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To assess the independent and joint contribution of the individual components of metabolic syndrome, and known risk factors for gestational diabetes (GDM), on risk of GDM. Two thousand nine hundred and fifteen women from Australia and New Zealand, who participated in The Screening for Pregnancy Endpoints Study (SCOPE), were included. Using the SCOPE clinical data set and biomarkers obtained at 14–16 weeks’ gestation, a logistic regression model was fitted to the binary outcome GDM, with individual metabolic syndrome components (waist circumference, blood pressure, glucose, HDL-C, triglycerides), recruitment site, and other established factors associated with GDM. Hierarchical partitioning was used to assess the relative contribution of each variable. Of the 2915 women, 103 women (3.5%) developed GDM. The deviance explained by the logistic regression model containing all variables was 18.65% and the AUC was 0.809. Seventy percent of the independent effect was accounted for by metabolic syndrome components. The highest independent relative contribution to GDM was circulating triglycerides (17 ± 3%), followed by waist circumference (13 ± 3%). Glucose and maternal BMI contributed 12 ± 2% and 12 ± 3%, respectively. The remaining factors had an independent relative contribution of

OBJECTIVES: To examine primary care provision of early medical abortion services in Australia. DESIGN: Cross-sectional study; analysis of Pharmaceutical Benefits Scheme (PBS) dispensing data. SETTING, PARTICIPANTS: Women of child-bearing age (15-54 years), Australia, 2015-2019. MAIN OUTCOME MEASURES: Age-standardised rates of MS-2 Step prescriptions dispensed by year for 2015-2019, and age-standardised rates by state, remoteness area, and level 3 statistical areas (SA3s) for 2019. Numbers and proportions of SA3s in which MS-2 Step was not prescribed by a GP or dispensed by a community pharmacy during 2019 (unweighted and weighted by number of women of reproductive age), by state and remoteness area. RESULTS: During 2015-2019, 91 643 PBS prescriptions for MS-2 Step were dispensed; the national age-standardised rate increased from 1.63 in 2015 to 3.79 prescriptions per 1000 women aged 15-54 years in 2019. In 2019, rates were higher in outer regional Australia (6.53 prescriptions per 1000 women aged 15-54 years) and remote Australia (6.02 per 1000) than in major cities (3.30 per 1000). However, about 30% of women in Australia lived in SA3s in which MS-2 Step had not been prescribed by a GP during 2019, including about 50% of those in remote Australia. CONCLUSIONS: The rate of early medical abortion is greater among women in remote, outer regional, and inner regional Australia than in major cities, but a considerable proportion of women live in areas in which MS-2 Step was not locally prescribed or dispensed during 2019. Supporting GPs in the delivery of early medical abortion services locally should be a focus of health policy.

Women are susceptible to unintended, rapid repeat pregnancies in the first 12 months postpartum. Access to postpartum contraception, specifically long-acting reversible contraception, enables better planning of pregnancy timing and spacing and allows optimisation of health before the next conception. Clinical Practice Guidelines (CPG), and implementation policies, supported by consumer input, can improve such access. We searched publicly available Australian and New Zealand guidelines and policy documents addressing postpartum contraception. One CPG detailed specific information about postpartum contraception and, although of high quality, requires modification to local contexts to support implementation and policy development.

Background Deprescribing may benefit older frail patients experiencing polypharmacy. We investigated the scope for deprescribing in acutely hospitalised patients and the long-term implications of continuation of medications that could potentially be deprescribed. Methods Acutely hospitalised patients (n = 170) discharged to Residential Aged Care Facilities, ≥75 years and receiving ≥5 regular medications were assessed during admission to determine eligibility for deprescribing of key drug classes, along with the actual incidence of deprescribing. The impact of continuation of nominated drug classes (anticoagulants, antidiabetics, antiplatelets, antipsychotics, benzodiazepines, proton pump inhibitors (PPIs), statins) on a combined endpoint (death/readmission) was determined. Results Hyperpolypharmacy (>10 regular medications) was common (49.4%) at admission. Varying rates of deprescribing occurred during hospitalisation for the nominated drug classes (8–53%), with considerable potential for further deprescribing (34–90%). PPI use was prevalent (56%) and 89.5% of these had no clear indication. Of the drug classes studied, only continued PPI use at discharge was associated with increased mortality/readmission at 1 year (hazard ratio 1.54, 95% confidence interval (1.06–2.26), P = 0.025), driven largely by readmission. Conclusion There is considerable scope for acute hospitalisation to act as a triage point for deprescribing in older patients. PPIs in particular appeared overprescribed in this susceptible patient group, and this was associated with earlier readmission. Polypharmacy in older hospitalised patients should be targeted for possible deprescribing during hospitalisation, especially PPIs.

We conducted an online survey of 249 Australian women who currently or previously experienced severe nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum (HG) and examined their experiences in being denied medications during pregnancy. One in four women reported being denied medications for NVP/HG, which most commonly involved doxylamine and encounters with community pharmacists. Women's experiences reflected that lack of awareness of guidelines and unfavourable risk-benefit assessments appeared to be key barriers to facilitating medication access. Approaches towards identifying and effectively addressing barriers to the provision of effective treatments for severe NVP and HG are urgently needed.

Objective To evaluate the safety of maternal pertussis vaccination on pregnancy and birth outcomes. Methods The study population comprised 1272 healthy nulliparous pregnant women who participated in Screening Tests to identify poor Outcomes in Pregnancy (STOP) study at two obstetric hospitals in South Australia between 2015 and 2018. Participants were followed prospectively, with vaccination (confirmed by medical records), extensive amounts of pregnancy and birth outcome data collected by research midwives. Adjusted relative risks (aRRs) and hazard ratios (aHRs) were estimated accounting for time-varying vaccine exposure and the temporal nature of each outcome. Results Of the 1272 women included in this study, 80.1% (n = 1019) received maternal pertussis vaccination. Vaccinated women had an average 0.22 weeks (95% CI 0.001, 0.44) longer gestation at delivery compared to unvaccinated women. Maternal pertussis vaccination was not associated with chorioamnionitis (aRR 0.71, 95% CI 0.27,1.82), gestational hypertension (aHR 1.24, 95% CI, 0.66, 2.30), preeclampsia (aHR 0.75, 95% CI 0.47, 1.18) nor preterm birth (aHR 0.99, 95% CI 0.47, 2.07). Neither risk of low birth weight (aHR 0.72, 95% CI 0.41, 1.27) nor small for gestational age infants (aHR 0.67,95% CI 0.29, 1.55) were increased following maternal pertussis vaccination. No associations between pertussis vaccination during pregnancy and adverse birth outcomes including admission to the neonatal care unit, low Apgar scores, and mechanical ventilation were observed. Results were not materially changed after adjustment for maternal influenza vaccination. Conclusion Our study provides reassuring evidence of the safety of maternal pertussis vaccination with no increased risk of adverse pregnancy and birth outcomes. These findings support recommendations for pertussis vaccination during pregnancy to prevent morbidity and mortality associated with early-infant pertussis disease.

Background Iron deficiency anaemia in pregnancy (IDAP) affects 11–18% of Australian pregnancies and is associated with adverse perinatal outcomes. National prescribing data suggests the use of intravenous iron in pregnancy is increasingly common. This study aimed to: 1) Establish the current patterns of intravenous iron use by Fellows of the Royal Australian and New Zealand College of Obstetricians (FRANZCOG) when treating iron deficiency and IDAP including immediately postpartum and; 2) Assess FRANZCOG opinions regarding potential trial of intravenous iron for first-line treatment of IDAP. Methods An online survey of RANZCOG Fellows practicing obstetrics was distributed in September 2018. Results were analysed descriptively and responses compared by clinician demographics using Chi-squared testing. Results Of 484 respondents (21% of FRANZCOG), 457 were currently practicing obstetrics. Most prescribed intravenous iron in pregnancy (96%) and/or postpartum (85%). Most intravenous iron was prescribed for IDAP (98%) rather than iron deficiency without anaemia (53%), and for IDAP most commonly second-line to failed oral iron supplementation and first-line in special circumstances (59%). Intravenous iron prescribing was associated with shorter time since FRANZCOG completion (p = 0.01), public hospital practice (p = 0.008) and higher hospital birth numbers (p = 0.01). Most respondents (90%) would consider a randomised controlled trial of first-line intravenous iron for IDAP, although views on appropriate thresholds differed. Conclusions Almost all respondents prescribed intravenous iron for IDAP, and while mostly used for second-line treatment over half sometimes used it first-line. With accelerating intravenous iron use, further research is required into its optimal use in pregnancy, recognizing important clinical outcomes and cost effectiveness.

