Modifiable and Non-Modifiable Risk Factors for Premature Coronary Heart Disease (PCHD): Systematic Review and Meta-Analysis.

AIM: We aimed to compare the prevalence of modifiable and non-modifiable coronary heart disease (CHD) risk factors among those with premature CHD and healthy individuals. METHODS: PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol is registered in PROSPERO CRD42020173216). The quality of studies was assessed using the National Heart, Lung and Blood Institute tool for cross-sectional, cohort and case-control studies. Meta-analyses were performed using Review Manager 5.3. Effect sizes for categorical and continuous variables, odds ratio (OR) and mean differences (MD)/standardised mean differences (SMD) with 95% confidence intervals (CI) were reported. RESULTS: A total of n=208 primary studies were included in this review. Individuals presenting with premature CHD (PCHD, age ≤65 years) had higher mean body mass index (MD 0.54 kg/m2, 95% CI 0.24, 0.83), total cholesterol (SMD 0.27, 95% CI 0.17, 0.38), triglycerides (SMD 0.50, 95% CI 0.41, 0.60) and lower high-density lipoprotein cholesterol (SMD 0.79, 95% CI: -0.91, -0.68) compared with healthy individuals. Individuals presenting with PCHD were more likely to be smokers (OR 2.88, 95% CI 2.51, 3.31), consumed excessive alcohol (OR 1.40, 95% CI 1.05, 1.86), had higher mean lipoprotein (a) levels (SMD 0.41, 95% CI 0.28, 0.54), and had a positive family history of CHD (OR 3.65, 95% CI 2.87, 4.66) compared with healthy individuals. Also, they were more likely to be obese (OR 1.59, 95% CI 1.32, 1.91), and to have had dyslipidaemia (OR 2.74, 95% CI 2.18, 3.45), hypertension (OR 2.80, 95% CI 2.28, 3.45), and type 2 diabetes mellitus (OR 2.93, 95% CI 2.50, 3.45) compared with healthy individuals. CONCLUSION: This meta-analysis confirms current knowledge of risk factors for PCHD, and identifying these early may reduce CHD in young adults.

Anxiety and Depression in Early Gestation and the Association with Subsequent Gestational Diabetes Mellitus in a Disadvantaged Population.

OBJECTIVES: Evaluate the association between poor mental health and risk of developing gestational diabetes mellitus (GDM) in a cohort of women from a socioeconomically disadvantaged community. METHODS: A total of 1363 nulliparous women with singleton pregnancies recruited to the Screening Tests to Predict Poor Outcomes of Pregnancy study in Adelaide, Australia. Women were assessed for mental health in the first trimester, including likelihood of depression, high functioning anxiety, perceived stress and risk of developing a mental health disorder. GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Socioeconomic status was measured using the New Zealand Socioeconomic Index (NZSEI). RESULTS: Complete mental health data was available for 1281 participants. There was no statistically significant difference in SEI, depression, risk of mental health issues, high functioning anxiety and perceived stress between women who developed GDM and those who did not. There was no difference in history of depression nor risk of developing a high mental health disorder in first trimester after adjusting for SEI, BMI in first trimester, smoking status in first trimester and maternal age between women with a GDM pregnancy and those who did not. CONCLUSIONS FOR PRACTICE: There was no difference in markers of poor mental health in early pregnancy between women who subsequently did or did not develop GDM. Cohort participants were socioeconomically disadvantaged, potentially contributing to the lack of apparent differences in depression observed between groups. Socioeconomically disadvantaged women should be targeted in pre-conception planning to reduce risk of GDM.

Risk Factors for Early-Onset Versus Late-Onset Coronary Heart Disease (CHD): Systematic Review and Meta-Analysis.

