ZCCHC3 is a stress granule zinc knuckle protein that strongly suppresses LINE-1 retrotransposition.

Retrotransposons have generated about half of the human genome and LINE-1s (L1s) are the only autonomously active retrotransposons. The cell has evolved an arsenal of defense mechanisms to protect against retrotransposition with factors we are only beginning to understand. In this study, we investigate Zinc Finger CCHC-Type Containing 3 (ZCCHC3), a gag-like zinc knuckle protein recently reported to function in the innate immune response to infecting viruses. We show that ZCCHC3 also severely restricts human retrotransposons and associates with the L1 ORF1p ribonucleoprotein particle. We identify ZCCHC3 as a bona fide stress granule protein, and its association with LINE-1 is further supported by colocalization with L1 ORF1 protein in stress granules, dense cytoplasmic aggregations of proteins and RNAs that contain stalled translation pre-initiation complexes and form when the cell is under stress. Our work also draws links between ZCCHC3 and the anti-viral and retrotransposon restriction factors Mov10 RISC Complex RNA Helicase (MOV10) and Zinc Finger CCCH-Type, Antiviral 1 (ZC3HAV1, also called ZAP). Furthermore, collective evidence from subcellular localization, co-immunoprecipitation, and velocity gradient centrifugation connects ZCCHC3 with the RNA exosome, a multi-subunit ribonuclease complex capable of degrading various species of RNA molecules and that has previously been linked with retrotransposon control.

The effectiveness of maternal pertussis vaccination for protecting Aboriginal and Torres Strait Islander infants against infection, 2012-2017: a retrospective cohort study.

OBJECTIVES: To evaluate the effectiveness of maternal pertussis vaccination for preventing pertussis infections in Aboriginal and Torres Strait Islander infants under seven months of age. STUDY DESIGN: Retrospective cohort study; analysis of linked administrative health data. SETTING, PARTICIPANTS: Mother-infant cohort (Links2HealthierBubs) including all pregnant women who gave birth to live infants (gestational age ≥ 20 weeks, birthweight ≥ 400 g) in the Northern Territory, Queensland, and Western Australia during 1 January 2012 - 31 December 2017. MAIN OUTCOME MEASURES: Proportions of women vaccinated against pertussis during pregnancy, rates of pertussis infections among infants under seven months of age, and estimated effectiveness of maternal vaccination for protecting infants against pertussis infection, each by Indigenous status. RESULTS: Of the 19 892 Aboriginal and Torres Strait Islander women who gave birth to live infants during 2012-2017, 7398 (37.2%) received pertussis vaccine doses during their pregnancy, as had 137 034 of 259 526 non-Indigenous women (52.8%; Indigenous v non-Indigenous: adjusted odds ratio, 0.66; 95% confidence interval [CI], 0.62-0.70). The annual incidence of notified pertussis infections in non-Indigenous infants declined from 16.8 (95% CI, 9.9-29) in 2012 to 1.4 (95% CI, 0.3-8.0) cases per 10 000 births in 2017; among Aboriginal and Torres Strait Islander infants, it declined from 47.6 (95% CI, 16.2-139) to 38.6 (95% CI, 10.6-140) cases per 10 000 births. The effectiveness of maternal vaccination for protecting non-Indigenous infants under seven months of age against pertussis infection during 2014-17 was 68.2% (95% CI, 51.8-79.0%); protection of Aboriginal and Torres Strait Islander infants was not statistically significant (36.1%; 95% CI, -41.3% to 71.1%). CONCLUSIONS: During 2015-17, maternal pertussis vaccination did not protect Aboriginal and Torres Strait Islander infants in the NT, Queensland, and WA against infection. Increasing the pertussis vaccination rate among pregnant Aboriginal and Torres Strait Islander women requires culturally appropriate, innovative strategies co-designed in partnership with Indigenous organisations and communities.

Interpregnancy interval and adverse birth outcomes: a population-based cohort study of twins.

BACKGROUND: To investigate associations between interpregnancy intervals (IPIs) and adverse birth outcomes in twin pregnancies. METHODS: This retrospective cohort study of 9,867 twin pregnancies in Western Australia from 1980-2015. Relative Risks (RRs) were estimated for the interval prior to the pregnancy (IPI) as the exposure and after the pregnancy as a negative control exposure for preterm birth (< 37 weeks), early preterm birth (< 34 weeks), small for gestational age (SGA: < 10th percentile of birth weight by sex and gestational age) and low birth weight (LBW: birthweight < 2,500 g). RESULTS: Relative to IPIs of 18-23 months, IPIs of < 6 months were associated with a higher risk of early preterm birth (aRR 1.41, 95% CI 1.08-1.83) and LBW for at least one twin (aRR 1.16, 95% CI 1.06-1.28). IPIs of 6-11 months were associated with a higher risk of SGA (aRR 1.24, 95% CI 1.01-1.54) and LBW for at least one twin (aRR 1.09, 95% CI 1.01-1.19). IPIs of 60-119 months and ≥ 120 months were associated with an increased risk of preterm birth (RR 1.12, 95% CI 1.03-1.22; and (aRR 1.25, 95% CI 1.10-1.41, respectively), and LBW for at least one twin (aRR 1.17, 95% CI 1.08-1.28; and aRR 1.20, 95% CI 1.05-1.36, respectively). IPIs of ≥ 120 months were also associated with an increased risk of early preterm birth (aRR 1.42, 95% CI 1.01-2.00). After negative control analysis, IPIs ≥ 120 months remained associated with early preterm birth and LBW. CONCLUSION: Evidence for adverse associations with twin birth outcomes was strongest for long IPIs.

Shoulder dystocia in babies born to Aboriginal mothers with diabetes: a population-based cohort study, 1998-2015.

BACKGROUND: Australian Aboriginal and Torres Strait Islander women with diabetes in pregnancy (DIP) are more likely to have glycaemic levels above the target range, and their babies are thus at higher risk of excessive fetal growth. Shoulder dystocia, defined by failure of spontaneous birth of fetal shoulder after birth of the head requiring obstetric maneuvers, is an obstetric emergency that is strongly associated with DIP and fetal size. The aim of this study was to investigate the epidemiology of shoulder dystocia in Aboriginal babies born to mothers with DIP. METHODS: Stratifying by Aboriginal status, characteristics of births complicated by shoulder dystocia in women with and without DIP were compared and incidence and time-trends of shoulder dystocia were described. Compliance with guidelines aiming at preventing shoulder dystocia in women with DIP were compared. Post-logistic regression estimation was used to calculate the population attributable fractions (PAFs) for shoulder dystocia associated with DIP and to estimate probabilities of shoulder dystocia in babies born to mothers with DIP at birthweights > 3 kg. RESULTS: Rates of shoulder dystocia from vaginal births in Aboriginal babies born to mothers with DIP were double that of their non-Aboriginal counterparts (6.3% vs 3.2%, p < 0.001), with no improvement over time. Aboriginal mothers with diabetes whose pregnancies were complicated by shoulder dystocia were more likely to have a history of shoulder dystocia (13.1% vs 6.3%, p = 0.032). Rates of guideline-recommended elective caesarean section in pregnancies with diabetes and birthweight > 4.5 kg were lower in the Aboriginal women (28.6% vs 43.1%, p = 0.004). PAFs indicated that 13.4% (95% CI: 9.7%-16.9%) of shoulder dystocia cases in Aboriginal (2.7% (95% CI: 2.1%-3.4%) in non-Aboriginal) women were attributable to DIP. Probability of shoulder dystocia among babies born to Aboriginal mothers with DIP was higher at birthweights > 3 kg. CONCLUSIONS: Aboriginal mothers with DIP had a higher risk of shoulder dystocia and a stronger association between birthweight and shoulder dystocia. Many cases were recurrent. These factors should be considered in clinical practice and when counselling women.

The hidden impact of alcohol on young victims: an analysis of alcohol-related police offences resulting in hospitalisation.

BACKGROUND: Alcohol-related harm (ARH) is a significant public health concern affecting young individuals, particularly those involved in alcohol-related police incidents resulting in hospitalisation. However, the impact of alcohol on young victims remains under researched. This study aimed to identify the characteristics of offenders and victims involved in these incidents, analyse the types of offences, and understand the under-ascertainment of ARH in hospital records. METHODS: A retrospective longitudinal study of 12-24-year-olds born between 1980 and 2005 was conducted using linked data from hospital admissions, emergency department presentations, and police incident records. Alcohol-related incidents were identified based on the attending officers' opinions in the Western Australia Police's Incident Management System (IMS). Logistic and log-binomial regression were utilised to analyse the factors associated with victimisation and under-ascertainment of ARH. RESULTS: Our study included 22,747 individuals (11,433 victims and 11,314 offenders) involved in alcohol-related police incidents, with a small majority of victims being female (53%, n = 6,074) and a large majority of offenders being male (84.3%, n = 9,532). Most victims did not receive a diagnosis of ARH (71%, n = 760). Women were 10 times more likely to have been a victim in ARH police incidents and 2 times more likely to have an undiagnosed alcohol-related hospital admission than men. Victims and offenders predominantly came from disadvantaged areas and major cities. Aboriginal individuals were overrepresented as both offenders and victims. A significant proportion of individuals experienced emergency department presentations or hospital admissions, with head injuries being the most common. Assault causing bodily harm was the most prevalent offence resulting in hospitalisation (66%, n = 2,018). CONCLUSIONS: There is a noteworthy disparity between the quantity of hospital admissions attributed to alcohol-related incidents and the number of cases that are formally classified as ARH in the hospital system. This disparity highlights a more profound issue of substantial under-ascertainment or inadequate identification of ARH than previously acknowledged. Our findings justify the prioritisation of prevention strategies, beyond improvement in the documentation of alcohol-related hospitalisation. Considering the scale of the problem, and the underestimation of the burden of alcohol-related hospitalisation, a proportional increase in investment is necessary to achieve population-level reductions in ARH.

