William T. Schnettler

Clinical characterization and outcomes of preeclampsia with normal angiogenic profile

Objective: To compare the clinical characteristics and outcomes of preeclamptic women presenting with a normal plasma angiogenic profile with those subjects who are characterized by an abnormal angiogenic profile. Methods: This was a secondary analysis of a prospective cohort study in women presenting to obstetrical triage at <37 weeks of gestation and diagnosed with preeclampsia within 2 weeks of enrollment and in whom angiogenic factors (sFlt1 and PlGF) measurements were available. Patients were divided into two groups based on their circulating levels of these factors described as a ratio; the sFlt1/PlGF ratio, non-angiogenic preeclampsia (sFlt1/PlGF ratio <85) and angiogenic preeclampsia (sFlt1/PlGF ratio ≥85). The data are presented by sFlt1/PlGF category using median and quartile 1–quartile 3 for continuous variables and by frequency and sample sizes for categorical variables. Results: In our cohort, the patients with non-angiogenic preeclampsia (N = 46) were more obese [BMI: 35.2 (31.6, 38.7) versus 31.1 (28.0, 39.0), p = 0.04], more likely to have preexisting diabetes (21.7% versus 2.0%, p = 0.002) and presented at a later gestational age [35 (32, 37) versus 32 (29, 34) weeks, p < 0.0001] as compared with women with angiogenic preeclampsia (N = 51). Women with non-angiogenic preeclampsia had no serious adverse outcomes (elevated liver function tests/low platelets: 0% versus 23.5%, abruption: 0% versus 9.8%, pulmonary edema: 0% versus 3.9%, eclampsia: 0% versus 2.0 %, small for gestational age: 0% versus 17.7% and fetal/neonatal death: 0% versus 5.9%) as compared with women with angiogenic preeclampsia. The rate of preterm delivery <34 weeks was 8.7% in non-angiogenic preeclampsia compared with 64.7% in angiogenic preeclampsia (p < 0.0001). Interestingly, delivery between 34 and 37 weeks and resource utilization (hospital admission days) were similar in the two groups. Conclusion: In contrast to the angiogenic form, the non-angiogenic form of preeclampsia is characterized by little to no risk of preeclampsia-related adverse outcomes, other than iatrogenic prematurity. Incorporation of angiogenic biomarkers in the evaluation of preeclampsia may allow accurate and early identification of severe disease.

Cost and resource implications with serum angiogenic factor estimation in the triage of pre-eclampsia

To analyse the economic and resource implications of using plasma soluble fms‐like tyrosine kinase‐1 s(Flt1) and placenta growth factor (PlGF) measurements in pre‐eclampsia evaluation and management.

Complexity-loss in fetal heart rate dynamics during labor as a potential biomarker of acidemia☆

BACKGROUND Continuous fetal heart rate (FHR) monitoring remains central to intrapartum care. However, advances in signal analysis are needed to increase its accuracy in diagnosis of fetal hypoxia. AIMS To determine whether FHR complexity, an index of multiscale variability, is lower among fetuses born with low (≤7.05) versus higher pH values, and whether this measure can potentially be used to help discriminate the two groups. STUDY DESIGN Evaluation of a pre-existing database of sequentially acquired intrapartum FHR signals. SUBJECTS FHR tracings, obtained from a continuous scalp electrocardiogram during labor, were analyzed using the multiscale entropy (MSE) method in 148 singletons divided in two groups according to umbilical artery pH at birth: 141 fetuses with pH>7.05 and 7 with pH≤7.05. A complexity index derived from MSE analysis was calculated for each recording. RESULTS The complexity of FHR signals for the last two hours before delivery was significantly (p<0.004) higher for non-acidemic than for acidemic fetuses. The difference between the two groups remained significant (p<0.003) when FHR data from the last 30min before delivery were excluded. CONCLUSION Complexity of FHR signals, as measured by the MSE method, was significantly lower for acidemic than non-acidemic fetuses. These results are consistent with previous studies showing that decreased nonlinear complexity is a dynamical signature of disrupted physiologic control systems. This analytic approach may have discriminative value in FHR analysis.