Objective To identify the psychosocial factors influencing women’s uptake and willingness to receive pertussis and influenza vaccine during pregnancy. Methods The study population comprised 1364 healthy nulliparous pregnant women who participated in a prospective cohort study at two obstetric hospitals in South Australia between 2015 and 2017. Information on women's vaccination status, sociodemographic, lifestyle and psychological state were collected at 9–16 weeks’ gestation and medical case notes were checked post-delivery to verify the reported vaccination status. Poisson regression models were used to estimate the crude and adjusted prevalence ratios (aPRs) to identify psychosocial factors influencing uptake of vaccination during pregnancy. Results Willingness to receive the recommended maternal vaccines was high (90%). Overall, 79% and 48% received maternal pertussis and influenza vaccines respectively. There was no evidence to support the influence of psychosocial factors on women’s willingness to receive immunization during pregnancy. High levels of anxiety (aPR 0.98, 95% CI: 0.87–1.09) was not associated with uptake of maternal pertussis vaccine. However, elevated depressive symptoms (aPR 1.14, 95% CI: 1.00–1.30) and very high-perceived stress during pregnancy were significantly associated with receipt of pertussis vaccination (aPR 0.87; 95% CI 0.76–0.99). Women with mild depressive symptoms (aPR 1.21, 95% CI 1.00–1.44) and mild anxiety symptoms (aPR 1.21, 95% CI: 0.99–1.48) were more likely to receive influenza vaccine during pregnancy (aPR 1.27, 95% CI: 1.08–1.49). A history of major depressive disorder was independently associated with receipt of pertussis (aPR 1.16, 95% CI 1.06–1.26) and influenza vaccination during pregnancy (aPR 1.32; 95% CI 1.14–1.58). Conclusion Regardless of psychosocial factors, most women reported a positive willingness to receive the recommended vaccinations during pregnancy. However, psychosocial factors influenced the uptake of pertussis and influenza vaccines during pregnancy. Psychosocial factors should be taken into consideration in designing interventions and implementation of maternal pertussis and influenza immunization programs.

While peanut oral immunotherapy (POIT) represents a promising treatment for peanut allergies in children, safety concerns remain a common barrier to widespread adoption. We aimed to systematically assess available evidence to determine the risk and frequency of adverse events occurring during POIT, and examine study-level characteristics associated with their occurrence and severity. A systematic search of MEDLINE, EMBASE, and Web of Science was conducted through April 2019. Controlled and non-controlled studies evaluating POIT were eligible. Twenty-seven studies, involving 1488 subjects, were included. Adverse events to POIT were common and led to treatment discontinuation in 6.6% of children (95% CI 4.4–9.0; 27 studies, I2 = 48.7%). Adverse events requiring treatment with epinephrine occurred among 7.6% (4.5–11.4; 26 studies, I2 = 75.5%) of participants, at a rate of 2.0 per 10,000 doses (0.8–3.7; 15 studies, I2 = 64.4). Use of a rush treatment phase and targeting a higher maintenance dose were associated with a higher risk and frequency of epinephrine use, while using co-treatments in addition to POIT was associated with a lower risk of treatment discontinuation due to adverse events. While adverse events to POIT are common, this study provides promising explorative evidence that certain modifications to existing treatment protocols could significantly improve treatment outcomes.

BACKGROUND Mastitis is a common and distressing maternal postpartum condition, but the relationship between mastitis timing and antibiotic treatment and breastfeeding outcomes and postnatal mental health is unclear. OBJECTIVES To describe the incidence of mastitis and treatment with antibiotics in first 6 months postpartum, and to investigate the impact of mastitis timing and antibiotic treatment on breastfeeding practices and postnatal mental health. METHODS This study is based on 79,985 mother-infant dyads in the Norwegian Mother, Father and Child Cohort Study (MoBa). Women were classified according to self-reported mastitis within first month ('early') or 1-6 months ('later') postpartum and antibiotic treatment. Breastfeeding outcomes included predominant or any breastfeeding and abrupt breastfeeding cessation until 6 months postpartum. Maternal mental health was assessed by self-report at 6 months postpartum. RESULTS The incidence of mastitis was 18.8%, with 36.8% reporting treatment with antibiotics. Women reporting early mastitis were less likely to report predominant breastfeeding (adjustedd relative risk [aRR] 0.92, 95% confidence interval [CI] 0.86, 0.99) and any breastfeeding for 6 months (aRR 0.97, 95% CI 0.96, 0.98) than women who did not report mastitis, and more likely to report abrupt breastfeeding cessation (aRR 1.37, 95% CI 1.23, 1.53). Late-onset mastitis was not associated with poorer breastfeeding outcomes. Among women reporting mastitis, the risk of abrupt breastfeeding cessation was higher in those also reporting antibiotic use. Mastitis was associated with an increased risk of mental health problems postpartum which was highest among those reporting no antibiotic use (aRR 1.29, 95% CI 1.18, 1.41), in contrast to those also reporting antibiotic use (aRR 1.08, 95% CI 0.96, 1.22). CONCLUSIONS Lactational mastitis and its associated treatment with antibiotics are common. Early (

Focus and outcomes for participants Modern technologies offer innovative ways of monitoring health outcomes. Electronic medical records (EMRs) stored in primary care databases provide comprehensive data on infectious and chronic conditions such as diagnosis, medications prescribed, vaccinations, laboratory results, and clinical assessments. Moreover, they allow the possibility of creating a retrospective cohort that can be tracked over time. This rich source of data can be used to generate results that support health policymakers to improve access, reduce health costs, and increase the quality of care. The symposium will discuss the use and future of routinely-collected EMR databases in monitoring health outcomes, using as an example studies based on the MedicineInsight program, a large general practice Australian database including more than 3.5 million patients. This symposium welcomes epidemiologists, researchers and health policymakers who are interested in primary care settings, big data analysis, and artificial intelligence. Rationale for the symposium, including for its inclusion in the Congress EMRs are becoming an important tool for monitoring health outcomes in different high-income countries and settings. However, most countries lack a national primary care database collating EMRs for research purposes. Monitoring of population health conditions is usually performed through surveys, surveillance systems, or census that tend to be expensive or performed over longer time intervals. In contrast, EMR databases are a useful and low-cost method to monitor health outcomes and have shown consistent results compared to other data sources. Although these databases only include individuals attending primary health settings, they tend to resemble the sociodemographic distribution from census data, as in countries such as Australia up to 90% of the population visit these services annually. Results from primary care-based EMRs can be used to inform practices and improve health policies. Analysis from EMRs can be used to identify, for example, those with undiagnosed medical conditions or patients who have not received recommended screenings or immunisations, therefore assessing the impact of government programmes. At a practice-level, healthcare staff can have better access to comprehensive patient histories, improving monitoring of people with certain conditions, such as chronic cardiac, respiratory, metabolic, neurological, or immunological diseases. This information provides feedback to primary care providers about the quality of their care and might help them develop targeted strategies for the most-needed areas or groups. Another benefit of EMRs is the possibility of using statistical modelling and machine learning to improve prediction of health outcomes and medical management, supporting general practitioners with decision making on the best management approach. In Australia, the MedicineInsight program is a large general practice database that since 2011 has been routinely collecting information from over 650 general practices varying in size, billing methods, and type of services offered, and from all Australian states and regions. In the last few years, diverse researchers have used MedicineInsight to investigate infectious and chronic diseases, immunization coverage, prescribed medications, medical management, and temporal trends in primary care. Despite being initially created for monitoring how medicines and medical tests are used, MedicineInsight has overcome some of the legal, ethical, social and resource-related barriers associated with the use of EMRs for research purposes through the involvement of a data governance committee responsible for the ethical, privacy and security aspects of any research using this data, and through applying data quality criteria to their data extraction. This symposium will discuss advances in the use of primary care databases for monitoring health outcomes using as an example the research activities performed based on the Australian MedicineInsight program. These discussions will also cover challenges in the use of this database and possible methodological innovations, such as statistical modelling or machine learning, that could be used to improve monitoring of the epidemiology and management of health conditions. Presentation program The use of large general practice databases for monitoring health outcomes in Australia: infectious and chronic conditions (Professor Nigel Stocks) How routinely collected electronic health records from MedicineInsight can help inform policy, research and health systems to improve health outcomes (Ms Rachel Hayhurst) Influenza-like illness in Australia: how can we improve surveillance systems in Australia using electronic medical records? (Dr Carla Bernardo) Long term use of opioids in Australian general practice (Dr David Gonzalez) Using routinely collected electronic health records to evaluate Quality Use of Medicines for women’s reproductive health (Dr Luke Grzeskowiak) The use of electronic medical records and machine learning to identify hypertensive patients and factors associated with controlled hypertension (Ms Jackie Roseleur) Names of presenters Professor Nigel Stocks, The University of Adelaide Ms Rachel Hayhurst, NPS MedicineWise Dr Carla Bernardo, The University of Adelaide Dr David Gonzalez-Chica, The University of Adelaide Dr Luke Grzeskowiak, The University of Adelaide Ms Jackie Roseleur, The University of Adelaide

