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Lyndsay Creswell,1 Neil O’Gorman,1 Kirsten Rebecca Palmer,2 Fabricio da Silva Costa,3 Daniel Lorber Rolnik2 1Coombe Women and Infants University Hospital, Dublin, Ireland; 2Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia; 3Maternal Fetal Medicine Unit, Gold Coast University Hospital and School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, AustraliaCorrespondence: Lyndsay Creswell, Coombe Women and Infants University Hospital, Cork Street, Dublin, D08XW7X, Ireland, Tel +44 7754235257, Email lcreswell@coombe.ieAbstract: Pre-eclampsia (PE) is a complex multisystem disease of pregnancy that is becoming increasingly recognized as a state of angiogenic imbalance characterized by low concentrations of placental growth factor (PlGF) and elevated soluble fms-like tyrosine kinase (sFlt-1). PlGF is a protein highly expressed by the placenta with vasculogenic and angiogenic properties, which has a central role in spiral artery remodeling and the development of a low-resistance placental capillary network. PlGF concentrations are significantly lower in women with preterm PE, and these reduced levels have been shown to precede the clinical onset of disease. Subsequently, the clinical utility of maternal serum PlGF has been extensively studied in singleton gestations from as early as 11 to 13 weeks’ gestation, utilizing a validated multimarker prediction model, which performs superiorly to the National Institute for Health and Care Excellence (NICE) and American College of Obstetricians and Gynecologists (ACOG) guidelines in the detection of preterm PE. There is extensive research highlighting the role of PlGF-based testing utilizing commercially available assays in accelerating the diagnosis of PE in symptomatic women over 20 weeks’ gestation and predicting time-to-delivery, allowing individualized risk stratification and appropriate antenatal surveillance to be determined. “Real-world” data has shown that interpretation of PlGF-based test results can aid clinicians in improving maternal outcomes and a growing body of evidence has implied a role for sFlt-1/PlGF in the prognostication of adverse pregnancy and perinatal events. Subsequently, PlGF-based testing is increasingly being implemented into obstetric practice and is advocated by NICE. This literature review aims to provide healthcare professionals with an understanding of the role of angiogenic biomarkers in PE and discuss the evidence for PlGF-based screening and triage. Prospective studies are warranted to explore if its implementation significantly improves perinatal outcomes, explore the value of repeat PlGF testing, and its use in multiple pregnancies.Keywords: pre-eclampsia, biomarkers, PlGF, sFlt-1, screening, aspirin, prevention, prediction, pregnancy complications

BACKGROUND: The Rockall scoring system was developed in unselected patients, the majority of whom did not receive endoscopic therapy. The aim of this study was to assess the validity of the Rockall system in high-risk patients who undergo endoscopic therapy for peptic ulcer hemorrhage. METHODS: Rockall scores were calculated in 247 patients with major peptic ulcer bleeding entered into a randomized trial of endoscopic therapy. The observed rates of recurrent bleeding and mortality after endoscopic therapy were compared with predicted rates derived from Rockall's study group. The validity of the Rockall system was assessed in terms of calibration and discrimination. RESULTS: Rates of recurrent bleeding and mortality after endoscopic therapy increased with an increasing Rockall score. Observed rates of recurrent bleeding and mortality were below predicted rates, and calibration of the Rockall system was poor (Mantel-Haenszel chi square = 25.8, p < 0.0001 for recurrent bleeding; Mantel-Haenszel chi square = 15.1, p < 0.0001 for death). For the prediction of recurrent bleeding, the area under the receiver operating characteristic curve was low (63.4%), but the system was satisfactory when predicting mortality (area under the resulting curve, 84.3%). CONCLUSIONS: After endoscopic therapy for a bleeding peptic ulcer, the Rockall scoring system can identify patients at high risk of death, but it is inadequate for the prediction of recurrent bleeding. [ABSTRACT FROM AUTHOR]

AIM: Health related quality of life is impaired in patients suffering from inflammatory bowel disease. Although counselling directed towards physical and psychological morbidity is assumed to improve health related quality of life, this has never been demonstrated. METHODS: Physical and psychological well-being were assessed using questionnaires administered to 100 out-patients in the United Kingdom suffering from inflammatory bowel disease, 50 subjects not suffering from inflammatory bowel disease and a disease control group comprising 28 patients with psoriatic arthritis. A specific nurse led counselling package was given to half the inflammatory bowel disease group and health related quality of life was assessed at baseline, 6 and 12 months. RESULTS: Inflammatory bowel disease and psoriatic arthritic patients had a range of physical disease activity, although none were severely ill during the course of the study. Medical therapy was similar in both groups throughout the duration of the trial. The mean Short Form 36 (SF-36) scores for mental health were low in inflammatory bowel disease patients; 62.9 +/- 9.1 (SD) in ulcerative colitis, 60 +/- 9.8 (SD) in Crohn's disease, compared