Peripartum Prediction of Fetal Weight in Gravidas With Obesity.

OBJECTIVES: Estimated fetal weight (EFW) is an important metric at delivery as neonates with abnormal birthweight and their mothers are at higher risk of birth complications. Data regarding optimal EFW assessment in gravidas with obesity is inconsistent, and with the increasing incidence of obesity, clarification of this question is crucial. We aimed to compare accuracy of ultrasound (US)-derived EFW and clinical assessments of EFW in predicting neonatal birthweight among gravidas with obesity. METHODS: This prospective cohort study enrolled gravidas with obesity and a singleton pregnancy admitted for delivery at term. EFW was determined using either US biometry or clinical assessment (Leopold's maneuvers, Johnson's formula, and Insler's formula) at time of admission. Our primary outcome was accurate EFW, defined as EFW within 500 g of birthweight. Secondary outcomes included ability to predict small-for-gestational age (SGA) and large-for-gestational age (LGA) birthweights. These outcomes were compared between all EFW methods. RESULTS: A total of 250 gravidas with a median body mass index of 36.4 kg/m2 were enrolled. Admission US outperformed Leopold's maneuvers in obtaining accurate EFW (81.6% versus 74.5%, P = .03). When comparing all methods, Johnson's and Insler's formulae performed the worst, accurately predicting EFW in only 27.4% and 14.3% of cases, respectively. Likewise, US-derived EFW outperformed Leopold's maneuvers and fundal height in the prediction of SGA and LGA neonates. CONCLUSIONS: US is more accurate than clinical assessment of EFW in gravidas with obesity both for estimation of actual birthweight and prediction of abnormal birthweight. Universal late third-trimester or peripartum US for EFW should be considered in gravidas with obesity.

Reference Ranges for Left Modified Myocardial Performance Index: Systematic Review and Meta-Analysis.

INTRODUCTION: The modified myocardial performance index (mod-MPI) is a noninvasive Doppler-derived metric used to evaluate fetal cardiac function. However, the reference ranges for mod-MPI in normal fetuses are not clearly defined, which limits the use of this technology in fetuses with potential cardiac compromise. Thus, we aimed to perform a systematic review and meta-analysis of published mod-MPI reference ranges across gestation. METHODS: The published literature was systematically searched, and all published articles in any language that provided values for the left ventricular mod-MPI obtained in low-risk, singleton fetuses were considered eligible for further review. All retrieved titles and abstracts were independently reviewed by two researchers. Mean and standard deviation by gestational week was extracted or calculated from published data. DerSimonian-Laird random-effects models were used to estimate pooled means and 95% confidence intervals (CIs). RESULTS: The search resulted in 618 unique citations, of which 583 did not meet inclusion criteria, leaving 35 abstracts selected for full-text review. Review of the references of these 35 articles identified another 5 studies of interest. Of the 40 articles reviewed, six met inclusion criteria. There was significant heterogeneity seen in the mod-MPI results reported. Mod-MPI increased as pregnancy progressed in all studies. The pooled mean mod-MPI at 11 weeks' gestation was 0.400 (95% CI 0.374-0.426) and increased to 0.585 (95% CI 0.533-0.637) at 41 weeks' gestation. The increase was linear in 5 of 6 studies, while in 1 study, the mod-MPI was stable until 27 weeks' gestation, and then increased throughout the third trimester. Despite all having trends increasing over pregnancy, there was no study in which all the weekly means fell within the pooled 95% CI. CONCLUSION: While mod-MPI does increase over gestation, the true "reference ranges" for fetuses remain elusive. Future efforts to further optimize calculation of time intervals possibly via automation are desperately needed to allow for reproducibility of this potentially very useful tool to assess fetal cardiac function.

Clinical significance of umbilical artery intermittent vs persistent absent end-diastolic velocity in growth-restricted fetuses.

