Relative Risks of Adverse Perinatal Outcomes in Three Australian Communities Exposed to Per- and Polyfluoroalkyl Substances: Data Linkage Study.

INTRODUCTION: Firefighting foams containing per- and polyfluoroalkyl substances (PFAS) have caused environmental contamination in several Australian residential areas, including Katherine in the Northern Territory (NT), Oakey in Queensland (Qld), and Williamtown in New South Wales (NSW). We examined whether the risks of adverse perinatal outcomes were higher in mothers living in these exposure areas than in selected comparison areas without known contamination. METHODS: We linked residential addresses in exposure areas to addresses collected in the jurisdictional Perinatal Data Collections of the NT (1986-2017), Qld (2007-2018), and NSW (1994-2018) to select all pregnancies from mothers who gave birth while living in these areas. We also identified one comparison group for each exposure area by selecting pregnancies where the maternal address was in selected comparison areas. We examined 12 binary perinatal outcomes and three growth measurements. For each exposure area, we estimated relative risks (RRs) of adverse outcomes and differences in means of growth measures, adjusting for sociodemographic characteristics and other potential confounders. RESULTS: We included 16,970 pregnancies from the NT, 4654 from Qld, and 7475 from NSW. We observed elevated risks of stillbirth in Oakey (RR = 2.59, 95% confidence interval (CI) 1.25 to 5.39) and of postpartum haemorrhage (RR = 1.94, 95% CI 1.13 to 3.33) and pregnancy-induced hypertension (RR = 1.88, 95% CI 1.30 to 2.73) in Williamtown. The risks of other perinatal outcomes were not materially different from those in the relevant comparison areas or were uncertain due to small numbers of events. CONCLUSIONS: There was limited evidence for increased risks of adverse perinatal outcomes in mothers living in areas with PFAS contamination from firefighting foams. We found higher risks of some outcomes in individual areas, but these were not consistent across all areas under study and could have been due to chance, bias, or confounding.

Incremental effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia hospitalisation among Australian Indigenous children: A record linkage study.

BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18-24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation. METHODS: Indigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders. RESULTS: 11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87-1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16-1.35) and specified (HR 0.89; 95% CI: 0.49-1.62) from unspecified causes (HR 1.13; 95% CI: 0.86-1.49). During the baseline period before PPV23 vaccination (12-18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30-2.28). CONCLUSION: In this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18-30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.

Psychological distress in three Australian communities living with environmental per- and polyfluoroalkyl substances contamination.

BACKGROUND: Environmental chemical contamination is a recognised risk factor for psychological distress, but has been seldom studied in the context of per- and polyfluoroalkyl substances (PFAS) contamination. We examined psychological distress in a cross-sectional study of three Australian communities exposed to PFAS from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities without environmental contamination. METHODS: Participation was voluntary following recruitment from a PFAS blood-testing program (exposed) or random selection (comparison). Participants provided blood samples and completed a survey on their exposure history, sociodemographic characteristics, and four measures of psychological distress (Kessler-6, Distress Questionnaire-5, Patient Health Questionnaire-15, and Generalised Anxiety Disorder-7). We estimated prevalence ratios (PR) of clinically-significant psychological distress scores, and differences in mean scores: (1) between exposed and comparison communities; (2) per doubling in PFAS serum concentrations in exposed communities; (3) for factors that affect the perceived risk of living in a community exposed to PFAS; and (4) in relation to self-reported health concerns. RESULTS: We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher levels of self-reported psychological distress in exposed communities than in comparison communities (e.g., Katherine compared to Alice Springs, Northern Territory: clinically-significant anxiety scores, adjusted PR = 2.82, 95 % CI 1.16-6.89). We found little evidence to suggest that psychological distress was associated with PFAS serum concentrations (e.g., Katherine, PFOS and anxiety, adjusted PR = 0.85, 95 % CI 0.65-1.10). Psychological distress was higher among exposed participants who were occupationally exposed to firefighting foam, used bore water on their properties, or were concerned about their health. CONCLUSION: Psychological distress was substantially more prevalent in exposed communities than in comparison communities. Our findings suggest that the perception of risks to health, rather than PFAS exposure, contribute to psychological distress in communities with PFAS contamination.

