Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

Pregestational maternal risk factors for preterm and term preeclampsia: A population-based cohort study

Introduction Most studies on factors affecting the risk of preeclampsia have not separated preterm from term preeclampsia, and we still know little about whether the predisposing conditions have a differentiated effect on the risk of preterm and term preeclampsia. Our aim was to assess whether diabetes type 1 and 2, chronic kidney disease, asthma, epilepsy, rheumatoid arthritis and chronic hypertension were differentially associated with preterm and term preeclampsia. Material and methods This is a nationwide, population-based cohort study containing all births registered in the Medical Birth Registry of Norway from 1999 to 2016. Multinomial logistic regression analysis was used to estimate relative risk ratios (RRRs) with 95% confidence intervals (95% CIs), adjusting for maternal age, parity, multiple gestation and all other studied maternal risk factors. Results We registered 1 044 860 deliveries, of which 9533 (0.9%) women had preterm preeclampsia (37 weeks). Most of the assessed maternal risk factors were associated with increased risk for both preterm and term preeclampsia, with adjusted RRRs ranging from 1.2 to 10.5 (preterm vs no preeclampsia) and 0.9–5.7 (term vs no preeclampsia). Diabetes type 1 and 2 (RRR preterm vs term preeclampsia 2.89, 95% CI 2.46–3.39 and RRR 1.68, 95% CI 1.25–2.25, respectively), chronic kidney disease (RRR 1.55, 95% CI 1.11–2.17) and chronic hypertension (RRR 1.85, 95% CI 1.63–2.10) were more strongly associated with preterm than term preeclampsia in adjusted analyses. For asthma, epilepsy and rheumatoid arthritis, RRRs were closer to one and not significant when comparing risk of preterm and term preeclampsia. Main results were similar when using a diagnosis at <34 weeks to define preterm preeclampsia. Conclusions Diabetes type 1 and 2, chronic kidney disease and chronic hypertension were more strongly associated with preterm than term preeclampsia.publishedVersio

Use of antihistamines before or during pregnancy and risk of early-onset pre-eclampsia in allergic women: a population-based cohort study

Objective: We have previously found that allergy is a risk factor for early-onset pre-eclampsia. The aim of this study was to assess the association between pregestational maternal use of antihistamines and early-onset pre-eclampsia. Design: A population-based cohort study. Setting and participants: All women giving birth in Norway 2004–2016, including 692 487 pregnancies. Data from the Medical Birth Registry of Norway were linked with data from the Norwegian Prescription Database. Prescriptions of antihistamines were divided into three groups: before pregnancy (<6 months), early pregnancy (<20 weeks) and late pregnancy (20–36 weeks). ORs with 95% CIs for pre-eclampsia <34 and <37 weeks by antihistamine use were estimated by logistic regression and stratified on multiple pregnancy and parity. Predicted proportions (%) with 95% CIs were estimated. Interventions: Use of antihistamines in relation to pregnancy in allergic women. Main outcome measures: Development of early-onset pre-eclampsia. Results: 2997 (0.43%) and 5769 (0.83%) women had pre-eclampsia <34 and <37 weeks, respectively. Use of antihistamines before and in early pregnancy was associated with a risk of developing early-onset pre-eclampsia that was comparable to the background population (OR 1.0, 95% CI 0.8 to 1.2 and OR 0.9, 95% CI 0.7 to 1.1, respectively). Antihistamine use only in late pregnancy was not treated as exposure, but as an indicator of allergy, and was associated with an increased risk of early-onset pre-eclampsia (OR 1.8, 95% CI 1.5 to 2.2). Predicted proportions of pre-eclampsia <34 weeks were significantly lower in women using antihistamines before (0.41%, 95% CI 0.34 to 0.49) and in early pregnancy (0.37%, 95% CI 0.31 to 0.44), compared with women using antihistamines after placentation (0.69%, 95% CI 0.57 to 0.83). Results were similar for pre-eclampsia <37 weeks. Conclusions: Antihistamine use before or during placentation was associated with reduced risk of developing early-onset pre-eclampsia in allergic women compared with women using antihistamines after placentation.publishedVersio

The effect of Zhang’s guideline versus the WHO partograph on childbirth experience measured by the Childbirth Experience Questionnaire in the Labor Progression Study (LaPS): A cluster randomized trial

Childbirth experience is an increasingly recognized and important measure of quality of obstetric care. Previous research has shown that it can be affected by intrapartum care and how labor is followed. A partograph is recommended to follow labor progression by recording cervical dilation over time. There are currently different guidelines in use worldwide to follow labor progression. The two main ones are the partograph recommended by the World Health Organization (WHO) based on the work of Friedman and Philpott and a guideline based on Zhang’s research. In our study we assessed the effect of adhering to Zhang’s guideline or the WHO partograph on childbirth experience. Zhang’s guideline describes expected normal labor progression based on data from contemporary obstetric populations, resulting in an exponential progression curve, compared with the linear WHO partograph. The choice of labor curve affects the intrapartum follow-up of women and this could potentially affect childbirth experience.publishedVersio

The effect of Zhang’s guideline versus the WHO partograph on childbirth experience measured by the Childbirth Experience Questionnaire in the Labor Progression Study (LaPS): A cluster randomized trial

Introduction Childbirth experience is an increasingly recognized and important measure of quality of obstetric care. Previous research has shown that it can be affected by intrapartum care and how labor is followed. A partograph is recommended to follow labor progression by recording cervical dilation over time. There are currently different guidelines in use worldwide to follow labor progression. The two main ones are the partograph recommended by the World Health Organization (WHO) based on the work of Friedman and Philpott and a guideline based on Zhang’s research. In our study we assessed the effect of adhering to Zhang’s guideline or the WHO partograph on childbirth experience. Zhang’s guideline describes expected normal labor progression based on data from contemporary obstetric populations, resulting in an exponential progression curve, compared with the linear WHO partograph. The choice of labor curve affects the intrapartum follow-up of women and this could potentially affect childbirth experience. Material and methods The Labor Progression Study (LaPS) study was a prospective, cluster randomized controlled trial conducted at 14 birth centers in Norway. Birth centers were randomized to either follow Zhang’s guideline or the WHO partograph. Nulliparous women in active labor, with one fetus in cephalic presentation at term and spontaneous labor onset were included. At 4 weeks postpartum, included women received an online login to complete the Childbirth Experience Questionnaire (CEQ). Total score on the CEQ, the four domain scores on the CEQ, and scores on the individual items on the CEQ were compared between the two groups. Results There were 1855 women in the Zhang group and 1749 women in the WHO partograph group. There was no difference in the total or domain CEQ scores between the two groups. We found statistically significant differences for two individual items; women in the Zhang group scored lower on positive memories and feeling of control. Conclusions Based on our findings on childbirth experience there is no reason to prefer Zhang’s guideline over the WHO partograph

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: The TRUFFLE 2 randomised trial protocol

Introduction Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise : the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is &lt;10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (&gt;= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy