Manju Chandiramani

Mayer – Rokitansky – Kuster – Hauser syndrome

A parous 34-year old woman booked at 10 weeks’ gestation in her third pregnancy, confirmed by ultrasound, having had a previous spontaneous vaginal delivery at term and a miscarriage at 7 weeks’ gestation. She had a medical history of hypothyroidism, which was controlled with 50 mg thyroxine daily. She was a Caucasian, a non-smoker, with no family history of significant congenital abnormality. General examination was unremarkable. Biochemical screening for Down’s syndrome at 16 weeks’ gestation showed a serum a-fetoprotein of 54 KU/L and human chorionic gonadotrophin (HCG) of 2 KIU/L with an agerelated risk of 1:470 and a combined risk of 1:999,999. Open neural tube defect assessment was within the normal reference range. A further ultrasound was performed because of the low HCG level and extremely low combined risk. It showed no fetal heart activity, confirming intrauterine death. She proceeded to medical termination of pregnancy with mifepristone followed by intravaginal misoprostol and she delivered a female fetus. The placenta was retained and required removal under general anaesthetic. Post-mortem examination revealed a severely macerated female fetus of size corresponding to the median for approximately 13.5 weeks’ gestation. The head and facies featured a flattened broad nose with patent nasal passages and low set ears. Right radial hypoplasia was present characterised by marked radial deviation of the right hand (‘club hand’) associated with absence of the thenar eminence and thumb (Figure 1). The left hand and both feet had five digits and normal nails respectively. The palmar creases were normal. The lower limbs looked normal within the confines of the examination and were of the same length. The external genitalia were female with a clear introitus. The anus was patent and there was no evidence of spina bifida. The scalp appeared normal and the skull had two fontanelles. The brain was unsatisfactory for detailed anatomical assessment due to severe maceration. A spleen could not be identified in the residual detail of the severely macerated viscera, and disseminated brain substance was present in the abdominal cavity and mouth, consistent with the effects of intrauterine pressure on the retained macerated fetus. Both kidneys were absent (Figure 2). A filamentous structure, consistent with a ureter, was identified on the left side. Its free proximal end was located near the inferior surface of the adrenal gland without evidence of attached renal tissue. Two ovaries and tubes were present but the uterus and upper vagina were absent (Figure 3). The lower part of the vagina could not be clearly identified in the residual detail of the macerated tissues in the pelvic cavity. The pituitary and thyroid glands were normal. Both adrenal glands were discoid in shape but otherwise normal. The thymus and lymph nodes were normal. Skeletal survey showed 11 pairs of ossifying ribs, an absent radius on the right and no fibula in the left leg (Figure 4). The placenta and membranes were macroscopically unremarkable but histology showed irregular villous outlines with trophoblastic inclusions associated with stromal and basement membrane calcification. There was no evidence of acute inflammation. It was not possible to karyotype the fetus due to failure of growth of skin fibroblasts in culture (as expected for the degree of maceration).

Fetal fibronectin as a predictor of spontaneous preterm labour in asymptomatic women with a cervical cerclage

Objectiveu2002 To assess the accuracy of fetal fibronectin (fFN) testing for prediction of preterm labour in asymptomatic high‐risk women with a cervical cerclage.

The Actim Partus test to predict pre-term birth in asymptomatic high-risk women

The Actim Partus test has been shown to be a useful predictor of pre-term birth in symptomatic women, but limited research has been carried out in high-risk asymptomatic women. This is a pilot study to evaluate the use of this test as a direct comparator with the fetal fibronectin test. All asymptomatic high-risk women attending a pre-term surveillance clinic over a 9-month period, took an Actim Partus and fetal fibronectin test, between 23 +0–24 +6 weeks’ gestation. A total of 45 women were eligible. The positive and negative predictive values of the Actim Partus test for delivery at ≤ 37 weeks’ gestation were 0% and 70%, respectively, compared with the fetal fibronectin test, with values of 67% and 79%, respectively. It was concluded that the Actim Partus test did not perform well as a predictor of pre-term birth in high-risk asymptomatic women.

Raised Trappin2/elafin Protein in Cervico-Vaginal Fluid Is a Potential Predictor of Cervical Shortening and Spontaneous Preterm Birth

Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide (cathelicidin), key components of the innate immune system, are altered in women who have a spontaneous preterm birth. The aim was to determine the relationship between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein concentrations with cervical length in woman at risk of spontaneous preterm birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal CVF samples (taken between 13 to 30 weeks gestation) from 74 asymptomatic high risk women (based on obstetric history) recruited prospectively. Thirty six women developed a short cervix (<25 mm) by 24 weeks and 38 women did not. Women who developed a short cervix had 2.71 times higher concentrations of CVF trappin2/elafin from 14 weeks versus those who did not (CI 1.94–3.79, p<0.0005). CVF trappin2/elafin before 24 weeks was 1.79 times higher in women who had a spontaneous preterm birth <37 weeks (CI: 1.05–3.05, pu200a=u200a0.034). Trappin2/elafin (>200 ng/ml) measured between 14+0–14+6 weeks of pregnancy predicted women who subsequently developed a short cervix (nu200a=u200a11, ROC areau200a=u200a1.00, pu200a=u200a0.008) within 8 weeks. Cathelicidin was not predictive of spontaneous delivery. Vitamin D status did not correlate with CVF antimicrobial peptide concentrations. Raised CVF trappin2/elafin has potential as an early pregnancy test for prediction of cervical shortening and spontaneous preterm birth. This justifies validation in a larger cohort.

Variation in management of women with threatened preterm labour

Spontaneous preterm delivery is an important cause of neonatal morbidity and mortality, but there is little consensus on the best way to manage women with signs and symptoms of preterm labour. We conducted a survey of all 198 consultant-led maternity units in the UK to establish management of women presenting with threatened preterm labour (April–July, 2014). We contacted a consultant obstetrician in each unit (labour ward lead consultant, preterm labour special interest consultant or clinical director) and asked them, or a deputy, to complete an online survey about their hospital protocols. Consultants from 133 of 198 (67.2%) consultant-led obstetrics units responded: 59.4% (79/133) with neonatal intensive care facilities, 21.1% (28/133) with high dependency facilities and 19.5% (26/133) with special care facilities.nnThere were 126/133 (94.7%) units that used one or more …

Does fetal fibronectin testing change patient management in women at risk of preterm labour

OBJECTIVEnTo determine clinicians indications for, and actions following, fetal fibronectin testing in both symptomatic and asymptomatic women between 23(+0) and 34(+6) weeks gestation.nnnSTUDY DESIGNnFollowing clinician education of the predictive ability of fetal fibronectin testing, results of all fetal fibronectin tests done at St Thomas Hospital over a 6-week period were analysed. Clinicians were asked if the result changed management and if a reciprocal result would have altered management.nnnRESULTSnNinety-seven fetal fibronectin tests were conducted of which 21 (22%) were positive. Follow-up was done for 91 tests of which 25 (28%) test results directly changed management; 81 (89%) test results had the potential to change management independent of the test result.nnnCONCLUSIONnThe results of fetal fibronectin testing directly influenced management in a significant number of patients. A large number of women were asymptomatic at testing. Fetal fibronectin testing could be offered more widely and has the potential to benefit patient management.

Time interval from elective removal of cervical cerclage to onset of spontaneous labour

OBJECTIVEnTo determine the time interval between elective removal of a cervical cerclage to the onset of spontaneous labour in women who had either a history- or ultrasound-indicated cervical cerclage.nnnSTUDY DESIGNnA retrospective cohort study of women with a singleton pregnancy that had either a modified Shirodkar or McDonald cervical cerclage inserted were evaluated for the time interval between elective cerclage removal and onset of spontaneous labour and also spontaneous labour with 72 h of cervical cerclage removal.nnnRESULTSnTwo hundred and sixty-nine singleton pregnancies with either a modified Shirodkar or McDonald cervical cerclage were analysed. The mean gestational age at cerclage removal was 36.7 ± 1.10 weeks and gestational age at spontaneous labour was 39.0 ± 1.94 weeks (mean ± SD). The median interval between cerclage removal and spontaneous labour was 14 days. Only 18% of women laboured spontaneously within 72 h. Women with ultrasound-indicated cerclage were more likely to deliver within 72 h, compared with women with a history-indicated cervical cerclage (odds ratio, 3.68; 95% confidence interval, 1.31-10.85, p=0.01).nnnCONCLUSIONnIndependent of the indication or technique used for cervical cerclage, the rate of early spontaneous labour following elective removal of cervical cerclage is sufficiently low to justify outpatient management.

Serum progesterone concentrations in women with a previous preterm birth treated with vaginal progesterone supplementation

Background Progesterone is being used for the prevention of spontaneous preterm birth(SPTB). It is proposed to promote maintenance of pregnancy via its anti-inflammatory properties and actions on prostaglandin synthesis and uterine smooth muscle. Objective To determine if women at high risk of cervical shortening have lower serum concentrations of progesterone and if vaginal supplementation influences concentrations. Methods Serum progesterone was measured using ELISA immunoassay in longitudinal samples (n=226) in 64 women (14-28 weeks) with a history of SPTB. As part of a prospective study, women had cervical length assessment every two weeks and if the cervix was short (<25 mm), they were randomly assigned to cerclage or progesterone. Concentrations of progesterone were measured in longitudinal serum samples. Data were log-transformed, analysed using STATA, and results expressed as geometric means and ratios (95% confidence intervals; CI). Results Thirty-six percent delivered <37 weeks. Baseline progesterone concentrations (14-18 weeks) were similar (36.1 versus 39.7ng/ml) in preterm and term deliveries (ratio 0.90,95%CI0.75-1.08;p=0.27). Concentrations in women destined to develop a short cervix were similar to those who did not (ratio 0.98,95%CI0.84-1.15;p=0.83). Randomisation to vaginal progesterone supplementation had little effect on serum concentrations (15% increase, 95%CI0.98-1.35;p=0.09). There was no significant difference between women who delivered <34 weeks (effect 0.89,95%CI0.74-1.06;p=0.19) and <37 weeks (effect 0.92,95%CI0.79-1.09;p=0.34) to those who delivered at term. Conclusions Serum progesterone concentrations were similar in women regardless of shortening, gestation at delivery or treatment. Any beneficial effect of vaginal progesterone supplementation, therefore, is more likely to be mediated via local effects on the cervix.

8.6 The evolution of the vaginal microbiome throughout uncomplicated pregnancy in a UK population

Introduction The vaginal microbiome plays an important role in maintaining reproductive health throughout pregnancy. Despite the presence of an ‘abnormal’ vaginal microbial community being associated with an increased risk of preterm birth, interventional trials of antibiotics have failed to demonstrate significant benefit, which is likely due to a poor understanding of the vaginal microbiome in pregnancy. We sought to characterise the vaginal microbiome in uncomplicated pregnancies in a UK-based cohort. Methods Vaginal swabs were collected at time points across gestation (8–12, 20–22, 28–30 and 34–36 weeks) and the postpartum period (6 weeks) from 43 women delivered at term. Resident bacterial communities were determined using the Illumina MiSeq platform generated from bar-coded amplicons of 16S rRNA gene fragments. Results Individual vaginal microbiomes in pregnancy fall within four categories; i) Lactobacillus crispatus dominant, ii) Lactobacillus iners dominant, iii) Lactobacillus gasseri mixed with Lactobacillus jensenii and iv) Lactobacillus depleted with a diverse microbiome. Two pregnancy related trends were identified. In one group the Lactobacillus-dominated microbiome remains stable throughout pregnancy whereas in the other, an initially more diverse microbiome in the first trimester becomes Lactobacillus-dominated and less diverse in the second trimester but then reverts back to greater diversity in the third trimester and postpartum. Lactobacillus crispatus was associated with lower diversity and greater stability throughout pregnancy. Conclusion The vaginal microbiome during pregnancy tends to be Lactobacillus-dominated and less diverse in the period prior to fetal viability. Stability appears to be dependent upon the Lactobacillus species which may have implications for probiotic therapy.

PPO.01 EQUIPP: Evaluation of Fetal Fibronectin with a novel bedside Quantitative Instrument for the Prediction of Preterm birth

Introduction Fetal fibronectin (fFN) is a leading predictor of spontaneous preterm birth (sPTB) in high-risk asymptomatic women. As a positive/negative test (threshold of 50 ng/mL) the negative predictive value is high but positive predictive value (PPV) modest. The EQUIPP study aimed to determine if quantitative analysis of fFN (qfFn) improved prediction. Methods A prospective masked observational study (n = 1387) of high-risk asymptomatic women who underwent qfFN testing between 22+0– 27+6 weeks’ gestation at 5 UK centres. Primary endpoint: sPTB <34 weeks’. Results sPTB rate <34 weeks’ was 7.1%. Only 2.8% (26/941) of women with qfFN concentration < 10 ng/mL delivered <34 weeks’. The PPV for sPTB <34 weeks’ increased from 16.6%, 24.1%, 36.8%. 45.0% with increasing thresholds (10, 50, 200, and 500 ng/mL) respectively. Compared with qfFN <10 ng/mL, the relative risk of sPTB was 3.8 (95% CI, 2.3–6.6), 5.7 (3.2–10.0), 12.3 (7.3–20.8) and 16.3 (8.8–30.1) (p < 0.0001). The area under the Receiver Operating Characteristic curve for sPTB <34 weeks’ was 0.79 (0.74–0.84). Women with a short cervix on ultrasound (<25 mm) had a ten-fold increase in sPTB with qfFN concentration ≥200 ng/mL (18/45, 40%) vs. qfFN <10 ng/mL (3/68, 4.4%). Conclusion qfFN provides alternative thresholds to define risk of sPTB compared with qualitative assessment. For high-risk women with qfFN <10 ng/mL (68% of cohort) risk of sPTB equalled background risk (3.3%) providing reassurance and potential discharge from intensive surveillance. qfFN ≥200 ng/mL offers improved positive prediction over conventional testing and is a valuable tool for risk assessment in women with a short cervix.