Evaluation of Fetal First and Second Cervical Vertebrae: Normal or Abnormal?

OBJECTIVES: To use 3-dimensional sonographic volumes to evaluate the variable appearance of the normal fetal cervical spine and craniocervical junction, which if unrecognized may lead to misdiagnosis of malalignment at the first and second cervical vertebrae (C1 and C2). METHODS: Three-dimensional sonographic volumes of the fetal cervical spine were obtained from 24 fetuses at gestational ages between 12 weeks 6 days and 35 weeks 1 day. The volumes were reviewed on 4-dimensional software, and the vertebral level was determined by labeling the first rib-bearing vertebra as the first thoracic vertebra. The ossification centers of the cervical spine and occipital condyles were then labeled accordingly and evaluated for alignment and structure by rotating the volumes in oblique planes. The appearance on multiplanar images was assessed for possible perceived anomalies, including malalignment, particularly at the C1 and C2 levels. Evidence of head rotation was correlated with the presence of possible malalignment at C1-C2. Head rotation was identified in the axial plane by measuring the angle of the anteroposterior axis of C1 to the anteroposterior axis of C2. RESULTS: Of the 24 fetuses, 16 had adequate quality to assess the entire cervical spine and craniocervical junction. All 16 cases showed an osseous component of C1 that did not align directly with C2 on some of the multiplanar images when the volumes were rotated, which could lead to suspected diagnosis of spinal malalignment or a segmental abnormality, as occurred in 2 clinical cases in our practice. All 16 cases showed at least some degree of head rotation, ranging from 2° to 36°, which may possibly explain the apparent malalignment. The lateral offset from C1 to C2 ranged from 0.0 to 3.3 mm. CONCLUSIONS: The normal C1 and C2 ossification centers may appear to be malaligned due to normal offsetting (lateral displacement) of C1 on C2. An understanding of the normal development of the cervical spine is important in assessing spinal anatomy.

Comparing the effectiveness of existing anxiety treatment options among patients evaluated for chest pain and anxiety in the emergency department setting: Study protocol for the PACER pragmatic randomized comparative effectiveness trial.

BACKGROUND: Anxiety disorders are a common underlying cause of symptoms among low-risk chest pain patients evaluated in the emergency department setting. However, anxiety is often undiagnosed and undertreated in any setting, and causes considerable functional impairment to work, family, and social life. OBJECTIVES: The Patient-Centered Treatment of Anxiety after Low-Risk Chest Pain in the Emergency Room (PACER) study is a pragmatic randomized trial to test the comparative effectiveness of existing anxiety treatments of graduated intensities and determine what options work best for patient subgroups based on anxiety severity and other comorbidities. METHODS: The PACER trial will enroll 375 emergency department patients with low-risk chest pain and anxiety (GAD-7 score ≥ 8) and randomize them to either: 1) referral to primary care with enhanced care coordination, 2) online self-administered cognitive behavioral therapy with guided peer support, or 3) therapist-administered cognitive behavior therapy. Outcomes include anxiety symptoms (primary) as well as physical symptom burden, depression symptoms, functional impairment, ED recidivism, and occurrence of major adverse cardiac events. Statistical analyses will be conducted primarily using linear mixed models to perform a repeated measures analysis of patient-reported outcomes, assessed at 3, 6, 9, and 12-month follow-ups. DISCUSSION: PACER is an innovative and pragmatic clinical trial that will compare the effectiveness of several evidence-based telecare-delivered treatments for anxiety. Results have the potential to inform clinical guidelines for evaluation and management of low-risk chest pain patients and promote adoption of findings in ED departments across the country.

Assessing the multidisciplinary team approaches to placenta accreta spectrum across five institutions within the University of California fetal Consortium (UCfC).

PURPOSE: To describe the multidisciplinary approaches to placenta accreta spectrum (PAS) across five tertiary care centers that comprise the University of California fetal Consortium (UCfC) and to identify potential best practices. MATERIALS AND METHODS: Retrospective review of all cases of pathologically confirmed invasive placenta delivered from 2009 to 2014 at UCfC. Differences in intraoperative management and outcomes based on prenatal suspicion were compared. Interventions assessed included ureteral stent use, intravascular balloon use, anesthetic type, gynecologic oncology (Gyn Onc) involvement, and cell saver use. Intervention variation by institution was also assessed. Analyses were adjusted for final pathologic diagnosis. Chi-square, Fisher's exact, Student's t-test, and Mann-Whitney's U-test were used as appropriate. Binary logistic regression and multivariable linear regression were used to adjust for confounders. RESULTS: One hundred and fifty-one cases of pathologically confirmed invasive placenta were identified, of which 82% (123) were suspected prenatally. There was no correlation between the degree of invasion on prenatal imaging and use of each intervention. Ureteral stents were placed in 33% (41) of cases and did not reduce GU injury. Intravascular balloons were placed in 29% (36) of cases and were associated with shorter OR time (161 versus 236 min, p < .01) and lower estimated blood loss (EBL) (1800 versus 2500 ml, p < .01). General endotracheal anesthesia (GETA) was used in 70% (86). EBL did not differ between GETA and regional anesthesia. Gyn Onc was involved in 58% (71) of cases and EBL adjusted for final pathology was reduced with their involvement (2200 versus 2250 ml, p = .02) while OR time and intraoperative complications did not differ. Cell saver was used in 20% (24) and was associated with longer OR time (296 versus 200 min, p < .01). Use of cell saver was not associated with a difference in EBL or number of units of packed red cells transfused. All analyses were adjusted for pathologic severity of invasion. CONCLUSIONS: Intravascular interventions such as uterine artery balloons and the inclusion of Gynecologic Oncologists as part of a multidisciplinary approach to treating PAS reduce EBL. Additionally, the placement of intravascular balloons may reduce OR time. No significant differences were seen in outcomes when comparing the use of ureteral stents, general anesthesia, or institutions. A team of experienced operators with a standard approach may be more significant than specific practices.

Maternal Human Papillomavirus and Preterm Premature Rupture of Membranes: A Retrospective Cohort Study.

Introduction: To determine whether maternal human papillomavirus (HPV) infection is associated with preterm premature rupture of membranes (PPROM). Materials and Methods: We conducted a retrospective cohort study of singleton deliveries at our institution from 2010 to 2015. Women, ages 16-49, with HPV genotyping or cervical cytology results 3 years before delivery were included. Chi-squared and logistic regression analyses were used. Results: In our cohort of 2153 women, 38.5% were HPV positive. PPROM was observed in 2.88% of women. HPV infection (p = 0.02), history of PPROM (p < 0.001), history of cervical conization or loop electrical excision procedure (LEEP) (p < 0.05), parity (p = 0.001), maternal body mass index at delivery (p < 0.001), drug use or smoking (p < 0.001), and ethnicity (p = 0.01) were associated with PPROM. HPV infection (odds ratio [OR] = 2.07, 95% confidence interval [CI]: 1.03-4.14) remained associated with PPROM when adjusting for history of PPROM, cervical conization, drug use or smoking, parity, ethnicity, and insurance. PPROM was associated with preterm delivery (OR = 105.50, 95% CI: 29.49-377.46) when adjusting for HPV infection, pregnancy-related hypertension, diabetes, placenta previa and abruption, cervical conization, smoking or drug use, ethnicity, and history of PPROM. HPV infection was associated with preterm delivery (p = 0.04) in univariate analysis, but not after adjusting for PPROM (p = 0.13). HPV infection had a univariate association with newborn septicemia (p = 0.02), respiratory distress syndrome (RDS) (p = 0.01), neonatal intensive care unit (NICU) admission (p = 0.001), and low birthweight (p = 0.03). Conclusions: HPV infection was associated with an increased risk of PPROM in this cohort. However, maternal HPV infection does not increase the risk of preterm delivery beyond those caused by PPROM. The observed association between maternal HPV infection and neonatal morbidity is likely due to the relationship between PPROM and preterm delivery.