Associations between endometriosis and adverse pregnancy and perinatal outcomes: a population-based cohort study.

PURPOSE: To examine the association between endometriosis and adverse pregnancy and perinatal outcomes (preeclampsia, placenta previa, and preterm birth). METHODS: A population-based retrospective cohort study was conducted among 468,778 eligible women who contributed 912,747 singleton livebirths between 1980 and 2015 in Western Australia (WA). We used probabilistically linked perinatal and hospital separation data from the WA data linkage system's Midwives Notification System and Hospital Morbidity Data Collection databases. We used a doubly robust estimator by combining the inverse probability weighting with the outcome regression model to estimate adjusted risk ratios (RR) and 95% confidence intervals (CIs). RESULTS: There were 19,476 singleton livebirths among 8874 women diagnosed with endometriosis. Using a doubly robust estimator, we found pregnancies in women with endometriosis to be associated with an increased risk of preeclampsia with RR of 1.18, 95% CI 1.11-1.26, placenta previa (RR 1.59, 95% CI 1.42-1.79) and preterm birth (RR 1.45, 95% CI 1.37-1.54). The observed association persisted after stratified by the use of Medically Assisted Reproduction, with a slightly elevated risk among pregnancies conceived spontaneously. CONCLUSIONS: In this large population-based cohort, endometriosis is associated with an increased risk of preeclampsia, placenta previa, and preterm birth, independent of the use of Medically Assisted Reproduction. This may help to enhance future obstetric care among this population.

Prenatal exposure to long-term heat stress and stillbirth in Ghana: A within-space time-series analysis.

INTRODUCTION: Few studies examined the association between prenatal long-term ambient temperature exposure and stillbirth and fewer still from developing countries. Rather than ambient temperature, we used a human thermophysiological index, Universal Thermal Climate Index (UTCI) to investigate the role of long-term heat stress exposure on stillbirth in Ghana. METHODS: District-level monthly UTCI was linked with 90,532 stillbirths of 5,961,328 births across all 260 local districts between 1st January 2012 and 31st December 2020. A within-space time-series design was applied with distributed lag nonlinear models and conditional quasi-Poisson regression. RESULTS: The mean (28.5 ± 2.1 °C) and median UTCI (28.8 °C) indicated moderate heat stress. The Relative Risks (RRs) and 95% Confidence Intervals (CIs) for exposure to lower-moderate heat (1st to 25th percentiles of UTCI) and strong heat (99th percentile) stresses showed lower risks, relative to the median UTCI. The higher-moderate heat stress exposures (75th and 90th percentiles) showed greater risks which increased with the duration of heat stress exposures and were stronger in the 90th percentile. The risk ranged from 2% (RR = 1.02, 95% CI 0.99, 1.05) to 18% (RR = 1.18, 95% CI 1.02, 1.36) for the 90th percentile, relative to the median UTCI. Assuming causality, 19 (95% CI 3, 37) and 27 (95% CI 3, 54) excess stillbirths per 10,000 births were attributable to long-term exposure to the 90th percentile relative to median UTCI for the past six and nine months, respectively. Districts with low population density, low gross domestic product, and low air pollution which collectively defined rural districts were at higher risk as compared to those in the high level (urban districts). DISCUSSION: Maternal exposure to long-term heat stress was associated with a greater risk of stillbirth. Climate change-resilient interventional measures to reduce maternal exposure to heat stress, particularly in rural areas may help lower the risk of stillbirth.

Inequity of antenatal influenza and pertussis vaccine coverage in Australia: the Links2HealthierBubs record linkage cohort study, 2012-2017.

BACKGROUND: Pregnancy and early infancy are increased risk periods for severe adverse effects of respiratory infections. Aboriginal and/or Torres Strait Islander (respectfully referred to as First Nations) women and children in Australia bear a disproportionately higher burden of respiratory diseases compared to non-Indigenous women and infants. Influenza vaccines and whooping cough (pertussis) vaccines are recommended and free in every Australian pregnancy to combat these infections. We aimed to assess the equity of influenza and/or pertussis vaccination in pregnancy for three priority groups in Australia: First Nations women; women from culturally and linguistically diverse (CALD) backgrounds; and women living in remote areas or socio-economic disadvantage. METHODS: We conducted individual record linkage of Perinatal Data Collections with immunisation registers/databases between 2012 and 2017. Analysis included generalised linear mixed model, log-binomial regression with a random intercept for the unique maternal identifier to account for clustering, presented as prevalence ratios (PR) and 95% compatibility intervals (95%CI). RESULTS: There were 445,590 individual women in the final cohort. Compared with other Australian women (n = 322,848), First Nations women (n = 29,181) were less likely to have received both recommended antenatal vaccines (PR 0.69, 95% CI 0.67-0.71) whereas women from CALD backgrounds (n = 93,561) were more likely to have (PR 1.16, 95% CI 1.10-1.13). Women living in remote areas were less likely to have received both vaccines (PR 0.75, 95% CI 0.72-0.78), and women living in the highest areas of advantage were more likely to have received both vaccines (PR 1.44, 95% CI 1.40-1.48). CONCLUSIONS: Compared to other groups, First Nations Australian families, those living in remote areas and/or families from lower socio-economic backgrounds did not receive recommended vaccinations during pregnancy that are the benchmark of equitable healthcare. Addressing these barriers must remain a core priority for Australian health care systems and vaccine providers. An extension of this cohort is necessary to reassess these study findings.

