Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies.

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE (n = 15), gestational hypertension (GH; n = 14), and normotensive controls (NC; n = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, P = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, P = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2).

Transabdominal and transcervical chorionic villus sampling models to teach maternal-fetal medicine fellows.

OBJECTIVE: Many fellowship programs in maternal-fetal medicine (MFM) lack sufficient exposure and training in chorionic villus sampling (CVS). We describe a novel training model of transabdominal and transcervical CVS. METHODS: A porcine heart simulated a 12-week human uterus with a cervical canal created at the apex of the heart. A piglet was placed within a water-filled condom, which was placed inside the "uterus." A second water-filled condom simulated a maternal bladder. Fresh human placenta was placed between the condom and uterine wall. A zipper-sealed freezer bag with ultrasonic gel simulated an abdominal wall. Transabdominal ultrasound was utilized with this model to perform CVS. RESULTS: The design involved four MFM specialists and three fellows. Twenty-three faculty MFM specialists and eight MFM fellows endorsed the fidelity of both models. One hundred percent of attendees of a procedural workshop agreed that these models could be used to teach proper technique to fellows and faculty. CONCLUSION: We report a novel training model for transabdominal and transcervical CVS to teach proper technique in a nonclinical setting.

Management of Complicated Monochorionic Twin Gestations: An Evidence-Based Protocol.

IMPORTANCE: Monochorionic (MC) twins are hemodynamically connected by vascular anastomoses within the single shared placenta. The transfer of fluid or blood from one fetus to the other may result in development of pathologic complications, such as twin-twin transfusion syndrome, twin anemia polycythemia sequence, selective intrauterine growth restriction, and twin reversed arterial perfusion sequence. Monoamniotic gestations, which comprise a small fraction of MC pregnancies, can also present with unique challenges, particularly antepartum umbilical cord entanglement. All these complications carry a high risk of fetal morbidity and mortality if not recognized and managed in a timely fashion. OBJECTIVE: The purpose of this article is to review evidence-based management of complicated MC twin gestations and propose a standardized approach to surveillance. EVIDENCE ACQUISITION: Monochorionic gestations account for the majority of complications that occur in twin pregnancies; however, there is unclear evidence on the appropriate surveillance for and management of specific complications associated with these pregnancies. RESULTS: This article summarizes management for each specific type of MC complication in a structured and clear manner. CONCLUSIONS: Early pregnancy ultrasound, ideally between 10 and 13 weeks' gestation, is critical for the diagnosis and characterization of twin pregnancies. To improve outcomes for MC twins, appropriate fetal surveillance should be initiated at 16 weeks' gestation and continued until delivery.

Sonographic diagnosis of conjoined diamniotic monochorionic twins.

According to traditional theories for the pathogenesis of conjoined twins, diamniotic placentation should not occur. We present an unusual case with diamniotic/monochorionic conjoined twins and discuss possible etiologic hypotheses. The diagnosis of this improbable case was made in the first trimester using ultrasound, which assisted in making an early decision regarding further management.

Cost-effective standardization of preterm labor evaluation.

OBJECTIVE: The purpose of this study was to determine the effect of a standardized evidence-based protocol for preterm labor evaluation on resource use and obstetrics outcomes. STUDY DESIGN: We conducted a retrospective 12-month observational study of patients with symptoms of preterm labor at the Mayo Clinic. All patients underwent triage evaluation per a standardized protocol with a combination of cervical length measurement with contingent fetal fibronectin assay. RESULTS: Of 201 patients who underwent evaluation, 3 women delivered within 7 days, and only 1 woman delivered after a negative evaluation. Mean gestational age at evaluation was 29 weeks 1 day, and delivery was at 38 weeks 3 days of gestation, with an average interval of 57.4 days until delivery. The rate of hospital admission was reduced by 56%, compared with the previous year; an estimated annual cost saving was $39,900. CONCLUSION: Implementation of a standardized protocol for evaluation of preterm labor reduces the rate of unnecessary hospital admissions for observation with consequent significant reduction in expenses.

Pain associated with chorionic villus sampling: transabdominal vs transcervical approach.

OBJECTIVE: The purpose of this study was to compare anticipated and perceived pain that is associated with transabdominal and transcervical chorionic villus sampling (CVS). STUDY DESIGN: Women with singleton pregnancies who were undergoing CVS completed a preprocedure 0-10 visual analog scale (VAS; 0 = no pain, 10 = excruciating pain) for anticipated transabdominal and transcervical CVS-related pain. After the procedure, patients completed a VAS for perceived pain. RESULTS: One hundred twenty-one women underwent transabdominal (n = 98) or transcervical (n = 23) CVS. Anticipated pain was 4.5 +/- 2.0, which was similar in patients who ultimately underwent transabdominal (score, 4.6 +/- 3.8) or transcervical (score, 4.1 +/- 2.2) CVS. Postprocedure perceived pain was similar for transabdominal CVS in women with an abdominal wall thickness of <4 cm (score, 2.3 +/- 0.8) and transcervical CVS (score, 2.6 +/- 2.2) but was significantly greater for transabdominal CVS among women with an abdominal wall thickness of > or =4 cm (score, 5.6 +/- 1.2; P < .0001) and nulliparous women who had transcervical CVS (score, 4.3 +/- 2.1; P = .01). CONCLUSION: Transabdominal CVS is more painful in heavier women, and transcervical CVS is more painful in nulliparous women.

Expectant management of uterine incarceration from an anterior uterine myoma: a case report.

