Hormone-secreting adrenal tumours cause severe hypertension and high rates of poor pregnancy outcome; a UK Obstetric Surveillance System study with case control comparisons.

OBJECTIVE: To examine the management and outcomes of adrenal tumours in pregnancy. DESIGN: A national observational, cohort study over 4 years using the UK Obstetric Surveillance System (UKOSS). SETTING: Consultant-led obstetric units. PATIENTS: Women with phaeochromocytoma, primary aldosteronism or Cushing's syndrome diagnosed before or during pregnancy. METHODS: Clinical features of UKOSS cases were compared with those of women with adrenal tumours reported from 1985-2015. Nested case-control comparisons involving the UKOSS cases as well as those identified in the literature were performed for pregnancy outcome data using UKOSS controls with uncomplicated singleton (n = 2250) pregnancy and data from the Office of National Statistics (ONS). MAIN OUTCOME MEASURES: Incidence, management and frequency of adverse maternal and offspring outcomes of adrenal tumours in pregnancy. RESULTS: Fifteen pregnant women met the inclusion criteria: ten phaeochromocytoma, three primary aldosteronism and two Cushing's syndrome. All of the tumours had an incidence rate <2 per 100 000 pregnancies. Clinical symptoms were similar to those in non-pregnant women due to the hormones released. All women had severe hypertension, and in those diagnosed in pregnancy prior to conception. There was a significantly increased risk of adverse pregnancy outcomes in affected women, with increased rates of stillbirth, preterm labour and operative delivery. CONCLUSIONS: Adrenal tumours are associated with increased risks for pregnant women and their babies. Data on these tumours to inform practice are limited and international collaborative efforts are likely to be needed. TWEETABLE ABSTRACT: Study of hormone-secreting adrenal tumours in pregnancy linked with high BP and high rates of fetal morbidity.

Novel circulating placental markers prokineticin-1, soluble fms-like tyrosine kinase-1, soluble endoglin and placental growth factor and association with late miscarriage.

STUDY QUESTION: Are novel circulating placental markers prokineticin-1 (PK-1), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) associated with late miscarriage in asymptomatic first trimester pregnant women? SUMMARY ANSWER: Increased serum sFlt-1 or PlGF, but not sEng or PK-1, were significantly associated with reduced miscarriage risk after adjustment for age, BMI, gestational age, smoking and blood pressure. WHAT IS KNOWN ALREADY: Abnormal placental development is observed in two-thirds of miscarriages. Identifying women at high risk of late miscarriage could help diagnose potentially treatable causes of miscarriage such as infection, thrombosis or immunological disease. Recently, the circulating placental markers PK-1, sFlt-1, sEng and PlGF have been identified; however, it is not known if circulating levels of these markers are associated with late miscarriage. STUDY DESIGN, SIZE, DURATION: A single-centre observational cohort study with prospectively collected data was carried out at a tertiary care centre 2010-2012, in 993 asymptomatic pregnant women. Plasma PK-1, and serum sEng, sFlt-1 and PlGF were measured once in each patient during the antenatal booking visit, and pregnancy outcome was monitored prospectively. Less than 1% of patients were lost to follow-up. Multiples of median (MOM) levels were calculated to adjust for gestational age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine-hundred and ninety-three asymptomatic pregnant women attending antenatal clinic for a routine booking antenatal appointment were recruited to the study, of whom 12 were lost to follow-up and excluded from analysis. Of the cohort, 50 of the remaining 981 women suffered late miscarriage. MAIN RESULTS AND THE ROLE OF CHANCE: Gestation-adjusted sEng, sFlt-1 and PlGF levels were 11% (P < 0.01), 36% (P < 0.001) and 30% (P < 0.001), respectively, lower in women who later suffered miscarriage compared with unaffected pregnancies, while PK-1 did not differ significantly. Logistic regression modelling suggested that increased sFlt-1 (odds ratio (OR) 0.15 95% confidence interval [0.08-0.26], P = 0.0001) and PlGF (OR 0.02 [0.01-0.05], P = 0.0001), but not sEng, were associated with reduced miscarriage risk after adjustment for age, BMI, gestational age, smoking and blood pressure. The combination of sFlt-1 and PlGF did not improve the diagnostic accuracy beyond the use of sFlt-1. LIMITATIONS, REASONS FOR CAUTION: First trimester levels of sFlt-1 and PlGF, but not sEng or PK-1, were associated with late miscarriage risk in asymptomatic women. However, a new prospective study is now required to investigate the utility of these markers to predict early (<10 weeks) and late miscarriage, as well as to predict other complications of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that circulating sFlt-1 and PlGF, but not sEng or PK-1, are independently associated with late miscarriage risk in asymptomatic pregnant women attending their antenatal visit. Therefore, sFlt-1 and PlGF may represent novel markers of placental viability. These data further our understanding of placental function, and have important potential implications for utilizing novel hormonal markers to detect adverse clinical outcomes during pregnancy. STUDY FUNDING/COMPETING INTERESTS: The authors have no competing interests. The Section of Investigative Medicine is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This project was funded by an NIHR grant (reference: CDF-2009-02-05). The following authors are also funded as follows: CNJ is supported by an NIHR Clinical Lectureship and AMS/ Wellcome Starter Grant for Clinical Lecturers. AA and ANC are supported by NIHR academic clinical lectureships. CI-E is supported by an Imperial College Healthcare NHS Trust Charity Research Fellowship. WSD is supported by an NIHR Career Development Fellowship. TRIAL REGISTRATION NUMBER: Q0406/80.

Multiple repeat caesarean section in the UK: incidence and consequences to mother and child. A national, prospective, cohort study.