Agreement and accuracy using the FIGO, ACOG and NICE cardiotocography interpretation guidelines

One of the limitations reported with cardiotocography is the modest interobserver agreement observed in tracing interpretation. This study compared agreement, reliability and accuracy of cardiotocography interpretation using the International Federation of Gynecology and Obstetrics, American College of Obstetrics and Gynecology and National Institute for Health and Care Excellence guidelines.

A modified fetal heart rate tracing interpretation system for prediction of cesarean section

Objective: To investigate whether a modified version of the 2008 National Institute of Child Health and Human Development (NICHD) interpretation system upon admission decreases cesarean delivery risk. Methods: This retrospective cohort study ascribed a modified category to the first 30 min of fetal heart rate (FHR) tracings in labor. Category I was divided into two subsets (Ia and Ib) by the presence of accelerations. Category II was divided into four subsets (IIa–IId) based on baseline FHR, variability, response to stimulation and decelerations. Log-binomial regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI). Results: A category was ascribed to 910 women. Most FHR tracings were Category Ia (65.8%), Ib (7.7%), IIb (11.8%) and IId (14.0%). Category Ib tracings (fewer than two accelerations) were 2.26 (95% CI: 1.13-4.52) times more likely to result in cesarean delivery for abnormal FHR tracing than Category Ia tracings. A similar increase in risk was seen when comparing Category IIb and Category IId with Category Ia. Conclusion: Application of a modified version of the 2008 NICHD FHR interpretation system to the initial 30 min of labor can identify women at increased risk of cesarean delivery for abnormal FHR tracing.

ACES: Accurate Cervical Evaluation With Sonography

Transvaginal sonographic cervical length screening is an important tool for the evaluation of preterm labor. However, a structured curriculum is lacking in obstetrics and gynecology residency programs. The Accurate Cervical Evaluation with Sonography (ACES) program was developed to address this deficiency and combines an online didactic course with a standardized performance assessment of live scans. We sought to evaluate the effectiveness of the ACES program to teach residents sonographic cervical length assessment.

Association of third-trimester abdominal circumference with provider-initiated preterm delivery

Abstract Objective: Evaluate the association of a small third-trimester abdominal circumference (AC < 10th percentile) in the setting of a normal estimated fetal weight (EFW ≥ 10th percentile) with gestational age at delivery, indication for delivery and neonatal outcomes. Methods: Retrospective cohort study at an academic hospital of women with singleton pregnancy seen for ultrasound from 28+0–33+6 weeks of gestation during 2009–2011. Outcomes were compared between two groups: normal AC (AC and EFW ≥ 10th percentile) and small AC (AC < 10th percentile and EFW ≥ 10th percentile). Results: Among 592 pregnancies, fetuses in the small AC group (n = 55) experienced a higher incidence of overall preterm delivery (RR: 2.2, 95% CI: 1.3–3.7) and provider-initiated preterm delivery (RR: 3.7, CI: 1.8–7.5) compared to those in the normal AC group (n = 537). Neonates in the small AC group had a lower median birth weight whether delivered at term (p < 0.001) or preterm (p = 0.04), but were not more likely to experience intensive care unit admission or respiratory distress syndrome (all p ≥ 0.35). Conclusions: Small AC, even in the setting of an EFW ≥ 10th percentile, was associated with a higher incidence of overall and provider-initiated preterm delivery despite similar neonatal outcomes. Further investigation is warranted to determine whether these preterm deliveries could be prevented.

