDV group had higher proportions of factors associated with poor neonatal outcomes including smoking (42.4%), substance use (23.0%), and mental health disorders (34.8%). Neonates born to AFDV mothers had significantly higher odds of congenital anomalies (OR: 1.51, 95% CI: 1.18-1.94), low birth weight (1.74, 1.45-2.10), and preterm birth (1.48, 1.22-1.79) compared with neonates born to NFDV mother. Neonatal health outcomes in those born to AFDV women were not significantly different from those born to HFDV women. CONCLUSIONS: Antenatal and historical FDV were associated with poor neonatal health outcomes. Additional pregnancy and social support should be offered to women who have experienced FDV during or prior to pregnancy.

Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond.

Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10-9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.

Opioid poisoning during pregnancy: prevalence, characteristics, and neonatal outcomes.

While it has been postulated that opioid poisoning during pregnancy may cause adverse maternal and neonatal outcomes, the harm associated with opioid poisoning during pregnancy has not been robustly examined. Pregnant women admitted to hospital or presenting to the emergency department (ED) in Western Australia (WA) with a diagnosis of opioid poisoning were identified by linking state midwifery records with hospital and ED administrative data. Maternal and neonatal outcomes were compared with opioid poisoning that occurred in the 12 months prior to conception or the 12 months following birth. Between 2003 and 2018, 57 neonates were born to women who had experienced opioid poisoning during pregnancy (14.1 per 100,000 births) in WA. The incidence of opioid poisoning in the year prior to pregnancy (IRR: 3.04, 95%CI: 2.30, 4.02) and the year following pregnancy (IRR: 1.96, 95%CI: 1.46, 2.64) was significantly higher than during pregnancy. Opioid poisoning during pregnancy was less likely to involve multiple substances and be intentional (rather than accidental). Neonatal conditions associated with in utero hypoxia were significantly less common in neonates born to women who experience opioid poisoning prior to pregnancy compared with during pregnancy (OR: 0.17, 95%CI: 0.04, 0.80). Opioid poisoning in pregnancy was not associated with an increased risk of other serious adverse neonatal outcomes. Opioid poisoning during pregnancy is uncommon and less likely to be intentional and involve multiple substances. Opioid poisoning during pregnancy is likely associated with an increased risk of conditions associated with in utero hypoxia.

Prevalence and Perinatal Outcomes Following In Utero Exposure to Prehospital Emergency Methoxyflurane: A 17-Year Retrospective Cohort Study.

OBJECTIVE: To examine the prevalence of exposure and perinatal outcomes associated with in utero exposure to methoxyflurane. DESIGN, SETTING AND POPULATION: Whole-population ambulance data in Western Australia (WA) were linked to the statutory perinatal data collection to identify pregnant women transferred by ambulance between 2000 and 2016. The proportion of neonates in WA exposed to methoxyflurane, fentanyl or no analgesia during an ambulance transfer was calculated. Perinatal outcomes of pregnancies exposed to methoxyflurane (n=1579) were compared to those exposed to fentanyl (n=203) or no analgesia (n=10524) using multivariable logistic regression modelling. Perinatal outcomes were considered overall and by trimester of exposure. MAIN OUTCOME MEASURES: Primary outcomes were the prevalence of in utero methoxyflurane exposure and Apgar score on the day of delivery. RESULTS: In the study period, 0.4% of all neonates born in WA were exposed to methoxyflurane in utero. Methoxyflurane exposure on the day of delivery (n=657) was not associated with an increased likelihood of a low Apgar score at five minutes compared with no analgesia (n=2667) (OR 1.23, 95% CI 0.91-1.67). Whereas fentanyl exposure (n=22) was associated with an increased likelihood of low Apgar score compared with methoxyflurane (OR 3.67, 95% CI 1.18-11.48). CONCLUSIONS: Methoxyflurane is commonly used by ambulance services to treat pain in pregnant women in WA. While not recommended for use in pregnancy, pregnancies exposed to methoxyflurane did not have an increased risk of adverse perinatal outcomes in this study.

Mortality Rates in Patients With Ankylosing Spondylitis With and Without Extraarticular Manifestations and Comorbidities: A Retrospective Cohort Study.

OBJECTIVE: To examine mortality rates in hospitalized patients with ankylosing spondylitis (AS) and the association of extraarticular manifestations (EAMs) and comorbidities with mortality rates. METHODS: This study was a retrospective, population-based cohort study using linked administrative data from patients with AS who were hospitalized (n = 1791) and patients in a matched comparison group (n = 8955). Mortality data for patients were obtained from the Western Australia Death Register. The presence of EAMs and comorbidities was identified from hospital records. Mortality rates were compared between the 2 groups using Cox proportional hazard models overall and stratified by a history of EAMs, comorbidities, and smoking status. RESULTS: Crude mortality rates were significantly higher among patients with AS than among patients in the comparison group (hazard ratio [HR] 1.85, 95% CI 1.62-2.12), with excess mortality in the AS group associated with cardiovascular disease (CVD; HR 5.32, 95% CI 3.84-7.35), cancer (HR 1.68, 95% CI 1.27-2.23), external causes (HR 3.92, 95% CI 2.28-6.77), and infectious diseases (HR 25.92, 95% CI 7.50-89.56). When patients were stratified by history of EAMs, CVD, and smoking, the risk of mortality was elevated in patients both with and without each risk factor. Among patients with AS, histories of CVD (HR 6.33, 95% CI 4.79-8.38), diabetes (HR 2.81, 95% CI 1.99-3.95), smoking (HR 1.49, 95% CI 1.18-1.89), and EAMs (HR 1.62, 95% CI 1.24-2.11) were associated with an increased risk of mortality. CONCLUSION: The presence of comorbidities, EAMs, and smoking contributes to an increased risk of all-cause mortality among patients with AS who are hospitalized compared to patients in the comparison group. These results support the need to prevent or reduce the occurrence of comorbidities and smoking in patients with AS.