Fasting Glucose Level on the Oral Glucose Tolerance Test Is Associated with the Need for Pharmacotherapy in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) has a rapidly increasing prevalence, which poses challenges to obstetric care and service provision, with known serious long-term impacts on the metabolic health of the mother and the affected offspring. The aim of this study was to evaluate the association between glucose levels on the 75 g oral glucose tolerance test and GDM treatment and outcomes. We performed a retrospective cohort study of women with GDM attending a tertiary Australian hospital obstetric clinic between 2013 and 2017, investigating the relationship between the 75 g oral glucose tolerance test (OGTT) glucose values, and obstetric (timing of delivery, caesarean section, preterm birth, preeclampsia), and neonatal (hypoglycaemia, jaundice, respiratory distress and NICU admission) outcomes. This time frame encompassed a change in diagnostic criteria for gestational diabetes, due to changes in international consensus guidelines. Our results showed that, based on the diagnostic 75 g OGTT, fasting hyperglycaemia, either alone or in combination with elevated 1 or 2 h glucose levels, was associated with the need for pharmacotherapy with either metformin and/or insulin (p < 0.0001; HR 4.02, 95% CI 2.88-5.61), as compared to women with isolated hyperglycaemia at the 1 or 2 h post-glucose load timepoints. Fasting hyperglycaemia on the OGTT was more likely in women with higher BMI (p < 0.0001). There was an increased risk of early term birth in women with mixed fasting and post-glucose hyperglycaemia (adjusted HR 1.72, 95% CI 1.09-2.71). There were no significant differences in rates of neonatal complications such as macrosomia or NICU admission. Fasting hyperglycaemia, either alone or in combination with post-glucose elevations on the OGTT, is a strong indicator of the need for pharmacotherapy in pregnant women with GDM, with significant ramifications for obstetric interventions and their timing.

Interventional radiology in obstetric patients: A population-based record linkage study of use and outcomes.

INTRODUCTION: Interventional radiology (IR) is a technique for controlling hemorrhage and preserving fertility for women with serious obstetric conditions such as placenta accreta spectrum (PAS) or postpartum hemorrhage. This study examined maternal, pregnancy and hospital characteristics and outcomes for women receiving IR in pregnancy and postpartum. MATERIAL AND METHODS: A population-based record linkage study was conducted, including all women who gave birth in hospital in New South Wales or the major tertiary hospital in the neighboring Australian Capital Territory, Australia, between 2003 and 2019. Data were obtained from birth and hospital records. Characteristics and outcomes of women who underwent IR in pregnancy or postpartum are described. Outcomes following IR were compared in a high-risk cohort of women: those with PAS who had a planned cesarean with hysterectomy. Women were grouped by those who did and those who did did not have IR and were matched using propensity score and other factors. RESULTS: We identified IR in 236 pregnancies of 1 584 708 (15.0 per 100 000), including 208 in the delivery and 26 in a postpartum admission. Two-thirds of women receiving IR in the birth admission received a transfusion of red cells or blood products, 28% underwent hysterectomy and 12.5% were readmitted within 6 weeks. Other complications included: severe maternal morbidity (29.8%), genitourinary tract trauma/repair (17.3%) and deep vein thrombosis/pulmonary embolism (4.3%). Outcomes for women with PAS who underwent planned cesarean with hysterectomy were similar for those who did and did not receive IR, with a small reduction in transfusion requirement for those who received IR. CONCLUSIONS: Interventional radiology is infrequently used in pregnant women. In our study it was performed at a limited number of hospitals, largely tertiary centers, with the level of adverse outcomes reflecting use in a high-risk population. For women with PAS undergoing planned cesarean with hysterectomy, most outcomes were similar for those receiving IR and those not receiving IR, but IR may reduce bleeding.

Estimating the excess burden of pertussis disease in Australia within the first year of life, that might have been prevented through timely vaccination.