BACKGROUND: Umbilical artery absent end-diastolic velocity indicates increased placental resistance and is associated with increased risk of perinatal demise and neonatal morbidity in fetal growth restriction. However, the clinical implications of intermittent vs persistent absent end-diastolic velocity are unclear. OBJECTIVE: We compared umbilical artery Doppler velocimetry changes during pregnancy and neonatal outcomes between pregnancies with fetal growth restriction and intermittent absent end-diastolic velocity and those with persistent absent end-diastolic velocity. STUDY DESIGN: In this retrospective study of singletons with fetal growth restriction and absent end-diastolic velocity, umbilical artery Doppler abnormalities were classified as follows: intermittent absent end-diastolic velocity (<50% of cardiac cycles with absent end-diastolic velocity) and persistent absent end-diastolic velocity (≥50% of cardiac cycles with absent end-diastolic velocity). The primary outcome was umbilical artery Doppler progression to reversed end-diastolic velocity. Secondary outcomes included sustained umbilical artery Doppler improvement, latency to delivery, gestational age at delivery, neonatal morbidity composite, rates of neonatal intensive care unit admission, and length of neonatal intensive care unit stay. Outcomes were compared between intermittent absent end-diastolic velocity and persistent absent end-diastolic velocity. Multivariate logistic regression was used to adjust for confounders. A receiver operating characteristic curve was generated to assess the sensitivity and specificity of the percentage of waveforms with absent end-diastolic velocity in predicting the neonatal composite. The Youden index was used to calculate the optimal absent end-diastolic velocity percentage cut-point for predicting the neonatal composite. RESULTS: Of the 77 patients included, 38 had intermittent absent end-diastolic velocity and 39 had persistent absent end-diastolic velocity. Maternal characteristics, including age, parity, and preexisting conditions did not differ significantly between the 2 groups. Progression to reversed end-diastolic velocity was less common in intermittent absent end-diastolic velocity than in persistent absent end-diastolic velocity (7.9% vs 25.6%; odds ratio, 0.25; 95% confidence interval, 0.06-0.99). Sustained umbilical artery Doppler improvement was more common in intermittent absent end-diastolic velocity than in persistent absent end-diastolic velocity (50.0% vs 10.3%; odds ratio, 8.75; 95% confidence interval, 2.60-29.5). Pregnancies with intermittent absent end-diastolic velocity had longer latency to delivery than those with persistent absent end-diastolic velocity (11 vs 3 days; P<.01), and later gestational age at delivery (33.9 vs 28.7 weeks; P<.01). Composite neonatal morbidity was less common in the intermittent absent end-diastolic velocity group (55.3% vs 92.3%; P<.01). Neonatal death occurred in 7.9% of intermittent absent end-diastolic velocity cases and 33.3% of persistent absent end-diastolic velocity cases (P<.01). The differences in neonatal outcomes were no longer significant when controlling for gestational age at delivery. The percentage of cardiac cycles with absent end-diastolic velocity was a modest predictor of neonatal morbidity, with an area under the receiver operating characteristic curve of 0.71 (95% confidence interval, 0.58-0.84). The optimal percentage cut-point for fetal cardiac cycles with absent end-diastolic velocity observed at the sentinel ultrasound for predicting neonatal morbidity was calculated to be 47.7%, with a sensitivity of 65% and specificity of 85%. CONCLUSIONS: Compared with persistent absent end-diastolic velocity, diagnosis of intermittent absent end-diastolic velocity in the setting of fetal growth restriction is associated with lower rates of progression to reversed end-diastolic velocity, higher likelihood of umbilical artery Doppler improvement, longer latency to delivery, and higher gestational age at delivery, leading to lower rates of neonatal morbidity and death. Our data support using an absent end-diastolic velocity percentage cut-point in 50% of cardiac cycles to differentiate intermittent absent end-diastolic velocity from persistent absent end-diastolic velocity. This differentiation in growth-restricted fetuses with absent end-diastolic velocity may allow further risk stratification.

The association of fetal acidemia with adverse neonatal outcomes at time of scheduled cesarean delivery.

BACKGROUND: Fetal acidemia at the time of a scheduled cesarean delivery is generally unexpected. In the setting of reassuring preoperative monitoring, the duration of fetal acidemia in this scenario is presumably brief. The neonatal sequelae and risks associated with brief fetal acidemia in this setting are unknown. OBJECTIVE: We aimed to assess whether fetal acidemia at the time of a scheduled prelabor cesarean delivery is associated with adverse neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of singleton, term, nonanomalous, liveborn neonates delivered by scheduled cesarean delivery that was performed under regional anesthesia from 2004 to 2014 at a single tertiary care center with a universal umbilical cord gas policy. Neonates born to laboring gravidas and those whose cesarean delivery was performed for nonreassuring fetal status were excluded. All included patients had reassuring preoperative fetal monitoring. The primary outcome was a composite adverse neonatal outcome that included neonatal death, encephalopathy, therapeutic hypothermia, seizures, intubation, and respiratory distress. This outcome was compared between patients with and those without fetal acidemia (umbilical artery pH <7.2). A multivariable logistic regression was used to adjust for confounders. Cases of fetal acidemia were further characterized as respiratory, metabolic, or mixed acidemia based on additional umbilical cord gas values. Secondary analyses examining the association between the type of acidemia and neonatal outcomes were also performed. RESULTS: Of 2081 neonates delivered via scheduled cesarean delivery, 252 (12.1%) had fetal acidemia at the time of delivery. Acidemia was more common in breech neonates and in neonates born to gravidas with obesity and gestational diabetes mellitus. Compared with fetuses with normal umbilical artery pH, those with fetal acidemia were at a significantly increased risk for adverse neonatal outcome (adjusted relative risk, 2.95; 95% confidence interval, 2.03-4.12). This increased risk was similar regardless of the type of acidemia. CONCLUSION: Even a brief period of mild acidemia is associated with adverse neonatal outcomes at the time of a scheduled cesarean delivery despite reassuring preoperative monitoring. Addressing modifiable intraoperative factors that may contribute to fetal acidemia at the time of a scheduled cesarean delivery, such as maternal hypotension and prolonged operative time, is an important priority to potentially decrease neonatal morbidity in full-term gestations.

