Case report of pregnancy management and genetic evaluation after negative carrier screening for spinal muscular atrophy in an affected family.

BACKGROUND: Screening for spinal muscular atrophy (SMA) is recommended for all pregnant women; however, interpreting the results of carrier screening in the context of family history can be challenging. CASE: We report the case of a 28-year-old woman (G4P3001) with two previous children affected with SMA and negative carrier screening via the Horizon 4 panel. SMN1/2 analysis was pursued to clarify risk for point mutations, carrier screening for her partner, and diagnostic testing for the fetus for SMA. Results of this testing confirmed her status as a silent carrier for SMA and the status of the fetus. CONCLUSION: Carrier screening does not account for family history and can therefore generate results inconsistent with known inheritance patterns. In these situations, additional genetic testing and genetic counseling are indicated to clarify risk for SMA in pregnancy and guide prenatal and neonatal healthcare.

A comparison of cervical ripening modalities among overweight and obese nulliparous gravidas.

Objective: To determine if differences exist among nulliparous overweight and obese gravidas undergoing cervical ripening employing three different agents (dinoprostone, misoprostol, or cervical catheter).Methods: A retrospective cohort study of nulliparous overweight and obese women who underwent induction of labor at two south-central Pennsylvania hospitals between January 2014 and December 2017. Nulliparous gravidas, ≥37 weeks' gestational age, with singleton pregnancies in the vertex presentation, were included in the study. We employed the following definitions: (1) overweight: BMI 25.0-29.9 kg/m2; (2) class I obesity: BMI 30.0-34.9 kg/m2; (3) class II obesity: BMI 35.0-39.9 kg/m2; and (4) class III obesity: BMI >40.0 kg/m2. The primary outcome measure was the mean difference in induction-to-birth time. A subanalysis was performed to assess the effect of BMI on the primary outcome. Secondary outcome measures included mode of delivery, induction-to-second-stage-of-labor time, estimated blood loss, neonatal feeding type, neonatal Apgar scores, and neonatal admission to triage or intensive care unit (ICU) after delivery. A priori power calculation estimated that 156 patients would be needed using the medium effective size. Data analysis was performed using ANOVA for continuous variables and chi-square tests for categorical variables.Results: Among 192 nulliparous overweight and obese gravidas, 70 received dinoprostone, 72 were given misoprostol, and 50 had cervical ripening with cervical catheters. There were no significant differences in mean induction to birth times among overweight and obese women when comparing the three cervical ripening agents (dinoprostone 24.5 ± 15.2 versus misoprostol 28.7 ± 12.3 and catheters 25.1 ± 12.9 hours), (p = .145, 95% CI -8.7 to 0.2 and -5.5 to 4.3, respectively). Overweight nulliparous women had shorter mean induction to birth time (22.9 ± 11.4 versus 29.2 ± 15.8 hours) as compared to class II obese women, (p = .037, 95% CI -12.0 to -0.38). When overweight women were compared to class III obese women, shorter mean induction to birth time (22.9 ± 11.4 versus 30.9 ± 13.9 hours) was also found, (p = .005, 95% CI -13.4 to -2.4).Conclusion: Among nulliparous overweight and obese gravidas, neither dinoprostone, misoprostol, or cervical catheter significantly impacted the induction to birth time. There was a longer induction to birth time for class II and class III obese women when compared to overweight women. Additional studies are warranted to improve cervical ripening in nulliparous overweight and obese women.

Maternal Bradycardia Associated with Betamethasone Administration During Pregnancy.

BACKGROUND: Maternal risks of betamethasone have been rarely reported. CASE: At 36 weeks' gestation, a previously healthy 23-year-old gravida with fetal intrauterine growth restriction was admitted to the hospital for steroid administration. Twenty-six hours after the first dose of betamethasone, a maternal bradycardia was initially noted and eventually nadired at 41 beats per minute. Consultation with the cardio-electrophysiology service revealed no other apparent etiologies for the sinus bradycardia. Due to the asymptomatic nature of the maternal bradycardia, pharmacologic interventions were not recommended. With observation alone, a normal maternal heart rate returned by forty-nine hours after the original betamethasone injection. The patient subsequently had an uneventful intrapartum course. CONCLUSION: Maternal bradycardia can be associated with antenatal betamethasone administration. Due to the transient nature of this side effect, expectant management is recommended as the treatment option for asymptomatic patients.

Evidence that Mifepristone, a progesterone receptor antagonist, can cross the blood brain barrier and provide palliative benefits for glioblastoma multiforme grade IV.

BACKGROUND: Mifepristone, a progesterone receptor antagonist, has been found to provide palliative benefits for various types of spontaneous murine cancer in randomized controlled trials and in anecdotal reports from a variety of advanced metastatic human cancer not known to be associated with progesterone receptors. The theory of its mechanism is that it prevents the secretion of a progesterone-induced immunomodulatory protein in the tumor microenvironment, or in the tumor cell itself, called the progesterone-induced blocking factor, which inhibits natural killer cells from attacking the cancer cell. Many anticancer chemotherapeutic agents fail to cross the blood-brain barrier and thus prove ineffective for brain cancer. The objective of the present study was to determine if mifepristone could provide palliative benefits to a patient with end-stage stage IV glioblastoma multiforme. CASE REPORT: A 43-year-old male with end-stage stage IV glioblastoma multiforme was exclusively treated with mifepristone 200 mg orally daily. RESULTS: The patient showed definite palliative effects for several weeks and his life was significantly extended beyond pre-treatment predictors. CONCLUSION: It appears that mifepristone does cross the blood-brain barrier and could be considered for palliative therapy of other patients with chemotherapy-resistant brain cancer.

Mifepristone causing complete remission of rapidly advancing leukemia with measurement of progesterone-induced blocking factor.

BACKGROUND: Mifepristone has been demonstrated to cause palliation from murine and human cancer, even in cancers not known to be positive for expression of progesterone receptors. The aim of the present study was to determine if rapidly advancing chronic lymphocytic leukemia responds to mifepristone therapy, and if so, is this effect related to increased expression of the progesterone-induced blocking factor? CASE REPORT: An 81-year-old woman with chronic lymphocytic leukemia whose condition progressed to the acute rapidly progressing stage agreed to be exclusively treated orally with 200 mg mifepristone daily. RESULTS: The patient showed a dramatic improvement after a short exposure time to mifepristone. Complete remission has persisted so far for 12 months on exclusive mifepristone therapy. Her PIBF levels were normal before mifepristone therapy and did not change after treatment. CONCLUSION: Mifepristone can provide marked improvement of human leukemia even in the absence of increased serum PIBF levels.