BACKGROUND: Previous Australian studies have shown that delayed vaccination with each of the three primary doses of diphtheria-tetanus-pertussis-containing vaccines (DTP) is up to 50 % in certain subpopulations. We estimated the excess burden of pertussis that might have been prevented if (i) all primary doses and (ii) each dose was given on time. METHODS: Perinatal, immunization, pertussis notification and death data were probabilistically linked for 1 412 984 infants born in two Australian states in 2000-12. A DTP dose administered >15 days after the recommended age was considered delayed. We used Poisson regression models to compare pertussis notification rates to 1-year of age in infants with ≥1 dose delayed (Aim 1) or any individual dose delayed (Aim 2) versus a propensity weighted counterfactual on-time cohort. RESULTS: Of all infants, 42% had ≥1 delayed DTP dose. We estimated that between 39 to 365 days of age, 85 (95% CI: 61-109) cases per 100 000 infants, could have been prevented if all infants with ≥1 delayed dose had received their three doses within the on-time window. Risk of pertussis was higher in the delayed versus the on-time cohort, so crude rates overestimated the excess burden (110 cases per 100 000 infants (95% CI: 95-125)). The estimated dose-specific excess burden per 100 000 infants was 132 for DTP1, 50 for DTP2 and 19 for DTP3. CONCLUSIONS: We provide robust evidence that improved DTP vaccine timeliness, especially for the first dose, substantially reduces the burden of infant pertussis. Our methodology, using a potential outcomes framework, is applicable to other settings.

Interaction effects of multimorbidity and frailty on adverse health outcomes in elderly hospitalised patients.

We quantified the interaction of multimorbidity and frailty and their impact on adverse health outcomes in the hospital setting. Using aretrospective cohort study of persons aged ≥ 75 years, admitted to hospital during 2010-2012 in New South Wales, Australia, and linked with mortality data, we constructed multimorbidity, frailty risk and outcomes: prolonged length of stay (LOS), 30-day mortality and 30-day unplanned readmissions. Relative risks (RR) of outcomes were obtained using Poisson models with random intercept for hospital. Among 257,535 elderly inpatients, 33.6% had multimorbidity and elevated frailty risk, 14.7% had multimorbidity only, 19.9% had elevated frailty risk only and 31.8% had neither. Additive interactions were present for all outcomes, with a further multiplicative interaction for mortality and LOS. Mortality risk was 4.2 (95% CI 4.1-4.4), prolonged LOS 3.3 (95% CI 3.3-3.4) and readmission 1.8 (95% CI 1.7-1.9) times higher in patients with both factors present compared with patients with neither. In conclusion, multimorbidity and frailty coexist in older hospitalized patients and interact to increase the risk of adverse outcomes beyond the sum of their individual effects. Their joint effect should be considered in health outcomes research and when administering hospital resources.

Differences in the pre-hospital management of women and men with stroke by emergency medical services in New South Wales.

OBJECTIVES: To examine whether pre-hospital emergency medical service care differs for women and men subsequently admitted to hospital with stroke. DESIGN, SETTING, PARTICIPANTS: Population-based cohort study; analysis of linked Admitted Patient Data Collection and NSW Ambulance data for people admitted to New South Wales hospitals with a principal diagnosis of stroke at separation, 1 July 2005 - 31 December 2018. MAIN OUTCOME MEASURES: Emergency medical service assessments, protocols, and management for patients subsequently diagnosed with stroke, by sex. RESULTS: Of 202 231 people hospitalised with stroke (mean age, 73 [SD, 14] years; 98 599 women [51.0%]), 101 357 were conveyed to hospital by ambulance (50.1%). A larger proportion of women than men travelled by ambulance (52.4% v 47.9%; odds ratio [OR], 1.09; 95% CI, 1.07-1.11), but time between the emergency call and emergency department admission was similar for both sexes. The likelihood of being assessed as having a stroke (adjusted OR [aOR], 0.97; 95% CI, 0.93-1.01) or subarachnoid haemorrhage (aOR, 1.22; 95% CI, 0.73-2.03) was similar for women and men, but women under 70 years of age were less likely than men to be assessed as having a stroke (aOR, 0.89; 95% CI, 0.82-0.97). Women were more likely than men to be assessed by paramedics as having migraine, other headache, anxiety, unconsciousness, hypertension, or nausea. Women were less likely than men to be managed according to the NSW Ambulance pre-hospital stroke care protocol (aOR, 0.95; 95% CI, 0.92-0.97), but the likelihood of basic pre-hospital care was similar for both sexes (aOR, 1.01; 95% CI, 0.99-1.04). CONCLUSION: Our large population-based study identified sex differences in pre-hospital management by emergency medical services of women and men admitted to hospital with stroke. Paramedics should receive training that improves the recognition of stroke symptoms in women.

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Medically At-Risk Children in Australia: A Record Linkage Study.