Risk Factors and Maternal Morbidity Associated with Unintentional Hysterotomy Extension at the Time of Cesarean Delivery.

OBJECTIVE: Our aim was to estimate the incidence of unintentional hysterotomy extension at the time of cesarean delivery and to identify associated risk factors and maternal morbidity. STUDY DESIGN: We conducted a secondary analysis of a randomized controlled trial evaluating chlorhexidine-alcohol versus iodine-alcohol for skin antisepsis in women undergoing cesarean delivery. We included patients with a low transverse hysterotomy. The primary outcome was the incidence of unintentional hysterotomy extension. Logistic regression was performed to identify independent factors associated with hysterotomy extension. Maternal morbidity was compared between patients with and without extension. RESULTS: Of 1,038 patients meeting the inclusion criteria, 71 (6.8%; 95% confidence interval [CI]: 5.4-8.5%) experienced a hysterotomy extension. Of several potential risk factors assessed, the second stage of labor was the only independent predictor of hysterotomy extension (adjusted odds ratio: 10.2; 95% CI: 2.6-39.8). Hysterotomy extension was associated with increased operative time (73 vs. 55.3 minutes; p< 0.01), need for blood transfusion (relative risk: 5; 95% CI: 1.6-15.2), and rate of additional surgical injury (RR: 17; 95% CI: 6.9-41.8). CONCLUSION: Hysterotomy extensions are not infrequent at the time of cesarean delivery and are associated with increased maternal morbidity. Cesarean delivery during the second stage of labor is the main independent risk factor for hysterotomy extension.

Predictors and timing of hydrocephalus treatment in patients undergoing prenatal versus postnatal surgery for myelomeningocele.

OBJECTIVE: Although hydrocephalus rates have decreased with intrauterine surgery for myelomeningocele (MMC), 40%-85% of children with MMC still go on to develop hydrocephalus. Prenatal ventricle size is known to be associated with later development of hydrocephalus; however, it is not known how prediction measures or timing of hydrocephalus treatment differ between pre- and postnatal surgery for MMC. The goal of this study was to determine anatomical, clinical, and radiological characteristics that are associated with the need for and timing of hydrocephalus treatment in patients with MMC. METHODS: The authors retrospectively identified patients from Barnes Jewish Hospital or St. Louis Children's Hospital between 2016 and 2021 who were diagnosed with MMC prenatally and underwent either pre- or postnatal repair. Imaging, clinical, and demographic data were examined longitudinally between treatment groups and hydrocephalus outcomes. RESULTS: Fifty-eight patients were included (27 females, 46.6%), with a mean gestational age at birth of 36.8 weeks. Twenty-three patients (39.7%) underwent prenatal surgery. For the overall cohort, the ventricle size at prenatal ultrasound (HR 1.175, 95% CI 1.071-1.290), frontal-occipital horn ratio (FOHR) at birth > 0.50 (HR 3.603, 95% CI 1.488-8.720), and mean rate of change in head circumference (HC) in the first 90 days after birth (> 0.10 cm/day: HR 12.973, 95% CI 4.262-39.486) were identified as predictors of hydrocephalus treatment. The factors associated with hydrocephalus in the prenatal cohort were FOHR at birth > 0.50 (HR 27.828, 95% CI 2.980-259.846) and the rate of change in HC (> 0.10 cm/day: HR 39.414, 95% CI 2.035-763.262). The factors associated with hydrocephalus in the postnatal cohort were prenatal ventricle size (HR 1.126, 95% CI 1.017-1.246) and the mean rate of change in HC (> 0.10 cm/day: HR 24.202, 95% CI 5.119-114.431). FOHR (r = -0.499, p = 0.008) and birth HC (-0.409, p = 0.028) were correlated with time to hydrocephalus across both cohorts. For patients who underwent treatment for hydrocephalus, those in the prenatal surgery group were significantly more likely to develop hydrocephalus after 3 months than those treated with postnatal surgery, although the overall rate of hydrocephalus was significantly higher in the postnatal surgery group (p = 0.018). CONCLUSIONS: Clinical and imaging factors associated with hydrocephalus treatment differ between those receiving pre- versus postnatal MMC repair, and while the overall rate of hydrocephalus is lower, those undergoing prenatal repair are more likely to develop hydrocephalus after 3 months of age. This has implications for clinical follow-up timing for patients treated prenatally, who may live at a distance from the treatment site.

