TAVR Beyond Fetal Viability: An Alternative to Preterm Delivery in Symptomatic Severe Aortic Stenosis.

A patient with structural valve degeneration of an aortic bioprosthesis with stenosis stage 3 underwent valve-in-valve transcatheter aortic valve replacement (TAVR) at 29 weeks with improvement. This is the first reported TAVR in the third trimester. TAVR may be an alternative to preterm delivery in cases of symptomatic aortic stenosis.

Structural Anomalies in Multifetal Gestations.

Multifetal gestations are at increased risk for structural anomalies relative to singletons. Determination of chorionicity is critical, as the risk is highest for monochorionic pregnancies. In a singleton gestation, counseling is structured around optimization of fetal outcomes and careful consideration of the patient's choices in management decisions. However, in multifetal gestations affected by a fetal anomaly, complex counseling with consideration for the pregnancy as a whole is necessary. We review the incidence of structural anomalies in twins and highlight unique considerations including selective termination for discordant anomalies. We emphasize the role of shared decision making between provider and patient.

Multidisciplinary approach to congenital central hypoventilation syndrome during pregnancy: case report.

Congenital central hypoventilation syndrome is a rare genetic disorder that affects control of breathing caused by variants in the paired-like homeobox 2B (PHOX2B) gene. During pregnancy, women with congenital central hypoventilation syndrome are at risk for hypoventilation and require frequent assessments of oxygenation and ventilation during wakefulness and sleep on their ventilator. This could potentially lead to adjustments in the ventilator settings or a change in the assisted ventilation modality. We report the case of a 31-year-old pregnant woman with congenital central hypoventilation syndrome and an implanted cardiac pacemaker who underwent prenatal genetic testing for congenital central hypoventilation syndrome and who delivered a healthy newborn by cesarean delivery. She received collaborative multidisciplinary care from a team that included specialists in obstetrics, maternal and fetal medicine, medical genetics, sleep and pulmonary medicine, cardiology, and anesthesiology. She used bilevel positive airway pressure therapy throughout pregnancy and after cesarean delivery without requiring adjustments in the bilevel positive airway pressure settings. Our case highlights the importance of multidisciplinary care in women with congenital central hypoventilation syndrome during pregnancy to optimize pregnancy and fetal outcomes.

A Survey of Women and Their Providers Regarding Gestational Weight Gain.

Background: Inappropriate gestational weight gain (GWG) is prevalent in the United States. About 20% of women gain below Institute of Medicine (IOM) recommendations; more than 50% gain above. GWG outside of recommendations is linked to poor birth outcomes and health issues for mother and baby. Counseling by health care providers is important to encourage appropriate GWG. Methods: Assess patient recall of counseling regarding GWG, provider knowledge, and opinions about IOM GWG guidance, and GWG outcomes in a subset of women. Cross-sectional, with questionnaires distributed by 8 medical centers across the United States to patients. Questionnaires were distributed to providers and data on maternal body mass index (BMI) and GWG collected at seven sites. Results: A total of 1,157 women returned questionnaires (1,820 maximum possible). A majority at all sites reported a provider discussed their expected GWG with them. Close to half reported that a provider had discussed potential harms from inappropriate GWG. Most of the women (71.2%) considered their obstetrician to be a helpful resource for GWG advice. Most providers (87.5%) reported they were aware of IOM guidelines. As many providers disagreed (18.8%) as agreed (20.8%) that they were successful helping their patients attain appropriate GWG (58.3% were neutral). Physician self-reported confidence was associated with whether they believed they could help their patients avoid excessive GWG. The most common outcome was GWG above recommendations (51.4%). Overweight and obese women were more likely to gain above recommendations. Providers underestimated the proportion of their patients that gained below IOM recommendations (8.5% vs. 18.6%). Conclusions: Providers are aware of the dangers of excessive GWG and a majority of patients report receiving counseling. Providers appear more cognizant of excessive GWG and underestimate inadequate GWG. Most women are not achieving an appropriate GWG, with overweight and obese women especially likely to gain above recommendations.

Cervical Ectopic Pregnancy: Persistence Despite a Serologically Negative ß-hCG. A Case Report.

BACKGROUND: Cervical pregnancy is a rare type of ectopic pregnancy that can be associated with significant hemorrhage and loss of fertility. Given its rarity, most effective treatment protocols are not well established. CASE: A 33-year-old primigravid woman at 11 weeks' gestation presented to our institution with a cervical ectopic pregnancy with an initial ß-hCG of 114,080 IU/L. She received 2 doses of systemic multidose methotrexate (1 mg/kg) with oral leucovorin on alternating days. Fetal intracardiac potassium chloride injection was also performed. Despite an appropriate decline to undetectable levels of serum ß-hCG, as well as resumption of menses, there was persistent sonographic demonstration of the cervical ectopic pregnancy. Surgery was ultimately required to remove the ectopic products of conception. CONCLUSION: Despite seemingly successful medical treatment of the cervical ectopic pregnancy with resultant undetectable serum ß-hCG levels, surgery was necessary for complete resolution of the cervical pregnancy. This report supports the need to integrate both serum ß-hCG levels and ultrasound to ensure complete resolution of these rare pregnancies.

