Differences in Factors Associated With Preterm and Term Stillbirth: A Secondary Cohort Analysis of the DESiGN Trial.

OBJECTIVE: To identify whether maternal and pregnancy characteristics associated with stillbirth differ between preterm and term stillbirth. DESIGN: Secondary cohort analysis of the DESiGN RCT. SETTING: Thirteen UK maternity units. POPULATION: Singleton pregnant women and their babies. METHODS: Multiple logistic regression was used to assess whether the 12 factors explored were associated with stillbirth. Interaction tests assessed for a difference in these associations between the preterm and term periods. MAIN OUTCOME MEASURE: Stillbirth stratified by preterm (<37+0 weeks') and term (37+0-42+6 weeks') births. RESULTS: A total of 195 344 pregnancies were included. Six hundred and sixty-seven were stillborn (3.4 per 1000 births), of which 431 (65%) were preterm. Significant interactions were observed for maternal age, ethnicity, IMD, BMI, parity, smoking, PAPP-A, gestational hypertension, pre-eclampsia and gestational diabetes but not for chronic hypertension and pre-existing diabetes. Stronger associations with term stillbirth were observed in women with obesity compared to BMI 18.5-24.9 kg/m2 (BMI 30.0-34.9 kg/m2 term adjusted OR 2.1 [95% CI 1.4-3.0] vs. preterm aOR 1.1 [0.8-1.7]; BMI ≥ 35.0 kg/m2 term aOR 2.2 [1.4-3.4] vs. preterm aOR 1.5 [1.2-1.8]; p-interaction < 0.01), nulliparity compared to parity 1 (term aOR 1.7 [1.1-2.7] vs. preterm aOR 1.2 [0.9-1.6]; p-interaction < 0.01) and Asian ethnicity compared with White (p-interaction < 0.01). A weaker or lack of association with term, compared to preterm, stillbirth was observed for older maternal age, smoking and pre-eclampsia. CONCLUSION: Differences in association exist between mothers experiencing preterm and term stillbirth. These differences could contribute to design of timely surveillance and interventions to further mitigate the risk of stillbirth.

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. CONCLUSIONS: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, ISRCTN67698474.

Pregnancy in women known to be living with a single kidney.

There is a paucity of data on pregnancy outcome in women living with a single kidney from all causes. Current thinking is extrapolated from living kidney donors, a group biased by strict selection criteria. We present a cohort of 26 women with a solitary functioning kidney; 11 women had an acquired single kidney of whom only 1 was a living donor and 15 had a congenital single kidney. Median time living with a single kidney was 28 years. None booked with hypertension or proteinuria. Urinary tract infection complicated 50% of pregnancies. Worryingly, 35% developed pre-eclampsia, gestational proteinuria or gestational hypertension. We propose pre-conceptual counselling, education on how to protect their single kidney, pre eclampsia prophylaxis with low-dose aspirin and close monitoring for urinary tract infection, hypertension and proteinuria with lower thresholds for pharmaceutical management. We have devised a Patient Information leaflet - 'Living with a single kidney, pregnancy and beyond'.

Diagnosis of abnormal uterine bleeding.

Abnormal uterine bleeding is an extremely common indication for referral to a gynaecologist. This chapter examines the modes of presentation and the causes of such symptoms, which range from physiological variations to more sinister underlying pathology. A thorough understanding of these causes is required to direct investigation in an appropriate manner. The full range of possible investigations is discussed with emphasis on how to choose the most appropriate tests for a particular patient. This is fundamental to ensure that tests are pertinent and streamlined, and to prevent unnecessary anxiety and delay. Once the underlying causes have been clarified, a suitable management plan can be made.