Targeted delivery at 34 versus 35 weeks in women with preterm prelabor rupture of membranes.

Objective: To compare planned delivery at 34 versus 35 weeks for women with preterm prelabor rupture of membranes (PPROM). Materials and methods: We performed a retrospective cohort study of singleton pregnancies with PPROM after 24 weeks delivered from 2006 to 2014. In 2009, an institutional practice change established 35 weeks as the target gestational age before induction of labor was initiated after PPROM. Demographic and outcome measures were compared for two cohorts: women delivered 2006-2008 - target 34 weeks (T34) and women delivered 2009-2014 - target 35 weeks (T35). The primary outcome was neonatal intensive care unit (NICU) admission. Results: Of the 382 women with PPROM, 153 (40%) comprized the T34 cohort and 229 (60%) comprized the T35 cohort. Demographic characteristics were similar between groups. There were no differences between groups in gestational age at PPROM (31.0 ± 3.3 weeks versus 31.2 ± 3.1 weeks; p = .50) or maternal complications. The mean gestational age at delivery was earlier in the T34 group (31.8 ± 3.2 weeks versus 32.4 ± 2.7 weeks; p = .04). The median predelivery maternal length of stay (LOS) was 1 day longer in the T35 group (p = .03); the total and postpartum LOS were similar between groups (p > .05). There were no differences in the rate of NICU admission (T34 89.5% versus T35 92.1%; p = .38) or median neonatal LOS (T34 14 days versus T35 17 days; p = .15). In those patients who reached their target gestational age, both maternal predelivery LOS and total LOS were longer in the T35 group (p > .05). The frequency of NICU admission in those reaching their target gestational age was similar between groups (T34 83.37% versus T35 76.19%; p = .46). Conclusions: A 35-week target for delivery timing for women with PPROM does not decrease NICU admissions or neonatal LOS. This institutional change increased maternal predelivery LOS, but did not increase maternal or neonatal complications.

Maternal and neonatal outcomes among scheduled versus unscheduled deliveries in women with prenatally diagnosed, pathologically proven placenta accreta.

OBJECTIVE: To evaluate maternal and neonatal outcomes among scheduled versus unscheduled deliveries in cases of prenatally diagnosed, pathologically proven placenta accreta. STUDY DESIGN: Retrospective cohort of placenta accreta cases delivered in five University of California hospitals. RESULTS: Of 151 cases of histopathologically proven placenta accreta, 82% were prenatally diagnosed. Sixty-seven percent of women underwent scheduled deliveries and 33% were unscheduled. There were no differences in demographics between groups except a higher rate of antepartum bleeding in the unscheduled delivery group (81 versus 53%; p = .003). Scheduled deliveries were associated with a later gestational age at delivery (34.6 versus 32.6 weeks; p = .001), lower blood loss (2.0 versus 2.5 l; p = .04), higher birth weight (2488 versus 2010 g; p < .001), shorter postpartum length of stay (4 versus 5 d; p = .03) and neonatal length of stay (12 versus 20 d; p = .005). CONCLUSION: Despite a prenatal diagnosis of placenta accreta, 1/3 of these cases require unscheduled delivery, portending poorer maternal and neonatal outcomes.

Salpingectomy Compared With Tubal Ligation at Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To estimate whether performance of salpingectomy compared with standard tubal ligation for sterilization at the time of cesarean delivery increases operating time or complication rates. METHODS: A randomized controlled noninferiority trial was performed at a single academic institution. Women undergoing planned cesarean delivery who desired sterilization were randomized to salpingectomy or standard tubal ligation. The primary outcome was length of time of the sterilization procedure, with the noninferiority margin set at 5 minutes. With a one-sided independent sample t test, to achieve a power of 90% with an α of 0.05, 18 women needed to complete each intervention. RESULTS: Forty-four women were enrolled, with 19 successfully undergoing salpingectomy and 18 undergoing standard tubal ligation. Salpingectomy could not be completed in 1 of 20 patients (as a result of adhesions). Baseline demographics were equivalent between groups. Salpingectomy procedure time was noninferior to standard tubal ligation, with a mean difference of 0.5 minutes, with a mean sterilization procedure time of 5.6 minutes in the salpingectomy group and 6.1 minutes in the standard tubal ligation group (P <.05, one-sided 95% CI upper bound 1.8 minutes). There was no difference between cesarean delivery with salpingectomy compared with cesarean delivery with standard tubal ligation in median total operating time (60 vs 68 minutes, P=.34) or estimated blood loss (600 vs 700 mL, P=.09). No patients in either group required reoperation or readmission. CONCLUSION: Salpingectomy procedure time was not longer than standard tubal ligation during cesarean delivery, with a mean difference of 30 seconds. There was a high completion rate for salpingectomy (95%) and no apparent increase in complications. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT03028623.