Impaired Ultrasonographic Cervical Assessment After Voiding: A Randomized Controlled Trial

OBJECTIVE: To estimate whether the timing of bladder emptying affects focal myometrial contraction development and image adequacy. METHODS: Women at 14 0/7–32 0/7 weeks of gestation undergoing a transvaginal ultrasound examination from January 1, 2012, to September 1, 2012, were eligible for this blinded randomized controlled trial. Participants were randomly assigned to undergo transvaginal imaging immediately after urination (within 5 minutes) or to defer the imaging by at least 15 minutes. The primary outcome was focal myometrial contraction development as determined by two independent blinded reviews of the images. Secondary outcomes included image adequacy and the diagnosis of placenta previa. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using repeated-measures log binomial regression. RESULTS: Two hundred twenty-one women provided 335 randomized encounters for analysis. Women in the deferred scan group were 30% less likely to experience a focal myometrial contraction (28.1% compared with 40.5%, RR 0.70, 95% CI 0.52–0.93) and 41% less likely to have inadequate images (18.6% compared with 31.5%, RR 0.59, 95% CI 0.40–0.86). The two groups were equally likely to be diagnosed with placenta previa (P=.13). However, participants in the deferred scan group were 76% less likely to have images demonstrating a placenta previa and focal myometrial contraction (3.0% compared with 12.5%, RR 0.24, 95% CI 0.09–0.62) than participants in the immediate scan group. Eight women would need to defer imaging for 15 minutes from bladder voiding to prevent one focal myometrial contraction of the lower uterine segment or inadequate imaging. CONCLUSIONS: A brief interval (at least 15 minutes) between voiding and transvaginal cervical evaluation is associated with decreased risk for focal myometrial contractions and improved imaging. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01513395. LEVEL OF EVIDENCE: I

Management of abnormal serum markers in the absence of aneuploidy or neural tube defects

Objective: Few guidelines address the management of pregnancies complicated by abnormal maternal serum analytes (MSAs) in the absence of aneuploidy or neural tube defects (NTDs). Our objective was to gather preliminary data regarding current opinions and management strategies among perinatologists in the US. Methods: This survey of Maternal Fetal Medicine (MFM) physicians and fellows used a secure electronic web-based data capture tool. Results: A total of 545 potential participants were contacted, and 136 (25%) responded. The majority were experienced academic physicians with robust practices. Nearly all (97.7%) respondents reported a belief in an association between abnormal MSAs and adverse pregnancy outcomes other than aneuploidy or NTDs. Plasma protein A (PAPP-A) and α-fetoprotein (AFP) were most often chosen as markers demonstrating a strong association with adverse outcomes. Most (86.9%) respondents acknowledged that abnormal MSAs influenced their counseling approach, and the majority (80.1%) offered additional ultrasound examinations. Nearly half started at 28 weeks and almost one-third at 32 weeks. Respondents acknowledging a relevant protocol in their hospital or practice were more likely to offer additional antenatal testing (p = 0.01). Conclusions: Although most perinatologists were in agreement regarding the association of MSAs with adverse pregnancy outcomes, a lack of consensus exists regarding management strategies.

The utility of midtrimester ultrasound assessment of the subcutaneous space in predicting cesarean wound complications

Abstract Objective: To evaluate the association between cesarean wound complications and thickness of the subcutaneous space within the anterior abdomen at the midtrimester fetal anatomical survey. Methods: In this case-control study, cases were identified using an ICD9 code for wound complications of cesarean delivery. For each case, we identified the woman with the next consecutive midtrimester ultrasound who had a cesarean delivery without a wound complication, matched on age and race, as the control. A blinded investigator measured subcutaneous space at three distinct suprapubic levels in the midsagital plane. Results: Of 7228 women with a cesarean delivery, 123 (1.7%) had a wound complication. Seventy-nine cases were eligible. Midline suprapubic subcutaneous thickness did not differ between cases and controls at the superior, middle or inferior locations (p ≥ 0.35). Body mass index was moderately correlated with ultrasound-derived measurements (r ≥ 0.63; p < 0.001). The incidence of vertical skin incision, stapled skin closure and classical hysterotomy differed between groups (p ≤ 0.046). There was no significant increase in wound complication risk with increasing subcutaneous space thickness, even after adjustment (p ≥ 0.34). Conclusion: Prenatal ultrasound can quantify the subcutaneous space. Vertical skin incision, stapled wound closure, and a classical hysterotomy were associated with cesarean wound complication, but midtrimester subcutaneous thickness was not.