Necrotising enterocolitis (NEC) is a devastating disease affecting preterm infants, with little improvement in mortality rates and treatment strategies in the last 30 years. Human milk oligosaccharides (HMOs) are emerging as a potential preventive therapy, with multiple protective functions postulated. Our aim is to summarise the evidence concerning the role of HMOs in NEC development and emerging strategies to tailor the delivery of HMOs to preterm infants. Most research efforts to date have focused on supplementing preterm infants with simple oligosaccharides, which are structurally different to HMOs and derived mainly from plants. Clinical trials demonstrate limited benefits for NEC prevention arising from the use of these supplements. Alternative strategies under investigation include optimising HMOs for infants receiving donor human milk, concentrating oligosaccharides from donor human milk and from animal milks, as well as more sophisticated synthetic oligosaccharide production strategies. Critically, high quality evidence to support implementation of any of these approaches in the neonatal unit is lacking. Whether it is a specific HMO alone or a combination of HMOs that exert protective effects remains to be elucidated. Further challenges include how best to manufacture and administer oligosaccharides whilst retaining bioactivity and safety, including evaluation of the long-term effects of altering the balance of HMOs and gut microbiota in preterm infants. While several human clinical trials are underway, further research is needed to understand whether a tailored approach to oligosaccharide supplementation is beneficial for preterm infants.

Objectives: To compare the effects on perinatal maternal and neonatal outcomes of intravenous and oral iron therapy as first-line treatment of iron deficiency anaemia (IDA) in pregnant women. Study design: A meta-analysis, applying fixed and random effects models, of randomised controlled trials (RCTs) that compared the effects of intravenous and oral iron therapy for pregnant women with IDA. Data sources: MEDLINE, EMBASE, Scopus, Cochrane Register of Controlled Trials, Web of Science; bibliographies of identified articles. Data synthesis: Fifteen eligible studies with a total of 1938 participants were identified. Each was at high risk of bias in at least one domain; ten were undertaken in low or middle income countries. Evidence (from nine RCTs) that intravenous iron was superior to oral iron in reducing the need for blood transfusion at delivery was low quality (Peto odds ratio, 0.19 [95% CI, 0.05–0.78]; number needed to treat, 95 [95% CI, 81–348]). Evidence that intravenous iron was superior to oral iron in increasing neonatal birthweight (eight RCTs: mean difference, 58 g; 95% CI, 4–112 g) or reducing the rate of breastfeeding cessation within 24 months of delivery (one RCT: hazard ratio, 0.70; 95% CI, 0.50–0.99) was of low or very low quality. While intravenous iron treatment was superior to oral iron for improving maternal haematological parameters at delivery, their effects on neonatal haematological parameters were similar. Conclusions: There is no strong evidence that first-line therapy with intravenous iron is superior to oral administration for treating IDA in pregnant women. The few identified differences in outcomes were small in magnitude and from studies at high risk of bias. Registration: International Prospective Register of Systematic Reviews (PROSPERO), CRD42019120652. Refereed/Peer-reviewed

Background Galactagogues are substances thought to increase breast milk production, however evidence to support their efficacy and safety remain limited. We undertook a survey among Australian women to examine patterns of use of galactagogues and perceptions regarding their safety and effectiveness. Methods An online, cross-sectional survey was distributed between September and December 2019 via national breastfeeding and preterm birth support organisations, and networks of several research institutions in Australia. Women were eligible to participate if they lived in Australia and were currently/previously breastfeeding. The survey included questions about galactagogue use (including duration and timing), side effects and perceived effectiveness (on a scale of 1 [Not at all effective] to 5 [Extremely effective]). Results Among 1876 respondents, 1120 (60%) reported using one or more galactagogues. Women were 31.5 ± 4.8 years (mean ± standard deviation) at their most recent birth. Sixty-five percent of women were currently breastfeeding at the time of the survey. The most commonly reported galactagogues included lactation cookies (47%), brewer’s yeast (32%), fenugreek (22%) and domperidone (19%). The mean duration of use for each galactagogue ranged from 2 to 20 weeks. Approximately 1 in 6 women reported commencing galactagogues within the first week postpartum. Most women reported receiving recommendations to use herbal/dietary galactagogues from the internet (38%) or friends (25%), whereas pharmaceutical galactagogues were most commonly prescribed by General Practitioners (72%). The perceived effectiveness varied greatly across galactagogues. Perceived effectiveness was highest for domperidone (mean rating of 3.3 compared with 2.0 to 3.0 among other galactagogues). Over 23% of domperidone users reported experiencing multiple side effects, compared to an average of 3% of women taking herbal galactagogues. Conclusions This survey demonstrates that galactagogues use is common in Australia. Further research is needed to generate robust evidence about galactagogues’ efficacy and safety to support evidence-based strategies and improve breastfeeding outcomes.

Objective: To determine the proportion of pregnancies resulting in birth that were conceived with the use of clomiphene citrate (CC) and the frequency of multiple pregnancy. Design: Whole-of-population cohort study, constructed through data linkage. Comprehensive Australian Government records of dispensed medications were linked to state Perinatal Registry records for all births of at least 20 weeks' gestation. Setting: The state of South Australia. Patient(s): Women who maintained pregnancy for at least 20 weeks and gave birth between July 2003 and December 2015, a total of 150,713 women with 241,561 pregnancies. Intervention(s): Not applicable. Main Outcome Measure(s): Ongoing pregnancy occurring in proximity to CC, defined as dispensing from 90 days before to the end of a conception window derived from newborn date of birth and gestational age. Result(s): Linkage to dispensed prescription records was achieved for 97.9% of women. Women who conceived with CC tended to be older and socioeconomically advantaged and more likely than other women to have a history of miscarriage. Ongoing pregnancies associated with CC comprised 1.6% of the total; 5.7% were multiple births (mostly twins, 94.6%) compared with 1.5% in the remainder (98.5% twins). Conclusion(s): In South Australia, 1.6% of pregnancies (1 in 60) of at least 20 weeks' gestation were conceived proximal to CC dispensing. Of these, 5.7% were multiple pregnancies. This takes the proportion of women who achieved an ongoing pregnancy with medical assistance from 4.4%, based on reports from assisted reproductive technology clinics, to 6% in total. Refereed/Peer-reviewed

