Summary Background Previous prospective cohort studies have shown that angiogenic factors have a high diagnostic accuracy in women with suspected pre-eclampsia, but we remain uncertain of the effectiveness of these tests in a real-world setting. We therefore aimed to determine whether knowledge of the circulating concentration of placental growth factor (PlGF), an angiogenic factor, integrated with a clinical management algorithm, decreased the time for clinicians to make a diagnosis in women with suspected pre-eclampsia, and whether this approach reduced subsequent maternal or perinatal adverse outcomes. Methods We did a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial in 11 maternity units in the UK, which were each responsible for 3000–9000 deliveries per year. Women aged 18 years and older who presented with suspected pre-eclampsia between 20 weeks and 0 days of gestation and 36 weeks and 6 days of gestation, with a live, singleton fetus were invited to participate by the clinical research team. Suspected pre-eclampsia was defined as new-onset or worsening of existing hypertension, dipstick proteinuria, epigastric or right upper-quadrant pain, headache with visual disturbances, fetal growth restriction, or abnormal maternal blood tests that were suggestive of disease (such as thrombocytopenia or hepatic or renal dysfunction). Women were approached individually, they consented for study inclusion, and they were asked to give blood samples. We randomly allocated the maternity units, representing the clusters, to blocks. Blocks represented an intervention initiation time, which occurred at equally spaced 6-week intervals throughout the trial. At the start of the trial, all units had usual care (in which PlGF measurements were also taken but were concealed from clinicians and women). At the initiation time of each successive block, a site began to use the intervention (in which the circulating PlGF measurement was revealed and a clinical management algorithm was used). Enrolment of women continued for the duration of the blocks either to concealed PlGF testing, or after implementation, to revealed PlGF testing. The primary outcome was the time from presentation with suspected pre-eclampsia to documented pre-eclampsia in women enrolled in the trial who received a diagnosis of pre-eclampsia by their treating clinicians. This trial is registered with ISRCTN, number 16842031. Findings Between June 13, 2016, and Oct 27, 2017, we enrolled and assessed 1035 women with suspected pre-eclampsia. 12 (1%) women were found to be ineligible. Of the 1023 eligible women, 576 (56%) women were assigned to the intervention (revealed testing) group, and 447 (44%) women were assigned to receive usual care with additional concealed testing (concealed testing group). Three (1%) women in the revealed testing group were lost to follow-up, so 573 (99%) women in this group were included in the analyses. One (<1%) woman in the co...

Abstracts Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in intrahepatic cholestasis of pregnancy and in a mouse model of hypercholanaemic pregnancy Abstracts 740The correlation between epigenetic change and neonatal plasma glucose level in maternal gestational diabetes offspring

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OBJECTIVE: To estimate normal ranges for maternal vital signs throughout pregnancy, which have not been well defined in a large contemporary population. METHODS: We conducted a three-center, prospective, longitudinal cohort study in the United Kingdom from August 2012 to September 2017. We recruited women at less than 20 weeks of gestation without significant comorbidities with accurately dated singleton pregnancies. We measured participants' blood pressure (BP), heart rate, respiratory rate, oxygen saturation and temperature following standardized operating procedures at 4–6 weekly intervals throughout pregnancy. RESULTS: We screened 4,279 pregnant women, 1,041 met eligibility criteria and chose to take part. Systolic and diastolic BP decreased slightly from 12 weeks of gestation: median or 50th centile (3rd–97th centile) 114 (95–138); 70 (56–87) mm Hg to reach minimums of 113 (95–136); 69 (55–86) mm Hg at 18.6 and 19.2 weeks of gestation, respectively, a change (95% CI) of −1.0 (−2 to 0); −1 (−2 to −1) mm Hg. Systolic and diastolic BP then rose to a maximum median (3rd–97th centile) of 121 (102–144); 78 (62–95) mm Hg at 40 weeks of gestation, a difference (95% CI) of 7 (6–9) and9 (8–10) mm Hg, respectively. The median (3rd–97th centile) heart rate was lowest at 12 weeks of gestation: 82 (63–105) beats per minute (bpm), rising progressively to a maximum of 91 (68–115) bpm at 34.1 weeks. SpO2 decreased from 12 weeks of gestation: median (3rd–97th centile) 98% (94–99%) to 97% (93–99%) at 40 weeks. The median (3rd–97th centile) respiratory rate at 12 weeks of gestation was 15 (9–22), which did not change with gestation. The median (3rd–97th centile) temperature at 12 weeks of gestation was 36.7 (35.6–37.5)°C, decreasing to a minimum of 36.5 (35.3–37.3)°C at 33.4 weeks. CONCLUSION: We present widely relevant, gestation-specific reference ranges for detecting abnormal BP, heart rate, respiratory rate, oxygen saturation and temperature during pregnancy. Our findings refute the existence of a clinically significant BP drop from 12 weeks of gestation. CLINICAL TRIAL REGISTRATION: ISRCTN, ISRCTN10838017.

ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 ) (accessed July 24, 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search?query=2011-005511-11 ) (accessed July 24, 2017).

BackgroundWomen with chronic kidney disease have an increased risk of maternal and fetal complications in pregnancy. Pre-pregnancy counselling is recommended but the format of the counselling process and the experience of the patient have never been assessed. This study examines the experience of women with chronic kidney disease attending pre-pregnancy counselling and evaluates their pregnancy outcomes.MethodsThis is a cross-sectional assessment of 179 women with chronic kidney disease attending a pre-pregnancy counselling clinic (2003–2011) with retrospective evaluation of aetiology, comorbidity, treatment and adverse pregnancy outcome compared with 277 hospital controls. It includes an analysis of descriptive data and free text content from 72 questionnaire responders.Results65/72 (90%) of women found the clinic informative. 66 women (92%) felt that the consultation had helped them decide about pursuing pregnancy. 12 women (17%) found the multidisciplinary process intimidating. Free text comments supported the positive nature of the counselling experience, but also highlighted issues of access and emotional impact. Adverse pregnancy outcome rates were significantly higher in women with chronic kidney disease: 7/35 (20%) had pre-eclampsia (p < 0.001), 8/35 (23%) infants were small for gestational age (p < 0.001), 11/35 (31%) had preterm deliveries (<37 weeks) (p < 0.001) and 5/35 (14%) had a pregnancy loss compared with 4%, 10%, 8% and 3% of controls respectively.ConclusionsWomen with a diverse range of renal disease severity and complexity attend pre-pregnancy counselling. Factors affecting pregnancy include hypertension, proteinuria and teratogenic medication. It is important to be able to inform women of the risks to them and their babies before pregnancy in order to facilitate informed-decision making. Most women with chronic kidney disease attending a pre-pregnancy counselling clinic report a positive experience.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0024-6) contains supplementary material, which is available to authorized users.

maternal morbidity in these women (post hoc analysis). 10 The study highlights the need to determine which antihypertensive agent(s) provides optimal control of chronic hypertension in pregnancy to ameliorate these risks.Choice of antihypertensive outside pregnancy depends on ethnicity with those of African/Caribbean family origin receiving calcium channel blockers as first-line agent 11 and is thought to relate to differences in the pathophysiology causing hypertension in those of differing ethnic backgrounds. 12Ethnic disparity in maternal and perinatal outcome in the general pregnant population is well described and likely to be multifactorial. 13 To our knowledge, no randomized controlled trials have investigated the impact of ethnicity on efficacy of antihypertensive treatment in pregnancy. The aims of the PANDA study (Pregnancy and Chronic Hypertension: Nifedipine Versus Labetalol as Antihypertensive Treatment) were 3-fold: to assess feasibility of such a randomized controlled trial, to evaluate mechanistic treatment effects, and to examine the impact of ethnicity on efficacy of nifedipine (a calcium channel blocker with a well-established safety profile in pregnancy) with labetalol (currently recommended as firstline by national UK guidance). MethodsThe study was an open-label, phase 4, randomized controlled clinical trial (EudraCT Number 2013-003144-23 +6 weeks (to allow for second trimester BP nadir), singleton pregnancies, aged >18 years, and the ability to provide written informed consent. Women were excluded if they had a contraindication (relative or absolute) to either antihypertensive agent, such as labetalol in women with asthma. Details of the randomization process, intervention, and outcome measures are contained in the online-only Data Supplement. Statistical AnalysisFor the primary analysis, the intention to treat principle was applied; women were analyzed in the groups into which they were randomly allocated regardless of allocation received. The statistical software Stata/SE version 14 for Windows was used for all analyses. The number and percentage were calculated for binary and categorical variables. The mean and SD or the median and interquartile range were calculated for continuous variables. Linear regression with robust SE was used for the primary and other continuous outcomes. Adjustment was made for baseline covariates, including ethnicity (black [determined by self-report of whether the woman had a parent or grandparent who was African or Caribbean] versus non-black [all other ethnicities]), gestational age at randomization, and center. For continuous measures, an adjustment was also made for corresponding baseline measurement (systolic BP at randomization for the primary clinical outcome). For binary outcomes, binary regression with a log link was used to calculate risk ratios (RR). Analysis of the primary clinical outcomes was repeated excluding women delivering their baby before 24 completed weeks of pregnancy because women who deliver before viability did not complete the inten...

