The duration of sexual relationship and its effects on adverse pregnancy outcomes

This study aims to determine if a short duration of sexual relationship is more common among women who experience adverse pregnancy outcomes including gestational hypertension (GHT), preeclampsia, small for gestational age (SGA) pregnancies and spontaneous preterm birth (sPTB) with or without abnormal uterine artery Doppler compared to women who have uncomplicated pregnancies. 5591 nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. The risk for pregnancy complications for women who had a duration of sexual relationship of ≤3 months, 4–6 months, 7–9 months, 10–12 months was compared with women who had a duration of sexual relationship of >12 months. Uterine artery Doppler was performed at 20 ± 1 weeks’ gestation. A short duration of sexual relationship (≤3 months) was more common among women with SGA in the presence of abnormal uterine artery Doppler [9.8% vs 3.0%, aOR (95% CI) 3.4 (1.6–7.08] compared to women who had uncomplicated pregnancies. A short duration of sexual relationship (≤3 months) was also more common among women who had abnormal uterine artery Doppler compared to those with normal uterine artery Doppler [6.1% vs 3.1%, aOR (95% CI) = 2.1 (1.4–3.2)]. A short duration of sexual relationship was not associated with preeclampsia after adjusting for confounders. A short duration of sexual relationship is more common among women who deliver SGA infants with features of placental insufficiency as indicated by abnormal uterine artery Doppler.Prabha Andraweera, Claire T. Roberts, Shalem Leemaqz, Lesley McCowan, Jenny Myers, Louise C. Kenny, James Walker, Lucilla Poston, Gus Dekker on behalf of the SCOP

Nudging towards COVID-19 and influenza vaccination uptake in medically at-risk children : EPIC study protocol of randomised controlled trials in Australian paediatric outpatient clinics

Introduction: Children with chronic medical diseases are at an unacceptable risk of hospitalisation and death from influenza and SARS-CoV-2 infections. Over the past two decades, behavioural scientists have learnt how to design non-coercive ‘nudge’ interventions to encourage positive health behaviours. Our study aims to evaluate the impact of multicomponent nudge interventions on the uptake of COVID-19 and influenza vaccines in medically at-risk children. Methods and analyses: Two separate randomised controlled trials (RCTs), each with 1038 children, will enrol a total of approximately 2076 children with chronic medical conditions who are attending tertiary hospitals in South Australia, Western Australia and Victoria. Participants will be randomly assigned (1:1) to the standard care or intervention group. The nudge intervention in each RCT will consist of three text message reminders with four behavioural nudges including (1) social norm messages, (2) different messengers through links to short educational videos from a paediatrician, medically at-risk child and parent and nurse, (3) a pledge to have their child or themselves vaccinated and (4) information salience through links to the current guidelines and vaccine safety information. The primary outcome is the proportion of medically at-risk children who receive at least one dose of vaccine within 3 months of randomisation. Logistic regression analysis will be performed to determine the effect of the intervention on the probability of vaccination uptake. Ethics and dissemination: The protocol and study documents have been reviewed and approved by the Women’s and Children’s Health Network Human Research Ethics Committee (HREC/22/WCHN/2022/00082). The results will be published via peer-reviewed journals and presented at scientific meetings and public forums. Trial registration number: NCT05613751

Angiogenesis regulating gene polymorphisms in adverse pregnancy outcomes.