Etiology and evaluation of stillbirth in patients with obesity.

OBJECTIVE: Maternal obesity is a risk factor for stillbirth, but whether or not the etiology of stillbirth differs in gravidas with and without obesity is unknown. We categorized stillbirths in a contemporary cohort to test the hypothesis that the etiology of stillbirth is different in gravidas with and without obesity. METHODS: This retrospective cohort study included all gravidas with a stillbirth ≥20 weeks' gestation between 2010 and 2017 and a normal mid-trimester anatomic survey by ultrasound assessment at a large academic institution. Pregnancies were excluded if delivery data were unavailable, a multifetal gestation was present, or there was an antenatally diagnosed fetal structural or genetic anomaly. Our primary exposure was maternal obesity, defined as a body mass index (BMI) ≥ 30 kg/m2 at the time of anatomic survey. Our primary outcome was stillbirth etiology, as classified by the initial causes of fetal death tool from the Stillbirth Collaborative Research Network and includes maternal, obstetric, hematologic, fetal, infectious, placental, other, or unexplained categories. Our secondary outcomes included the evaluation performed on each stillbirth, compliance with the recommended stillbirth evaluation by the American College of Obstetricians and Gynecologists (ACOG), and the percentage of abnormal results for each of the tests ordered for stillbirth evaluation. RESULTS: Of 118 stillbirths meeting the inclusion criteria, 44 (37.3%) occurred in gravidas with obesity and 74 (62.7%) were in patients without obesity. An obstetric complication was the most commonly identified etiology for stillbirth, found in 40.9% of cases with obesity versus in 29.7% of cases without obesity (aOR 1.09, 95% CI 0.47-2.66). The likelihood of any specific etiology of stillbirth was not significantly different in gravidas of the two weight groups, after controlling for confounders. However, assignment to the unexplained stillbirth category was significantly less common in women with obesity, compared to those without obesity (aOR 0.18, 95% CI 0.05-0.67). There was no difference in testing performed on each stillbirth between the groups. Compliance with the ACOG-recommended diagnostic evaluation for stillbirth was similar in the two groups but was only performed in 10.2% of all cases of stillbirth. Placental pathology was the test most likely to yield an abnormal result in both groups, but the percentage of abnormal results for this and all other tests was the same in the presence and absence of obesity. CONCLUSION: There is no specific etiology of stillbirth seen in gravidas with obesity, compared to those without obesity, after controlling for maternal confounders. We surmise that the evaluation recommended for stillbirth assessment in the general population is appropriate for stillbirth evaluation in gravidas with obesity. Testing pursued was similar between groups, but compliance with ACOG recommendations for testing after stillbirth was deficient in the cohort. Future work should aim to identify and address barriers to completing the recommended stillbirth evaluation.

Simulation Training for Operative Vaginal Delivery Among Obstetrics and Gynecology Residents: A Systematic Review.

OBJECTIVE: To perform a systematic review of the literature on the effect of simulation training of operative vaginal delivery on learner technique and knowledge, operator comfort, and patient-centered outcomes. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, ERIC, The Cochrane Library, and ClinicalTrials.gov were searched from inception through April 2017. The search criteria used MeSH terms ("simulation training," "high fidelity simulation training," "teaching," "obstetrical extraction," "obstetrical forceps," "vaginal delivery," "clinical competence," and "internship and residency"). METHODS OF STUDY SELECTION: A total of 30,813 articles were reviewed for inclusion. Studies detailing operative vaginal delivery simulation using forceps or vacuums and reporting health care provider or patient outcomes were eligible. TABULATION, INTEGRATION, AND RESULTS: All studies were independently reviewed by two investigators for inclusion. Only eight articles assessed the effect of simulation on trainee skill and comfort or patient outcomes and were included. Four were pretest-posttest studies, two were cross-sectional studies, one was a case-control study, and one was a cohort study. No randomized trials were identified. Simulation was associated with improved forceps placement accuracy and generated force during extraction, as well as increased operator knowledge and comfort with operative vaginal delivery. Additionally, simulation had no association with forceps failure rates, but there was an association with decreased rates of maternal lacerations and neonatal injury. The quality of the included studies was assessed with the Medical Education Research Study Quality Instrument, with a median score of 9.75 (range 9.0-13.5), indicating low-to-moderate quality. CONCLUSION: The available evidence suggests that improved technique, comfort, knowledge, and patient outcomes are associated with operative vaginal delivery simulation, but additional studies are required to further characterize such benefits for both forceps and vacuum. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018087343.

AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer.

The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer.