Showing papers by "Mark Walker published in 2013"

Identification of heart rate–associated loci and their effects on cardiac conduction and rhythm disorders

Abstract: Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Expanding the fluorine chemistry of living systems using engineered polyketide synthase pathways.

Abstract: Organofluorines represent a rapidly expanding proportion of molecules that are used in pharmaceuticals, diagnostics, agrochemicals, and materials. Despite the prevalence of fluorine in synthetic compounds, the known biological scope is limited to a single pathway that produces fluoroacetate. Here, we demonstrate that this pathway can be exploited as a source of fluorinated building blocks for introduction of fluorine into natural-product scaffolds. Specifically, we have constructed pathways involving two polyketide synthase systems, and we show that fluoroacetate can be used to incorporate fluorine into the polyketide backbone in vitro. We further show that fluorine can be inserted site-selectively and introduced into polyketide products in vivo. These results highlight the prospects for the production of complex fluorinated natural products using synthetic biology.

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes

Abstract: Aims/hypothesis Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. Methods The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m 2 and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p<0.05) with case–control status, from four selected annotation categories or from

Importance of Weight Loss Maintenance and Risk Prediction in the Prevention of Type 2 Diabetes: Analysis of European Diabetes Prevention Study RCT

Abstract: Background Prevalence of type 2 diabetes (T2D) is increasing worldwide. T2D prevention by lifestyle intervention is effective. Pragmatic scalable interventions are needed, with evidence to efficiently target and monitor such interventions. We report pooled analyses of data from three European trial cohorts: to analyse T2D incidence, sustained weight loss and utility of risk predictors. Methods We analysed data on 749 adults with impaired glucose tolerance (278 men and 471 women, mean age 56 years, mean BMI 31 kgm−2) recruited between 1993 and 2003, and randomised to intensive lifestyle intervention (I) or lifestyle advice control (C). The intervention aimed to increase physical activity, modify diet, and promote weight loss≥5%. Using Cox-regression survival analysis, we assessed T2D incidence and the impact on T2D incidence of sustained weight loss, and of baseline cut-point values of FINDRISC score, fasting plasma glucose (FPG), and HbA1c. Results Mean follow-up duration was 3.1 years. T2D was diagnosed in 139 participants (I = 45/379, C = 94/370). Cumulative T2D incidence was 57% lower in the intervention compared with the control group (HR 0.42 (95% CI 0.29 to 0.60) P<0.001). Participants with ≥5% weight loss at one year had 65% lower T2D incidence (HR 0.35 (95% CI 0.22 to 0.56) P<0.001); maintaining ≥5% weight loss for two and three years further reduced T2D incidence. Recommended cut-points to identify those at high risk for T2D would have identified different proportions of European Diabetes Prevention Study (EDIPS) participants with similar hazard-ratios for intervention effect. Conclusions Pooled analysis of EDIPS trial data reinforces evidence for T2D prevention by lifestyle intervention. Analysis showed the preventive effect of ≥5% weight loss, especially if maintained long term, which has utility for intervention monitoring. Analysis of proposed cut-points demonstrates difficulties in balancing risk and benefit, to efficiently target interventions and suggests evidence is needed to define clinical policy. Trial registrations The Finnish Diabetes Prevention study, Helsinki, Finland: ClinicalTrials.gov; NCT00518167 The SLIM diabetes prevention study, Maastricht, The Netherlands: Clinical Trials.gov; NCT00381186 The EDIPS-Newcastle diabetes prevention study, Newcastle upon Tyne, UK: International Standard Randomised Controlled Trial Number; ISRCTN15670600.

Mendelian Randomization Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

Abstract: Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: -0.03 SD; 95% CI -0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes.