Introduction: Both placental vascular defects and a genetic contribution are documented in pregnancies complicated by preeclampsia, small-for-gestational-age infants (SGA) and spontaneous preterm birth (sPTB). Our primary aim was to investigate the association between polymorphisms in genes regulating placental vascular integrity including vascular endothelial growth factor (VEGFA), placenta growth factor (PGF), kinase insert domain receptor (KDR), fms-like tyrosine kinase 1 receptor (FLT1), angiopoietin 1 (ANGPT1) and thrombospondin 1 (TSP1) and these pregnancy complications in a Caucasian cohort. The secondary aims were to investigate the association between these polymorphisms and (1) preeclampsia in Sri Lankan women (2) first trimester placental gene expression (3) abnormal uterine and umbilical artery Doppler (4) environment and lifestyle interactions that modify the risk of pregnancy complications and to (5) compare term placental angiogenic gene mRNA expression in complicated pregnancy with uncomplicated pregnancy. Methods: Nulliparous pregnant women, their partners and infants (3234 trios) were recruited to a prospective multicenter cohort study (SCOPE study) in Adelaide, Australia and Auckland, New Zealand. Pregnancy outcomes were classified using international guidelines. Uterine and umbilical artery Doppler was performed at 20 weeks gestation. Mean uterine or umbilical artery resistance indices (RI) above the 90th percentile or the presence of bilateral notching of the uterine artery waveform were considered abnormal. A second Sri Lankan cohort comprised 175 nulliparous preeclamptic women and 171 matched controls. The polymorphisms in the Caucasian parent-infant trios, Sri Lankan women and first trimester placental tissue from elective pregnancy terminations (n = 74) were genotyped using the Sequenom Mass ARRAY system. Term placentae were collected from women with preeclampsia (n = 18), gestational hypertension (n = 15), normotensive SGA infants (n = 13), spontaneous preterm birth (n = 10) and uncomplicated pregnancy (n = 30). Placental mRNA expression was analysed by quantitative RT-PCR. Results: In the Caucasian cohort, maternal ANGPT1 1414T/A and paternal and infant KDR -604T/C polymorphisms were associated with preeclampsia; maternal ANGPT1 1414T/A, paternal and infant KDR -604T/C, paternal and infant TSP1 2210A/G and infant VEGFA+936C/T were associated with SGA. In the Sri Lankan cohort, PGF 642C/A was associated with preeclampsia. The ANGPT1 1414T/A was associated with abnormal uterine Doppler and the VEGFA +936C/T was associated with abnormal uterine and umbilical artery Doppler and reduced first trimester placental VEGFA mRNA expression suggesting that these polymorphisms may have a role in the pathogenesis of pregnancy complications. We also found that the maternal ANGPT1 1414T/A and VEGFA -2578C/A polymorphisms interact with maternal BMI to modify the risk of sPTB and that the maternal KDR -604T/C interacts with smoking to influence the risk of preeclampsia and SGA. In all these polymorphisms, genotypes associated with pro-angiogenic phenotypes reduced the risk and genotypes associated with anti-angiogenic phenotypes increased the risk of pregnancy complications. We were also able to demonstrate that term placental expression of VEGFA, PGF, KDR and FLT1 mRNA were reduced in pregnancy complications compared to uncomplicated pregnancy. Conclusion: This project demonstrates that inherited susceptibility to altered angiogenic gene expression in the placenta contributes to the risk of pregnancy complications.Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 201

A rapid global review of strategies to improve influenza vaccination uptake in Australia

This study aimed to identify effective strategies for improving the uptake of influenza vaccination and to inform recommendations for influenza vaccination programs in Australia. A rapid systematic review was conducted to assimilate and synthesize peer-reviewed articles identified in PubMed. The National Health and Medical Research Council (NHMRC) Hierarchy of Evidence was used to appraise the quality of evidence. A systematic search identified 4373 articles and 52 that met the inclusion criteria were included. The evidence suggests influenza vaccination uptake may be improved by interventions that (1) increase community/patient demand and access to influenza vaccine and overcome practice-related barriers; (2) reinforce the critical role healthcare providers play in driving influenza vaccination uptake. Strategies such as standing orders, reminder and recall efforts were successful in improving influenza vaccination rates. Community pharmacies, particularly in regional/remote areas, are well positioned to improve influenza vaccine coverage. The findings of this rapid review can be utilized to improve the performance of influenza immunization programs in Australia and other countries with comparable programs; and recommend priorities for future evaluation of interventions to improve influenza vaccination uptake

Single-nucleotide polymorphisms in the KDR gene in pregnancies complicated by gestational hypertensive disorders and small-for-gestational-age infants

