Maternal plasma syndecan-1: a biomarker for fetal growth restriction.

OBJECTIVE: The identification of fetal growth disorders is an important clinical priority given that they increase the risk of perinatal morbidity and mortality as well as long-term diseases. A subset of small-for-gestational-age (SGA) infants are growth-restricted, and this condition is often attributed to placental insufficiency. Syndecan-1, a product of the degradation of the endothelial glycocalyx, has been proposed as a biomarker of endothelial damage in different pathologies. During pregnancy, a "specialized" form of the glycocalyx-the "syncytiotrophoblast glycocalyx"-covers the placental villi. The purpose of this study was to determine whether the concentration of maternal plasma syndecan-1 can be proposed as a biomarker for fetal growth restriction. STUDY DESIGN: A cross-sectional study was designed to include women with normal pregnancy (n = 130) and pregnant women who delivered an SGA neonate (n = 50). Doppler velocimetry of the uterine and umbilical arteries was performed in women with an SGA fetus at the time of diagnosis. Venipuncture was performed within 48 h of Doppler velocimetry and plasma concentrations of syndecan-1 were determined by a specific and sensitive immunoassay. RESULTS: (1) Plasma syndecan-1 concentration followed a nonlinear increase with gestational age in uncomplicated pregnancies (R2 = 0.27, p < .001); (2) women with a pregnancy complicated with an SGA fetus had a significantly lower mean plasma concentration of syndecan-1 than those with an appropriate-for-gestational-age fetus (p = .0001); (3) this difference can be attributed to fetal growth restriction, as the mean plasma syndecan-1 concentration was significantly lower only in the group of women with an SGA fetus who had abnormal umbilical and uterine artery Doppler velocimetry compared to controls (p = .00071; adjusted p = .0028). A trend toward lower syndecan-1 concentrations was also noted for SGA with abnormal uterine but normal umbilical artery Doppler velocimetry (p = .0505; adjusted p = .067); 4) among women with an SGA fetus, those with abnormal umbilical and uterine artery Doppler findings had a lower mean plasma syndecan-1 concentration than women with normal Doppler velocimetry (p = .02; adjusted p = .04); 5) an inverse relationship was found between the maternal plasma syndecan-1 concentration and the umbilical artery pulsatility index (r = -0.5; p = .003); and 6) a plasma syndecan-1 concentration ≤ 850 ng/mL had a positive likelihood ratio of 4.4 and a negative likelihood ratio of 0.24 for the identification of a mother with an SGA fetus who had abnormal umbilical artery Doppler velocimetry (area under the ROC curve 0.83; p < .001). CONCLUSION: Low maternal plasma syndecan-1 may reflect placental diseases and this protein could be a biomarker for fetal growth restriction. However, as a sole biomarker for this condition, its accuracy is low.

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis.

BACKGROUND: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. METHODS: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 µmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. FINDINGS: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35-3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04-2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86-1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39-0·91; p=0·016). INTERPRETATION: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. FUNDING: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.

Two cases of coronavirus 2019-related cardiomyopathy in pregnancy.

At our institution, 2 of the initial 7 pregnant patients with confirmed coronavirus disease 2019 severe infection (28.6%; 95% CI, 8.2%-64.1%) developed cardiac dysfunction with moderately reduced left ventricular ejection fractions of 40%-45% and hypokinesis. Viral myocarditis and cardiomyopathy have also been reported in nonpregnant coronavirus disease 2019 patients. A case series of nonpregnant patients with coronavirus disease 2019 found that 33% of those in intensive care developed cardiomyopathy. More data are needed to ascertain the incidence of cardiomyopathy from coronavirus disease 2019 in pregnancy, in all pregnant women with coronavirus disease 2019, and those with severe disease (eg, pneumonia). We suggest an echocardiogram in pregnant women with coronavirus disease 2019 pneumonia, in particular those necessitating oxygen, or those who are critically ill, and we recommend the use of handheld, point-of-care devices where possible to minimize contamination of staff and traditional large echocardiogram machines.

Grade III subcapsular liver hematoma secondary to HELLP syndrome: A case report of conservative management.

Subcapsular liver hematoma (SLH) is a rare condition that is associated with preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. A high level of suspicion, early diagnosis, and coordinated, intensive multidisciplinary management are necessary to monitor for serious complications and prevent death. Options include conservative management, hepatic resection, hepatic artery ligation and liver transplantation. This paper describes a 34-year-old woman with HELLP syndrome who developed a large grade III SLH that was managed conservatively.

Robotic-Assisted Laparoscopic Cervicovaginal Myomectomy.

STUDY OBJECTIVE: To illustrate a robotic-assisted laparoscopic resection for cervicovaginal myomectomy. DESIGN: Step-wise instruction using video and case report (Canadian Task Force classification III). SETTING: A tertiary referral center. PATIENT: A 39-year-old woman. INTERVENTION: Robotic-assisted laparoscopy resection of leiomyoma. MEASUREMENTS AND MAIN RESULTS: A 39-year-old woman, gravida 0, body mass index of 23.0 kg/m2, with a known cervicovaginal myoma that in the past underwent uterine artery embolization, presented with recurrence of her severe abnormal vaginal bleeding. She was referred for surgical resection of the mass. Magnetic resonance imaging revealed a 5-cm posterior cervicovaginal leiomyoma. The patient wanted to preserve her reproductive organs. A total robotic procedure lasted 123 minutes, with an estimated blood loss of 100 mL. She was discharged uneventfully on the day 0 postoperatively. Pathology results showed a 37-g leiomyoma of the uterus. The patient presented at her 2-weeks postoperative visit with no more complaint of vaginal bleeding. CONCLUSION: Robot-assisted laparoscopic surgery is a feasible approach for cervicovaginal myoma with minimal complications.

Mayer-Rokitansky-Küster-Hauser Syndrome With Bilateral Ovarian Sertoli Cell Tumors: Review of the Literature and Report of a Rare Case.

BACKGROUND: Patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome are infertile secondary to hypoplasia or complete agenesis of the uterus, yet they remain at risk of primary neoplasms of the ovaries because embryologically the uterus and ovaries develop via separate mechanisms. CASE: A 72-year-old nulliparous woman with a history of primary amenorrhea underwent an exploratory laparotomy for a suspected uterine fibroid. In addition to the pelvic mass, the patient was found to have findings consistent with MRKH syndrome. Postoperative pathological examination demonstrated bilateral ovarian Sertoli cell tumors. CONCLUSIONS: The case presented is unique in that 2 rare pathologies, bilateral Sertoli cell tumors of the ovary and MRKH syndrome, developed concomitantly in the same patient.