Examining Caesarean Section Rates in Canada Using the Robson Classification System

Abstract: Objective To determine the groups within the obstetric population contributing most substantially to the Caesarean section rate in five Canadian provinces. Methods Hospital births from five participating provinces were grouped into Robson's 10 mutually exclusive and totally inclusive classification categories. The relative contribution of each group to the overall CS rate, relative size of group, and CS rate were calculated for British Columbia, Alberta, Ontario, Nova Scotia, and Newfoundland and Labrador for the four-year period from 2007-2008 to 2010-2011. Results In all five provinces (accounting for approximately 64% of births in Canada), and for all years examined, the group making the largest relative contribution to the CS rate was women with at least one previous CS and a term, singleton, cephalic-presenting pregnancy (Robson Group 5). The CS rate for this group ranged from 76.1% in Alberta to 89.9% in Newfoundland and Labrador in 2010 to 2011, accounting for 11.3% of all deliveries. The rate of CS for Group 5 decreased slightly over the four years, except in Ontario The next largest contributing group was nulliparous women with a term, singleton, cephalic-presenting pregnancy Those with induced labour or Caesarean section before labour (Robson Group 2) had CS rates ranging from 34.4% in Nova Scotia to 44.6% in British Columbia (accounting for 13.1% of all deliveries), and those with spontaneous onset of labour (Robson Group 1) had CS rates of 14.5% to 20.3% in 2010 to 2011 (accounting for 23.6% of all deliveries). Conclusion All hospitals and health authorities can use this standardized classification system as part of a quality improvement initiative to monitor Caesarean section rates This classification system identifies relevant areas for interventions and resources to reduce rates of Caesarean section.

Breastfeeding in women with diabetes: lower rates despite greater rewards. A population-based study

Abstract: Aims To explore intention to breastfeed and breastfeeding rates in hospital and on discharge across women with pre-gestational or gestational diabetes mellitus, or no diabetes. Methods A retrospective cohort analysis was conducted using data from four Ontario hospitals. Women who delivered a viable infant between 1 April 2008 and 31 March 2010 were included in the study. Unadjusted and adjusted odds ratios were calculated for each outcome measure and were used to compare the breastfeeding rates among women with and without diabetes. Results After controlling for potential confounders, women with insulin-treated diabetes were less likely to intend to breastfeed, when compared with women without diabetes (adjusted odds ratio 0.49, 95% CI 0.27–0.89). In hospital, women with insulin-treated diabetes were least likely to breastfeed (odds ratio 0.42, 95% CI 0.26–0.67), followed by women with non-insulin-treated diabetes (odds ratio 0.50, 95% CI 0.26–0.96) and women with gestational diabetes (odds ratio 0.77, 95% CI 0.68–0.87) when compared with women without diabetes. On discharge, women with insulin-treated diabetes were least likely to breastfeed (odds ratio 0.38, 95% CI 0.24–0.60), followed by women with gestational diabetes (odds ratio 0.75, 95% CI 0.66–0.85); rates of breastfeeding among women with non-insulin-treated diabetes were comparable on discharge with those of women without diabetes. Women seeking care from an antenatal provider other than a physician were 2–3 times more likely to breastfeed in hospital and on discharge. Conclusions Women with insulin-treated diabetes had the poorest outcomes with respect to breastfeeding rates. Gestational and non-insulin-treated diabetes were associated with lower rates of breastfeeding in hospital, while gestational diabetes was additionally associated with lower breastfeeding rates on discharge.

Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes

Abstract: Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity–related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites—glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)—and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits.

The impact of increasing obesity class on obstetrical outcomes.

Abstract: Objective Nationally, rates of obesity continue to rise, resulting in increased health concerns for women of reproductive age Identifying the impact of maternal obesity on obstetrical outcomes is important to enhance patient care. Methods We conducted a retrospective cohort study of 6674 women who delivered a singleton infant at ≥ 20 weeks' gestation between December 1, 2007, and March 31, 2010, at The Ottawa Hospital. Maternal pre-pregnancy BMI was used to classify women into normal, overweight, and obese (class I/II/III) categories according to WHO classifications. Obstetrical outcomes among obese women were compared with those of women with normal BMI Multivariable regression models were used to determine adjusted odds ratios and 95% confidence intervals. Results Compared with women with normal BMI, obese women had significantly higher rates of preeclampsia, gestational hypertension, and gestational diabetes, and these rates increased with increasing BMI (trend-test P Conclusion Increasing BMI is associated with increasing rates of preeclampsia, gestational hypertension, and gestational diabetes There is a significant increase in rates of induction of labour with increasing obesity class, and a significantly increased Caesarean section rate with higher BMI Obstetrical care providers should counsel obese patients about the risks they face and the importance of weight loss before pregnancy.

Large Pre- and Postexercise Rapid-Acting Insulin Reductions Preserve Glycemia and Prevent Early- but Not Late-Onset Hypoglycemia in Patients With Type 1 Diabetes

Abstract: OBJECTIVE To examine the acute and 24-h glycemic responses to reductions in postexercise rapid-acting insulin dose in type 1 diabetic patients. RESEARCH DESIGN AND METHODS After preliminary testing, 11 male patients (24 ± 2 years, HbA 1c 7.7 ± 0.3%; 61 ± 3.4 mmol/mol) attended the laboratory on three mornings. Patients consumed a standardized breakfast (1 g carbohydrate ⋅ kg −1 BM; 380 ± 10 kcal) and self-administered a 25% rapid-acting insulin dose 60 min prior to performing 45 min of treadmill running at 72.5 ± 0.9% VO 2peak . At 60 min postexercise, patients ingested a meal (1 g carbohydrate ⋅ kg −1 BM; 660 ± 21 kcal) and administered a Full, 75%, or 50% rapid-acting insulin dose. Blood glucose concentrations were measured for 3 h postmeal. Interstitial glucose was recorded for 20 h after leaving the laboratory using a continuous glucose monitoring system. RESULTS All glycemic responses were similar across conditions up to 60 min postexercise. After the postexercise meal, blood glucose was preserved under 50%, but declined under Full and 75%. Thence at 3 h, blood glucose was highest under 50% (50% [10.4 ± 1.2] vs. Full [6.2 ± 0.7] and 75% [7.6 ± 1.2 mmol ⋅ L −1 ], P = 0.029); throughout this period, all patients were protected against hypoglycemia under 50% (blood glucose ≤3.9; Full, n = 5; 75%, n = 2; 50%, n = 0). Fifty percent continued to protect patients against hypoglycemia for a further 4 h under free-living conditions. However, late-evening and nocturnal glycemia were similar; as a consequence, late-onset hypoglycemia was experienced under all conditions. CONCLUSIONS A 25% pre-exercise and 50% postexercise rapid-acting insulin dose preserves glycemia and protects patients against early-onset hypoglycemia (≤8 h). However, this strategy does not protect against late-onset postexercise hypoglycemia.

Chronic perinatal pain as a risk factor for postpartum depression symptoms in Canadian women.

Abstract: OBJECTIVE: To examine whether problematic perinatal pain is associated with postpartum depression (PPD) symptoms in a large nationally representative sample of Canadian mothers. METHODS: We conducted a secondary data analysis using the 2006 Canadian Maternity Experiences Survey data (n=5,614). The main exposures of interest were the presence of problematic perinatal pain at three months postpartum, the duration of problematic perinatal pain, and the number of types of perinatal pain (vagina, caesarean incision site, breasts, back, severe headaches) at the time of interview (mean=7.3 months, range 5-14 months). For each exposure, full multivariate logistic regression models as well as six submodels were fitted. RESULTS: Odds of screening positive for PPD symptoms for respondents reporting problematic perinatal pain in the first three months postpartum were 1.7 (95% CI 1.2-2.5). Compared to respondents without problematic perinatal pain, the odds of PPD symptoms for women reporting problematic perinatal pain at the time of interview was 2.4 (95% CI 1.6-3.6). A dose–response association between the number of types of perinatal pain at the time of interview and PPD symptoms was also observed. CONCLUSION: Mothers reporting persistent perinatal pain are at increased risk of developing PPD, and pain control services for these women may be needed.

Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: The Folic Acid Clinical Trial Study

Abstract: Preeclampsia (PE) is hypertension with proteinuria that develops during pregnancy and affects at least 5% of pregnancies. The Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: the Folic Acid Clinical Trial (FACT) aims to recruit 3,656 high risk women to evaluate a new prevention strategy for PE: supplementation of folic acid throughout pregnancy. Pregnant women with increased risk of developing PE presenting to a trial participating center between 80/7 and 166/7 weeks of gestation are randomized in a 1 : 1 ratio to folic acid 4.0 mg or placebo after written consent is obtained. Intent-to-treat population will be analyzed. The FACT study was funded by the Canadian Institutes of Health Research in 2009, and regulatory approval from Health Canada was obtained in 2010. A web-based randomization system and electronic data collection system provide the platform for participating centers to randomize their eligible participants and enter data in real time. To date we have twenty participating Canadian centers, of which eighteen are actively recruiting, and seven participating Australian centers, of which two are actively recruiting. Recruitment in Argentina, UK, Netherlands, Brazil, West Indies, and United States is expected to begin by the second or third quarter of 2013. This trial is registered with NCT01355159.