AIM: We aimed to systematically compare literature on prevalence of modifiable and non-modifiable risk factors for early compared to late-onset coronary heart disease (CHD). METHODS: PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol registered in PROSPERO CRD42020173216). Study quality was assessed using the National Heart, Lung and Blood Institute tool for observational and case-control studies. Review Manager 5.3 was used for meta-analysis. Effect sizes were expressed as odds ratio (OR) and mean differences (MD)/standardised MD (SMD) with 95% confidence intervals (CI) for categorical and continuous variables. RESULTS: Individuals presenting with early-onset CHD (age <65 years) compared to late-onset CHD had higher mean body mass index (MD 1.07 kg/m2; 95% CI 0.31-1.83), total cholesterol (SMD 0.43; 95% CI 0.23-0.62), low-density lipoprotein (SMD 0.26; 95% CI 0.15-0.36) and triglycerides (SMD 0.50; 95% CI 0.22-0.68) with lower high-density lipoprotein-cholesterol (SMD 0.26; 95% CI -0.42--0.11). They were more likely to be smokers (OR 1.76, 95% CI 1.39-2.22) and have a positive family history of CHD (OR 2.08, 95% CI 1.74-2.48). They had lower mean systolic blood pressure (MD 4.07 mmHg; 95% CI -7.36--0.78) and were less likely to have hypertension (OR 0.47, 95% CI 0.39-0.57), diabetes mellitus (OR 0.56, 95% CI 0.51-0.61) or stroke (OR 0.31, 95% CI 0.24-0.42). CONCLUSION: A focus on weight management and smoking cessation and aggressive management of dyslipidaemia in young adults may reduce the risk of early-onset CHD.

Maternal metabolic factors and the association with gestational diabetes: A systematic review and meta-analysis.

Gestational diabetes (GDM) is associated with several adverse outcomes for the mother and child. Higher levels of individual lipids are associated with risk of GDM and metabolic syndrome (MetS), a clustering of risk factors also increases risk for GDM. Metabolic factors can be modified by diet and lifestyle. This review comprehensively evaluates the association between MetS and its components, measured in early pregnancy, and risk for GDM. Databases (Cumulative Index to Nursing and Allied Health Literature, PubMed, Embase, and Cochrane Library) were searched from inception to 5 May 2021. Eligible studies included ≥1 metabolic factor (waist circumference, blood pressure, fasting plasma glucose (FPG), triglycerides, and high-density lipoprotein cholesterol), measured at <16 weeks' gestation. At least two authors independently screened potentially eligible studies. Heterogeneity was quantified using I2 . Data were pooled by random-effects models and expressed as odds ratio and 95% confidence intervals (CIs). Of 7213 articles identified, 40 unique articles were included in meta-analysis. In analyses adjusting for maternal age and body mass index, GDM was increased with increasing FPG (odds ratios [OR] 1.92; 95% CI 1.39-2.64, k = 7 studies) or having MetS (OR 2.52; 1.65, 3.84, k = 3). Women with overweight (OR 2.17; 95% CI 1.89, 2.50, k = 12) or obesity (OR 4.34; 95% CI 2.79-6.74, k = 9) also were at increased risk for GDM. Early pregnancy assessment of glucose or the MetS, offers a potential opportunity to detect and treat individual risk factors as an approach towards GDM prevention; weight loss for pregnant women with overweight or obesity is not recommended. Systematic review registration: PROSPERO CRD42020199225.

Cardiovascular risk factors in women with previous gestational diabetes mellitus: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to synthesize evidence on conventional cardiovascular disease (CVD) risk factors among women with previous Gestational Diabetes Mellitus (GDM). The review protocol is registered with PROSPERO (CRD42019118149). PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. Studies reporting on CVD risk factors in women with previous GDM compared to women without previous GDM were selected. A total of 139 studies were eligible, of which 93 were included in the meta-analysis. Women with previous GDM have significantly higher systolic blood pressure (2.47 mmHg 95% CI 1.74 to 3.40, n = 48, 50,118 participants) diastolic blood pressure (1.89 mmHg 95% CI 1.32 to 2.46, n = 48, 49,495 participants), BMI (1.54 kg/m2 95% CI 1.32 to 2.46, n = 78, 255,308 participants), total cholesterol (0.26 SMD 95% CI 0.15 to 0.37, n = 48, 38,561 participants), LDL cholesterol (0.19 SMD 95% CI 0.08 to 0.30, n = 44, 16,980 participants), triglycerides (0.56 SMD 95% CI 0.42 to 0.70, n = 46, 13,175 participants), glucose (0.69 SMD 95% CI 0.56 to 0.81, n = 55, 127,900 participants), insulin (0.41 SMD 95% CI 0.23 to 0.59, n = 32, 8881 participants) and significantly lower HDL cholesterol (-0.28 SMD 95% CI -0.39 to -0.16, n = 56, 35,882 participants), compared to women without previous GDM. The increased blood pressure, total cholesterol, triglycerides and glucose are seen as early as <1 year post-partum.Women with previous GDM have a higher risk of CVD based on significant increases in conventional risk factors. Some risk factors are seen as early as <1 year post-partum. Women with GDM may benefit from early screening to identify modifiable CVD risk factors.

Maternal folate, one-carbon metabolism and pregnancy outcomes.

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 <800 µg daily FA at 15-week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 µg (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L-1 vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre- and early-pregnancy dietary factors, are independent risk factors for pregnancy complications.

The metabolic syndrome in pregnancy and its association with child telomere length.

AIMS/HYPOTHESIS: The aim of this study was to determine whether presence of the metabolic syndrome in pregnancy associates with child telomere length or child anthropometry (weight, BMI) and BP, measured at 10 years of age. METHODS: The Screening for Pregnancy Endpoints study (SCOPE) was a multicentre, international prospective cohort of nulliparous pregnant women recruited from Australia, New Zealand, Ireland and the UK (N = 5628). The current analysis is a 10 year follow-up of SCOPE pregnant women and their children, from the Australian cohort. Clinical data collected at 14-16 weeks' gestation during the SCOPE study were used to diagnose the metabolic syndrome using IDF criteria. Telomere length, a biomarker of ageing, was assessed by quantitative PCR from children's saliva collected at 10 years of age. RESULTS: In women who completed follow-up (n = 255), 20% had the metabolic syndrome in pregnancy. After adjusting for a range of confounders, children of mothers who had the metabolic syndrome in pregnancy had 14% shorter telomeres than children of mothers without the metabolic syndrome in pregnancy (mean difference -0.36 [95% CI -0.74, 0.01]). Height- and weight-for-age, and BMI z scores were similar in children of mothers who did and did not have the metabolic syndrome during pregnancy. CONCLUSIONS/INTERPRETATION: Children of mothers who had the metabolic syndrome in pregnancy have shorter telomeres, a biomarker of accelerated ageing. These findings warrant further studies in larger cohorts of children, as well as investigations into whether telomere length measured in cord blood associates with telomere length in childhood.

The deleterious effects of cannabis during pregnancy on neonatal outcomes.

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.

Cardiovascular Risk Factors in Offspring of Preeclamptic Pregnancies-Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate evidence for increased cardiovascular disease (CVD) risk factors in children exposed to preeclampsia in utero. STUDY DESIGN: PubMed, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and EMBASE electronic databases were searched with an end of search date of June 4, 2018. Prospective and retrospective studies that compared CVD risk factors in those exposed to preeclampsia in utero with controls were eligible. Information was extracted on established CVD risk factors, including blood pressure, lipid profile, blood glucose, fasting insulin, body mass index, and endothelial/microvascular function. RESULTS: Thirty-six studies provided cumulated data on 53 029 individuals. In utero exposure to preeclampsia was associated with 5.17 mm Hg (95% CI 1.60-8.73) greater mean systolic, 4.06 mm Hg (95% CI 0.67-7.44) greater mean diastolic blood pressure, and 0.36 kg/m2 (95% CI 0.04-0.68) greater mean body mass index during childhood or young adulthood. No significant association was seen between exposure to preeclampsia in utero and other CVD risk factors. CONCLUSIONS: Offspring of preeclamptic pregnancies demonstrate risk factors for CVD during childhood and young adult life. Early blood pressure screening of children born after preeclamptic pregnancies may identify those that require interventions or preventive strategies to reduce later life CVD risk.

The INSR rs2059806 single nucleotide polymorphism, a genetic risk factor for vascular and metabolic disease, associates with pre-eclampsia.

Pre-eclampsia is a risk factor for later life vascular and metabolic diseases. This study postulates that this reflects a common genetic cause, and investigates whether the INSR rs2059806 single nucleotide polymorphism (SNP) (a risk factor for essential hypertension, type 2 diabetes and metabolic syndrome) is also associated with pre-eclampsia. The association of INSR rs2059806 with pre-eclampsia was tested in two cohorts - a Caucasian case control group (123 pre-eclamptic mother-father-baby trios and 1185 mother-father-baby trios from uncomplicated pregnancies) and an independent cohort of Sinhalese women (175 women with pre-eclampsia and 171 women with uncomplicated pregnancies). In the Caucasian cohort, the prevalence of the INSR rs2059806 AA genotype was greater among pre-eclamptic women compared with the uncomplicated pregnancies (12.7% versus 4.7%, OR[95%CI] = 3.1[1.6-5.8], P = 0.0003). In the Sinhalese cohort, maternal INSR rs2059806 AA genotype was greater among pre-eclamptic women who delivered small for gestational age infants compared with the uncomplicated pregnancies (10.8% versus 4.2%, OR[95%CI] = 2.8[1.0-7.4], P = 0.03). Thus, it was found that the INSR rs2059806 SNP is also associated with pre-eclampsia phenotypes in two independent cohorts suggesting that genetic susceptibility may be implicated in the link between pre-eclampsia and subsequent vascular and metabolic diseases.

Insulin family polymorphisms in pregnancies complicated by small for gestational age infants.

Being born small for gestational age (SGA) increases the risk for adverse perinatal outcomes and later life vascular and metabolic disorders. The insulin family plays a vital role in intrauterine growth. We investigated the association of functional SNPs in insulin (INS), insulin receptor (INSR) and insulin receptor substrate 2 (IRS2) with small for gestational age (SGA) pregnancies, uterine and umbilical artery Doppler and plasma insulin level. We conducted a nested case-control study of 1401 nulliparous Caucasian women, their partners and babies (216 SGA and 1185 uncomplicated). SGA was defined as a birthweight less than the 10th customized birthweight percentile adjusted for maternal height, weight, parity, ethnicity, gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 ± 1 week gestation. The SNPs in the parent infant trios were genotyped using Sequenom MassARRAY. Plasma insulin was measured by double antibody RIA in 188 healthy non-pregnant adults to assess correlations between SNP genotypes and circulating insulin. Paternal [odds ratio (OR) (95% CI) = 2.2 (1.3-3.9), P = 0.005] and infant [OR (95% CI) = 3.3 (1.7-6.2), P = 0.0001] INSR rs2059806 AA genotype was associated with SGA. Infant INSR rs2059806 A allele was associated with abnormal umbilical artery Doppler [OR (95% CI) = 1.3(1.0-1.7), P = 0.04]. INSR rs2059806 AA homozygous individuals had lower plasma insulin compared with heterozygotes (P = 0.03) and GG homozygotes (P = 0.03). The INSR rs2059806 SNP previously associated with adult vascular and metabolic diseases is also associated with SGA pregnancies. This polymorphism may associate with the risk of vascular and metabolic disorders across the life course.

The obesity-related FTO gene variant associates with the risk of recurrent miscarriage.

OBJECTIVE: To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single nucleotide polymorphism with recurrent miscarriage. DESIGN: Candidate gene association study. SETTING: Human Genetics Unit, Colombo, Sri Lanka. POPULATION: A total of 202 Sinhalese women with two or more first-trimester miscarriages and no living children (cases) and 202 age- and ethnicity-matched women with no history of miscarriage and having two or more living children (controls). METHODS: Peripheral blood was collected from the participants and DNA was extracted. Genotyping was performed at the Australian genome Research Facility using the Sequenom MassARRAY system. Genotype and allele frequencies of cases were compared with controls using chi-squared testing. MAIN OUTCOME MEASURES: The prevalence of the single nucleotide polymorphism in cases and controls. RESULTS: The mean age of the women in the recurrent miscarriage group was 31.9 ± 0.4 years and that of the control group was 32.3 ± 0.3 years. Of the women in the recurrent miscarriage group, 140 (69.3%) had experienced three or more first-trimester miscarriages. The prevalence of the AA genotype [p = 0.0002, odds ratio (95% CI) = 3.8 (1.8-8.0)] and A allele [p = 0.002, odds ratio (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 single nucleotide polymorphism were increased in women in the recurrent miscarriage group compared with the control group. CONCLUSION: The obesity-related FTO rs9939609 single nucleotide polymorphism associates with recurrent miscarriage. This finding warrants further investigation with controlling for important factors such as body mass index, diabetes and cardiovascular disease status. The single nucleotide polymorphism may be useful in predicting the risk of recurrent miscarriage.

Polymorphisms in the fibrinolytic pathway genes and the risk of recurrent spontaneous abortion.

Impaired fibrinolytic activity is implicated in the pathogenesis of recurrent spontaneous abortion (RSA). This case-control study assessed the prevalence of polymorphisms in fibrinolytic system genes in RSA. Cases comprised 202 Sinhalese women who had experienced at least two first-trimester spontaneous abortions and had no living children; controls were 202 women with no history of spontaneous abortion and two or more living children. The groups were matched for age and ethnicity. DNA was genotyped using the Sequenom MassARRAY system. The PLAUR rs4251923 A (OR 95% CI 2.3 [1.3 to 4.0]), SERBP2 rs6098 A (OR 95% CI 1.4 [1.1 to 1.9]) and SERBP2 rs6103 C alleles (OR 95% CI 1.4 [1.1 to 1.9]) were increased in the RSA group compared with controls. The prevalence of PLAUR rs4251923/ SERBP2 rs6098/ SERBP2 rs6103 GG/AA/CC (OR 95% CI 2.4 [1.2 to 4.9], GA/GA/GC(OR 95% CI 3.9 [1.3 to 11.2]), GA/AA/CC (OR 95% CI 2.9 [1.0 to 8.6] and GA/GG/GG (OR 95% CI 21.3 [1.1 to 410.3]) genotypes were also increased in cases. Polymorphisms in the fibrinolytic system genes are associated with RSA in Sinhalese women. These likely impair implantation.

Vaccine effectiveness and impact of meningococcal vaccines against gonococcal infections: A systematic review and meta-analysis.

OBJECTIVES: To systematically review and synthesis the evidence of vaccine effectiveness (VE) and impact (VI) of meningococcal vaccines in preventing gonorrhoea. METHODS: We systematically evaluated studies. Literature searches were conducted in PubMed, Embase, Cochrane Library, CINAHL, Google Scholar, clinical trial registries, and major health and immunisation conferences. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled VE. RESULTS: Twelve studies met the criteria for inclusion. VE of meningococcal B (MenB) outer membrane vesicle (OMV) vaccines was evaluated in nine studies, with one study evaluating a non-OMV vaccine, MenB-FHbp. The majority of studies targeted individuals aged 15-30 years. Adjusted VE for OMV vaccines against gonorrhoea ranged from 22% to 46%. MenB-FHbp did not show protection against gonorrhoea. The pooled VE estimates of OMV vaccines against any gonorrhoea infection following the full vaccine series were 33-34%. VI was assessed for 4CMenB in Canada and Australia, for VA-MENGOC-BC in Cuba; and for MenBvac in Norway. VI ranged from a 30% to 59% reduction in gonorrhoea incidence. CONCLUSIONS: 4CMenB and other MenB-OMV vaccines show moderate effectiveness against gonorrhoea. Further research is required to explore the factors associated with vaccine protection, informing more effective vaccination strategies for the management of gonococcal infections.

Influence of Socioeconomic Status on the Association Between Pregnancy Complications and Premature Coronary Artery Disease: Linking Three Cohorts.

Background: We hypothesized that there is an influence of socioeconomic status (SES) on association between pregnancy complications and premature coronary artery disease (PCAD) risk. Materials and Methods: This project involved a data linkage approach merging three databases of South Australian cohorts using retrospective, age-matched case-control study design. Cases (n = 721), that is, women aged <60 years from Coronary Angiogram Database of South Australia (CADOSA) were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain prior pregnancy outcomes and SES. Controls (n = 194) were selected from North West Adelaide Health Study (NWAHS), comprising women who were healthy or had health conditions unrelated to CAD, age matched to CADOSA (±5 years), and linked to SAPSC to determine prior pregnancy outcomes and SES. This project performed comparative analysis of SES using socioeconomic indexes for areas-index of relative socioeconomic advantage and disadvantage (SEIFA-IRSAD) scores across three databases. Results: Findings revealed that SEIFA-IRSAD scores at the time of pregnancy (p-value = 0.005) and increase in SEIFA-IRSAD scores over time (p-value = 0.040) were significantly associated with PCAD. In addition, when models were adjusted for SEIFA-IRSAD scores at the time of pregnancy and age, risk factors including placenta-mediated pregnancy complications such as preterm birth (odds ratio [OR] = 4.77, 95% confidence interval [CI]: 1.74-13.03) and history of a miscarriage (OR = 2.14, 95% CI: 1.02-4.49), and cardiovascular disease (CVD) risk factors including smoking (OR = 8.60, 95% CI: 3.25-22.75) were significantly associated with PCAD. When the model was adjusted for change in SEIFA-IRSAD scores (from CADOSA/NWAHS to SAPSC) and age, pregnancy-mediated pregnancy complications including preterm birth (OR = 4.40, 95% CI: 1.61-12.05) and history of a miscarriage (OR = 2.09, 95% CI: 1.00-4.35), and CVD risk factor smoking (OR = 8.75, 95% CI: 3.32-23.07) were significantly associated with PCAD. Conclusion: SES at the time of pregnancy and change in SES were not associated with PCAD risk.