Effect of maternal cystic fibrosis genotype on diabetes in pregnancy.

OBJECTIVE: To evaluate the association between the cystic fibrosis (CF) genotype and the rate of diabetes complicating pregnancy. METHODS: We conducted a retrospective cohort analysis of all pregnant patients with CF from 1972-2011 at a single institution. Patients who were homozygous for the ΔF508 mutation were compared with patients who were heterozygous for the ΔF508 mutation. Primary outcomes measured were incidence of CF-related diabetes and gestational diabetes mellitus (GDM) stratified by CF genotype. Secondary outcomes measured included pancreatic insufficiency, preterm premature rupture of membranes, preterm delivery, mode of delivery, gestational age at delivery, and maternal mortality. RESULTS: We identified 54 pregnancies among 36 women who met inclusion criteria. Of these pregnancies, 28 (51.9%) were carried by women who were homozygous for the ΔF508 mutation. Homozygous women had a significantly greater incidence of pancreatic insufficiency (89.3% compared with 61.5%, P=.03) and diabetes complicating pregnancy (60.7% compared with 23.1%, P<.01) compared with heterozygous women. In addition, there was some evidence of an increased incidence of GDM specifically among homozygous women (35.7% compared with 15.4%, P=.12). Regarding neonatal outcome, there was a lower mean birthweight (2,881 g compared with 3,203 g, P=.04) among the women who were homozygous for the ΔF508 mutation. There was no statistical difference in preterm deliveries, mode of delivery, gestational age at delivery, rate of preterm premature rupture of membranes, or incidence of maternal mortality between the two groups. CONCLUSION: Women with CF who are homozygous for the ΔF508 mutation have an increased risk of having a pregnancy complicated by diabetes.

Role of TAp73alpha in induction of apoptosis by transforming growth factor-beta in gastric cancer cells.

Transforming growth factor-beta (TGF-beta) is implicated as a tumor suppressor because it eliminates cancer cells from normal tissues by inhibiting cell growth and inducing apoptosis. Although p53 tumor suppressor is required for TGF-beta-induced p21 WAF1 expression and cell growth inhibition, its role in TGF-beta-induced apoptosis remains unclear. Here, we report that TAp73alpha, which is a member of the p53 family, binds to p53-binding sites in the promoters of proapoptotic Bax and Puma to activate their transcription, and mediates TGF-beta-induced apoptosis in gastric cancer cells. Our findings reveal a novel role of TAp73alpha in the induction of apoptosis by TGF-beta in cancer cells.

Sonographic findings of trisomy 18 in the second trimester of pregnancy.

OBJECTIVE: The purpose of this study was to examine the sonographic findings in fetuses with trisomy 18 in the second trimester of pregnancy. METHODS: A retrospective review of the cytogenetic laboratory databases at 6 tertiary referral centers identified all cases of trisomy 18. The prenatal sonographic studies in fetuses at 15 to 21 weeks' gestation, done before invasive testing for the karyotype, were reviewed for anatomic and biometric findings. We defined abnormal fetal biometric findings as a biometric measurement (biparietal diameter, abdominal circumference, or femur length) below the fifth percentile in the second trimester. RESULTS: Of 98 fetuses with trisomy 18, 95 (97%) were detected sonographically; an anomaly was found in 92 (94%). A biometric measurement below the fifth percentile was noted in 50 (51%). Cardiac (63%) and central nervous system (34%) anomalies were most frequently detected. Although choroid plexus cysts were commonly seen, no fetuses with trisomy 18 and isolated choroid plexus cysts were found. CONCLUSIONS: Targeted sonography identified abnormal fetal anatomy or abnormal biometric findings in 97% of fetuses with trisomy 18 in the second trimester. A biometric measurement below the fifth percentile was noted in half of the cases in the second trimester.

Management of mild fetal pyelectasis: a comparative analysis.