BACKGROUND: Children with chronic medical conditions are at higher risk of invasive pneumococcal disease (IPD), but little is known about the effectiveness of the primary course of pneumococcal conjugate vaccine (PCV) in these children. METHODS: A cohort born in 2001-2004 from two Australian states and identified as medically at-risk (MAR) of IPD either using ICD-coded hospitalizations (with conditions of interest identified by 6 months of age) or linked perinatal data (for prematurity) were followed to age 5 years for notified IPD by serotype. We categorized fully vaccinated children as either receiving PCV dose 3 by <12 months of age or ≥1 PCV dose at ≥12 months of age. Cox proportional hazard modeling was used to estimate hazard ratios (HRs), adjusted for confounders, and vaccine effectiveness (VE) was estimated as (1-HR) × 100. RESULTS: A total of 9220 children with MAR conditions had 53 episodes of IPD (43 vaccine-type); 4457 (48.3%) were unvaccinated and 4246 (46.1%) were fully vaccinated, with 1371 (32.3%) receiving dose 3 by 12 months and 2875 (67.7%) having ≥1 dose at ≥12 months. Estimated VE in fully vaccinated children was 85.9% (95% CI: 33.9-97.0) against vaccine-type IPD and 71.5% (95% CI: 26.6-88.9) against all-cause IPD. CONCLUSION: This is the first population-based study evaluating the effectiveness of PCV in children with MAR conditions using record linkage. Our study provides evidence that the VE for vaccine-type and all-cause IPD in MAR children in Australia is high and not statistically different from previously reported estimates for the general population. This method can be replicated in other countries to evaluate VE in MAR children.

Maternal factors and risk of spontaneous preterm birth due to high ambient temperatures in New South Wales, Australia.

BACKGROUND: Exposure to high ambient temperatures has been shown to increase the risk of spontaneous preterm birth. Determining which maternal factors increase or decrease this risk will inform climate adaptation strategies. OBJECTIVES: This study aims to assess the risk of spontaneous preterm birth associated with exposure to ambient temperature and differences in this relationship between mothers with different health and demographic characteristics. METHODS: We used quasi-Poisson distributed lag non-linear models to estimate the effect of high temperature-measured as the 95th percentile of daily minimum, mean and maximum compared with the median-on risk of spontaneous preterm birth (23-36 weeks of gestation) in pregnant women in New South Wales, Australia. We estimated the cumulative lagged effects of daily temperature and analyses on population subgroups to assess increased or decreased vulnerability to this effect. RESULTS: Pregnant women (n = 916,678) exposed at the 95th percentile of daily mean temperatures (25ºC) had an increased risk of preterm birth (relative risk 1.14, 95% confidence interval 1.07, 1.21) compared with the median daily mean temperature (17℃). Similar effect sizes were seen for the 95th percentile of minimum and maximum daily temperatures compared with the median. This risk was slightly higher among women with diabetes, hypertension, chronic illness and women who smoked during pregnancy. CONCLUSIONS: Higher temperatures increase the risk of preterm birth and women with pre-existing health conditions and who smoke during pregnancy are potentially more vulnerable to these effects.

Place of birth and outcomes associated with large volume transfusion: an observational study.

BACKGROUND: Guidelines recommend that women at high risk of postpartum haemorrhage deliver at facilities able to handle heavy bleeding. However postpartum haemorrhage is often unexpected. This study aims to compare outcomes and health service use related to transfusion of ≥4 units of red blood cells between women delivering in tertiary and lower level hospitals. METHODS: The study population was women giving birth in public hospitals in New South Wales, Australia, between July 2006 and December 2010. Data were obtained from linked hospital, birth and blood bank databases. The exposure of interest was transfusion of four or more units of red cells during admission for delivery. Outcomes included maternal morbidity, length of stay, neonatal morbidity and need for other blood products or transfer to higher care. Multivariable regression models were developed to predict need of transfusion of ≥4 units of red cells using variables known early in pregnancy and those known by the birth admission. RESULTS: Data were available for 231,603 births, of which 4309 involved a blood transfusion, with 1011 (0.4%) receiving 4 or more units. Women giving birth in lower level and/or smaller hospitals were more likely to receive ≥4 units of red cells. Women receiving ≥4 units in tertiary settings were more likely to receive other blood products and have longer hospital stays, but morbidity, readmission and hysterectomy rates were similar. Although 46% of women had no identifiable risk factors early in pregnancy, 20% of transfusions of ≥4 units occurred within this group. By the birth admission 70% of women had at least one risk factor for requiring ≥4 units of red cells. CONCLUSIONS: Overall outcomes for women receiving ≥4 units of red cells were comparable between tertiary and non-tertiary facilities. This is important given the inability of known risk factors to predict many instances of postpartum haemorrhage.

The Comparative Effectiveness of Varenicline and Nicotine Patches for Smoking Abstinence During Pregnancy: Evidence From a Population-based Cohort Study.

INTRODUCTION: In the general population, varenicline is consistently shown to be more efficacious for smoking cessation than nicotine replacement therapy (NRT). Current clinical guidelines for the management of smoking during pregnancy recommend against the use of varenicline, whilst supporting the use of NRT. However, little is known about the comparative effectiveness of these smoking cessation therapies among pregnant women. AIMS AND METHODS: Routinely-collected records of all births in two Australian States during 2011 and 2012 were used to create a population-based cohort of women who smoked during the first half of pregnancy. Pharmaceutical dispensing data were used to identify varenicline and nicotine patch dispensings in the first half of pregnancy. Propensity score matching was used to account for the potentially different distribution of confounding factors between the treatment groups. The outcome was defined as smoking abstinence during the second half of pregnancy. RESULTS: After propensity score-matching, our cohort comprised 60 women who used varenicline and 60 who used nicotine patches during the first half of pregnancy. More varenicline users (33.3%, 95% CI: 21.7%-46.7%) quit smoking than nicotine patch users (13.3%, 95% CI: 5.9%-24.6%). The adjusted rate difference was 24.2% (95% CI: 10.2%-38.2%) and the adjusted relative risk was 2.8 (95% CI: 1.4-5.7). CONCLUSIONS: Varenicline was almost three times more effective than nicotine patches in assisting pregnant women to quit smoking. Further studies are needed to corroborate our results. Together with data on the safety of varenicline during pregnancy, evidence regarding the relative benefit of varenicline and NRT during pregnancy important for informing clinical decisions for pregnant smokers. IMPLICATIONS: This study is the first to measure the comparative effectiveness of varenicline and nicotine patches during pregnancy - women using varenicline were almost three times as likely to quit smoking than those using nicotine patches. This study addressed a clinically important question using an observational study, noting that there is an absence of evidence from randomized controlled trials because of the ethical issues associated with including pregnant women in clinical trials of medicines of unknown safety.

Sex differences in emergency medical services management of patients with myocardial infarction: analysis of routinely collected data for over 110,000 patients.

Emergency medical services (EMS) activation is an integral component in managing individuals with myocardial infarction (MI). EMS play a crucial role in early MI symptom recognition, prompt transport to percutaneous coronary intervention centres and timely administration of management. The objective of this study was to examine sex differences in prehospital EMS care of patients hospitalized with Ml using data from a retrospective population-based cohort study of linked health administrative data for people with a hospital diagnosis of MI in Australia (2001-18).

Are newly introduced criteria for the diagnosis of gestational diabetes mellitus associated with improved pregnancy outcomes and/or increased interventions in New South Wales, Australia? A population-based data linkage study.

INTRODUCTION: The incidence of gestational diabetes mellitus (GDM) is increasing in Australia, influenced by changed diagnostic criteria. We aimed to identify whether the diagnostic change was associated with improved outcomes and/or increased obstetric interventions using state-wide data in New South Wales (NSW), Australia. RESEARCH DESIGN AND METHODS: Perinatal and hospital data were linked for singleton births, 33-41 weeks' gestation, 2006-2015, NSW. An adjusted Poisson model was used to split pregnancies from 2011 onwards into those that would have been diagnosed under the old criteria ('previous GDM') and newly diagnosed cases ('additional GDM'). We compared actual rates of total and early (<39 weeks) planned births, cesareans, and maternal and neonatal adverse outcomes for GDM-diagnosed pregnancies using three predicted scenarios, where the 'additional GDM' group was assumed to have the same rates as: the 'previous GDM' group <2011 (scenario A); the 'non-GDM' group <2011 (scenario B); or the 'non-GDM' group ≥2011 (scenario C). RESULTS: GDM incidence more than doubled over the study period, with an inflection point observed at 2011. For those diagnosed with GDM since 2011, the actual incidence of interventions (planned births and cesareans) and macrosomia was consistent with scenario A, which meant higher intervention rates, but lower rates of macrosomia, than those with no GDM. Incidence of neonatal hypoglycemia was lower than scenario A and closer to the other scenarios. There was a reduction in perinatal deaths among those with GDM, lower than that predicted by all scenarios, indicating an improvement for all with GDM, not only women newly diagnosed. Incidence of maternal and neonatal morbidity indicators was within the confidence bounds for all three predicted scenarios. CONCLUSIONS: Our study suggests that the widely adopted new diagnostic criteria for GDM are associated with increased obstetric intervention rates and lower rates of macrosomic babies, but with no clear impacts on maternal or neonatal morbidity.