BACKGROUND: Uterine incarceration is an infrequent complication of pregnancy in the early second trimester. Although imaging can be confirmatory, the diagnosis is made primarily on clinical grounds, and definitive treatment involves manual reduction to restore the proper anatomic position. Except for preexisting uterine retroversion, often this event is idiopathic. CASE: A 30-year-old primigravida presented at 15 weeks' gestation with uterine incarceration. Manual replacement was unsuccessful. Spontaneous resolution occurred at 20 weeks, followed by uneventful pregnancy. The patient underwent a classical cesarean section at term due to fetal malpresentation. CONCLUSION: Uterine incarceration may be managed conservatively, with a favorable outcome.

Fetoscopic Therapy for Severe Pulmonary Hypoplasia in Congenital Diaphragmatic Hernia: A First in Prenatal Regenerative Medicine at Mayo Clinic.

OBJECTIVE: To introduce the prenatal regenerative medicine service at Mayo Clinic for fetal endoscopic tracheal occlusion (FETO) care for severe congenital diaphragmatic hernia (CDH). PATIENTS AND METHODS: Two cases of prenatal management of severe CDH with FETO between January and August 2017 are reported. Per protocol, FETO was offered for life-threatening severe CDH at between 26 and 29 weeks' gestation. Regenerative outcome end point was fetal lung growth. Gestational age at procedure and maternal and perinatal outcomes were additional monitored parameters. RESULTS: Diagnosis by ultrasonography of severe CDH was based on extremely reduced lung size (observed-to-expected lung area to head circumference ratio [o/e-LHR], eg, o/e-LHR of 20.3% for fetus 1 and 23.0% for fetus 2) along with greater than one-third of the liver herniated into the chest in both fetuses. Both patients underwent successful FETO at 28 weeks. At the time of intervention, no maternal or fetal complications were observed. Postintervention, fetal lung growth was observed in both fetuses, reaching an o/e-LHR of 62.7% at 36 weeks in fetus 1 and 52.4% at 32 weeks in fetus 2. The balloons were removed successfully at 35 weeks and 4 days by ultrasound-guided puncture in the first patient and at 32 weeks and 3 days by ex utero intrapartum therapy-to-airway procedure in the second patient. Postnatal management followed standard of care with patch CDH therapy. At discharge, one patient was breathing normally, whereas the other required minimal nasal cannula oxygen support. CONCLUSION: The successful launch of the first fetoscopic therapy for CDH at Mayo Clinic reveals its feasibility and safety, with early signs of benefit documented by fetal lung growth and reversal of severe pulmonary hypoplasia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: G170062.

Preeclampsia/Eclampsia candidate genes show altered methylation in maternal leukocytes of preeclamptic women at the time of delivery.

OBJECTIVE: To analyze methylation profiles of known preeclampsia/eclampsia (PE) candidate genes in normal (NL) and preeclamptic (PE) women at delivery. METHODS: A matched case-control study comparing methylation in 79 CpG sites/33 genes from an independent gene set in maternal leukocyte DNA in PE and NL (n = 14 each) on an Illumina BeadChip platform. Replication performed on second cohort (PE = 12; NL = 32). RESULTS: PE demonstrates differential methylation in POMC, AGT, CALCA, and DDAH1 compared with NL. CONCLUSION: Differential methylation in four genes associated with PE may represent a potential biomarker or an epigenetic pathophysiologic mechanism altering gene transcription.

Factitious disorder-by-proxy simulating fetal growth restriction.

BACKGROUND: Although a variety of presentations have been described in the literature, the true prevalence of factitious disorder, also commonly known as Münchausen syndrome, and factitious disorder-by-proxy in pregnancy is unknown. The authors present a unique case in which intrauterine fetal growth restriction was simulated through fabrication of prenatal records. CASE: A 30-year-old woman, gravida 6 para 3113, was transferred at 38 4/7 weeks of gestation for severe fetal growth restriction. The clinic listed in the patient-provided prenatal record was contacted to obtain original ultrasonographic reports for verification of gestational age; however, further investigation revealed the patient had never attended this clinic nor was the ostensible treating physician ever employed there. The initial prenatal record subsequently was determined to be entirely fabricated. CONCLUSION: In this era of extensive technologic resources, health care providers should consider the possibility of factitious disorder when patient-provided medical record-derived information is inconsistent with the clinical presentation.

Hypoplastic right-heart syndrome presenting as multiple miscarriages.

Reversible causes of miscarriage are many, but they affect only 1% of women who are trying to conceive. Herein, we describe the case of a 23-year-old woman who presented for evaluation of repeated miscarriages and was found to have hypoxemia and erythrocytosis. Further evaluation revealed hypoplastic right-heart syndrome with an intracardiac shunt. She underwent hybrid repair with pulmonary valve balloon valvuloplasty, followed by surgery to perform atrial septal defect closure and a Glenn anastomosis. The erythrocytosis and hypoxemia resolved, and she was able to conceive and deliver a healthy baby at term 2 years later. This is a unique case of a rare congenital heart defect that went unnoticed until adulthood, when attempts at pregnancy failed because of the associated hypoxemia. Timely and appropriate treatment led to a successful pregnancy after repeated miscarriages. This case exemplifies the need for a comprehensive medical evaluation of every woman with a history of multiple miscarriages to determine whether a reversible cause exists.

Vulval Keratoacanthoma: a case report.

BACKGROUND: Vulval Keratoacanthoma (KA) is very rare and its differential diagnosis from the commonly occurring Vulval Squamous Cell Carcinoma (SCC) is important to avoid overtreatment. CASE: A case of Vulval KA in a 79-year-old lady is reported. She presented with a 9-mm firm raised lesion on the antero-lateral left side of the clitoris of a few months' duration with no associated symptoms. The lesion was resected with clear margins and the excision site was well healed at her appointment 4 weeks later. CONCLUSION: We share our experience reporting the fifth case of a vulval KA in the world literature. Consideration to the occurrence of vulval KA is important to avoid both an erroneous diagnosis of vulval SCC and the associated consequences of radical surgery.