OBJECTIVE: The purpose of this study was to compare 2 protocols for the antenatal management of isolated mild fetal pyelectasis and perform a cost analysis. METHODS: A retrospective analysis of unilateral and bilateral mild fetal pyelectasis followed at our institution from 2003 to 2006 was conducted. Fetuses with additional congenital anomalies or aneuploidy were excluded. Chi(2) analysis was used, and P < .05 was considered significant. RESULTS: Two hundred forty-four cases were identified, of which the majority were male (75.4% versus 24.6%). Eighty-eight patients were reevaluated every 4 weeks (protocol 1). The remaining 156 patients were reevaluated once in the third trimester (protocol 2). The mean number of ultrasound examinations in protocol 1 was 3.24, at a cost of $1187, compared with protocol 2, at $798. Resolution occurred in 59%, stabilization in 29%, and progression in 12%. There were no cases of progression to severe pyelectasis or a need for in utero intervention in either group. CONCLUSIONS: Mild fetal pyelectasis can be managed with 1 additional third-trimester ultrasound examination without a compromise in patient care. Average cost savings were $389 per patient for protocol 2, suggesting a benefit from this protocol over protocol 1.

Sonographic detection of trisomy 13 in the first and second trimesters of pregnancy.

OBJECTIVE: The purpose of this study was to examine sonographic findings in fetuses with trisomy 13. METHODS: A retrospective review of the cytogenetic laboratory databases at 6 tertiary referral centers identified all cases of trisomy 13. The prenatal sonographic studies in fetuses of less than 22 weeks' gestation, done before invasive testing for karyotype, were reviewed for anatomic and biometric findings. We defined abnormal fetal biometric findings as a biometric measurement (biparietal diameter, abdominal circumference, or femur length) below the fifth percentile in the second trimester. RESULTS: There were 8 cases of trisomy 13 found in the first trimester and 54 cases found in the second trimester, a total of 62 in all. In the first trimester, 6 of 8 had an anomaly identified (4 with cystic hygroma). In the second trimester, 49 of 54 were identified by sonography; 45 had an anomaly, and 4 had an abnormal fetal biometric measurement without an anomaly. The 5 missed diagnoses had early gestational age (<17 weeks; n = 3) or an inadequate survey secondary to poor visualization. Overall, 22 of 54 fetuses with trisomy 13 had an abnormal biometric measurement. The most common anomalies detected in the second trimester were heart defects (n = 34), central nervous system anomalies (n = 30), facial clefts (n = 19), abnormal hands (n = 13), and genitourinary anomalies (n = 9). CONCLUSIONS: Targeted sonography identified abnormal fetal anatomy or abnormal biometric measurements in 95% of fetuses with trisomy 13 in the second trimester after 17 weeks' gestation. A biometric measurement below the fifth percentile was noted in nearly half of cases in the second trimester.

Trial of vaginal breech delivery: current role.

Breech presentation occurs at term in approximately 3% to 4% of singleton gestations. This presentation is associated with a variety of maternal and fetal conditions including preterm labor, abnormal amniotic fluid volume, hydrocephaly, anencephaly, mullerian anomalies, abnormal placentation, and multifetal gestation. Cesarean delivery has been associated with increased risk of subsequent accreta, placenta previa, hemorrhage, and hysterectomy. The Term Breech Trial initially suggested that planned vaginal breech delivery is associated with increased neonatal morbidity and mortality compared with planned cesarean delivery. Long-term follow-up of these vaginally delivered infants contradict the initial findings. Current debate surrounds the dilemma of whether the untoward complications of cesarean delivery are warranted given uncertain minimal increases in neonatal survival and improvement in neurologic outcome with planned cesarean.

RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells.

The transcription factor RUNX3, which mediates apoptosis and cell growth inhibition in gastric epithelial cells, is a candidate tumor suppressor that is frequently lost in gastric cancer cells. Here, we found that restoration of RUNX3 expression in the cell line not expressing RUNX3 induced apoptosis and that it physically interacted with the Forkhead transcription factor FoxO3a/FKHRL1, known to be an important regulator of apoptosis and the cell cycle. Active unphosphorylated FoxO3a/FKHRL1 was expressed in the gastric cancer cell lines. RUNX3-induced apoptosis depended on the expression of Bim, a proapoptotic BH3-only protein, and both RUNX3 and FoxO3a/FKHRL1 were required for induction of Bim expression. Furthermore, we showed that interaction of RUNX3 and FoxO3a/FKHRL1 was also indispensable for Bim expression and apoptosis in mouse embryonic fibroblasts. In the Bim promoter, RUNX3 bound to two conserved RUNX-binding elements (RBE1 and RBE2), with RBE1 being immediately downstream of a FoxO-binding element. The physical interaction of RUNX3 and FoxO3a/FKHRL1 on the Bim promoter activated transcription of Bim. These findings show that RUNX3 cooperates with FoxO3a/FKHRL1 to participate in the induction of apoptosis by activating Bim and may play an important role in tumor suppression in gastric cancer.