The effect of oral contraceptives on bone mass and stress fractures in female runners.

PURPOSE: To determine the effect of oral contraceptives (OC) on bone mass and stress fracture incidence in young female distance runners. METHODS: One hundred fifty competitive female runners ages 18-26 yr were randomly assigned to OC (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) or control (no intervention) for 2 yr. Bone mineral density (BMD) and content (BMC) were measured yearly by dual x-ray absorptiometry. Stress fractures were confirmed by x-ray, magnetic resonance imaging, or bone scan. RESULTS: Randomization to OC was unrelated to changes in BMD or BMC in oligo/amenorrheic (N=50) or eumenorrheic runners (N=100). However, treatment-received analyses (which considered actual OC use) showed that oligo/amenorrheic runners who used OC gained about 1% per year in spine BMD (P<0.005) and whole-body BMC (P<0.005), amounts similar to those for runners who regained periods spontaneously and significantly greater than those for runners who remained oligo/amenorrheic (P<0.05). Dietary calcium intake and weight gain independently predicted bone mass gains in oligo/amenorrheic runners. Randomization to OC was not significantly related to stress fracture incidence, but the direction of the effect was protective in both menstrual groups (hazard ratio [95% CI]: 0.57 [0.18, 1.83]), and the effect became stronger in treatment-received analyses. The trial's statistical power was reduced by higher-than-anticipated noncompliance. CONCLUSION: OC may reduce the risk for stress fractures in female runners, but our data are inconclusive. Oligo/amenorrheic athletes with low bone mass should be advised to increase dietary calcium and take steps to resume normal menses, including weight gain; they may benefit from OC, but the evidence is inconclusive.

Maternal and neonatal outcomes in women with twin pregnancies with excessive gestational weight gain.

OBJECTIVE: To determine if an excessive rate of gestational weight gain (GWG) in twin pregnancies is associated with adverse obstetric outcomes. METHODS: Retrospective cohort study of twin pregnancies delivered at the University of California, San Diego 2001-2014. Women were included if they had adequate or excessive rates of GWG as determined by Institute of Medicine guidelines. Demographic and outcome variables were collected by chart review. RESULTS: Four hundred and eighty-nine twin pregnancies met inclusion criteria. Of which, 40.5% had adequate rates of GWG and 41.5% had excessive rates of GWG. The rates of preterm birth and gestational diabetes were similar between the two groups. Gestational hypertension and preeclampsia were more common in women with excessive GWG (37.9% versus 19.7%; p < 0.01). This finding persisted in multivariate analysis. The mean birth weight percentiles were higher in the excessive GWG group and these women were also less likely to have an infant with a birth weight <10th percentile (21.4% versus 35.9%, p < 0.01). CONCLUSIONS: Excessive GWG is associated with a higher risk for gestational hypertension and preeclampsia, but no other adverse perinatal outcomes. Infants born to mothers with excessive GWG are less likely to be small for gestational age than those born to women with adequate GWG.

Placental Sonolucencies in the First Trimester: Incidence and Clinical Significance.