A systematic review and meta-analysis of the diagnosis and surgical management of carcinoid heart disease.

Introduction: Carcinoid heart disease (CHD), a complication of carcinoid syndrome (CS), is a rare condition that can lead to right sided valvular heart disease and has been traditionally associated with a poor prognosis. We conducted a systematic review and meta-analysis to explore the accuracy of biomarkers and echocardiography in diagnosing CHD amongst patients who are already known to have neuroendocrine tumours and to assess whether surgical management of CHD leads to a reduction in mortality. Methods: A systematic literature search of MEDLINE, EMBASE, EBM Reviews, Google Scholar, ClinicalTrials.gov was conducted. All studies on patients with carcinoid heart disease (CHD) reporting on biomarkers, echocardiographic and surgical outcomes were included. The National Heart, Lung, and Blood Institute quality assessment tool was used to assess the methodological study quality. Data analysis was performed using Stata Statistical Software and R Studio, and individual meta-analyses were performed for biomarkers, echocardiographic findings, and surgical outcomes. Results: A total of 36 articles were included in the systematic review analysis. N terminal pro-brain natriuretic peptide (NTproBNP) and 5-hydroxyindole acetate (5-HIAA) levels were higher in patients with CHD compared with those without CHD. 32% of CS patients had echocardiographic evidence of cardiac involvement, of which 79% involved tricuspid valve abnormalities. Moderate-severe tricuspid regurgitation was the most common echocardiographic abnormality (70% of patients). However, these analyses had substantial heterogeneity due to the high variability of cardiac involvement across studies. Pooled surgical mortality for CHD was 11% at 1 month, 31% at 12 months and 56% at 24 months. When assessing surgical outcomes longitudinally, the one-month surgical results showed a trend towards more recent surgeries having lower mortality rates than those reported in earlier years, however this was not statistically significant. Discussion: There is not enough data in current literature to determine a clear cut-off value of NTproBNP and 5-HIAA to help diagnose or determine CHD severity. Surgical management of CHD is yet to show significant mortality benefit, and there are no consistent comparisons to medical treatment in current literature.

Comprehensive observational study evaluating the enduring effectiveness of 4CMenB, the meningococcal B vaccine against gonococcal infections in the Northern Territory and South Australia, Australia: study protocol.

INTRODUCTION: The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections. METHODS AND ANALYSES: This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison. ETHICS AND DISSEMINATION: The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.

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.

Asymmetric dimethylarginine and gestational diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: Emerging evidence demonstrates that asymmetric dimethylarginine (ADMA) levels are elevated in patients with or at risk of cardiovascular disease (CVD). Since women with gestational diabetes mellitus (GDM) are at high risk of future CVD, we conducted a systematic review and meta-analysis to compare ADMA concentrations between women with and without GDM during pregnancy and postpartum. METHODS: PubMed, Google Scholar, EMBASE, and CINAHL databases were searched. The review protocol is registered in PROSPERO (CRD42021276796). Study selection, data extraction, and data analyses were performed in accordance with PRISMA guidelines. Random-effects model was used to quantify ADMA levels in the study groups. RESULTS: Eleven studies provided data on 1148 women. Mean plasma ADMA concentration was 0.04 µmol/L (95% confidence interval (CI) -0.06-0.15) higher in pregnant women with GDM than those without GDM, but no significant difference was observed. In contrast, our meta-analysis demonstrated a significant increase in postpartum mean ADMA concentration (Mean Difference (MD) 0.11 µmol/L; 95% CI 0.05-0.16) among women with previous GDM compared to women without previous GDM. CONCLUSION: Elevated ADMA levels in GDM may be a CVD risk factor, suggesting that ADMA may be a potential biomarker for early CVD risk prediction in women with GDM.

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.