Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.

BACKGROUND: Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. METHODS: The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. FINDINGS: Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15-24; 69 of 352 fetuses) for selective ultrasonography and 57% (51-62; 199 of 352 fetuses) for universal ultrasonography (relative sensitivity 2·9, 95% CI 2·4-3·5, p<0·0001). Of the 3977 fetuses, 562 (14·1%) were identified by universal ultrasonography with an estimated fetal weight of less than the 10th percentile and were at an increased risk of neonatal morbidity (relative risk [RR] 1·60, 95% CI 1·22-2·09, p=0·0012). However, estimated fetal weight of less than the 10th percentile was only associated with the risk of neonatal morbidity (pinteraction=0·005) if the fetal abdominal circumference growth velocity was in the lowest decile (RR 3·9, 95% CI 1·9-8·1, p=0·0001). 172 (4%) of 3977 pregnancies had both an estimated fetal weight of less than the 10th percentile and abdominal circumference growth velocity in the lowest decile, and had a relative risk of delivering an SGA infant with neonatal morbidity of 17·6 (9·2-34·0, p<0·0001). INTERPRETATION: Screening of nulliparous women with universal third trimester fetal biometry roughly tripled detection of SGA infants. Combined analysis of fetal biometry and fetal growth velocity identified a subset of SGA fetuses that were at increased risk of neonatal morbidity. FUNDING: National Institute for Health Research, Medical Research Council, Sands, and GE Healthcare.This work was supported by the National Institute for Health Research (NIHR) Cambridge Comprehensive Biomedical Research Centre and the Stillbirth and Neonatal Death Society. DP was supported by a Medical Research Council (MRC) Clinical Training Fellowship. IRW is supported by a MRC Unit Programme (number U105260558). GE Healthcare (Fairfield, CT, USA) donated two Voluson i ultrasound systems for this study. This study was also supported by the NIHR Cambridge Clinical Research Facility, where all visits at about 20, 28, and 36 weeks took place. No direct or indirectly supporting bodies for the project were involved in any aspect of preparation of this paper for publication. We thank the Perinatal Institute for providing a bulk calculator for customised percentiles of estimated fetal weight. We thank all the women who participated in the study, and all the staff in the Rosie Hospital (Cambridge, UK) and NIHR Cambridge Clinical Research Facility who provided direct or indirect assistance for the study.This is the final published version of the article. It was originally published in The Lancet (Sovio U, White IR, Dacey A, Pasupathy D, Smith GCS, The Lancet, 2015, doi:10.1016/S0140-6736(15)00131-2). The final version is available at http://dx.doi.org/10.1016/S0140-6736(15)00131-2

Trends in socioeconomic inequalities in risk of sudden infant death syndrome, other causes of infant mortality, and stillbirth in Scotland: population based study

Objectives To compare changes in inequalities in sudden infant death syndrome with other causes of infant mortality and stillbirth in Scotland, 1985-2008

Study protocol. A prospective cohort study of unselected primiparous women: the pregnancy outcome prediction study.

BACKGROUND: There have been dramatic changes in the approach to screening for aneuploidy over the last 20 years. However, the approach to screening for other complications of pregnancy such as intra-uterine growth restriction, pre-eclampsia and stillbirth remains largely unchanged. Randomised controlled trials of routine application of high tech screening methods to the general population have generally failed to show improvement in outcome. We have previously reviewed this and concluded it was due, in large part, to poor performance of screening tests. Here, we report a study design where the primary aim is to generate clinically useful methods to screen women to assess their risk of adverse pregnancy outcome. METHODS/DESIGN: We report the design of a prospective cohort study of unselected primiparous women recruited at the time of their first ultrasound scan. Participation involves serial phlebotomy and obstetric ultrasound at the dating ultrasound scan (typically 10-14 weeks), 20 weeks, 28 weeks and 36 weeks gestation. In addition, maternal demographic details are obtained; maternal and paternal height are measured and maternal weight is serially measured during the pregnancy; maternal, paternal and offspring DNA are collected; and, samples of placenta and membranes are collected at birth. Data will be analysed as a prospective cohort study, a case-cohort study, and a nested case-control study. DISCUSSION: The study is expected to provide a resource for the identification of novel biomarkers for adverse pregnancy outcome and to evaluate the performance of biomarkers and serial ultrasonography in providing clinically useful prediction of risk

Time of birth and risk of neonatal death at term: retrospective cohort study

Objective To determine the effect of time and day of birth on the risk of neonatal death at term

Clinicians’ perspectives and experiences of providing cervical ripening at home or in-hospital in the United Kingdom

Acknowledgements We are grateful to those who gave their time for interviews and focus groups despite the severe workload pressures and ongoing COVID-19 pandemic. CHOICE is funded by the National Institute of Healthcare Research Health Technology and Assessment (NIHR HTA) NIHR 127569. SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of the National Institute of Healthcare Research or the Department of Health and Social Care.Peer reviewedPublisher PD

Validation of ethnicity in administrative hospital data in women giving birth in England: cohort study.

