Commentary on a combined approach to the problem of developing biomarkers for the prediction of spontaneous preterm labor that leads to preterm birth.

INTRODUCTION: Globally, preterm birth has replaced congenital malformation as the major cause of perinatal mortality and morbidity. The reduced rate of congenital malformation was not achieved through a single biophysical or biochemical marker at a specific gestational age, but rather through a combination of clinical, biophysical and biochemical markers at different gestational ages. Since the aetiology of spontaneous preterm birth is also multifactorial, it is unlikely that a single biomarker test, at a specific gestational age will emerge as the definitive predictive test. METHODS: The Biomarkers Group of PREBIC, comprising clinicians, basic scientists and other experts in the field, with a particular interest in preterm birth have produced this commentary with short, medium and long-term aims: i) to alert clinicians to the advances that are being made in the prediction of spontaneous preterm birth; ii) to encourage clinicians and scientists to continue their efforts in this field, and not to be disheartened or nihilistic because of a perceived lack of progress and iii) to enable development of novel interventions that can reduce the mortality and morbidity associated with preterm birth. RESULTS: Using language that we hope is clear to practising clinicians, we have identified 11 Sections in which there exists the potential, feasibility and capability of technologies for candidate biomarkers in the prediction of spontaneous preterm birth and how current limitations to this research might be circumvented. DISCUSSION: The combination of biophysical, biochemical, immunological, microbiological, fetal cell, exosomal, or cell free RNA at different gestational ages, integrated as part of a multivariable predictor model may be necessary to advance our attempts to predict sPTL and PTB. This will require systems biological data using "omics" data and artificial intelligence/machine learning to manage the data appropriately. The ultimate goal is to reduce the mortality and morbidity associated with preterm birth.

Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial.

OBJECTIVE: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. DESIGN: Multicentre randomised controlled trial. SETTING: Five hospitals in Denmark. POPULATION: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2 ) undergoing elective or emergency caesarean section. METHOD: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life. RESULTS: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. CONCLUSION: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. TWEETABLE ABSTRACT: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.

Cost-effectiveness of incisional negative pressure wound therapy compared with standard care after caesarean section in obese women: a trial-based economic evaluation.

OBJECTIVE: To evaluate the cost-effectiveness of incisional negative pressure wound therapy (iNPWT) in preventing surgical site infection in obese women after caesarean section. DESIGN: A cost-effectiveness analysis conducted alongside a clinical trial. SETTING: Five obstetric departments in Denmark. POPULATION: Women with a pregestational body mass index (BMI) ≥30 kg/m2 . METHOD: We used data from a randomised controlled trial of 876 obese women who underwent elective or emergency caesarean section and were subsequently treated with iNPWT (n = 432) or a standard dressing (n = 444). Costs were estimated using data from four Danish National Databases and analysed from a healthcare perspective with a time horizon of 3 months after birth. MAIN OUTCOME MEASURES: Cost-effectiveness based on incremental cost per surgical site infection avoided and per quality-adjusted life-year (QALY) gained. RESULTS: The total healthcare costs per woman were €5793.60 for iNPWT and €5840.89 for standard dressings. Incisional NPWT was the dominant strategy because it was both less expensive and more effective; however, no statistically significant difference was found for costs or QALYs. At a willingness-to-pay threshold of €30,000, the probability of the intervention being cost-effective was 92.8%. A subgroup analysis stratifying by BMI shows that the cost saving of the intervention was mainly driven by the benefit to women with a pre-pregnancy BMI ≥35 kg/m2 . CONCLUSION: Incisional NPWT appears to be cost saving compared with standard dressings but this finding is not statistically significant. The cost savings were primarily found in women with a pre-pregnancy BMI ≥35 kg/m2 . TWEETABLE ABSTRACT: Prophylactic incisional NPWT reduces the risk of SSI after caesarean section and is probably dominant compared with standard dressings #healtheconomics.

Development of composite outcomes for individual patient data (IPD) meta-analysis on the effects of diet and lifestyle in pregnancy: a Delphi survey.

OBJECTIVE: To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. DESIGN: Delphi survey. SETTING: The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. METHODS: A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. MAIN OUTCOME MEASURES: Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. RESULTS: Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). CONCLUSIONS: Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis.

Metabolic effects of lifestyle intervention in obese pregnant women. Results from the randomized controlled trial 'Lifestyle in Pregnancy' (LiP).

AIMS: The Lifestyle in Pregnancy intervention in obese pregnant women resulted in significantly lower gestational weight gain compared with the control group, but without improvement in rates of clinical pregnancy complications. The impact of the lifestyle intervention on metabolic measurements in the study participants is now reported. METHODS: The Lifestyle in Pregnancy study was a randomized controlled trial among 360 obese women (BMI 30-45 kg/m²) who were allocated in early pregnancy to lifestyle interventions with diet counselling and physical activities or to the control group. Fasting blood samples, including plasma glucose, insulin, lipid profile and capillary blood glucose during a 2-h oral glucose tolerance test were carried out three times throughout pregnancy. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance. RESULTS: Three hundred and four women (84%) were followed until delivery. Women in the intervention group had a significantly lower change in insulin resistance (HOMA-IR) from randomization to 28-30 weeks' gestation compared with control subjects (mean ± SD: 0.7 ± 1.3 vs. 1.0 ± 1.3, P = 0.02). Despite a significantly lower gestational weight gain in the intervention group, there was no difference between the groups with respect to total cholesterol, HDL, LDL or triglycerides. CONCLUSIONS: Lifestyle intervention in obese pregnant women resulted in attenuation of the physiologic pregnancy-induced insulin resistance. Despite restricted gestational weight gain, there were no changes in glucose or lipid metabolism between the groups.

Pregestational body mass index is related to neonatal abdominal circumference at birth--a Danish population-based study.

OBJECTIVES: To examine the impact of maternal pregestational body mass index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth. To define reference curves for birth AC and weight in offspring of healthy, nonsmoking, normal weight women. DESIGN: Population-based study. SETTING: Data from the Danish Medical Birth Registry. POPULATION: All live singletons without congenital malformations in Denmark 2004-10. METHODS: Data on 366,886 singletons at 35(+0) to 41(+6) weeks(+days) of gestation were extracted and analysed using multivariate linear regressions. MAIN OUTCOME MEASURES: Birth AC and weight in relation to pregestational maternal BMI, maternal smoking and medical conditions (any). RESULTS: Birth AC and weight increased with increasing pregestational BMI, and decreased with smoking (P < 0.0001). Reference curves were created for offspring of healthy, nonsmoking mothers with normal pregestational BMI. Mean AC ranged from 30.1 cm and 30.2 cm at 35 weeks of gestation to 33.9 cm and 34.1 cm at 41 weeks of gestation, for girls and boys, respectively. Mean birthweight ranged from 2581 and 2666 g at 35 weeks to 3705 and 3852 g at 41 weeks of gestation for girls and boys, respectively. Pregestational BMI correlated more to the Z score of birthweight than to the Z score of AC (P < 0.0001). CONCLUSION: Birth AC and weight are affected by maternal smoking status and pregestational BMI. Pregestational BMI correlated more to birthweight than to AC. Using data from healthy, nonsmoking mothers with normal pregestational BMI we have provided new reference curves for birth AC and birthweight.