Interpregnancy interval and the risk of oppositional defiant disorder in offspring.

The study aimed to investigate the association between interpregnancy interval (IPI) and parent-reported oppositional defiant disorder (ODD) in offspring at 7 and 10 years of age. We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), an ongoing population-based longitudinal study based in Bristol, United Kingdom (UK). Data included in the analysis consisted of more than 3200 mothers and their singleton children. The association between IPI and ODD was determined using a series of log-binomial regression analyses. We found that children of mothers with short IPI (<6 months) were 2.4 times as likely to have a diagnosis of ODD at 7 and 10 years compared to mothers with IPI of 18-23 months (RR = 2.45; 95%CI: 1.24-4.81 and RR = 2.40; 95% CI: 1.08-5.33), respectively. We found no evidence of associations between other IPI categories and risk of ODD in offspring in both age groups. Adjustment for a wide range of confounders, including maternal mental health, and comorbid ADHD did not alter the findings. This study suggests that the risk of ODD is higher among children born following short IPI (<6 months). Future large prospective studies are needed to elucidate the mechanisms explaining this association.

Probiotic supplementation in neonates and long-term gut colonisation: A systematic review of randomised controlled trials.

BACKGROUND: Probiotic supplementation in the neonatal period results in improved gut colonisation with probiotic bacteria in the short term. There is limited information on the long-term sustainability of this colonisation. AIMS: To evaluate whether oral probiotic supplementation in the neonatal period results in sustained gut colonisation with probiotic bacteria at or beyond 6 months after its cessation. METHODS: A systematic review of neonatal probiotic randomised controlled trials (RCTs) that reported on the stool microbiota during post-discharge follow-up was carried out using guidelines of the Cochrane neonatal group. RESULTS: Four RCTs (n = 605 infants) were included in the review. The studies were heterogeneous in case selection, choice of probiotics, duration of supplementation, timing and the method of stool microbial analysis. Three RCTs (n = 471) showed the presence of intestinal probiotic bacteria at 6-12 months. The overall certainty of evidence was very low in view of small sample size, heterogeneity and identification only to the genus/species level. CONCLUSION: Low certainty of evidence suggests that probiotic supplementation in the neonatal period may result in sustained gut colonisation 6-12 months post-cessation, but not at 24 months. Adequately powered, well-designed RCTs with strain-specific assays are needed in this area.

Timing and temporal trends of influenza and pertussis vaccinations during pregnancy in three Australian jurisdictions: The Links2HealthierBubs population-based linked cohort study, 2012-2017.

BACKGROUND: Antenatal inactivated influenza (IIV) and pertussis-containing vaccines (dTpa) offer protection against severe respiratory infections for pregnant women and infants <6 months of age. Both vaccines are recommended in pregnancy; however, little is known about temporal or jurisdictional trends and predictors of uptake. AIMS: To identify gaps and predictors of IIV and/or dTpa vaccinations in Australian pregnancies from 2012 to 2017. MATERIALS AND METHODS: We conducted a probabilistically linked, multi-jurisdictional population-based cohort study, drawing from perinatal data collections and immunisation databases. We used a generalised linear mixed model with a random effect term to account for clustering of multiple pregnancies within mothers, to calculate vaccination uptake, and identify predictors of uptake by maternal demographic, pregnancy, and health characteristics. RESULTS: Of 591 868 unique pregnancies, IIV uptake was 15%, dTpa 27% and 12% received both vaccines. Pertussis vaccinations in First Nations pregnancies were 20% lower than non-Indigenous pregnancies; dTpa was strongly associated with IIV uptake (risk ratio (RR): 8.60, 95% CI 8.48-8.73). This trend was temporally and jurisdictionally consistent. First Nations women were more likely to have had IIV in pregnancy before the introduction of dTpa in the pregnancy program: (RR: 1.48, 95% CI 1.40-1.57), but less likely after dTpa implementation (RR: 0.78, 95% CI 0.76-0.80). CONCLUSIONS: Inequity in vaccine uptake between First Nations and non-Indigenous pregnancies, and dismal rates of vaccination in pregnancy overall need urgent review, particularly before the next influenza pandemic or pertussis outbreak. If antenatal dTpa is driving IIV uptake, changes in antenatal healthcare practices are needed to ensure vaccines are offered equitably and optimally to protect against infection.