Galactagogues are foods, herbs or medications thought to support or increase breast milk supply. The use of galactagogues during lactation is becoming increasingly common despite limited evidence regarding effectiveness and safety, and no definitive recommendations for use in clinical practice. The aim of this study is to explore factors influencing women’s decisions to use galactagogues during lactation. Twenty-two semi-structured interviews were conducted in October and November 2019 (over the telephone or in person) with participants located in most Australian states and territories, including metro and regional areas. Interviews were audio-recorded, transcribed verbatim and thematically analysed using NVivo. Analysis revealed that following a concern about breast milk supply, the decision to use galactagogues was influenced by three core and interrelated domains: access to and quality of breastfeeding support, maternal agency and determination to provide breast milk. Women revealed many problematic experiences with health care professionals that left them feeling dismissed and confused due to provision of inconsistent and insufficient information that was sometimes at odds with their desire to provide breast milk. In this instance, some women turned to galactagogues to regain agency. A range of broader dimensions influencing decision-making also emerged. These were separated into categories that emphasise distinctions relating to breast milk supply, which included: maternal emotional wellbeing, social norms and pressures, concerns about infant development, maternal physical health and lactation history, as well as those relating specifically to galactagogue use, including: desire for a guaranteed/urgent response, risk-risk trade-off, acceptance and trust, and accessibility and cost. In understanding the complexity of decision-making concerning these substances, we identify opportunities to improve breastfeeding counselling and support. We recommend that support be individually tailored to manage conflicting information, adopt communication styles that encourage trust and processes that enable shared decision-making to enhance or restore maternal agency. There is also considerable need to address evidence gaps regarding the effectiveness and safety of commonly used galactagogues, so that women can be appropriately counselled about potential benefits and harms.

Background Women may experience differing types of pain and discomfort following birth, including cramping pain (often called after-birth pain) associated with uterine involution, where the uterus contracts to reduce blood loss and return the uterus to its non-pregnant size. This is an update of a review first published in 2011. Objectives To assess the effectiveness and safety of pharmacological and non-pharmacological pain relief/analgesia for the relief of after-birth pains following vaginal birth. Search methods For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 October 2019), and reference lists of retrieved studies. Selection criteria Randomised controlled trials comparing two different types of analgesia or analgesia versus placebo or analgesia versus no treatment, for the relief of after-birth pains following vaginal birth. Types of analgesia included pharmacological and non-pharmacological. Quasi-randomised trials were not eligible for inclusion. Data collection and analysis Two review authors independently assessed trials for inclusion, conducted 'Risk of bias' assessment, extracted data and assessed the certainty of the evidence using the GRADE approach. Main results In this update, we include 28 studies (involving 2749 women). The evidence identified in this review comes from middle- to high-income countries. Generally the trials were at low risk of selection bias, performance bias and attrition bias, but some trials were at high risk of bias due to selective reporting and lack of blinding. Our GRADE certainty of evidence assessments ranged from moderate to very low certainty, with downgrading decisions based on study limitations, imprecision, and (for one comparison) indirectness. Most studies reported our primary outcome of adequate pain relief as reported by the women. No studies reported data relating to neonatal adverse events, duration of hospital stay, or breastfeeding rates. Almost half of the included studies (11/28) excluded breastfeeding women from participating, making the evidence less generalisable to a broader group of women. Non-steroidal anti-inflammatory drugs (NSAIDs) compared to placebo NSAIDs are probably better than placebo for adequate pain relief as reported by the women (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.45 to 1.91; 11 studies, 946 women; moderate-certainty evidence). NSAIDs may reduce the need for additional pain relief compared to placebo (RR 0.15, 95% CI 0.07 to 0.33; 4 studies, 375 women; low-certainty evidence). There may be a similar risk of maternal adverse events (RR 1.05, 95% CI 0.78 to 1.41; 9 studies, 598 women; low-certainty evidence). NSAIDs compared to opioids NSAIDs are probably better than opioids for adequate pain relief as reported by the women (RR 1.33, 95% CI 1.13 to 1.57; 5 studies, 560 women; moderate-certainty evidence) and may reduce the risk of maternal adverse events (RR 0.62, 95% CI 0.43 to 0.89; 3 studies, 255 women; low-certainty evidence). NSAIDs may be better than opioids for the need for additional pain relief, but the wide CIs include the possibility that the two classes of drugs are similarly effective or that opioids are better (RR 0.37, 95% CI 0.12 to 1.12; 2 studies, 232 women; low-certainty evidence). Opioids compared to placebo Opioids may be better than placebo for adequate pain relief as reported by the women (RR 1.26, 95% CI 0.99 to 1.61; 5 studies, 299 women; low-certainty evidence). Opioids may reduce the need for additional pain relief compared to placebo (RR 0.48, 95% CI 0.28 to 0.82; 3 studies, 273 women; low-certainty evidence). Opioids may increase the risk of maternal adverse events compared with placebo, although the certainty of evidence is low (RR 1.59, 95% CI 0.99 to 2.55; 3 studies, 188 women; low-certainty evidence). Paracetamol compared to placebo Very low-certainty evidence means we are uncertain if paracetamol is better than placebo for adequate pain relief as reported by the women, the need for additional pain relief, or risk of maternal adverse events (2 studies, 123 women). Paracetamol compared to NSAIDs Very low-certainty evidence means we are uncertain if there are any differences between paracetamol and NSAIDs for adequate pain relief as reported by the women, or the risk of maternal adverse events. No data were reported about the need for additional pain relief comparing paracetamol and NSAIDs (2 studies, 112 women). NSAIDs compared to herbal analgesia We are uncertain if there are any differences between NSAIDs and herbal analgesia for adequate pain relief as reported by the women, the need for additional pain relief, or risk of maternal adverse events, because the certainty of evidence is very low (4 studies, 394 women). Transcutaneous nerve stimulation (TENS) compared to no TENS Very low-certainty evidence means we are uncertain if TENS is better than no TENS for adequate pain relief as reported by the women. No other data were reported comparing TENS with no TENS (1 study, 32 women). Authors' conclusions NSAIDs may be better than placebo and are probably better than opioids at relieving pain from uterine cramping/involution following vaginal birth. NSAIDs and paracetamol may be as effective as each other, whereas opioids may be more effective than placebo. Due to low-certainty evidence, we are uncertain about the effectiveness of other forms of pain relief. Future trials should recruit adequate numbers of women and ensure greater generalisability by including breastfeeding women. In addition, further research is required, including a survey of postpartum women to describe appropriately their experience of uterine cramping and involution. We identified nine ongoing studies, which may help to increase the level of certainty of the evidence around pain relief due to uterine cramping in future updates of this review.

Background: Long-acting reversible contraceptives (LARCs) are promoted internationally as a key strategy for reducing unintended pregnancy and abortion rates. Aims: To examine trends in use of hormonal LARCs among reproductive-aged women in Australia between 2006 and 2018 and explore trends according to age groups and state/territory of dispensing. Materials and Methods: Retrospective population-based study using Pharmaceutical Benefits Scheme (PBS) dispensing claims of a 10% random sample of females aged 15–44. We investigated rates and annual trends in dispensing claims of etonorgestrel implant and levonorgestrel intrauterine systems (IUS). Results: Between 2006 and 2018, annual PBS claims for LARCs increased approximately two-fold from 21.7 to 41.5 per 1000 women, with a plateau observed from 2015 onward. Absolute rate increases were similar for the implant (9.0/1000) and IUS (10.8/1000), with increases observed across all age groups and states/territories. Overall dispensing rates varied by two-fold according to state/territory of dispensing and four-fold according to age groups. Rate increases for the implant were highest among the 15–19 and 20–24 age groups, while rate increases for the IUS were highest among the 35–39 and 40–44 age groups. It is estimated that in 2018, 10.8% of women aged 15–44 were using a LARC; 4.5% for the implant and 6.3% for the IUS. Conclusions: Rates of hormonal LARC use have doubled over the past decade. Investigating underlying reasons for the large observed differences in rates of use according to age and state/territory could help further improve uptake for these most effective methods of contraception Refereed/Peer-reviewed

Background: Medication errors are common in neonatal care and can lead to significant harm. We sought to explore utilization of various medication error prevention strategies across Australian and New Zealand neonatal units (NNUs) through a clinical practice survey. Methods: An electronic survey was distributed in October 2016 to relevant staff at each of the 29 level III NNUs identified as members of the Australian and New Zealand Neonatal Network (ANZNN). The survey contained questions relating to a range of medication error prevention strategies identified from a previous systematic review on the topic. The evaluated interventions targeted different aspects of the medication-use process including prescribing, evaluation/checking of orders by clinical pharmacists, transmission, preparation and dispensing of orders, storage of medications, and medication administration. Results: From the 20 respondents, the evidence-based strategies most commonly utilized were use of smart pumps ( n = 18; 90%), and ward-based clinical pharmacists ( n = 17; 85%). Interventions least commonly utilized included barcode scanning with medication administration ( n = 0; 0%), electronic prescribing and clinical decision support ( n = 1; 5%), and dedicated medication administration nurse ( n = 2; 10%). The total number of evidence-based medication error prevention strategies utilized in each NNU ranged from 2 to 10 (median = 7), 10 of 16 strategies were utilized by less than 50% of NNUs. Conclusion: While evidence supports utilization of a number of medication error prevention strategies, these appear inconsistently utilized across current practice settings.

Introduction: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear. Methods: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations. Results: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses >= 25 cigarettes per day. Conclusions: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.

AIMS The aims of the present study were to examine the association between late pregnancy exposure to serotonin reuptake inhibitor (SRI) antidepressants and difficulties in achieving an adequate breast milk supply in women who have given birth to preterm infants, while accounting for the potential impacts of underlying maternal psychiatric illness. METHODS A retrospective cohort study was carried out of 3024 women delivering liveborn preterm infants (

Galactagogues represent substances used to enhance breast milk production. Between 2001 and 2014 we identified 2034 phone calls regarding the use of galactagogues made to MotherSafe. The majority involved discussion of domperidone (n = 1884; 92.6%), with the remainder relating to metoclopramide (n = 153; 7.5%) or other herbal galactagogues (eg fenugreek, milk thistle; n = 262; 12.9%). A 50% decrease in total calls occurred from 2011 to 2014, while the percentage of calls regarding herbal galactagogues increased from 0% in 2001 to 23% in 2014. These findings support the need for more robust research surrounding the use of galactagogues in clinical practice.

Oral immunotherapy (OIT) using roasted peanut flour can effectively desensitize peanut-allergic children [1] but is considered not to be ready for clinical practice [2] due to high rates (≥45%) of adverse events (AEs) [3] [4]. This necessitates medically supervised up-dosing in hospital and limits the number of patients that can be treated. In 2001 Beyer et. al proposed that the prevalence of peanut allergy in China was lower than that of the Western world because peanuts consumed in China were boiled, not roasted [5]. They demonstrated that boiling peanuts for 20 minutes reduced IgE binding in vitro when compared to roasted peanut. We have subsequently shown that extended boiling progressively reduced peanut IgE binding to 12.5% at 2 hours and to 5.3% at 12 hours compared to raw peanut while still retaining T cell reactivity [6]. Further, Inhibition ELISAs demonstrated that boiled peanuts have restricted ability (2-h ~70%, 12-h ~50%) to block the binding of patient IgE to raw peanut [6] suggesting boiled peanuts possess an incomplete repertoire of epitopes. This indicates that boiled peanuts alone are unlikely to expose a patient to the full spectrum of peanut epitopes and will therefore require a roasted peanut phase following the initial boiled peanut therapy. We hypothesize that AEs can be reduced by commencing OIT with hypoallergenic boiled peanut. Here we describe a pilot study that aims to characterize the incidence of AEs and successful desensitization in mild/moderate peanut allergic children using hypoallergenic 2-hour boiled peanut prior to roasted peanut OIT. Due to the home-based up-dosing procedure, a cautious approach was adopted which excluded severely allergic children. This article is protected by copyright. All rights reserved.

Background: Intravenous (IV) iron in pregnancy is useful where oral iron is not tolerated or a rapid replenishment of iron is required. Aims: To review the literature on the efficacy and safety of different IV iron preparations in the management of antenatal iron-deficiency anaemia (IDA). Materials and methods: We searched MEDLINE, Embase and Scopus from inception to June 2016. Eligible studies were randomised controlled trials (RCTs) and observational studies, involving administration of IV iron (ferric carboxymaltose (FCM), iron polymaltose (IPM) or iron sucrose (IS)), regardless of comparator, to manage antenatal IDA. Two independent reviewers selected studies, extracted data and assessed quality. Results: A total of 47 studies were eligible (21 RCTs and 26 observational studies), investigating IS (n = 2635; 41 studies), FCM (n = 276; four studies) and IPM (n = 164; three studies). All IV preparations resulted in significant improvements in haematological parameters, with a median increase of 21.8 g/L at 3–4 weeks and 30.1 g/L by delivery, but there was no evidence of any associated improvements in clinical outcomes. A greater median increase in Hb was observed with a high (25 g/L; range: 20–39.6 g/L) compared with low dose (20 g/L; range: 6.2–50.3 g/L). The median prevalence of adverse drug reactions for IPM (2.2%; range: 0–4.5%) was lower than FCM (5.0%; range: 0–20%) and IS (6.7%; range: 0–19.5%). Conclusion: While IV iron in pregnancy improves haematological parameters, there is an absence of evidence for improvements in important maternal or perinatal outcomes. No single preparation of IV iron appeared to be superior, with the current IV iron preparation of choice largely determined by cost and convenience around administration. Refereed/Peer-reviewed

To determine the impact of self-reported maternal depression/anxiety on asthma control during pregnancy.Pregnant women with a doctor diagnosis of asthma (n = 189) were prospectively recruited at their antenatal booking visit, and the presence of maternal depression and anxiety was identified using self-report and routine questionnaire assessments. Data on exacerbations and asthma control were collected during gestation. Asthma control was assessed using the Juniper Asthma Control Questionnaire (ACQ) and women were classified as having recurrent uncontrolled asthma if their ACQ score was1.5 during two or more consecutive study visits. Exacerbations were defined as events that led to increased treatment requirements, and doctor or hospital visits.There were 85 women with self-reported depression/anxiety and 104 women without self-reported depression/anxiety. The presence of depression/anxiety was associated with an increased likelihood (adjusted hazard ratio (HR) 1.67: 95% confidence interval (CI) 1.03-2.72) and incidence (adjusted incidence rate ratio (IRR) 1.71: 95% CI 1.13-2.58) of uncontrolled asthma during pregnancy, as well as an increased risk of recurrent uncontrolled asthma during 2 or more study visits (adjusted relative risk (RR) 1.98: 95% CI 1.00-3.91). No impact of depression/anxiety was observed with respect to the likelihood (adjusted HR 0.70: 95% CI 0.35-1.41) or incidence of exacerbations during pregnancy (adjusted IRR 0.66: 95% CI 0.35-1.26).This study provides evidence that the presence of maternal depression/anxiety is associated with an increased likelihood and incidence of uncontrolled asthma during pregnancy. Given the high prevalence of co-morbid depression/anxiety among asthmatics, further research investigating such associations is urgently required.