Estimating pneumococcal vaccine coverage among Australian Indigenous children and children with medically at-risk conditions using record linkage.

BACKGROUND: Risk-based recommendations are common for pneumococcal vaccines but little is known about their uptake. In Australia, pneumococcal conjugate vaccine (PCV) was funded only for Aboriginal or Torres Strait Islander (Indigenous) children and those with underlying medical conditions in 2001, and then there were different booster dose recommendations depending on risk after the introduction of universal PCV vaccination in 2005. METHODS: We measured coverage of PCV dose 3 and additional PCV and 23-valent pneumococcal polysaccharide vaccine (PPV23) doses by risk group among children born in July 2001-December 2012 in two Australian states using linked immunisation and hospitalisation data (available until December 2013). We ascertained medical risk conditions using hospitalisation diagnosis codes and Indigenous status using an established algorithm, comparing coverage for children born pre (2001-2004) and post (2005-2012) universal PCV funding. RESULTS: Among 1.3 million children, 63,897 (4.9%) were Indigenous and 32,934 (2.5%) had at least one medically at-risk condition identified by age 6 months. For births in 2001-2004, coverage for PCV dose 3 by 1 year of age was 37% for Indigenous, 15% for medically at-risk and 11% in other children, increasing to 83%, 91% and 92%, respectively for births in 2005-2012. In children with medically at-risk conditions, PCV dose 4 coverage by 2 years was 1% for 2001-2004 births, increasing to 9% for 2005-2012 births, with PPV23 coverage by 6 years 3% in both cohorts. Among eligible Indigenous children, PPV23 coverage by 3 years was 45% for 2001-2004 births and 51% for 2005-2012 births. CONCLUSIONS: Coverage with additional recommended booster doses was very low among children with medical conditions, and only modest among Indigenous children. If additional PCV doses are recommended for some risk groups, especially in the context of routine schedules with reduced doses (e.g. 2 + 1 and 1 + 1), measures to improve implementation will be required.

Rates of neonatal morbidity by maternal region of birth and gestational age in New South Wales, Australia 2003-2016.

INTRODUCTION: Research suggests that neonatal morbidity differs by maternal region of birth at different gestational ages. This study aimed to determine the overall and gestation-specific risk of neonatal morbidity by maternal region of birth, after adjustment for maternal, infant and birth characteristics, for women giving birth in New South Wales, Australia, from 2003 to 2016. MATERIAL AND METHODS: The study utilized a retrospective cohort study design using linked births, hospital and deaths data. Modified Poisson regression was used to determine risk with 95% confidence intervals (95% CI) of neonatal morbidity by maternal region of birth, overall and at each gestational age, compared with Australian or New Zealand-born women giving birth at 39 weeks. RESULTS: There were 1 074 930 live singleton births ≥32 weeks' gestation that met the study inclusion criteria, and 44 394 of these were classified as morbid, giving a neonatal morbidity rate of 4.13 per 100 live births. The gestational age-specific neonatal morbidity rate declined from 32 weeks' gestation, reaching a minimum at 39 weeks in all maternal regions of birth. The unadjusted neonatal morbidity rate was highest in South Asian-born women at most gestations. Adjusted rates of neonatal morbidity between 32 and 44 weeks were significantly lower for babies born to East (adjusted relative risk [aRR] 0.65, 95% CI 0.62-0.68), South-east (aRR 0.76, 95% CI 0.73-0.79) and West Asian-born (aRR 0.93, 95% CI 0.88-0.98) mothers, and higher for babies of Oceanian-born (aRR 1.11, 95% CI 1.04-1.18) mothers, compared with Australian or New Zealand-born mothers. Babies of African, Oceanian, South Asian and West Asian-born women had a lower adjusted risk of neonatal morbidity than Australian or New Zealand-born women until 37 or 38 weeks' gestation, and thereafter an equal or higher risk in the term and post-term periods. CONCLUSIONS: Maternal region of birth is an independent risk factor for neonatal morbidity in New South Wales.