OBJECTIVE: To describe the accuracy of coding of ethnicity in National Health Service (NHS) administrative hospital records compared with self-declared records in maternity booking systems, and to assess the potential impact of misclassification bias. DESIGN: Secondary analysis of data from records of women giving birth in England (2015-2017). SETTING: NHS Trusts in England participating in a national audit programme. PARTICIPANTS: 1 237 213 women who gave birth between 1 April 2015 and 31 March 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Proportion of women with complete ethnicity; (2) agreement on coded ethnicity between maternity (maternity information systems (MIS)) and administrative hospital (Hospital Episode Statistics (HES)) records; (3) rates of caesarean section and obstetric anal sphincter injury by ethnic group in MIS and HES. RESULTS: 91.3% of women had complete information regarding ethnicity in HES. Overall agreement between data sets was 90.4% (κ=0.83); 94.4% when collapsed into aggregate groups of white/South Asian/black/mixed/other (κ=0.86). Most disagreement was seen in women coded as mixed in either data set. Rates of obstetrical events and complications by ethnicity were similar regardless of data set used, with the most differences seen in women coded as mixed. CONCLUSIONS: Levels of accuracy in ethnicity coding in administrative hospital records support the use of ethnicity collapsed into groups (white/South Asian/black/mixed/other), but findings for mixed and other groups, and more granular classifications, should be treated with caution. Robustness of results of analyses for associations with ethnicity can be improved by using additional primary data sources

The effect of delaying childbirth on primary cesarean section rates.

BACKGROUND: The relationship between population trends in delaying childbirth and rising rates of primary cesarean delivery is unclear. The aims of the present study were (1) to characterize the association between maternal age and the outcome of labor, (2) to determine the proportion of the increase in primary cesarean rates that could be attributed to changes in maternal age distribution, and (3) to determine whether the contractility of uterine smooth muscle (myometrium) varied with maternal age. METHODS AND FINDINGS: We utilized nationally collected data from Scotland, from 1980 to 2005, and modeled the risk of emergency cesarean section among women delivering a liveborn infant in a cephalic presentation at term. We also studied isolated myometrial strips obtained from 62 women attending for planned cesarean delivery in Cambridge, England, from 2005 to 2007. Among 583,843 eligible nulliparous women, there was a linear increase in the log odds of cesarean delivery with advancing maternal age from 16 y upwards, and this increase was unaffected by adjustment for a range of maternal characteristics (adjusted odds ratio for a 5-y increase 1.49, 95% confidence interval [CI] 1.48-1.51). Increasing maternal age was also associated with a longer duration of labor (0.49 h longer for a 5-y increase in age, 95% CI 0.46-0.51) and an increased risk of operative vaginal birth (adjusted odds ratio for a 5-y increase 1.49, 95% CI 1.48-1.50). Over the period from 1980 to 2005, the cesarean delivery rate among nulliparous women more than doubled and the proportion of women aged 30-34 y increased 3-fold, the proportion aged 35-39 y increased 7-fold, and the proportion aged > or =40 y increased 10-fold. Modeling indicated that if the age distribution had stayed the same over the period of study, 38% of the additional cesarean deliveries would have been avoided. Similar associations were observed in multiparous women. When studied in vitro, increasing maternal age was associated with reduced spontaneous activity and increased likelihood of multiphasic spontaneous myometrial contractions. CONCLUSIONS: Delaying childbirth has significantly contributed to rising rates of intrapartum primary cesarean delivery. The association between increasing maternal age and the risk of intrapartum cesarean delivery is likely to have a biological basis

Early antenatal prediction of gestational diabetes in obese women: development of prediction tools for targeted intervention

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most

Metabolic phenotyping by treatment modality in obese women with gestational diabetes suggests diverse pathophysiology: An exploratory study

Background and purpose: Excess insulin resistance is considered the predominant pathophysiological mechanism in obese women who develop gestational diabetes (GDM). We hypothesised that obese women requiring differing treatment modalities for GDM may have diverse underlying metabolic pathways. Methods: In this secondary analysis of the UK pregnancies Better Eating and Activity Trial (UPBEAT) we studied women from the control arm with complete biochemical data at three gestational time points; at 15–18+6 and 27–28+6 weeks (before treatment), and 34–36+0 weeks (after treatment). A total of 89 analytes were measured (plasma/serum) using a targeted nuclear magnetic resonance (NMR) platform and conventional assays. We used linear regression with appropriate adjustment to model metabolite concentration, stratified by treatment group. Main findings: 300 women (median BMI 35kg/m2; inter quartile range 32.8–38.2) were studied. 71 developed GDM; 28 received dietary treatment only, 20 metformin, and 23 received insulin. Prior to the initiation of treatment, multiple metabolites differed (p&lt;0.05) between the diet and insulin-treated groups, especially very large density lipoprotein (VLDL) and high density lipoprotein (HDL) subclasses and constituents, with some differences maintained at 34–36 weeks’ gestation despite treatment. Gestational lipid profiles of the diet treatment group were indicative of a lower insulin resistance profile, when compared to both insulin-treated women and those without GDM. At 28 weeks’ the diet treatment group had lower plasma fasting glucose and insulin than women treated with insulin, yet similar to those without GDM, consistent with a glycaemic mechanism independent of insulin resistance. Conclusions/Interpretation: This exploratory study suggests that GDM pathophysiological processes may differ amongst obese women who require different treatment modalities to achieve glucose control and can be revealed using metabolic profiling