Background Domperidone may be used off-label to increase breastmilk supply. In the absence of manufacturer dosage recommendations, there is a need to compare the clinical practice guidelines used in Australian hospitals. Aim To compare existing clinical practice guidelines regarding the use of domperidone for increasing maternal breastmilk supply within Australian neonatal units (NNUs). Methods An electronic survey was distributed from April to July 2015 to relevant staff at each Level III NNU across Australia. Results Responses were received from 16 of 22 (73%) NNUs. All 16 (100%) NNUs considered domperidone their first line pharmacological agent of choice in the management of low milk supply, with 12 (75%) having a clinical guideline. Of the NNUs with a guideline, 11 (92%) recommended a standard maintenance dose of 10 mg three times daily (TDS). Duration of treatment was specified in 10 (83%) guidelines. Seven of 10 (70%) recommend a minimum duration of at least 2 weeks treatment before evaluating a response. Three of 11 (27%) guidelines that recommended 10 mg TDS permitted an increase to 20 mg TDS depending on response. Ten of 12 (83%) guidelines were modified in the previous 2–3 years, with eight revising their maximum dose to 30 mg/day, one limiting treatment duration to 7 days, and one removing the authority of NNU doctors to prescribe domperidone. Conclusion While all Australian neonatal units consider domperidone first-line for pharmacological management of low milk supply, variability across clinical guidelines may suggest a lack of reliable evidence or awareness of evidence on which to base practice.

Single nucleotide polymorphisms and pre‐ and peri‐conception folic acid (FA) supplementation and dietary data were used to identify one‐carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with

OBJECTIVES To evaluate whether cannabis use during pregnancy is associated with adverse neonatal outcomes that are independent of cigarette smoking. DESIGN Prospective cohort study. SETTING Adelaide (Australia), Auckland (New Zealand), Cork (Ireland), and Leeds, London and Manchester (United Kingdom). PARTICIPANTS 5610 pregnant nulliparous women with low risk pregnancies recruited for the Screening for Pregnancy Endpoints (SCOPE) study, November 2004 - February 2011. At 14-16 weeks of pregnancy, women were grouped by self-reported cannabis use. MAIN OUTCOME MEASURES Infant birthweight, head circumference, birth length, gestational age, and severe neonatal morbidity or mortality. RESULTS 314 women (5.6%) reported using cannabis in the 3 months before or during their pregnancy; 97 (31%) stopped using it before and 157 (50%) during the first 15 weeks of pregnancy, while 60 (19%) were still using cannabis at 15 weeks. Compared with babies of mother who had never used cannabis, infants of those who still used it at 15 weeks had lower mean values for birthweight (adjusted mean difference [aMD], -127 g; 95% CI, -238 to -17 g), head circumference (aMD, -0.5 cm; 95% CI, -0.8 to -0.1 cm), birth length (aMD, -0.8 cm; 95% CI, -1.4 to -0.2 cm), and gestational age at birth (aMD, -8.1 days; 95% CI, -12.1 to -4.0 days). The differences for all outcomes except gestational age were greater for women who used cannabis more than once a week than for those who used it less frequently. CONCLUSIONS Continuing to use cannabis during pregnancy is an independent risk factor for poorer neonatal outcomes.

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 &plusmn, 1 weeks&rsquo, gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive, subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99&ndash, 1.44)) or who had lower selenium concentrations (1.19 (1.01&ndash, 1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06&ndash, 2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.

This is a brief summary of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) evidence-based guideline for the management of nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum (HG). The full guideline and executive summary including auditable outcomes are freely available on the SOMANZ website [https://www.somanz.org/guidelines.asp]. The guideline includes a proposed SOMANZ definition of NVP and HG and evidence-based practical advice regarding the investigation and management of NVP, HG and associated conditions including thyroid dysfunction. A practical algorithm for assessment and management as well as an individual patient management plan and self-assessment tools are included.

Inadequate breast milk supply is a frequently reported reason for early discontinuation of breastfeeding and represents a critical opportunity for intervening to improve breastfeeding outcomes. For women who continue to experience insufficient milk supply despite the utilisation of non-pharmacological lactation support strategies, pharmacological intervention with medications used to augment lactation, commonly referred to as galactagogues, is common. Galactagogues exert their pharmacological effects through altering the complex hormonal milieu regulating lactation, particularly prolactin and oxytocin. This narrative review provides an appraisal of the existing evidence regarding the efficacy and safety of pharmaceutical treatments for lactation insufficiency to guide their use in clinical practice. The greatest body of evidence surrounds the use of domperidone, with studies demonstrating moderate short-term improvements in breast milk supply. Evidence regarding the efficacy and safety of metoclopramide is less robust, but given that it shares the same mechanism of action as domperidone it may represent a potential treatment alternative where domperidone is unsuitable. Data on remaining interventions such as oxytocin, prolactin and metformin is too limited to support their use in clinical practice. The review provides an overview of key evidence gaps and areas of future research, including the impacts of pharmaceutical galactagogues on breast milk composition and understanding factors contributing to individual treatment response to pharmaceutical galactagogues.

Objective To determine: (1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility; (2) associations between individual and an increasing number of MetS components, TTP, and infertility; and (3) whether these relationships differ by body mass index (BMI Design Retrospective cohort study. Setting Multiple centres (in Australia, Ireland, New Zealand, and the UK). Population Five thousand five hundred and nineteen low-risk nulliparous pregnant women. Methods Data on retrospectively reported TTP (number of months to conceive) and a blood sample to assess metabolic health were collected between 14 and 16 weeks of gestation. MetS was defined according to the International Diabetes Federation criteria. Accelerated failure time models with log-normal distribution were conducted to estimate time ratios (TRs) and 95% CIs. Differences in MetS on infertility (TTP > 12 months) were compared using a generalised linear model (Poisson distribution) with robust variance estimates (relative risks, RRs; 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounding factors. Main outcome measures Time to pregnancy and infertility. Results Of the 5519 women included, 12.4% (n = 684) had MetS. Compared with women without MetS, women with MetS had a longer TTP (adjusted TR 1.30; 95% CI 1.15-1.46), which was similar in women who were obese and in women who were not obese. Marginal estimates for median TTP in women with MetS versus without MetS was 3.1 months (3.0-3.3 months) versus 4.1 months (3.6-4.5 months), respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62; 95% CI 1.15-2.29) or not (adjusted RR 1.73; 95% CI 1.33-2.23). Reduced high-density lipoprotein cholesterol (HDL-C) and raised triglycerides (TGs) were the main individual components associated with risk for infertility. Conclusion Metabolic syndrome is associated with longer TTP and infertility, independent of obesity. Additional studies, before pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose the greatest risk to delayed fertility, or whether individual components are amenable to modification. Tweetable abstract Metabolic syndrome is associated with longer time to pregnancy and infertility, independent of obesity.

Background Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes, in nulliparous pregnant women, has not been investigated. Methods and findings Low-risk, nulliparous women were recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) cohort between 11 November 2004 and 28 February 2011. Women were assessed for a range of demographic, lifestyle, and metabolic health variables at 15 ± 1 weeks’ gestation. MetS was defined according to International Diabetes Federation (IDF) criteria for adults: waist circumference ≥80 cm, along with any 2 of the following: raised trigycerides (≥1.70 mmol/l [≥150 mg/dl]), reduced high-density lipoprotein cholesterol (, Claire Trelford Roberts and colleagues report on the association of metabolic syndrome in pregnant women with increased risk for adverse pregnancy outcomes such as gestational diabetes and preeclampsia., Author summary Why was this study done? Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes in nulliparous pregnant women has not been thoroughly investigated. What did the researchers do and find? We assessed the association between MetS, measured at 15 ± 1 weeks’ gestation, and a range of pregnancy complications in low-risk, nulliparous women recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) study. Women with MetS in early pregnancy had an increased risk for GDM and PE, after adjustment for a range of demographic and lifestyle variables. What do these findings mean? Diagnosis of MetS may be useful to broadly identify a group of women at risk for pregnancy complications, which may additionally associate with future CVD risk. Future studies are required to substantiate our findings and to determine whether MetS is a useful discriminator of pregnancy complications in lean and obese women. Future studies are also encouraged to define clear metabolic health phenotypes that will produce the optimal probability threshold for each outcome.

To examine the patterns and predictors of inter-pregnancy body mass index (BMI) change and its impact on perinatal outcomes in the second pregnancy.Retrospective cohort study.Tertiary teaching hospital in Adelaide, Australia.Women with their first and second consecutive, singleton deliveries occurring between 2000 and 2012 (N=5371).Inter-pregnancy weight change calculated based on difference between BMI at respective antenatal booking visits. Association between inter-pregnancy weight change and perinatal outcomes investigated using multivariate generalised linear models, with stratification according to initial maternal BMI category in first pregnancy.Gestational diabetes (GDM); pregnancy induced hypertensive disorders; small-for-gestational age (SGA); preterm birth; large-for-gestational age (LGA) and macrosomia (4500g).On average, women with a normal BMI gained 1kg/m(2) between first and second pregnancies, while women who were overweight or obese gained 1.37kg/m(2). Among women with a normal BMI in their first pregnancy, a BMI increase of ≥4kg/m(2) was associated with increased risk of developing GDM (aRR 1.97; 95% CI 1.22-3.19), a macrosomic (aRR 4.06; 95% CI 2.25-7.34) or LGA infant (aRR 1.31 0.96-1.78) in the second pregnancy, while a reduction in BMI (≤-2kg/m(2)) was associated with an increased risk of SGA (aRR 1.94; 1.19-3.16). Among women who were overweight or obese in their first pregnancy, a BMI increase of ≥2-4 and ≥4kg/m(2) was associated with increased risks of developing GDM in the second pregnancy (aRR 1.39; 95% CI 1.01-1.91 and aRR 1.64 95% CI 1.16-2.31; ptrend0.001), while no associations were observed for a BMI increase and risk of a macrosomic, SGA, or LGA infant. In contrast, reduction in BMI (≤-2kg/m(2)) was associated with a reduced risk of GDM (aRR 0.58 95% CI 0.37-0.90) and SGA (aRR 0.47; 95% CI 0.25-0.87).Increases in BMI between pregnancies is associated with an increased risk for perinatal complications, even in normal-weight women, while a reduction in BMI is associated with improved perinatal outcomes among women who are overweight/obese. Inter-pregnancy weight control is an important target to reduce the risk of an adverse perinatal outcome in a subsequent pregnancy.

Hypericum perforatum (HP; also known as St. John’s Wort) is one of the most commonly used herbal therapies in the management of depressive illness. The aim of this study was to evaluate the potential side effects of HP during pregnancy on pregnancy outcome. Using data from the Danish National Birth Cohort (DNBC), we investigated outcomes among 38 HP exposed pregnancies compared to a group of 90,128 women. Associations between HP use and gestational age, preterm birth, birth weight, malformations and Apgar scores were investigated. Preterm birth did not differ across the groups. While the prevalence of malformations in the HP exposed group was slightly higher (8.1%) than observed in the control groups (3.3%; p = 0.13), this was based on only three cases and was not of any specific pattern.

Background Our study aimed to assess the safety and protective effect of maternal influenza vaccination on pregnancy and birth outcomes. Methods The study population comprised 1253 healthy nulliparous pregnant women in South Australia between 2015 and 2018. Participants were followed prospectively, with vaccination status (confirmed by medical records), pregnancy, and birth outcome data collected by midwives. Adjusted relative risks (aRRs) and adjusted hazard ratios (aHRs) were estimated accounting for time-varying vaccine exposure and temporal nature of each outcome. Findings Maternal influenza vaccination (48%, 603 of 1253) reduced the risk for pre-delivery hospitalisation with influenza like illness (aHR 0•61; 95% CI 0•39, 0•97). Maternal influenza vaccination was not associated with spontaneous abortion (aHR 0•42, 95% CI 0•12, 1•45), chorioamnionitis (aRR 0•78, 95% CI, 0•32, 1•88), gestational hypertension (aHR 0•78, 95% CI 0•47, 1•29), pre-eclampsia (aHR 0.84, 95% CI 0•54, 1•27), gestational diabetes (aHR 1•16, 95% CI 0•82, 1•66) nor preterm birth (aHR 0•94, 95% CI 0•59, 1•49). No associations between antenatal influenza vaccination and congenital anomalies, admission to the neonatal care unit, low Apgar scores, and mechanical ventilation were observed. Results were not materially changed after adjustment for pertussis vaccination. We observed a protective effect of maternal influenza vaccination on low birth weight (aHR 0•46, 95% CI 0•23, 0•94) and a marginal protective effect on small for gestational age births (aHR 0•65, 95% CI 0•40, 1•04) during periods of high influenza activity. Interpretation These results support the safety of maternal influenza vaccination and suggest a protective effect in reducing the rates of low birthweight and small for gestational age births. Funding There was no funding for this study.

Background Pregnant women are at increased susceptibility to vitamin D deficiency. Hence, there is continuing interest in determining how vitamin D influences pregnancy health. We aimed to compare vitamin D status in two distinct populations of pregnant women in Australia and New Zealand and to investigate the relationship between vitamin D status and pregnancy outcome. This included evaluating possible effect measure modifications according to fetal sex. Methods Serum 25-hydroxy vitamin D (25(OH)D) was measured at 15 ± 1 weeks’ gestation in 2800 women from Adelaide and Auckland who participated in the multi-centre, prospective cohort SCreening fOr Pregnancy Endpoints (SCOPE) study. Results Mean serum 25(OH)D in all women was 68.1 ± 27.1 nmol/L and 28% (n = 772) were considered vitamin D deficient ( 81 nmol/L) “standardised” vitamin D status when compared to moderate-high (63–81 nmol/L, aRR, 0.47; 95% CI: 0.23, 0.96). Marginal sex-specific differences occurred between vitamin D status and GDM: women carrying a female fetus had a 56% decreased risk for GDM in those with low-moderate levels of standardised vitamin D (44–63 nmol/L) compared to moderate-high levels (aRR: 0.44; 95% CI: 0.20, 0.97), whilst in women carrying a male fetus, a 55% decreased risk of GDM was found with high standardised vitamin D when compared to moderately-high vitamin D, but this was not statistically significant (aRR: 0.45; 95% CI: 0.15, 1.38). Conclusions High serum 25(OH)D at 15 ± 1 weeks’ gestation was shown to be protective against the development of GDM. A possible association between fetal sex, vitamin D status and GDM provides further questions and encourages continual research and discussion into the role of vitamin D in pregnancy, particularly in vitamin D replete populations. Electronic supplementary material The online version of this article (10.1186/s12884-018-1887-x) contains supplementary material, which is available to authorized users.

STUDY QUESTIONIs preconception dietary intake associated with reduced fecundity as measured by a longer time to pregnancy (TTP)?SUMMARY ANSWERLower intake of fruit and higher intake of fast food in the preconception period were both associated with a longer TTP.WHAT IS KNOWN ALREADYSeveral lifestyle factors, such as smoking and obesity, have consistently been associated with a longer TTP or infertility, but the role of preconception diet in women remains poorly studied. Healthier foods or dietary patterns have been associated with improved fertility, however, these studies focused on women already diagnosed with or receiving treatments for infertility, rather than in the general population.STUDY DESIGN, SIZE, DURATIONThis was a multi-center pregnancy-based cohort study of 5628 nulliparous women with low-risk singleton pregnancies who participated in the Screening for Pregnancy Endpoints (SCOPE) study.PARTICIPANTS/MATERIALS, SETTING, METHODSA total of 5598 women were included. Data on retrospectively reported TTP and preconception dietary intake were collected during the first antenatal study visit (14–16 weeks’ gestation). Dietary information for the 1 month prior to conception was obtained from food frequency questions for fruit, green leafy vegetables, fish and fast foods, by a research midwife. Use of any fertility treatments associated with the current pregnancy was documented (yes, n = 340, no, n = 5258). Accelerated failure time models with log normal distribution were conducted to estimate time ratios (TR) and 95% CIs. The impact of differences in dietary intake on infertility (TTP >12 months) was compared using a generalized linear model (Poisson distribution) with robust variance estimates, with resulting relative risks (RR) and 95% CIs. All analyses were controlled for a range of maternal and paternal confounders. Sensitivity analyses were conducted to explore potential biases common to TTP studies.MAIN RESULTS AND THE ROLE OF CHANCELower intakes of fruit and higher intakes of fast food were both associated with modest increases in TTP and infertility. Absolute differences between the lowest and highest categories of intake for fruit and fast food were in the order of 0.6–0.9 months for TTP and 4–8% for infertility. Compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1–Ptrend = 0.007). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2–0–Ptrend Ptrend = 0.043). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2–0–Ptrend LIMITATIONS, REASONS FOR CAUTIONCollection of dietary data relied on retrospective recall and evaluated a limited range of foods. Paternal dietary data was not collected and the potential for residual confounding cannot be eliminated. Compared to prospective TTP studies, retrospective TTP studies are prone to a number of potential sources of bias.WIDER IMPLICATIONS OF THE FINDINGSThese findings underscore the importance of considering preconception diet for fecundity outcomes and preconception guidance. Further research is needed assessing a broader range of foods and food groups in the preconception period.

To examine differences in longer-term breastfeeding outcomes among mothers of preterm infants according to domperidone exposure status, as well as examine the potential for effect modification according to maternal weight. Retrospective cohort study of 198 mothers of very preterm infants (born ≤ 30 weeks’ gestation) who initiated breastfeeding and whose infants survived until hospital discharge. Data on domperidone use were obtained from hospital pharmacy records, with the primary outcome defined as continuation of breastfeeding at infant discharge from the Neonatal Unit. The relationship between domperidone exposure and breastfeeding status was investigated using multivariable regression analysis, adjusting for potential confounders. Additional pre-determined analyses were undertaken following stratification according to maternal weight to investigate the presence of effect modification. No overall difference was observed in the proportion of mothers continuing to breastfeed at the time of infant discharge from the Neonatal Unit according to whether or not they received domperidone (aRR 0.99; 0.86–1.13). Notably, effect modification was observed according to maternal weight, with use of domperidone associated with a reduced likelihood of breastfeeding at discharge among women ≥ 70 kg (aRR 0.72; 0.54–0.97), but not among those

Background Mothers of preterm infants often struggle to produce enough breast milk to meet the nutritional needs of their infant. Galactagogues such as domperidone are often prescribed to increase breast milk supply but evidence supporting their role in clinical practice is uncertain. Objective To evaluate the efficacy and safety of domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants. Search strategy MEDLINE, Embase and Web of Science were searched without language restrictions from first publication until January 2017. Bibliographies of articles and reviews were hand-searched for additional reports. Selection criteria Randomised controlled trials that compared domperidone with placebo in mothers of preterm infants ( Data collection and analysis Two review authors independently assessed studies for inclusion, extracted data and evaluated study quality. Differences in breast milk volume and adverse events were combined using fixed effects meta-analysis. Main results The pooled analysis of five trials consisting of 194 women demonstrated a moderate increase in daily breast milk volume of 88.3 ml/day (95% CI 56.8-119.8) with the use of domperidone compared with placebo. No difference was evident with respect to maternal adverse events (odds ratio 1.05, 95% CI 0.65-1.71), with no reported cases of prolonged QTc syndrome or sudden cardiac death. Sensitivity analyses showed no important differences in the estimates of effects. Conclusions Domperidone is well tolerated and results in a moderate short-term increase in expressed breast milk volume among mothers of preterm infants previously identified as having insufficient breast milk supply. Tweetable abstract Domperidone leads to short-term improvements in breast milk volume in mothers of preterm infants.

Background: Intravenous iron polymaltose (IPM) is commonly utilised in pregnancy when oral treatment is not tolerated or where rapid replenishment of iron stores is required, but data on use in pregnancy is scarce. Aim: To examine the use, safety and efficacy of intravenous IPM in pregnancy. Methods: Retrospective cohort study of pregnant women administered intravenous IPM between January 2014 and January 2016 at a Tertiary teaching hospital in Adelaide, Australia. Data on maternal characteristics, intravenous iron infusion details, and haematological parameters were collected from case notes and electronic records. Main outcome measures included indication for intravenous iron infusion, prevalence of infusion reactions, change in haemoglobin and correction of anaemia prior to delivery. Results: Intravenous IPM was administered in 213 pregnancies, 62.0% of women with iron deficiency anaemia (IDA) and the remainder (38.0%) with non-anaemic iron deficiency. Adverse drug reactions (ADRs) occurred in 24% of women, of which 32% required infusion cessation. Anaemia was still present at delivery among 7%, and 17% of women with mild, and moderate/severe anaemia respectively. Approximately one in five anaemic women received an intravenous IPM dose below that recommended by the local guideline, particularly in women with a body mass index ≥ 25 kg/m 2 compared with < 25 kg/m 2 (30.9% vs 6.3%; P < 0.001). Doses 'at recommended' resulted in a greater increase in haemoglobin from treatment until delivery than doses 'below recommended' (adjusted beta coefficient 8.4 g/L; 95% CI 2.7-14.1 g/L). Conclusion: Intravenous IPM is effective in treating IDA in pregnancy but is associated with a high prevalence of ADRs and treatment cessation. Refereed/Peer-reviewed

Background/objectives: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose–response relationship across number of cigarettes and whether this differs by sex remains unclear. Subject/methods: Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex. Results: Of 26 identified studies, 16 authors provided data on a total of 238,340 mother–child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02–1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results. Conclusions: A linear dose–response relationship of maternal smoking was observed in the range of 1–15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.

The objective was to investigate the association between early and late maternal smoking during pregnancy on offspring body mass index (BMI). We undertook a retrospective cohort study using linked records from the Women’s and Children’s Health Network in South Australia. Among a cohort of women delivering a singleton, live-born infants between January 2000 and December 2005 (n=7658), 5961 reported not smoking during pregnancy, 297 reported quitting smoking during the first trimester of pregnancy, and 1400 reported continued smoking throughout pregnancy. Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance programme. The main outcome measure was age- and sex-specific BMI z-score. At 4 to 5 years, mean (s.d.) BMI z-score was 0.40 (1.05), 0.60 (1.07) and 0.65 (1.18) in children of mothers who reported never smoking, quitting smoking and continued smoking during pregnancy, respectively. Compared with the group of non-smokers, both quitting smoking and continued smoking were associated with an increase in child BMI z-score of 0.15 (95% confidence interval: 0.01–0.29) and 0.21 (0.13–0.29), respectively. A significant dose–response relationship was also observed between the number of cigarettes smoked per day on average during the second half of pregnancy and the increase in offspring BMI z-score (P

Objective To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH). Design Retrospective cohort study. Setting Tertiary teaching hospital in Adelaide, Australia. Population A total of 30 198 women delivering between 2002 and 2008. Methods Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n = 558), women with a psychiatric illness but no antidepressant use (n = 1292), and women with neither antenatal exposures (n = 28 348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia. Main outcome measures The primary outcome was PPH, defined as a recorded blood loss of ≥500 mL for vaginal deliveries and ≥1000 mL for caesarean sections. Secondary outcomes included severe PPH (≥1000 mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records). Results Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR 1.53; 95% confidence interval, 95% CI 1.25–1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR 1.04; 95% CI 0.89–1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR 1.84; 95% CI 1.39–2.44), as well as postpartum anaemia (aRR 1.80; 95% CI 1.46–2.22). Conclusions Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH. Tweetable abstract Late gestation antidepressant exposure is associated with a significantly increased risk of postpartum haemorrhage.