with 72.4 +/- 7.2 (SD) in healthy controls (P < 0.05). Mean SF-36 scores for social function were also reduced in Crohn's disease patients; 68.4 +/- 10.1 (SD) in Crohn's disease, compared with 87 +/- 10.1 (SD) in healthy controls (P < 0.05). As expected, the mean SF-36 scores in psoriatic arthritic patients were significantly low 61.9 +/- 1.5 (SD) compared with 82.4 +/- 14 (SD) in healthy controls (P < 0.05). Crohn's disease patients were significantly more anxious than the other groups, mean HAD score was 10 +/- 3.7 (SD) in Crohn's disease patients and 6.86 +/- 3.5 (SD) in healthy volunteers (P < 0.05), although mean HAD scores for depression were similar in all groups. Maladaptive coping mechanisms were present in a significant proportion of Crohn's disease patients. At follow-up all aspects of psychological morbidity returned to the normal range in the Crohn's disease patients without significant change in the mean physical disease index. CONCLUSION: Health related quality of life can be improved over 6 months by provision of a nurse led counselling service but the effects are not sustained for 12 months. [ABSTRACT FROM AUTHOR]

AIM: To report on the preliminary development of a short scale, the Edinburgh inflammatory bowel disease questionnaire (EIBDQ) to measure disease specific aspects of inflammatory bowel disease (IBD) in terms of both physical impact and health related quality of life (HRQoL) consequences.METHODS: A survey of individuals with Crohn's disease (n=50), ulcerative colitis (n=50) and psoriatic arthritis (n=28) was carried out using the EIBDQ. The data were subject to factor analysis in order to investigate underlying dimension of the EIBDQ which were then analysed for internal consistency. Data for disease specific aspects of the EIBDQ were compared between IBD patients and psoriatic arthritis patients using contingency tables and the underlying dimension of the EIBDQ were correlated with measures of quality of life and psychological morbidity and a disease specific measure.RESULTS: There are three underlying dimensions to the EIBDQ: a disease specific factor, a bowel specific factor and an information factor. The disease specific factor and the bowel specific factor are internally consistent and correlate with other measures of disease activity, quality of life and psychological morbidity. The EIBDQ is able to discriminate between IBD and another inflammatory disease: psoriatic arthritis.CONCLUSION: The EIBDQ is a reliable and valid instrument for measuring disease specific aspects of IBD but further development is required. [ABSTRACT FROM AUTHOR]

Background: In response to the COVID-19 pandemic, Victoria's largest maternity service provider implemented a telehealth-integrated antenatal care (ANC) schedule for high- and low-risk pregnancies. The program has been maintained since March 2020. Given ever-increasing healthcare costs, economic evaluation is crucial to ensure value and guide ongoing use., Methods: The aim of the study was to perform a cost-minimisation analysis of telehealth integrated ANC compared to conventional in-person ANC, from the hospital and patient perspectives. We hypothesised that the costs associated with telehealth integrated ANC would be less than in-person ANC. We generated propensity score matched pre- and post-telehealth cohorts from women with a singleton pregnancy who received ANC and birthed at Monash Health from 1 Jan 2018-22 Mar 2020 (pre-telehealth), and 20 Apr 2020-31 Dec 2021 (post-telehealth). Data were extracted from electronic medical and finance records. We assigned costs for all Monash Health outpatient, inpatient, and emergency department episodes to calculate mean cost per birth. Patient travel costs were estimated based on distance residing from hospital., Findings: Matched pre- and post-telehealth cohorts of n = 13,534 each were created. There were no significant differences in stillbirth, pre-eclampsia, severe maternal morbidity, or death. There was a AU$133 (0.98%, 95% CI [-0.17%, 2.16%]) increase in cost per birth in the post-telehealth cohort. This was driven by increased hospital costs (AU$340 or 2.64% increase, [1.44%, 3.86%]), due to a 4.78% increase in antenatal inpatient episodes and 3.51% increase in outpatient appointments post-telehealth. Increased care complexity was noted in the post-telehealth period with increased rates of gestational diabetes, caesarean birth, and specialty-led care (p-values all <0.0001). In contrast, patient costs of accessing healthcare fell significantly from AU$562 pre-telehealth to AU$355 post-telehealth (difference -AU$207 (-36.81%, [-37.46%, -36.16%])., Interpretation: Telehealth supported the provision of a greater volume of antenatal care to more complex pregnancies, while maintaining safety and quality of care, for only a minimal cost increase to health funders and substantial cost savings to patients. This finding provides reassurance regarding the financial viability of telehealth-integrated antenatal care., Funding: None., Competing Interests: BWM and KRP are supported by National Health and Medical Research Council (NHMRC) Investigator grants (GNT1176437 and GNT2009765, respectively). BWM reports research funding from Merck KGaA; consultancy for Organon, Norgine, and Merck KGaA; travel support from Merck KGaA; and holds stock in ObsEva. RJH has received research funding from the NHMRC. KRP has received travel support from Mercy Perinatal. All other authors declare no competing interests., (© 2024 The Authors.)

Objective: To compare specific perinatal outcomes in nulliparas with a singleton infant in cephalic presentation at term, with and without exposure to the COVID-19 pandemic during pregnancy. We hypothesised that the pandemic conditions in Melbourne may have been an independent contributor to trends in maternal Body Mass Index ≥ 25 kg/m 2 , macrosomia and caesarean section., Design: Multi-centre retrospective cohort study and interrupted time-series analysis., Setting: Metropolitan Melbourne, Victoria., Population: Singleton infants ≥ 20 weeks gestational age born between 1 January 2019 and 31 March 2022., Main Outcome Measures: Rates of maternal Body Mass Index ≥ 25 kg/m 2 , macrosomia (birthweight ≥ 4000 g) and caesarean section., Results: 25 897 individuals gave birth for the first time to a singleton infant in cephalic presentation at term in the pre-pandemic cohort, and 25 298 in the pandemic-exposed cohort. Interrupted time-series analysis demonstrated no significant additional effect of the pandemic on pre-existing upward trends in maternal Body Mass Index ≥ 25 kg/m 2 , caesarean section or macrosomia. The rate of maternal Body Mass Index ≥ 25 kg/m 2 was higher in the pandemic-exposed cohort compared with the pre-pandemic cohort, (45.82% vs. 44.58% respectively, p = 0.041) as was the overall rate of caesarean section (33.09% vs. 30.80%, p < 0.001). However, this increase in caesarean section was confined to individuals who had either an induction of labour or no labour. There was also a nonsignificant trend to higher rates of macrosomia in the pandemic-exposed cohort compared with the pre-pandemic cohort (8.55% vs. 7.99% respectively, p = 0.124)., Conclusions: While rates of Body Mass Index ≥ 25 kg/m 2 , pre-labour caesarean section, and caesarean section following induction of labour were higher among pandemic-exposed nulliparas, these findings represented a continuation of pre-existing upward trends, with no significant independent contribution from the pandemic. These trends are forecast to continue, with long term implications for population health., (© 2024. The Author(s).)

Objectives: Induction of labor is commonly undertaken when ongoing pregnancy poses a risk to either the mother or fetus. Often cervical preparation is required with mechanical methods increasingly popular due to their improved safety. This study evaluates the efficacy, safety, and acceptability of digital versus speculum-based balloon insertion for cervical preparation, aiming to identify gaps and inform future research., Data Source: PubMed, Ovid MEDLINE, EMBASE, and Scopus were searched from database inception until 30 June 2023., Study Eligibility Criteria: Included studies were randomized controlled trials comparing digital versus speculum-based insertion of catheter-related balloons for labor induction in individuals with viable singleton pregnancies, in both inpatient and outpatient settings, written in English. Exclusions included studies not using cervical balloons, comparisons to nonballoon methods, nonhuman studies, and nonprimary literature like guidelines, reviews, commentaries, and opinion pieces., Methods: Title and abstract screening were performed by 4 authors. Full-text articles were assessed against inclusion criteria. Selection was agreed upon by consensus among 3 authors, with a fourth consulted for disputes. The risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0 for randomized trials. A meta-analysis was also performed., Results: Out of 3397 studies, 4 met the inclusion criteria, all being randomized controlled trials with some concerns in at least one domain but no high risk of bias. Two studies found digital insertion significantly less painful than speculum-based insertion (P<.001), while one reported no difference (P=.72). Maternal satisfaction was comparable, with one study favoring digital insertion (P=.011). Meta-analysis findings for other outcome measures suggest no difference between speculum or digital insertion. However, due to substantial heterogeneity, findings for procedural time, time from induction to delivery, and epidural rate should be cautiously interpreted., Conclusions: Digital insertion for cervical preparation appears associated with reduced pain and higher patient acceptability compared to speculum-based insertion. Additionally, efficacy and safety were comparable, indicating it is a preferable option for clinical use. There was no difference in other procedural, obstetric, or neonatal outcomes, however, more rigorous research employing standardized outcome measures is needed to facilitate a clinically meaningful interpretation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objective: Medication use is increasing to treat both pre-existing and pregnancy-related medical conditions or complications. This study aims to investigate factors associated with multiple medication use during pregnancy, as well as any increased risk of pregnancy complications for women taking multiple medications., Methods: A retrospective analysis of routinely collected medical records of singleton pregnant women was conducted in Southeast Melbourne, Australia, between 2016 and 2021. Self-reported medication use was recorded as part of routine medical care, starting from the first antenatal booking appointment and continuing for every subsequent antenatal appointment until birth. Multimorbidity was defined as having two or more medical conditions. Logistic regression was used to assess factors influencing multiple medication use (defined as taking two or more non-supplemental medications at any stage of pregnancy) and associations with pregnancy complications., Results: Of 48,502 participants, 34.9% used one medication, while 11.7% used multiple medications. Women of older age (30-34, 35-39, and ≥  40 years), higher body mass index (25.0-29.9 kg/m 2 and ≥  30 kg/m 2 ), born in Australasia and Oceania, higher socioeconomic status, and multimorbidity were more likely to use multiple medications during pregnancy. Women taking multiple medications had a higher risk of preterm and caesarean deliveries, fetal death, and neonatal admissions to intensive care. Sensitivity analyses exploring different morbidity categories produced no changes to findings., Conclusions: Medication use during pregnancy is prevalent, with many pregnant mothers taking multiple medications. Given the rising maternal age, body mass index, and morbidities in pregnancy, the use of medications during pregnancy is increasing. Such use correlates with an increased chance of adverse pregnancy outcomes. In the context of limited trials on the safety and efficacy of medications in pregnancy, timely harnessing of the information available within routine medical records for post-marketing surveillance is important., (© 2024. The Author(s).)

Importance: Transplant recipients experience high rates of adverse pregnancy outcomes; however, contemporary estimates of the association between solid organ transplantation and adverse pregnancy outcomes are lacking., Objective: To evaluate the association between solid organ transplantation and adverse pregnancy outcomes and to quantify the incidence of allograft rejection and allograft loss during pregnancy., Data Sources: PubMed/MEDLINE, EMBASE and Scopus databases were searched from January 1, 2000, to June 20, 2024, and reference lists were manually reviewed., Study Selection: Cohort and case-control studies that reported at least 1 adverse pregnancy outcome in pregnant women with solid organ transplantation vs without solid organ transplant or studies that reported allograft outcomes in pregnant women with solid organ transplantation were included following independent dual review of abstracts and full-text articles., Data Extraction and Synthesis: Two investigators abstracted data and independently appraised risk of bias using the Newcastle Ottawa Scale. A random-effects model was used to calculate overall pooled estimates using the DerSimonian-Laird estimator. Reporting followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline., Main Outcomes and Measures: Primary pregnancy outcomes were preeclampsia, preterm birth (<37 weeks), and low birth weight (<2500 g). Secondary pregnancy outcomes were live birth rate, gestation, very preterm birth (<32 weeks), very low birth weight (<1500 g), and cesarean delivery. Allograft outcomes were allograft loss and rejection during pregnancy., Results: Data from 22 studies and 93 565 343 pregnancies (4786 pregnancies in solid organ transplant recipients) were included; 14 studies reported adverse pregnancy outcomes, and 13 studies provided data for allograft outcomes. Pregnancies in organ transplant recipients were associated with significantly increased risk of preeclampsia (adjusted odds ratio [aOR], 5.83 [95% CI, 3.45-9.87]; I2 = 77.4%), preterm birth (aOR, 6.65 [95% CI, 4.09-12.83]; I2 = 81.8%), and low birth weight (aOR, 6.51 [95% CI, 2.85-14.88]; I2 = 90.6%). The incidence of acute allograft rejection was 2.39% (95% CI, 1.20%-3.96%; I2 = 68.5%), and the incidence of allograft loss during pregnancy was 1.55% (95% CI, 0.05%-4.44%; I2 = 69.2%)., Conclusions and Relevance: In this systematic review and meta-analysis, pregnancies in recipients of a solid organ transplant were associated with a 4 to 6 times increased risk of preeclampsia, preterm birth, and low birth weight during pregnancy. There was a low overall risk of graft rejection or loss during pregnancy.

Not discounting the important foetal or placental contribution, the endometrium is a key determinant of pregnancy outcomes. Given the inherently linked processes of menstruation, pregnancy and parturition with the endometrium, further understanding of menstruation will help to elucidate the maternal contribution to pregnancy. Endometrial health can be assessed via menstrual history and menstrual fluid, a cyclically shed, easily and non-invasively accessible biological sample that represents the distinct, heterogeneous composition of the endometrial environment. Menstrual fluid has been applied to the study of endometriosis, unexplained infertility and early pregnancy loss; however, it is yet to be examined regarding adverse pregnancy outcomes. These adverse outcomes, including preeclampsia, foetal growth restriction (FGR), spontaneous preterm birth and perinatal death (stillbirth and neonatal death), lay on a spectrum of severity and are often attributed to placental dysfunction. The source of this placental dysfunction is largely unknown and may be due to underlying endometrial abnormalities or endometrial interactions during placentation. We present existing evidence for the endometrial contribution to adverse pregnancy outcomes and propose that a more comprehensive understanding of menstruation can provide insight into the endometrial environment, offering great potential value as a diagnostic tool to assess pregnancy risk. As yet, this concept has hardly been explored.

Background: During the COVID-19 pandemic, mitigation measures were associated with a reduction in preterm birth rates; while not clearly proven, this observation has sparked significant interest., Aim: To understand the cause of this reduction by exploring the characteristics of preterm birth cohorts., Material and Methods: We performed a retrospective cohort study where we compared women who delivered preterm in three Melbourne maternity hospitals and conceived between November 2019 and February 2020 (mitigation measures-exposed cohort) to women who delivered preterm and conceived between November 2018 and February 2019 (non-exposed cohort). We compared maternal characteristics, pregnancy complications, antenatal interventions, intrapartum care, and indications for delivery., Results: In the exposed cohort, 252/3129 women delivered preterm (8.1%), vs 298/3154 (9.4%) in the non-exposed cohort (odds ratio (OR) 0.84, 95% CI 0.70-1.00, P = 0.051). The baseline characteristic of two cohorts were comparable. Rates of spontaneous preterm labour (sPTL) without preterm pre-labour rupture of membranes (PPROM) were lower in the exposed cohort (13.1% vs 24.2%, OR 0.47, P = 0.001) while PPROM occurred more often (48.0% vs 35.6%, OR 1.67, P = 0.003). With a non-statistically significant prolongation of pregnancy in the cohort exposed to mitigation measures for both sPTL without PPROM (35.4 vs 34.9 weeks, P = 0.703) and PPROM (35.6 vs 34.9 weeks, P = 0.184). The rate of spontaneous labour after PPROM was higher in the exposed cohort compared to the non-exposed cohort (40.1% vs 24.1%, OR 2.09, P < 0.001)., Conclusion: The reduction in preterm delivery during mitigation measures may have been driven by a reduction in spontaneous labour without PPROM, which seemed to result in more PPROM later in pregnancy., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Physiological adaptations during pregnancy alter nutrient and energy metabolism. Creatine may be important for maintaining cellular energy homeostasis throughout pregnancy. However, the impact of pregnancy on endogenous and exogenous creatine availability has never been comprehensively explored., Objectives: To undertake a prospective cohort study and determine the physiological ranges of creatine and associated metabolites throughout human pregnancy., Methods: Females with a singleton low-risk pregnancy were recruited at an Australian health service. Maternal blood and urine were collected at 5-time points from 10-36 weeks of gestation, and cord blood and placental samples were collected at birth. Creatine and associated amino acids and metabolites of creatine synthesis were analyzed. Dietary data were captured to determine effects of exogenous creatine intake. Associations between creatine metabolism and neonatal growth parameters were examined., Results: Two hundred and eighty-two females were included. Maternal plasma creatine remained stable throughout pregnancy [β: -0.003 μM; 95% confidence interval (CI): -0.07, 0.07; P = 0.94], though urinary creatine declined in late gestation (β: 0.38 μM/mmol/L creatinine (CRN); 95% CI: -0.47, -0.29; P < 0.0001). Plasma guanidinoacetate (GAA; the precursor to creatine during endogenous synthesis) fell from 10-29 weeks of gestation before rising until birth (β: -0.38 μM/mmol/L CRN; 95% CI: -0.47, -0.29; P < 0.0001). Urinary GAA followed an opposing pattern (β: 2.52 μM/mmol/L CRN; 95% CI: 1.47, 3.58, P < 0.001). Animal protein intake was positively correlated with maternal plasma creatine until ∼32 weeks of gestation (β: 0.07-0.18 μM; 95% CI: 0.006, 0.25; P ≤ 0.001). There were no links between creatine and neonatal growth, but increased urinary GAA in early pregnancy was associated with a slight reduction in head circumference at birth (β: -0.01 cm; 95% CI: -0.02, -0.004; P = 0.003)., Conclusions: Although maternal plasma creatine concentrations were highly conserved, creatine metabolism appears to adjust throughout pregnancy. An ability to maintain creatine concentrations through diet and shifts in endogenous synthesis may impact fetal growth. This trial was registered at [registry name] as ACTRN12618001558213., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

Introduction: Preterm birth is a leading cause of perinatal morbidity and mortality. During the COVID-19 pandemic, reduction in rates of preterm birth in women exposed to viral mitigation measures was reported by multiple studies. In addition, others and we observed a more pronounced reduction of preterm birth in women who had previously experienced a preterm birth. The aim of this pilot study is to establish the feasibility of a lifestyle intervention based on viral mitigation measures in high-risk pregnancies, with the ultimate aim to reduce the incidence of preterm birth., Methods and Analysis: One hundred pregnant women, enrolled in antenatal clinics at two tertiary maternity centres in Melbourne, Australia, who have had a previous preterm birth between 22 and 34 weeks gestation will be recruited. This is a two-arm, parallel group, open-label randomised controlled feasibility trial: 50 women will be randomised to the intervention group, where they will be requested to comply with a set of lifestyle changes (similar to the viral mitigation measures observed during the pandemic). Another 50 women will be randomised to the control group, where they will undergo standard pregnancy care. The primary outcome of this trial is feasibility, which will be assessed by measuring patient eligibility rate, recruitment rate, compliance rate and data completion rate. Secondary outcomes include incidence of preterm birth, maternal satisfaction, maternal quality of life and other pregnancy outcomes. Standard methods in statistical analysis for randomised controlled trials on an intention to treat basis will be followed., Ethics and Dissemination: This trial has been approved by the Monash Human Research Ethics Committee; approval reference number RES-22-0000-122A. Study findings will be reported and submitted to peer-reviewed journals for publication, and presentation at conferences., Trial Registration Number: ACTRN12622000753752; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes., Methods: Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. Multivariable log-binomial regression models were used to compare perinatal outcomes between a pre-pandemic group to women in whom weeks 20 +0 to 40 +0 of gestation occurred entirely during one of two lockdown-exposure periods: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022., Results: Total preterm births < 37 weeks were significantly lower in exposure 1 compared with the pre-pandemic period (63.1% vs 68.3%; adjusted risk ratio 0.92 95% CI 0.87-0.98, p = 0.01). This was mainly driven by fewer spontaneous preterm births (18.9% vs 20.3%; adjusted risk ratio 0.95 95% CI 0.90-0.99, p = 0.04). There were also lower rates of preterm birth < 34 weeks (19.9% vs 23.0%, adjusted risk ratio 0.93 95% CI 0.89-0.98 p = 0.01) and total iatrogenic births for fetal compromise (13.4% vs 20.4%; adjusted risk ratio 0.94 95% CI 0.89-0.98, p = 0.01). There were fewer special care nursery admissions (38.5% vs 43.4%; adjusted risk ratio 0.91 95% CI 0.87-0.95, p < 0.001) but no significant changes in stillbirth (1.5% vs 1.6%; adjusted risk ratio 1.00 95% CI 0.99-1.01, p = 0.82). Compared with the pre-pandemic period, there were more preterm births < 28 weeks and neonatal intensive care unit admissions in exposure 2., Conclusions: Melbourne's first lockdown-exposure period was associated with lower preterm births in twins without significant differences in adverse newborn outcomes. Our findings provide insights into the influences on preterm birth and the optimal timing of delivery for twins., (© 2023. The Author(s).)

Creatine metabolism likely contributes to energy homeostasis in the human uterus, but whether this organ synthesizes creatine and whether creatine metabolism is adjusted throughout the menstrual cycle and with pregnancy are largely unknown. This study determined endometrial protein expression of creatine-synthesizing enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), creatine kinase (CKBB), and the creatine transporter (SLC6A8) throughout the menstrual cycle in fertile and primary infertile women. It also characterized creatine metabolism at term pregnancy, measuring aspects of creatine metabolism in myometrial and decidual tissue. In endometrial samples, AGAT, GAMT, SLC6A8, and CKBB were expressed in glandular and luminal epithelial cells. Except for SLC6A8, the other proteins were also located in stromal cells. Irrespective of fertility, AGAT, GAMT, and SLC6A8 high-intensity immunohistochemical staining was greatest in the early secretory phase of the menstrual cycle. During the proliferative phase, staining for SLC6A8 protein was greater (P = 0.01) in the primary infertile compared with the fertile group. Both layers of the term pregnant uterus contained creatine, phosphocreatine, guanidinoacetic acid, arginine, glycine, and methionine; detectable gene and protein expression of AGAT, GAMT, CKBB, and ubiquitous mitochondrial CK (uMt-CK); and gene expression of SLC6A8. The proteins AGAT, GAMT, CKBB, and SLC6A8 were uniformly distributed in the myometrium and localized to the decidual glands. In conclusion, endometrial tissue has the capacity to produce creatine and its capacity is highest around the time of fertilization and implantation. Both layers of the term pregnant uterus also contained all the enzymatic machinery and substrates of creatine metabolism., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To compare pharmacokinetics (PK) and safety of heat-stable inhaled (IH) oxytocin with intramuscular (IM) oxytocin in women in third stage of labour (TSL), the primary endpoint being PK profiles of oxytocin IH and secondary endpoint of safety., Methods: A phase 1, randomized, cross-over study was undertaken in 2 UK and 1 Australian centres. Subjects were recruited into 2 groups: Group 1, women in TSL; Group 2, nonpregnant women of childbearing potential (Cohort A, combined oral contraception; Cohort B, nonhormonal contraception). Participants were randomized 1:1 to: Group 1, oxytocin 10 IU (17 μg) IM or oxytocin 240 IU (400 μg) IH immediately after delivery; Group 2, oxytocin 5 IU (8.5 μg) intravenously and oxytocin 240 IU (400 μg) IH at 2 separate dosing sessions., Results: Participants were recruited between 23 November 2016 to 4 March 2019. In Group 1, 17 participants were randomized; received either IH (n = 9) or IM (n = 8) oxytocin. After IH and IM administration, most plasma oxytocin concentrations were below quantification limits (2 pg/mL). In Group 2 (n = 14), oxytocin IH concentrations remained quantifiable ≤3 h postdose. Adverse events were reported in both groups, with no deaths reported: Group 1, IH n = 3 (33%) and IM n = 2 (25%); Group 2, n = 14 (100%)., Conclusion: Safety profiles of oxytocin IH and IM were similar. However, PK profiles could not be established for oxytocin IH or IM in women in TSL, despite using a highly sensitive and specific assay., (© 2023 GSK. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: During the COVID-19 pandemic, rapid integration of telehealth into antenatal care occurred to support ongoing maternity care. A programme of this scale had not been previously implemented. We evaluated whether telehealth-integrated antenatal care in an Australian public health system could achieve pregnancy outcomes comparable to those of conventional care to assess its safety and efficacy., Methods: Routinely collected data for individuals who gave birth at Monash Health (Melbourne, VIC, Australia) during a conventional care period (Jan 1, 2018, to March 22, 2020) and telehealth-integrated period (April 20, 2020, to April 25, 2021) were analysed. We included all births that occurred at 20 weeks' gestation or later or with a birthweight of at least 400 g (if duration of gestation was unknown). We excluded multiple births, births for which private antenatal care was received, and births to individuals transferred from other hospitals or who had no antenatal care. Baseline demographics, telehealth uptake, and pregnancy complications (related to pre-eclampsia, fetal growth restriction [FGR], gestational diabetes, stillbirth, neonatal intensive care [NICU] admission, and preterm birth [<37 weeks' gestation]) were compared using comparative statistics and an interrupted time-series analysis. Results were stratified by care stream, with high-risk models consisting of obstetric specialist-led care, and all other streams categorised as low-risk models. The impact of the integrated period on outcomes was also assessed with stratification by parity., Findings: 17 873 births occurred in the conventional period and 8131 in the integrated period. Compared with the conventional period, women giving birth during the integrated period were slightly older (30·63 years vs 30·88 years) and had slightly higher BMI (25·52 kg/m 2 vs 26·14 kg/m 2 ), and more Australian-born women gave birth during the integrated period (37·37% vs 39·79%). There were no significant differences in smoking status or parity between the two groups. 107 (0·08%) of 129 514 antenatal consultations in the conventional period and 34 444 (45·94%) of 74 982 in the integrated period were delivered by telehealth. No significant differences between the conventional and integrated periods were seen in median gestational age at pre-eclampsia diagnosis (low-risk models 37·4 weeks in the conventional period vs 37·1 weeks in the integrated period, difference -0·3 weeks [-0·7 to 0·1]; high-risk models 35·5 weeks vs 36·3 weeks, difference 0·3 weeks [-0·3 to 1·1]), incidence of FGR below the 3rd birthweight percentile (low-risk models 1·62% vs 1·74%, difference 0·12 percentage points [-0·26 to 0·50]; high-risk 4·04% vs 4·13%, difference 0·089 percentage points [-1·08 to 1·26]), and incidence of preterm birth (low-risk models 4·99% vs 5·01%, difference 0·02% [-0·62 to 0·66]; high-risk models 15·76% vs 14·43%, difference -1·33% [-3·42 to 0·77]). Parity did not affect these findings. Interrupted time-series analysis showed a significant reduction in induction of labour for singletons with suspected FGR among women in low-risk models during the integrated period (-0·04% change per week [95% CI -0·07 to -0·01], p=0·0040), and NICU admission declined after telehealth integration (low-risk models -0·02% change per week [-0·03 to -0·003], p=0·018; high-risk models -0·10% change per week, -0·19 to -0·001; p=0·047). No significant differences in stillbirth rates were observed. The proportion of women diagnosed with gestational diabetes was significantly higher in the integrated period compared with the conventional period for both low-risk care models (22·28% vs 25·13%, difference 2·85 percentage points [1·60 to 4·11]) and high-risk care models (28·70% vs 34·02%, difference 5·32 percentage points [2·57 to 8·07]). However overall, when compared with the conventional period, there was no significant difference in proportion of women with gestational diabetes requiring insulin therapy (low-risk models 8·08% vs 7·73%, difference -0·35 percentage points [-1·13 vs 0·44]; high-risk models 14·81% vs 15·71%, difference 0·89 percentage points [-1·23 to 3·02]), or proportion of women with gestational diabetes who gave birth to a baby with macrosomia in the integrated period (low-risk models 3·16% vs 2·33%, difference -0·83 percentage points [-1·77 to 0·12]; high-risk models 5·58% vs 4·81%, difference -0·77 percentage points [-3·06 to 1·52])., Interpretation: Telehealth-integrated antenatal care replaced around 46% of in-person consultations without compromising pregnancy outcomes. It might be associated with a reduction in labour induction for suspected FGR, particularly for women in low-risk models, without compromising FGR detection or perinatal morbidity. These findings support the ongoing use of telehealth in providing flexible antenatal care., Funding: None., Competing Interests: Declaration of interests BWM and KRP are supported by National Health and Medical Research Council Investigator grants (GNT1176437 and GNT2009765, respectively). BWM reports consultancy for ObsEva, Guerbet, and Merck, and travel support from Merck. KRP has provided consultancy for Janssen. DLR reports consultancy for Alexion Pharmaceutical, as well as conference support from the International Society of Ultrasound in Obstetrics and Gynaecology and Asia Pacific Congress. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Evidence comparing double-balloon vs single-balloon catheter for induction of labor is divided. We aim to compare the efficacy and safety of double-vs single-balloon catheters using individual participant data., Material and Methods: A search of Ovid MEDLINE, Embase, Ovid Emcare, CINAHL Plus, Scopus, and clinicaltrials.gov was conducted for randomized controlled trials published from March 2019 until April 13, 2021. Earlier trials were identified from the Cochrane Review on Mechanical Methods for Induction of Labour. Randomized controlled trials that compared double-balloon with single-balloon catheters for induction of labor in singleton gestations were eligible. Participant-level data were sought from trial investigators and an individual participant data meta-analysis was performed. The primary outcomes were rates of vaginal birth achieved, a composite measure of adverse maternal outcomes and a composite measure of adverse perinatal outcomes. We used a two-stage random-effects model. Data were analyzed from the intention-to-treat perspective., Results: Of the eight eligible randomized controlled trials, three shared individual-level data with a total of 689 participants, 344 women in the double-balloon catheter group and 345 women in the single-balloon catheter group. The difference in the rate of vaginal birth between double-balloon catheter and single-balloon catheter was not statistically significant (relative risk [RR] 0.93, 95% confidence interval [CI] 0.86-1.00, p = 0.050; I 2 0%; moderate-certainty evidence). Both perinatal outcomes (RR 0.81, 95% CI 0.54-1.21, p = 0.691; I 2 0%; moderate-certainty evidence) and maternal composite outcomes (RR 0.65, 95% CI 0.15-2.87, p = 0.571; I 2 55.46%; low-certainty evidence) were not significantly different between the two groups., Conclusions: Single-balloon catheter is at least comparable to double-balloon catheter in terms of vaginal birth rate and maternal and perinatal safety outcomes., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Excess inflammation and oxidative stress are common themes in many pathologies of pregnancy including preeclampsia and more recently severe COVID-19. The risk of preeclampsia increases following maternal infection with COVID-19, potentially relating to significant overlap in pathophysiology with endothelial, vascular and immunological dysfunction common to both. Identifying a therapy which addresses these injurious processes and stabilises the endothelial and vascular maternal system would help address the significant global burden of maternal and neonatal morbidity and mortality they cause. Sulforaphane is a naturally occurring phytonutrient found most densely within cruciferous vegetables. It has anti-inflammatory, antioxidant and immune modulating properties via upregulation of phase-II detoxification enzymes. This review will cover the common pathways shared by COVID-19 and preeclampsia and offer a potential therapeutic target via nuclear factor erythroid 2-related factor upregulation in the form of sulforaphane., Competing Interests: Declaration of competing interest All authors disclose no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since its discovery in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to be responsible for at least 769.3 million infections and over 6.95 million deaths. Despite significant global vaccination efforts, there are limited therapies that are considered safe and effective for use in the management of COVID-19 during pregnancy despite the common knowledge that pregnant patients have a much higher risk of adverse outcomes. A bioactive compound found in broccoli sprout-sulforaphane-is a potent inducer of phase-II detoxification enzymes promoting a series of potentially beneficial effects notably as an antioxidant, anti-inflammatory, and anti-viral. A pilot, double-blinded, placebo-controlled randomised trial is to be conducted in Melbourne, Australia, across both public and private hospital sectors. We will assess a commercially available broccoli sprout extract in pregnant women between 20 +0 and 36 +0 weeks gestation with SARS-CoV-2 infection to investigate (i) the duration of COVID-19 associated symptoms, (ii) maternal and neonatal outcomes, and (iii) biomarkers of infection and inflammation. We plan to enrol 60 outpatient women with COVID-19 irrespective of vaccination status diagnosed by PCR swab or RAT (rapid antigen test) within five days and randomised to 14 days of oral broccoli sprout extract (42 mg of sulforaphane daily) or identical microcrystalline cellulose placebo. The primary outcome of this pilot trial will be to assess the feasibility of conducting a larger trial investigating the duration (days) of COVID-19-associated symptoms using a broccoli sprout supplement for COVID-19-affected pregnancies. Pregnant patients remain an at-risk group for severe disease following infection with SARS-CoV-2 and currently unclear consequences for the offspring. Therefore, this study will assess feasibility of using a broccoli sprout supplement, whilst providing important safety data for the use of sulforaphane in pregnancy.