OBJECTIVE: To estimate the incidence of multiple repeat caesarean section (MRCS) (five or more) in the UK and to describe the outcomes for women and their babies relative to women having fewer repeat caesarean sections. DESIGN: A national population-based prospective cohort study using the UK Obstetric Surveillance System (UKOSS). SETTING: All UK hospitals with consultant-led maternity units. POPULATION: Ninety-four women having their fifth or greater MRCS between January 2009 and December 2009, and 175 comparison women having their second to fourth caesarean section. METHODS: Prospective cohort and comparison identification through the UKOSS monthly mailing system. MAIN OUTCOME MEASURES: Incidence, maternal and neonatal complications. Relative risk, unadjusted (OR) and adjusted (aOR) odds ratio estimates. RESULTS: The estimated UK incidence of MRCS was 1.20 per 10 000 maternities [95% confidence interval (CI), 0.97-1.47]. Women with MRCS had significantly more major obstetric haemorrhages (>1500 ml) (aOR, 18.6; 95% CI, 3.89-88.8), visceral damage (aOR, 17.6; 95% CI, 1.85-167.1) and critical care admissions (aOR, 15.5; 95% CI, 3.16-76.0), than women with lower order repeat caesarean sections. These risks were greatest in the 18% of women with MRCS who also had placenta praevia or accreta. Neonates of mothers having MRCS were significantly more likely to be born prior to 37 weeks of gestation (OR, 6.15; 95% CI, 2.56-15.78) and therefore had higher rates of complications and admissions. CONCLUSIONS: MRCS is associated with greater maternal and neonatal morbidity than fewer caesarean sections. The associated maternal morbidity is largely secondary to placenta praevia and accreta, whereas higher rates of preterm delivery are most likely a response to antepartum haemorrhage.

Association of pre-eclampsia with the R563Q mutation of the beta-subunit of the epithelial sodium channel.

The R563Q mutation of the beta-subunit of the epithelial sodium channel (ENaC) is associated with hypertension in black and mixed ancestry (MA) men and women in South Africa. The frequency of the R563Q mutation in black and MA women with pre-eclampsia (n= 230) and in controls (n= 198) was studied. The R563Q mutation was found in 7.8% of the women with pre-eclampsia and in 2.6% of controls (P= 0.014). This remained significant if the black women were analysed separately (P= 0.031). We have demonstrated that a genetic variant of the ENaC is associated with pre-eclampsia. This has implications for understanding the pathogenesis and treatment of pre-eclampsia.

A retrospective comparison of water births and conventional vaginal deliveries.

The aim of this study was to document the practice of water births and compare their outcome and safety with normal vaginal deliveries. A retrospective case-control study was conducted over a five year period from 1989 to 1994 at the Maternity Unit, Rochford Hospital, Southend, UK. Three hundred and one women electing for water births were compared with the same number of age and parity matched low risk women having conventional vaginal deliveries. Length of labour; analgesia requirements; apgar scores; maternal complications including perineal trauma, postpartum haemorrhages, infections; fetal and neonatal complications including shoulder dystocias; admissions to the Special Care Baby Unit, and infections were noted. Primigravidae having water births had shorter first and second stages of labour compared with controls (P<0.05 and P<0.005 respectively), reducing the total time spent in labour by 90 min (95% confidence interval 31 to 148). All women having water births had reduced analgesia requirements. No analgesia was required by 38% (95% confidence interval 23.5 to 36.3, P<0.0001) and 1.3% requested opiates compared to 56% of the controls (95% confidence interval 46. 3 to 58.1, P<0.0001). Primigravidae having water births had less perineal trauma (P<0.05). Overall the episiotomy rate was 5 times greater in the control group (95% confidence interval 15 to 26.2, P<0.0001), but more women having water births had perineal tears (95% confidence interval 6.6 to 22.6, P<0.001). There were twice as many third degree tears, post partum haemorrhages and admissions to the Special Care Baby Unit in the controls, although these differences were not significant. Apgar scores were comparable in both groups. There were no neonatal infections or neonatal deaths in the study. This study suffers from many of the methodological problems inherent in investigation of uncommon modes of delivery. However, we conclude that water births in low risk women delivered by experienced professionals are as safe as normal vaginal deliveries. Labouring and delivering in water is associated with a reduction in length of labour and perineal trauma for primigravidae, and a reduction in analgesia requirements for all women.

The detection of IgE-secreting cells in the peripheral blood of patients with atopic dermatitis.

We report, for the first time, the identification of IgE-secreting cells in human peripheral blood with an ELISA plaque assay that detects the fingerprint of individual IgE-secreting cells. No IgE-secreting cells could be detected in the blood of normal individuals (IgE, less than 100 IU/ml) or atopic patients (IgE, less than 1000 IU/ml), but in patients with atopic dermatitis (AD) whose IgE was greater than 2000 IU/ml, there was an average of 49 +/- 9 IgE-secreting cells per 10(6) peripheral blood mononuclear cells (PBMNCs). The rate of IgE production per cell per day from the PBMNCs of patients with AD varied from 0.051 to 0.628 IU/ml, and the number of IgE-secreting cells was positively correlated with the serum-IgE levels of these subjects (r = 0.74; p less than 0.001) and the amount of IgE detected in the culture supernatant (r = 0.085; p less than 0.02). Secretion of IgE by these cells could be completely inhibited (96.2% +/- 3%) by the addition of 75 micrograms of cyclohexamide to the cultures. Preformed intracellular IgE comprised 10% of the IgE detected in the supernatants of 7-day cultures. PBMNCs from patients with AD depleted of monocytes by adherence and T cells by E rosetting, all contained some detectable IgE-secreting cells, whereas isolated T cells and monocytes did not, supporting the view that cells secreting IgE that were detected were indeed B cells.