Prenatal influenza vaccination and allergic and autoimmune diseases in childhood: A longitudinal, population-based linked cohort study.

BACKGROUND: Few studies have evaluated the effect of maternal influenza vaccination on the development of allergic and autoimmune diseases in children beyond 6 months of age. We aimed to investigate the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and subsequent diagnosis of allergic and autoimmune diseases. METHODS AND FINDINGS: This longitudinal, population-based linked cohort study included 124,760 singleton, live-born children from 106,206 mothers in Western Australia (WA) born between April 2012 and July 2016, with up to 5 years of follow-up from birth. In our study cohort, 64,169 (51.4%) were male, 6,566 (5.3%) were Aboriginal and/or Torres Strait Islander children, and the mean age at the end of follow-up was 3.0 (standard deviation, 1.3) years. The exposure was receipt of seasonal IIV during pregnancy. The outcomes were diagnosis of an allergic or autoimmune disease, including asthma and anaphylaxis, identified from hospital and/or emergency department (ED) records. Inverse probability of treatment weights (IPTWs) accounted for baseline probability of vaccination by maternal age, Aboriginal and/or Torres Strait Islander status, socioeconomic status, body mass index, parity, medical conditions, pregnancy complications, prenatal smoking, and prenatal care. The models additionally adjusted for the Aboriginal and/or Torres Strait Islander status of the child. There were 14,396 (11.5%) maternally vaccinated children; 913 (6.3%) maternally vaccinated and 7,655 (6.9%) maternally unvaccinated children had a diagnosis of allergic or autoimmune disease, respectively. Overall, maternal influenza vaccination was not associated with diagnosis of an allergic or autoimmune disease (adjusted hazard ratio [aHR], 1.02; 95% confidence interval [CI], 0.95 to 1.09). In trimester-specific analyses, we identified a negative association between third trimester influenza vaccination and the diagnosis of asthma (n = 40; aHR, 0.70; 95% CI, 0.50 to 0.97) and anaphylaxis (n = 36; aHR, 0.67; 95% CI, 0.47 to 0.95).We did not capture outcomes diagnosed in a primary care setting; therefore, our findings are only generalizable to more severe events requiring hospitalization or presentation to the ED. Due to small cell sizes (i.e., <5), estimates could not be determined for all outcomes after stratification. CONCLUSIONS: In this study, we observed no association between in utero exposure to influenza vaccine and diagnosis of allergic or autoimmune diseases. Although we identified a negative association of asthma and anaphylaxis diagnosis when seasonal IIV was administered later in pregnancy, additional studies are needed to confirm this. Overall, our findings support the safety of seasonal inactivated influenza vaccine during pregnancy in relation to allergic and autoimmune diseases in early childhood and support the continuation of current global maternal vaccine programs and policies.

Interpregnancy interval and adverse pregnancy outcomes among pregnancies following miscarriages or induced abortions in Norway (2008-2016): A cohort study.

BACKGROUND: The World Health Organization recommends to wait at least 6 months after miscarriage and induced abortion before becoming pregnant again to avoid complications in the next pregnancy, although the evidence-based underlying this recommendation is scarce. We aimed to investigate the risk of adverse pregnancy outcomes-preterm birth (PTB), spontaneous PTB, small for gestational age (SGA) birth, large for gestational age (LGA) birth, preeclampsia, and gestational diabetes mellitus (GDM)-by interpregnancy interval (IPI) for births following a previous miscarriage or induced abortion. METHODS AND FINDINGS: We conducted a cohort study using a total of 49,058 births following a previous miscarriage and 23,707 births following a previous induced abortion in Norway between 2008 and 2016. We modeled the relationship between IPI and 6 adverse pregnancy outcomes separately for births after miscarriages and births after induced abortions. We used log-binomial regression to estimate unadjusted and adjusted relative risk (aRR) and 95% confidence intervals (CIs). In the adjusted model, we included maternal age, gravidity, and year of birth measured at the time of the index (after interval) births. In a sensitivity analysis, we further adjusted for smoking during pregnancy and prepregnancy body mass index. Compared to births with an IPI of 6 to 11 months after miscarriages (10.1%), there were lower risks of SGA births among births with an IPI of <3 months (8.6%) (aRR 0.85, 95% CI: 0.79, 0.92, p < 0.01) and 3 to 5 months (9.0%) (aRR 0.90, 95% CI: 0.83, 0.97, p = 0.01). An IPI of <3 months after a miscarriage (3.3%) was also associated with lower risk of GDM (aRR 0.84, 95% CI: 0.75, 0.96, p = 0.01) as compared to an IPI of 6 to 11 months (4.5%). For births following an induced abortion, an IPI <3 months (11.5%) was associated with a nonsignificant but increased risk of SGA (aRR 1.16, 95% CI: 0.99, 1.36, p = 0.07) as compared to an IPI of 6 to 11 months (10.0%), while the risk of LGA was lower among those with an IPI 3 to 5 months (8.0%) (aRR 0.84, 95% CI: 0.72, 0.98, p = 0.03) compared to an IPI of 6 to 11 months (9.4%). There was no observed association between adverse pregnancy outcomes with an IPI >12 months after either a miscarriage or induced abortion (p > 0.05), with the exception of an increased risk of GDM among women with an IPI of 12 to 17 months (5.8%) (aRR 1.20, 95% CI: 1.02, 1.40, p = 0.02), 18 to 23 months (6.2%) (aRR 1.24, 95% CI: 1.02, 1.50, p = 0.03), and ≥24 months (6.4%) (aRR 1.14, 95% CI: 0.97, 1.34, p = 0.10) compared to an IPI of 6 to 11 months (4.5%) after a miscarriage. Inherent to retrospective registry-based studies, we did not have information on potential confounders such as pregnancy intention and health-seeking bahaviour. Furthermore, we only had information on miscarriages that resulted in contact with the healthcare system. CONCLUSIONS: Our study suggests that conceiving within 3 months after a miscarriage or an induced abortion is not associated with increased risks of adverse pregnancy outcomes. In combination with previous research, these results suggest that women could attempt pregnancy soon after a previous miscarriage or induced abortion without increasing perinatal health risks.