Rates of stillbirth by maternal region of birth and gestational age in New South Wales, Australia 2004-2015.

BACKGROUND: Research suggests that in Australia, maternal region of birth is a risk factor for stillbirth. AIMS: We aimed to examine the relationship between stillbirth and maternal region of birth in New South Wales (NSW), Australia from 2004 to 2015. METHODS: Adjusted logistic regression was used to determine odds of stillbirth by maternal region of birth, compared with Australian or New Zealand-born (AUS/NZ-born) women. Intervention rates (induction or pre-labour caesarean) by maternal region of birth, over time, were also examined. Interaction terms were used to assess change in relative odds of stillbirth, over two time periods (2004-2011 and 2012-2015). RESULTS: There were 944 457 singleton births ≥24 weeks gestation that met the study inclusion criteria and 3221 of these were stillbirths, giving a stillbirth rate of 3.4 per 1000 births. After adjustment for confounders, South Asian (adjusted odds ratio (aOR) 1.42, 95% CI 1.24-1.62), Oceanian (aOR 1.45, 95% CI 1.17-1.80) and African (aOR 1.46, 96% CI 1.19-1.80) born women had significantly higher odds of stillbirth that AUS/NZ-born women. Intervention rates increased from the earlier to the later time period by 13.1% across the study population, but the increase was larger in African and South Asian-born women (18.1% and 19.6% respectively) than AUS/NZ-born women (11.2%). There was a significant interaction between ethnicity and time period for South Asian-born women in the all-births model, with their stillbirth rates becoming closer to AUS/NZ-born women in the later period. CONCLUSION: South Asian, African and Oceanian maternal region of birth are independent risk factors for stillbirth in NSW.

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study.

BACKGROUND: Varenicline, bupropion and nicotine replacement therapy (NRT) are three effective pharmacotherapies for smoking cessation, but data about their safety in pregnancy are limited. We assessed the risk of adverse perinatal outcomes and major congenital anomalies associated with the use of these therapies in pregnancy in Australia. METHODS: Perinatal data for 1,017,731 deliveries (2004 to 2012) in New South Wales and Western Australia were linked to pharmaceutical dispensing, hospital admission and death records. We identified 97,875 women who smoked during pregnancy; of those, 233, 330 and 1057 were exposed to bupropion, NRT and varenicline in pregnancy, respectively. Propensity scores were used to match exposed women to those who were unexposed to any smoking therapy (1:10 ratio). Propensity scores and gestational age at exposure were used to match varenicline-exposed to NRT-exposed women (1:1 ratio). Time-dependent Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for any adverse perinatal event (a composite of 10 unfavourable maternal and neonatal outcomes) and any major congenital anomaly. RESULTS: The risk of any adverse perinatal event was not significantly different between bupropion-exposed and unexposed women (39.2% versus 39.3%, HR 0.93, 95% CI 0.73-1.19) and between NRT-exposed and unexposed women (44.8% vs 46.3%, HR 1.02, 95% CI 0.84-1.23), but it was significantly lower in women exposed to varenicline (36.9% vs 40.1%, HR 0.86, 95% CI 0.77-0.97). Varenicline-exposed infants were less likely than unexposed infants to be born premature (6.5% vs 8.9%, HR 0.72, 95% CI 0.56-0.92), be small for gestational age (11.4% vs 15.4%, HR 0.68, 95% CI 0.56-0.83) and have severe neonatal complications (6.6% vs 8.2%, HR 0.74, 95% CI 0.57-0.96). Among infants exposed to varenicline in the first trimester, 2.9% had a major congenital anomaly (3.5% in unexposed infants, HR 0.91, 95% CI 0.72-1.15). Varenicline-exposed women were less likely than NRT-exposed women to have an adverse perinatal event (38.7% vs 51.4%, HR 0.58, 95% CI 0.33-1.05). CONCLUSIONS: Pregnancy exposure to smoking cessation pharmacotherapies does not appear to be associated with an increased risk of adverse birth outcomes. Lower risk of adverse birth outcomes in varenicline-exposed pregnancies is inconsistent with recommendations that NRT be used in preference to varenicline.