Summary: Seventy-three pregnancies in 43 women with SPK have now been described by the US National Transplantation Pregnancy Registry (NTPR) (established in 1991), which contains self-reported data from questionnaires and hospital records. These women have high rates of complications despite normoglycaemia and restoration of renal function. We describe the pregnancies of three SPK recipients in the UK managed in joint renal obstetric clinics and discuss the antenatal and postnatal complications specific to SPK transplants.Keywords: pregnancy, pancreas -kidney transplant CASE 1A 36-year-old Caucasian woman presented at seven weeks gestation in her first pregnancy. Four years earlier she had a simultaneous pancreas-kidney transplant (SPK) for type 1 diabetes and nephropathy with pancreatico-duodenal anastomosis to the small bowel. Initial immunosuppression included tacrolimus and mycophenolate mofetil (MMF) but sirolimus was started following neutropenia secondary to MMF. The pregnancy was unplanned. Prior to pregnancy laboratory markers were as follows: serum creatinine (Cr) 110 mmol/L (estimated Glomerular Filtration Rate [eGFR] 52 mL/minute/1.73 m 2 ), HbA1C 5.1% and serum amylase 58 mmol/L. Atorvastatin and lansoprazole were discontinued and immunosuppression was left unchanged (tacrolimus 3 mg twice daily and sirolimus 1 mg once daily). She continued taking aspirin 75 mg once daily, which she had been taking since transplantation. She was counselled about the unknown risks of sirolimus in pregnancy and relative safety of tacrolimus. Following discontinuation of lansoprazole she developed heartburn and was prescribed gaviscon and ranitidine.She was normotensive and protein:creatinine ratios (PCR) (65 mg/mmol Cr) remained stable throughout the pregnancy. Tacrolimus was sequentially increased to 5 mg twice daily between 13 and 23 weeks gestation because levels were repeatedly low (2.7-5.8 ng/mL). She had a normal glucose tolerance test at 27 weeks. Sirolimus levels were adequate (1.5-3.0 ng/ mL). Serum Cr initially fell to 80 mmol at 13 weeks but increased to 114 mmol/L at 34 weeks gestation. An ultrasound of the allograft excluded obstruction and Cr peaked at 121 mmol/L at 35 weeks. Fetal ultrasound showed normal fetal growth. An elective caesarean section with Pfannensteil incision was performed at 37 þ 1 weeks when Cr was 95 mmol. A 2594 g male infant was delivered (Apgar scores at 1, 5 and 10 minutes: 8, 8 and 10) and fetal arterial and venous cord blood were 7.255 and 7.326, respectively. The baby was transferred to the neonatal unit for temporary non-invasive ventilation. Good perfusion of the maternal kidney and pancreas allografts was demonstrated on ultrasound postpartum. Serum Cr postpartum was 103 mmol/L and amylase 59 mmol/L. She was discharged home with the baby on day 4 and received thromboprophylaxis with enoxaparin (40 mg once daily) for 10 days. Most recent serum Cr is 107 mmol/L (eGFR 58 mL/ minute/1.73 m 2 ) at 16 weeks postpartum. CASE 2A 29-year-old Caucasian woman with type 1 diabetes devel...