The role of intervening pregnancy loss in the association between interpregnancy interval and adverse pregnancy outcomes.

OBJECTIVE: To investigate whether intervening miscarriages and induced abortions impact the associations between interpregnancy interval after a live birth and adverse pregnancy outcomes. DESIGN: Population-based cohort study. SETTING: Norway. PARTICIPANTS: A total of 165 617 births to 143 916 women between 2008 and 2016. MAIN OUTCOME MEASURES: We estimated adjusted relative risks for adverse pregnancy outcomes using log-binomial regression, first ignoring miscarriages and induced abortions in the interpregnancy interval estimation (conventional interpregnancy interval estimates) and subsequently accounting for intervening miscarriages or induced abortions (correct interpregnancy interval estimates). We then calculated the ratio of the two relative risks (ratio of ratios, RoR) as a measure of the difference. RESULTS: The proportion of short interpregnancy interval (<6 months) was 4.0% in the conventional interpregnancy interval estimate and slightly increased to 4.6% in the correct interpregnancy interval estimate. For interpregnancy interval <6 months, compared with 18-23 months, the RoR was 0.97 for preterm birth (PTB) (95% confidence interval [CI] 0.83-1.13), 0.97 for spontaneous PTB ( 95% CI 0.80-1.19), 1.00 for small-for-gestational age ( 95% CI 0.86-1.14), 1.00 for large-for-gestational age (95% CI 0.90-1.10) and 0.99 for pre-eclampsia (95% CI 0.71-1.37). Similarly, conventional and correct interpregnancy intervals yielded associations of similar magnitude between long interpregnancy interval (≥60 months) and the pregnancy outcomes evaluated. CONCLUSION: Not considering intervening pregnancy loss due to miscarriages or induced abortions, results in negligible difference in the associations between short and long interpregnancy intervals and adverse pregnancy outcomes. TWEETABLE ABSTRACT: Not considering pregnancy loss in interpregnancy interval estimation resulted no meaningful differences in observed risks of adverse pregnancy outcomes.

Trends and burden of diabetes in pregnancy among Aboriginal and non-Aboriginal mothers in Western Australia, 1998-2015.

BACKGROUND: Diabetes in pregnancy (DIP), which includes pre-gestational and gestational diabetes, is more prevalent among Aboriginal women. DIP and its adverse neonatal outcomes are associated with diabetes and cardiovascular disease in the offspring. This study investigated the impact of DIP on trends of large for gestational age (LGA) in Aboriginal and non-Aboriginal populations, and added to the limited evidence on temporal trends of DIP burden in these populations. METHODS: We conducted a retrospective cohort study that included all births in Western Australia between 1998 and 2015 using linked population health datasets. Time trends of age-standardised and crude rates of pre-gestational and gestational diabetes were estimated in Aboriginal and non-Aboriginal mothers. Mixed-effects multivariable logistic regression was used to estimate the association between DIP and population LGA trends over time. RESULTS: Over the study period, there were 526,319 births in Western Australia, of which 6.4% were to Aboriginal mothers. The age-standardised annual rates of pre-gestational diabetes among Aboriginal mothers rose from 4.3% in 1998 to 5.4% in 2015 and remained below 1% in non-Aboriginal women. The comparable rates for gestational diabetes increased from 6.7 to 11.5% over the study period in Aboriginal women, and from 3.5 to 10.2% among non-Aboriginal mothers. LGA rates in Aboriginal babies remained high with inconsistent and no improvement in pregnancies complicated by gestational diabetes and pre-gestational diabetes, respectively. Regression analyses showed that DIP explained a large part of the increasing LGA rates over time in Aboriginal babies. CONCLUSIONS: There has been a substantial increase in the burden of pre-gestational diabetes (Aboriginal women) and gestational diabetes (Aboriginal and non-Aboriginal) in recent decades. DIP appears to substantially contribute to increasing trends in LGA among Aboriginal babies.

Maternal and neonatal outcomes of women with gestational diabetes and without specific medical conditions: an Australian population-based study comparing induction of labor with expectant management.

BACKGROUND/AIMS: To evaluate maternal birth and neonatal outcomes among women with gestational diabetes mellitus (GDM), but without specific medical conditions and eligible for vaginal birth who underwent induction of labour (IOL) at term compared with those who were expectantly managed. MATERIALS AND METHODS: Population-based cohort study of women with GDM, but without medical conditions, who had a singleton, cephalic birth at 38-41 completed weeks gestation, in New South Wales, Australia between January 2010 and December 2016. Women who underwent IOL at 38, 39, 40 weeks gestation (38-, 39-, 40-induction groups) were compared with those who were managed expectantly and gave birth at and/or beyond the respective gestational age group (38-, 39-, 40-expectant groups). Multivariable logistic regression analysis was used to assess the association between IOL and adverse maternal birth and neonatal outcomes taking into account potential confounding by maternal age, country of birth, smoking, residential location, residential area of socioeconomic disadvantage and birth year. RESULTS: Of 676 762 women who gave birth during the study period, 66 606 (10%) had GDM; of these, 34799 met the inclusion criteria. Compared with expectant management, those in 38- (adjusted odds ratio (aOR) 1.11; 95% CI, 1.04-1.18), 39- (aOR 1.21; 95% CI, 1.14-1.28) and 40- (aOR 1.50; 95% CI, 1.40-1.60) induction groups had increased risk of caesarean section. Women in the 38-induction group also had an increased risk of composite neonatal morbidity (aOR 1.10; 95% CI, 1.01-1.21), which was not observed at 39- and 40-induction groups. We found no difference between groups in perinatal death or neonatal intensive care unit admission for births at any gestational age. CONCLUSION: In women with GDM but without specific medical conditions and eligible for vaginal birth, IOL at 38, 39, 40 weeks gestation is associated with an increased risk of caesarean section.

Prehospital continuous positive airway pressure (CPAP) for acute respiratory distress: a randomised controlled trial.

OBJECTIVE: To compare the efficacy of continuous positive airway pressure (CPAP) versus usual care for prehospital patients with severe respiratory distress. METHODS: We conducted a parallel group, individual patient, non-blinded randomised controlled trial in Western Australia between March 2016 and December 2018. Eligible patients were aged ≥40 years with acute severe respiratory distress of non-traumatic origin and unresponsive to initial treatments by emergency medical service (EMS) paramedics. Patients were randomised (1:1) to usual care or usual care plus CPAP. The primary outcomes were change in dyspnoea score and change in RR at ED arrival, and hospital length of stay. RESULTS: 708 patients were randomly assigned (opaque sealed envelope) to usual care (n=346) or CPAP (n=362). Compared with usual care, patients randomised to CPAP had a greater reduction in dyspnoea scores (usual care -1.0, IQR -3.0 to 0.0 vs CPAP -3.5, IQR -5.2 to -2.0), median difference -2.0 (95% CI -2.5 to -1.6); and RR (usual care -4.0, IQR -9.0 to 0.0 min-1 vs CPAP -8.0, IQR -14.0 to -4.0 min-1), median difference -4.0 (95% CI -5.0 to -4.0) min-1. There was no difference in hospital length of stay (usual care 4.2, IQR 2.1 to 7.8 days vs CPAP 4.8, IQR 2.5 to 7.9 days) for the n=624 cases admitted to hospital, median difference 0.36 (95% CI -0.17 to 0.90). CONCLUSIONS: The use of prehospital CPAP by EMS paramedics reduced dyspnoea and tachypnoea in patients with acute respiratory distress but did not impact hospital length of stay. TRIAL REGISTRATION NUMBER: ACTRN12615001180505.

Risk of adverse maternal and foetal outcomes associated with inactivated influenza vaccination in first trimester of pregnancy.

BACKGROUND: In many countries, influenza vaccination is routinely recommended during any stage of pregnancy, yet uptake remains low, particularly in the first trimester. This is thought to be due to maternal concerns regarding vaccine safety. OBJECTIVE: To evaluate the safety of influenza vaccination in the first trimester of pregnancy. METHODS: In a 4-year retrospective cohort study using probabilistic record linkage of administrative health data, we established a population-based cohort of 2391 women vaccinated in first trimester and 68 447 never vaccinated women with a date of conception between 2012 and 2015 in Western Australia. We estimated the relative risk (RR) of perinatal health outcomes among first trimester vaccinated women as compared to never vaccinated women using log-binomial logistic regression following a propensity score matched (PSM) analyses (2391 vaccinated women matched with 9564 never vaccinated women). RESULTS: First trimester vaccination was not associated with increased risk of stillbirth (RR 1.18, 95% confidence interval [CI] 0.64, 2.19), small for gestational age (RR 0.96, 95% CI 0.83, 1.11) or preeclampsia (RR 0.97, 95% CI 0.74, 1.28). The risk of spontaneous birth at 32-36 weeks was higher in first trimester vaccinated women compared with never vaccinated women (RR 1.40, 95% CI 1.11, 1.77). Vaccination was associated with a 10-19% increase in the risk of gestational diabetes (RR 1.18, 95% CI 0.94, 1.49), premature rupture of membranes (RR 1.10, 95% CI 0.82, 1.48), and threatened preterm labour (RR 1.19, 95% CI 0.90, 1.59). CONCLUSIONS: With exception to spontaneous preterm birth, findings suggest that first trimester vaccination is not associated with adverse maternal and foetal outcomes. Results can be used to support patient and provider-level vaccine decision making during first trimester.

Association between interpregnancy interval and hypertensive disorders of pregnancy: Effect modification by maternal age.

BACKGROUND: Short and long interpregnancy intervals (IPI) are associated with increased risk of hypertensive disorders of pregnancy, yet whether this association is modified by maternal age remains unclear. OBJECTIVES: To examine if the association between IPI and hypertensive disorders of pregnancy varies by maternal age at birth prior to IPI. METHODS: We conducted a population-based cohort study of all mothers who had their first two (n = 169 896) consecutive births in Western Australia (WA) between 1980 and 2015. We estimated the risk of preeclampsia and gestational hypertension for 6 to 60 months of IPI according to maternal age at birth prior to IPI (<20 years, 20-24, 25-29, 30-34 and ≥35 years). We modelled IPI using restricted cubic splines and reported adjusted relative risk (RRs) with 95% CI at 6, 12, 24, 36, 48 and 60 months, with 18 months as reference. RESULTS: The risk of preeclampsia was increased at longer IPIs (60 months) compared to 18 months for mothers 35 years or older (RR 2.19, 95% confidence interval (CI) 1.14, 4.18) and to a lesser extent for mothers 30- to 34 years old (RR 1.43, 95% CI 1.10, 1.84). Compared to 18 months, the risk of preeclampsia was lower at 12 months of IPI for mothers younger than 20 years (RR 0.74, 95% CI 0.57, 0.96), but not for mothers 35 years or older (RR 0.62, 95% CI 0.36, 1.07). There was insufficient evidence for increased risk of hypertensive disorders of pregnancy at shorter IPIs of <18 months for mothers of all ages. CONCLUSIONS: Our findings challenge the "one size fits all" recommendation for an optimal IPI, and a more tailored approach to family planning counselling may be required to improve health.

Interpregnancy interval and hypertensive disorders of pregnancy: A population-based cohort study.

BACKGROUND: Despite extensive research on risk factors and mechanisms, the extent to which interpregnancy interval (IPI) affects hypertensive disorders of pregnancy in high-income countries remains unclear. OBJECTIVES: To examine the association between IPI and hypertensive disorders of pregnancy in a high-income country setting using both within-mother and between-mother comparisons. METHODS: A retrospective population-based cohort study was conducted among 103 909 women who delivered three or more consecutive singleton births (n = 358 046) between 1980 and 2015 in Western Australia. We used conditional Poisson regression with robust variance, matching intervals of the same mother and adjusted for factors that vary within-mother across pregnancies, to investigate the association between IPI categories (reference 18-23 months), and the risk of hypertensive disorders of pregnancy. For comparison with previous studies, we also applied unmatched Poisson regression (between-mother analysis). RESULTS: The incidence of preeclampsia and gestational hypertension during the study period was 4%, and 2%, respectively. For the between-mother comparison, mothers with intervals of 6-11 months had lower risk of preeclampsia with adjusted relative risk (RR) 0.92 (95% confidence interval [CI] 0.85, 0.98) compared to reference category of 18-23 months. With the within-mother matched design, we estimated a larger effect of long IPI on risk of preeclampsia (RR 1.29, 95% CI 1.18, 1.42 for 60-119 months; and RR 1.30, 95% CI 1.10, 1.53 for intervals ≥120 months) compared to 18-23 months. Short IPIs were not associated with hypertensive disorders of pregnancy. CONCLUSIONS: In our cohort, longer IPIs were associated with increased risk of preeclampsia. However, there was insufficient evidence to suggest that short IPIs (<6 months) increase the risks of hypertensive disorders of pregnancy.