OBJECTIVES: The aims of this study were to determine the incidence of placental sonolucencies on first-trimester screening sonograms in a general obstetric population and assess whether these findings are associated with adverse obstetric outcomes. METHODS: A retrospective cohort analysis of 201 pregnant patients screened at a high-risk prenatal diagnostic center was conducted with first-trimester cine clips reviewed by 2 radiologists. Placental sonolucencies were defined as intraplacental anechoic or heterogeneous areas 0.7 cm or greater. Obstetric and neonatal outcomes were collected by chart review. RESULTS: Placental sonolucencies 0.7 cm or greater were seen in 45 (22.4%) of first-trimester ultrasound examinations. The ultrasonographic presence of a placenta previa, marginal sinus, and subchorionic hemorrhage was not more common in those with placental sonolucencies 0.7 cm or greater (P > 0.05). Sonolucencies were not associated with prior cesarean deliveries (P > 0.05). Both the groups with and without sonolucencies 0.7 cm or greater had similar rates of antepartum hemorrhage, preeclampsia, preterm delivery, cesarean delivery, postpartum hemorrhage, and delivery of small-for-gestational-age infants. One placenta accreta and no fetal demises occurred in the study population. CONCLUSIONS: Placental sonolucencies detected on first-trimester screening sonograms in the general obstetric population are not predictive of poor obstetric outcomes.

The association of antenatal corticosteroids with neonatal hypoglycemia and hyperbilirubinemia.

OBJECTIVE: While antenatal corticosteroids reduce the risk of neonatal morbidity and mortality, perhaps the maternal hyperglycemia they produce has other neonatal effects. Thus, we sought to examine the association between antenatal betamethasone exposure and neonatal hypoglycemia and hyperbilirubinemia. METHODS: We designed a retrospective cohort study of all preterm deliveries from 32 to 37 weeks of gestation at a single university hospital from 1990 to 2007. Data were collected on antenatal betamethasone administration and the neonatal outcomes. Univariable, multivariable and stratified analyses were conducted. RESULTS: Of 6675 preterm deliveries, significantly higher rates of neonatal hypoglycemia (5.7% versus 4.2%, p<0.05) and hyperbilirubinemia (45.9% versus 24.1%, p<0.05) were observed in neonates exposed to antenatal betamethasone. Controlling for potential confounders including gestational age, these findings persisted with betamethasone-exposed neonates 1.6 times more likely to have hypoglycemia (aOR 1.60, 95% CI 1.24-2.07) and 3.2 times more likely to have hyperbilirubinemia (aOR 3.23, 95% CI 2.92-3.58). CONCLUSIONS: Antenatal betamethasone was associated with neonatal hypoglycemia and hyperbilirubinemia. Further work to determine whether this association is related to maternal hyperglycemia should be conducted, given this could be addressed with strict maternal glycemic control during betamethasone administration.

Ultrasound estimation of fetal weight in small for gestational age pregnancies.

OBJECTIVE: Approximately half of small for gestational age (SGA) cases are due to maternal or fetal pathology, and may result in significant neonatal morbidity and mortality. The estimated fetal weight (EFW) measurement is the cornerstone of ultrasonographic findings when diagnosing and managing SGA pregnancies. Our objective was to determine the ultrasound accuracy of EFW in SGA pregnancies. METHODS: A retrospective chart review was performed of all pregnancies complicated by SGA from a single institution (Stanford University) over a 2-year-period (2004-2006). SGA was defined as EFW < or = 10%. 98 neonates whose last ultrasound for EFW occurred within 7 days of delivery were included in the study. The absolute differences between the EFW and birthweight (BW) were analyzed, and the absolute percent errors were calculated as (EFW - BW)/BW x 100. The mean absolute differences and mean absolute percent errors were analyzed across all gestational ages (GA) and EFWs using one-way analysis of variance. RESULTS: The mean absolute percent error for the entire cohort was 8.7% (+/-6.3%). There was no statistically significant difference in the mean absolute percent error across all GAs (<32 weeks, 32-36 weeks, >36 weeks), and EFWs (<1500 g, 1500-2000 g, >2000 g). CONCLUSION: Ultrasound measurement of EFW in SGA pregnancies is consistent across all GAs and EFW measurements.