Breastfeeding intention and early post-partum practices among overweight and obese women in Ontario: a selective population-based cohort study.

Abstract: Objective: To explore the relationship between overweight and obesity and breastfeeding behaviors, a cohort study was conducted among 22,131 women who delivered in Ontario hospitals between April 1 2008 and March 31 2010. Methods: Data regarding maternal characteristics, maternal body mass index (BMI), infant characteristics, and breastfeeding practices were obtained through the Better Outcomes Registry & Network birth records Database. Multivariate linear regression analysis was used to determine the rates of three outcome measures - intention to breastfeed, exclusive breastfeeding in hospital, and exclusive breastfeeding upon discharge from hospital – between non-obese, overweight and obese patients. Results: While overweight mothers have similar intentions to breastfeed compared to non-overweight mothers (OR 1.03 (0.87–1.21), obese mothers were less likely to intend to breastfeed (OR 0.84 (0.70–0.99). Overweight and obese mothers were less likely to exclusively breastfeed in hospital compared to non-ov...

Measuring quality in maternal-newborn care: developing a clinical dashboard.

Abstract: Pregnancy, birth, and the early newborn period are times of high use of health care services. As well as opportunities for providing quality care, there are potential missed opportunities for health promotion, safety issues, and increased costs for the individual and the system when quality is not well defined or measured. There has been a need to identify key performance indicators (KPIs) to measure quality care within the provincial maternal-newborn system. We also wanted to provide automated audit and feedback about these KPIs to support quality improvement initiatives in a large Canadian province with approximately 140 000 births per year. We therefore worked to develop a maternal-newborn dashboard to increase awareness about selected KPIs and to inform and support hospitals and care providers about areas for quality improvement. We mapped maternal-newborn data elements to a quality domain framework, sought feedback via survey for the relevance and feasibility of change, and examined current data and the literature to assist in setting provincial benchmarks. Six clinical performance indicators of maternal-newborn quality care were identified and evidence-informed benchmarks were set. A maternal-newborn dashboard with "drill down" capacity for detailed analysis to enhance audit and feedback is now available for implementation. While audit and feedback does not guarantee individuals or institutions will make practice changes and move towards quality improvement, it is an important first step. Practice change and quality improvement will not occur without an awareness of the issues.

The Use of a Quality Indicator to Reduce Elective Repeat Caesarean Section for Low-Risk Women Before 39 Weeks’ Gestation: The Eastern Ontario Experience

Abstract: Objective Elective repeat Caesarean section (ERCS) for low-risk women at Methods All hospitals within the region providing care during labour and birth (n = 10) were asked to participate. Representatives from each hospital received information about their site-specific rates and knowledge-translation resources to assist them with the project. A benchmark rate for ERCS Results The proportion of ERCS at Conclusion A reduction in the rate of ERCS

The Use of a Quality Indicator to Reduce Elective Repeat Caesarean Section for Low-Risk Women Before 39 Weeks' Gestation: The Eastern

Abstract: Objective: Elective repeat Caesarean section (ERCS) for low-risk women at < 39 weeks’ gestation has consistently been associated with increased risks to the neonate, including respiratory morbidity, NICU admission, and lengthier hospital stays than ERCS at 39 to 40 weeks’ gestation . The objective of this quality improvement project was to reduce high rates of ERCS < 39 weeks across the Eastern Ontario region . Methods: All hospitals within the region providing care during labour and birth (n = 10) were asked to participate . Representatives from each hospital received information about their site-specific rates and knowledge-translation resources to assist them with the project . A benchmark rate for ERCS < 39 weeks was set at 30% . The rates of ERCS < 39 weeks were calculated for two different times (the 2009–2010 and 2010–2011 fiscal years) and the relative difference and 95% confidence intervals were calculated to quantify the magnitude and statistical significance of any change . Qualitative interviews were completed with key informants from each hospital . Results: The proportion of ERCS at < 39 weeks’ gestation across the region in the fiscal year 2010–2011 (n = 197/497; 39 .6%) was significantly decreased (relative difference: −21%; 95% CI −31% to −8%, P = 0 .002) from the previous fiscal year 2009–2010 (n = 229/459; 49 .9%) . A number of barriers to, and facilitators of, practice change were identified . Conclusion: A reduction in the rate of ERCS < 39 weeks among low-risk women was achieved across the region . Awareness of the issue, possession of site-specific data, and agreement about the evidence and the need for change are critical first steps to improving practice .

Exploring risk, prevention and educational approaches for the non‐diabetic offspring of patients with type 2 diabetes – a qualitative study

Abstract: Aim To understand the knowledge and perceptions of type 2 diabetes and to explore preferable educational strategies in the non-diabetic offspring of patients with the disease. Background Type 2 diabetes is an increasingly prevalent disease with significant long-term consequences. Offspring of patients with type 2 diabetes have an increased risk of developing the disease compared with the general population. Previous studies have shown that offspring have a poor perception of their own risk. Design A qualitative study was carried out using semi-structured one-to-one interviews. Analysis was completed using a structured framework approach. Methods Research was carried out during January–March 2011 in the north east of UK. Six offspring of patients diagnosed with the disease were interviewed. Results Participants balanced positive and negative aspects of their lifestyle behaviours to estimate their own risk. They had adequate knowledge of healthy lifestyle behaviours, but were uncertain about the long-term effects and seriousness of the disease and the role of inheritance. Behavioural changes at an individual level would only be motivated by an event, which would impact on their own health. Participants believed that ‘fear’-based strategies to health promotion would be most effective to encourage behaviour change. Conclusion Knowledge of individual risk and why diabetes was serious was limited and variable. The health behaviours of this at-risk group were complex. Nurses engaged in the care of at-risk individuals must take this complexity into account when developing and implementing multi-faceted strategies to improve awareness.

Are dopamine-related genotypes risk factors for excessive gestational weight gain?

Abstract: Background Excessive gestational weight gain is associated with postpartum weight retention and downstream child obesity. Dopamine plays a critical role in the regulation of energy intake and body weight. The purpose of this study was to examine the relationship between excessive gestational weight gain and dopamine pathway-related polymorphisms, namely the variable nucleotide tandem repeat in the 3′untranslated region (UTR) region of the SLC6A3 (DAT-1) dopamine transporter gene and the 30-base pair variable nucleotide tandem repeat polymorphism of the 5′UTR of the monoamine oxidase-A (MAO-A) gene.

Migration and DNA methylation: a comparison of methylation patterns in type 2 diabetes susceptibility genes between indians and europeans.

Abstract: Background: Type 2 diabetes is a global problem that is increasingly prevalent in low and middle income countries including India, and is partly attributed to increased urbanisation. Genotype clearly plays a

Occurrence and Predictors of Vacuum and Forceps Used Sequentially for Vaginal Birth

Abstract: Background Sequential use of vacuum and obstetric forceps for vaginal delivery is associated with increased risks of adverse maternal and infant outcomes. Methods We conducted a retrospective cohort study to estimate the frequency of sequential use of vacuum and forceps for planned vaginal delivery and to identify predictors, using data collected in Ontario between 2004 and 2007. Multivariate logistic regression models were used to estimate the adjusted odds ratios and 95% confidence intervals of predictors of sequential use of vacuum and forceps. Results Of 186 988 pregnant women with a singleton, vertex presentation at term and a planned vaginal birth, 1062 (0.57%) required the sequential use of vacuum and forceps for delivery. The major predictors for sequential use of vacuum and forceps were mother's primary language being other than English or French, nulliparity, a history of Caesarean section, dystocia, use of epidural or other pain relief, labour induction, labour augmentation, fetal macrosomia, and advanced gestational age. Conclusion In this population-based study we found that 0.57% of planned vaginal births were delivered with sequential use of vacuum and obstetric forceps. Abnormal labour, fetal macrosomia, language barriers, and advanced gestational age are significant predictors of requiring this sequential use.