Jemma Johns

Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning

We have previously demonstrated placentas from laboring deliveries at high altitude have lower binding of hypoxia-inducible transcription factor (HIF) to DNA than those from low altitude. It has recently been reported that labor causes oxidative stress in placentas, likely due to ischemic hypoxic insult. We hypothesized that placentas of high-altitude residents acquired resistance, in the course of their development, to oxidative stress during labor. Full-thickness placental tissue biopsies were collected from laboring vaginal and nonlaboring cesarean-section term (37–41 wk) deliveries from healthy pregnancies at sea level and at 3,100 m. After freezing in liquid nitrogen within 5 min of delivery, we quantified hydrophilic and lipid metabolites using 31P and 1H NMR metabolomics. Metabolic markers of oxidative stress, increased glycolysis, and free amino acids were present in placentas following labor at sea level, but not at 3,100 m. In contrast, at 3,100 m, the placentas were characterized by the presence of concentrations of stored energy potential (phosphocreatine), antioxidants, and low free amino acid concentrations. Placentas from pregnancies at sea level subjected to labor display evidence of oxidative stress. However, laboring placentas at 3,100 m have little or no oxidative stress at the time of delivery, suggesting greater resistance to ischemia-reperfusion. We postulate that hypoxic preconditioning might occur in placentas that develop at high altitude.

Threatened miscarriage as a predictor of obstetric outcome.

OBJECTIVE: To investigate prospectively the risk of adverse pregnancy outcome in women presenting with first-trimester threatened miscarriage. METHODS: A prospective cohort study was performed on 214 women presenting with bleeding in the first trimester and 214 asymptomatic age-matched controls. Main outcome measures included gestational age and weight at delivery and incidence of adverse pregnancy outcome. RESULTS: The first-trimester miscarriage rate, after confirmation of viability in the threatened miscarriage group, was 9.3%. Compared with controls, women presenting with threatened miscarriage were more likely to deliver prematurely, 5.6% compared with 11.9%, respectively, (relative risk 2.29, 95% confidence interval 1.4–4.6), and this was most likely to be between 34 and 37 weeks. They were also more likely to have preterm prelabor rupture of membranes, 1.9% compared with 7%, respectively, (relative risk 3.72, 95% confidence interval 1.2–11.2). Overall, there was no difference in mean birth weight and in the incidence of other obstetric complications between the 2 groups; however, women in the threatened miscarriage group were more likely to deliver neonates between 1,501 g and 2,000 g (P = .04). CONCLUSION: Women with threatened miscarriage in the first trimester are at increased risk of premature delivery, and this risk factor should be taken into consideration when deciding upon antenatal surveillance and management of their pregnancies. LEVEL OF EVIDENCE: II-0

Natural history of early first‐trimester pregnancies implanted in Cesarean scars

To describe the ultrasound findings and natural history of pregnancies implanted within or on Cesarean section scars in the first trimester of pregnancy.

Maternal serum hormone concentrations for prediction of adverse outcome in threatened miscarriage.

Many serum markers have been investigated in attempts to predict the outcome of pregnancy in the first trimester, with varying degrees of success. The objective of this study was to investigate whether they can be related to pregnancy outcome in women presenting with first trimester threatened miscarriage. A cohort study of women attending the Early Pregnancy Unit of a London teaching hospital was studied. A total of 122 women presenting with bleeding in the first trimester and an ongoing pregnancy, and 33 women undergoing termination of pregnancy, were recruited. The main outcome measures were gestation at delivery, birth weight and the incidence of adverse pregnancy outcome. Inhibin A, activin A, human chorionic gonadotrophin (HCG), pregnancy-associated plasma protein-A and follistatin concentrations were all significantly lower in women who subsequently miscarried when compared with live births. Serum HCG concentrations were significantly higher in cases of threatened miscarriage compared with controls (P = 0.0009). Logistic regression analysis indicated that inhibin A alone provided the best predictor for first trimester miscarriage. This pilot study suggests that placental hormone concentrations could be useful in predicting adverse pregnancy outcome in women presenting with threatened miscarriage. Inhibin A was best at predicting the likelihood of subsequent miscarriage in this group.

Impact of Pregnancy at High Altitude on Placental Morphology in Non-native Women With and Without Preeclampsia

Previous data indicate that placentas from normotensive pregnancies in non-native women at 3100 m (Leadville, CO) are not hypoxic at term, despite lower uterine artery blood flow, than in the same population at sea-level. We hypothesized that placental vascular development is greater at 3100 m in compensation. Further, because the incidence of preeclampsia (PE), which has been linked to placental hypoxia, is 3-4 fold higher in this population, we investigated if preeclamptic placentas have altered vascularity compared to normotensive controls at 3100 m. Placentas from normotensive (NT) pregnancies at sea-level, 1600 and 3100 m, and late-onset preeclamptic placentas were collected at 3100 m. Placental and birth weights were determined, and stereology performed on paraffin- and resin-embedded tissue. Both normal and preeclamptic placentas at high altitude were smaller than those at sea-level, and birth weights trended down with no change in the placental index. Volume fractions of the placental and villous compartments were similar between all conditions, but the absolute volume of each compartment was reduced at 3100 m compared to sea-level. Villous volume was equivalent between sea-level and 1600 m. There were no differences between PE and NT placentas at 3100 m. Placental vascularity was similar at all altitudes, and the gas-exchange area was preserved at 1600 m but not 3100 m. Late-onset preeclampsia was not associated with placental changes at 3100 m.

Clinical significance of first-trimester chorionic bumps: a matched case-control study

To determine the clinical significance of a chorionic bump diagnosed by ultrasound in women attending an early pregnancy unit in a teaching hospital.

Ultrasound diagnosis of molar pregnancy

Introduction The primary aims of this study were to establish what proportion of ultrasonically suspected molar pregnancies were proven on histological examination and what proportion of histologically diagnosed molar pregnancies were identified by ultrasound pre-operatively. The secondary aim was to review the features of these scans to help identify criteria that may improve ultrasound diagnosis. Methods This was a retrospective observational study conducted in the Early Pregnancy Unit at King’s College Hospital London over an 11-year period. Cases of ultrasonically suspected molar pregnancy or other gestational trophoblastic disease were identified and compared with the final histopathological diagnosis. In addition, cases which were diagnosed on histopathology that were not suspected on ultrasound were also examined. In discrepant cases, the images were reviewed unblinded by two senior sonographers. Statistical analysis for likelihood ratio and post-test probabilities was performed. Results One hundred eighty-two women had gestational trophoblastic disease suspected on ultrasound examination (1:360, 0.3%); 106/182 (58.2%, 95% CI 51.0 to 65.2%) had histologically confirmed gestational trophoblastic disease. The likelihood ratio for gestational trophoblastic disease after a positive ultrasound was 607.27, with a post-test probability of 0.628.The sensitivity of ultrasound for gestational trophoblastic disease was 70.7% (95% CI 62.9% to 77.4%) with an estimated specificity of 99.88% (95% CI 99.85% to 99.91%); 102/143 (71.3%, 95% CI 63.4 to 78.1%) molar pregnancies were suspected on pre-op ultrasound; 60/68 (88.2%, 95% CI 78.2 to 94.2%) of complete moles were suspected on pre-op ultrasound, compared with 42/75 (56.0%, 95% CI 44.7 to 66.7%) of partial moles. On retrospective review of the pre-op ultrasound images, there were cases that could have been suspected prior to surgery. Conclusion Detecting molar pregnancy by ultrasound remains a diagnostic challenge, particularly for partial moles. These data suggest that there has been an increase in both the predictive value and the sensitivity of ultrasound over time, with a high LR and post-test probability; however, the diagnostic criteria remain ill-defined and could be improved.

New insights in the pathophysiology of complete hydatidiform mole

OBJECTIVEnThe majority of complete hydatidiform moles (CHM) are detected on ultrasound examination by the end of the first trimester when they present as multiple sonolucent cysts. To better understand the pathophysiology of this unique placental pathology and improve its prenatal diagnosis and management we have reviewed the ultrasound features of CHM before the appearance of cystic changes.nnnSTUDY DESIGNnWe searched our database to identify all women diagnosed with a complete hydatidiform mole confirmed by histopathology who had an ultrasound examination before 9 weeks gestation. We reviewed their ultrasound reports and all the corresponding images.nnnRESULTSnThe study group included 39 women with a positive pregnancy test and vaginal bleeding, 36 of whom had at least two ultrasound examinations before 9 weeks gestation. At the first scan (mean gestation age 7xa0+xa01 weeks; SD 1.1), 29 out 39 (74.4%) of CHM presented as a heterogeneous hyperechogenic mass with or without gestational sac and the remaining ten (25.6%) cases as a regular 4-week gestational sac. Cystic molar changes became apparent from the end of the second month of gestation.nnnCONCLUSIONnThe development of a CHM follows a well-defined pattern starting with a macroscopically normal gestation sac at 4 weeks, which transforms into a polypoid mass between 5 and 7 weeks of gestation. The hydropic changes of the villous tissue is progressive and rarely visible in utero on ultrasound before 8 weeks of gestation. These findings should allow an earlier diagnosis and assist in the management counselling of women with CHM.

OC03.03: *The significance of first trimester subchorionic haematomas or ‘chorionic bumps’

Results: In the early pregnancy group, there was good to very good agreement between PUM and HSUM for identifying the presence or absence of an embryo, gestational sac, fetal heart motion, pregnancy location, and final diagnostic outcome (Kappa coefficient was 0.844, 0.843, 0.729, 0.785, and 0.812 respectively, P < 0.0001). In the late pregnancy group there was good to very good agreement for fetal presentation, placental location, and placental position (Kappa coefficient of 0.924, 0.924, and 0.647 respectively, P < 0.0001). In the gynecology group, there was very good agreement for final diagnosis, and type of ovarian mass (low risk, complex) (Kappa coefficient of 0.846, and 0.930 respectively, P < 0.0001). For the measured continuous variables, there was close agreement for crown-rump length, mean sac diameter, femur length, and mean diameter of an ovarian mass, but not for endometrial thickness. Patient age, BMI, operator experience, and familiarity with PUM had no impact on agreement between the two machines. Conclusions: The findings and final diagnosis in the three study groups were similar for both a PUM used transabdominally and a HSUM used transvaginally and/or transabdominally.