INTRODUCTION: Pregnancies complicated by preeclampsia and small-for-gestational-age (SGA) infants share placental vascular abnormalities and both disorders confer increased risk of later life coronary artery disease. Kinase insert domain receptor (KDR) is the main receptor for vascular endothelial growth factor A, a potent angiogenic factor which regulates the development of the placental vasculature. Two polymorphisms in KDR (-604T/C and Val297Ile) are known to be associated with coronary artery disease. We investigated the association of these polymorphisms with preeclampsia, gestational hypertension, and SGA infants. METHOD: Nulliparous pregnant women, their partners, and infants were recruited to a prospective cohort study (n ¼ 1169). Doppler ultrasound of the uterine and umbilical arteries was performed at 20 weeks of gestation. Preeclampsia, gestational hypertension, and SGA were defined according to international guidelines. DNA extracted from peripheral venous or cord blood was genotyped using the Sequenom MassARRAY system. Multivariable logistic regression was used to compare the odds for the pregnancy complications between the genotype groups adjusting for potential confounders. RESULTS: Among 937 Caucasian pregnancies, 427 (45.6%) were uncomplicated, 75 (8.0%) developed preeclampsia, 102 (10.9%) developed gestational hypertension, and 72 (7.7%) had SGA infants in the absence of maternal hypertensive disease. Paternal and neonatal KDR-604T/C was associated with preeclampsia (adjusted odds ratio [aOR] 1.6, 95% confidence interval [CI] 1.0-3.0 and aOR 2.2, 95% CI 1.0-4.4), SGA (aOR 1.9, 95% CI 1.1-3.3 and aOR 2.2, 95% CI 1.2-3.9), and SGA with abnormal Doppler (aOR 2.7, 95% CI 1.2-5.9 and aOR 3.2, 95% CI 1.2-5.9). CONCLUSION: Paternal and neonatal carriage of the KDR-604T/C polymorphism is associated with the risk of preeclampsia and SGA infants.Prabha H. Andraweera, Gustaaf A. Dekker, Steven D. Thompson and Claire T. Robert

The interaction between the maternal BMI and angiogenic gene polymorphisms associates with the risk of spontaneous preterm birth

Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case–control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4–4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7–10.9, P = 0.003). Among women with a BMI < 25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2–4.4, P = 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1–9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs. Trial Registry Name: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, small-for-gestational-age babies and spontaneous preterm birth (https://www.anzctr.org.au). Registration number: ACTRN12607000551493.Prabha H. Andraweera, Gustaaf A. Dekker, Steven D. Thompson, Robyn A. North, Lesley M.E. McCowan and Claire T. Roberts on behalf of the SCOPE Consortiu

A Systematic Review and Meta-Analysis on the Real-World Effectiveness of COVID-19 Vaccines against Infection, Symptomatic and Severe COVID-19 Disease Caused by the Omicron Variant (B.1.1.529)

Real-world data on the effectiveness of COVID-19 vaccines against the Omicron variant (B.1.1.529) is limited. This systematic review aimed to investigate the real-world effectiveness and durability of protection conferred by primary course and booster vaccines against confirmed Omicron infection, and severe outcomes. We systematically searched literature up to 1 August 2022. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled vaccine effectiveness (VE). Overall, 28 studies were included representing 11 million individuals. The pooled VE against Omicron infection was 20.4% (95%CI: 12.1–28.7%) and 23.4% (95%CI: 13.5–33.3%) against symptomatic infection with variation based on vaccine type and age groups. VE sharply declined from 28.1% (95%CI: 19.1–37.1%) at three months to 3.9% (95%CI: −24.8–32.7%) at six months. Similar trends were observed for symptomatic Omicron infection. A booster dose restored protection against Omicron infection up to 51.1% (95%CI: 43.8–58.3%) and 57.3% (95%CI: 54.0–60.5%) against symptomatic infection within three months; however, this waned to 32.8% (95%CI: 16.8–48.7%) within six months. VE against severe Omicron infection following the primary course was 63.6% (95%CI: 57.5–69.7%) at three months, decreased to 49% (95%CI: 35.7–63.4%) within six months, and increased to 86% after the first or second booster dose