Interventions for Intrapartum Fetal Heart Rate Abnormalities.

Intrapartum fetal heart rate (FHR) decelerations may represent interrupted oxygen transfer to the fetus. In many cases, these interruptions are transient and do not result in progressive fetal acidemia with risk for asphyxia and neurological compromise. When significant FHR decelerations are present, reversible causes of reduced fetal oxygen delivery should be considered and corrective measures should be undertaken to optimize oxygenation. In this review, we describe potential intrapartum causes of reduced fetal oxygen delivery and the efficacy of common interventions for an abnormal FHR tracing.

Management of the Category II Fetal Heart Rate Tracing.

Management of the category II fetal heart rate (FHR) tracing presents a common challenge in obstetrics. Up to 80% of women will have a category II FHR tracing at some point during labor. Here we propose a management algorithm to identify specific features of the FHR tracing that correlate with risk for fetal acidemia, target interventions to address FHR decelerations, and guide clinicians about when to proceed toward operative vaginal delivery or cesarean to achieve delivery before there is a high risk for significant fetal acidemia with potential for neurological injury or death.

Perinatal outcomes associated with intrahepatic cholestasis of pregnancy.

OBJECTIVE: The objective of this study is to examine perinatal outcomes associated with cholestasis of pregnancy according to bile acid level and antenatal testing practice. STUDY DESIGN: Retrospective cohort study of women with symptoms and bile acid testing from 2005 to 2014. Women were stratified by bile acid level: no cholestasis (<10 µmol/L), mild (10-39 µmol/L), moderate (40-99 µmol/L), and severe (≥100 µmol/L). The primary outcome was composite neonatal morbidity (hypoxic ischemic encephalopathy, severe intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or death). RESULTS: 785 women were included; 487 had cholestasis (347 mild, 108 moderate, 32 severe) and 298 did not. After controlling for gestational age (GA), severe cholestasis was associated with the composite neonatal outcome (aRR 5.6, 95% CI 1.3-23.5) and meconium-stained fluid (aRR 4.82, 95%CI 1.6-14.2). Bile acid levels were not correlated with the frequency of testing (p = .50). Women who underwent twice weekly testing were delivered earlier (p = .016) than women tested less frequently, but the difference in GA was ≤4 d. Abnormal testing prompting delivery was uncommon. Among women with cholestasis, there were three stillbirths. One of these women was undergoing antenatal testing, which was normal 1 d prior to the fetal demise. CONCLUSION: Severe cholestasis is associated with neonatal morbidity which antenatal testing may not predict.

Interobserver variability of sonography for prediction of placenta accreta.

OBJECTIVES: The sensitivity of sonography to predict accreta has been reported as higher than 90%. However, most studies are from single expert investigators. Our objective was to analyze interobserver variability of sonography for prediction of placenta accreta. METHODS: Patients with previa with and without accreta were ascertained, and images with placental views were collected, deidentified, and placed in random sequence. Three radiologists and 3 maternal-fetal medicine specialists interpreted each study for the presence of accreta and specific findings reported to be associated with its diagnosis. Investigator-specific sensitivity, specificity, and accuracy were calculated. κ statistics were used to assess variability between individuals and types of investigators. RESULTS: A total of 229 sonographic studies from 55 patients with accreta and 56 control patients were examined. Accuracy ranged from 55.9% to 76.4%. Of imaging studies yielding diagnoses, sensitivity ranged from 53.4% to 74.4%, and specificity ranged from 70.8% to 94.8%. Overall interobserver agreement was moderate (mean κ ± SD = 0.47 ± 0.12). κ values between pairs of investigators ranged from 0.32 (fair agreement) to 0.73 (substantial agreement). Average individual agreement ranged from fair (κ = 0.35) to moderate (κ = 0.53). CONCLUSIONS: Blinded from clinical data, sonography has significant interobserver variability for the diagnosis of placenta accreta.

Accuracy of ultrasound for the prediction of placenta accreta.

OBJECTIVE: Ultrasound has been reported to be greater than 90% sensitive for the diagnosis of accreta. Prior studies may be subject to bias because of single expert observers, suspicion for accreta, and knowledge of risk factors. We aimed to assess the accuracy of ultrasound for the prediction of accreta. STUDY DESIGN: Patients with accreta at a single academic center were matched to patients with placenta previa, but no accreta, by year of delivery. Ultrasound studies with views of the placenta were collected, deidentified, blinded to clinical history, and placed in random sequence. Six investigators prospectively interpreted each study for the presence of accreta and findings reported to be associated with its diagnosis. Sensitivity, specificity, positive predictive, negative predictive value, and accuracy were calculated. Characteristics of accurate findings were compared using univariate and multivariate analyses. RESULTS: Six investigators examined 229 ultrasound studies from 55 patients with accreta and 56 controls for 1374 independent observations. 1205/1374 (87.7% overall, 90% controls, 84.9% cases) studies were given a diagnosis. There were 371 (27.0%) true positives; 81 (5.9%) false positives; 533 (38.8%) true negatives, 220 (16.0%) false negatives, and 169 (12.3%) with uncertain diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 53.5%, 88.0%, 82.1%, 64.8%, and 64.8%, respectively. In multivariate analysis, true positives were more likely to have placental lacunae (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), loss of retroplacental clear space (OR, 2.4; 95% CI, 1.1-4.9), or abnormalities on color Doppler (OR, 2.1; 95% CI, 1.8-2.4). CONCLUSION: Ultrasound for the prediction of placenta accreta may not be as sensitive as previously described.

The impact of noninvasive fetal evaluation: its effect on education, training, and the maintenance of clinical competence in prenatal diagnosis.

PURPOSE OF REVIEW: To highlight the evolution of prenatal diagnosis from invasive procedures to noninvasive assessments and to describe the efforts to educate both trainees and experienced physicians via simulation techniques. RECENT FINDINGS: The rapid development of noninvasive serum analyte screening as well as molecular genetic and sonographic techniques to evaluate the fetus has altered our ability to both educate trainees as well as to maintain physician competence to perform invasive procedures. Simulation-based learning is being incorporated into medical training across a broad range of specialties, including obstetrics and gynecology. SUMMARY: Prenatal diagnosis procedures will continue to be necessary for direct fetal assessment but on a much more limited scale. It is possible that all trainees will not be able to become competent in amniocentesis and other even less common procedures. Furthermore, experienced physicians may lose competence, given the lack of available procedures for skill retention. Innovative methods of skill acquisition and maintenance may be required in the near future. Although long-term assessments of efficacy are currently lacking, the introduction of comprehensive, simulation-based curriculia has the potential to both educate trainees and help maintain physician competence.

Risk factors for placenta accreta: a large prospective cohort.

OBJECTIVE: Placenta previa and prior cesarean delivery are known risk factors for placenta accreta. However, other risk factors have not been identified. Our objective was to examine risk factors for accreta using data collected prospectively in a large multicenter cohort. STUDY DESIGN: Secondary analysis of women with accreta compared to those without accreta in a large multicenter cesarean delivery cohort. Potential accreta risk factors were examined by univariate and multivariate analyses. RESULTS: In this study, 196 of 73,257 (0.27%) cesarean deliveries were complicated by accreta. As expected, women with increasing numbers of prior cesareans were more likely to have an accreta (p < 0.001), as were women with previa (adjusted odds ratio [OR], 34.9; 95% confidence interval [CI], 22.4-54.3). We also considered only patients with previa and examined the following variables: maternal demographics, prior cesareans, interval between deliveries, parity, body mass index, tobacco use, and coexisting hypertension or diabetes. In this model, patients with previa and two or three prior cesarean deliveries had an adjusted OR for accreta of 4.9 (95% CI, 1.7-14.3) or 7.7 (95% CI, 2.4-24.9), respectively. However, no other variables were significantly associated with accreta. CONCLUSION: Patients with previa have increased risk for accreta that increases with the number of prior cesarean deliveries. However, no other maternal characteristics were associated with accreta.

Risk factors for unscheduled delivery in patients with placenta accreta.

OBJECTIVE: Patients with suspected placenta accreta have improved outcomes with scheduled delivery. Our objective was to identify risk factors for unscheduled delivery in patients with suspected placenta accreta. STUDY DESIGN: This was a cohort study of women with antenatally suspected placenta accreta. Women who delivered prior to a planned delivery date were compared with women who had a scheduled delivery. Data were analyzed using a Student t test, χ(2), logistic regression, and survival analyses. Variables included in the analyses were episodes of antenatal vaginal bleeding, preterm premature rupture of membranes (PPROM), uterine contractions, prior cesarean deliveries, interpregnancy interval, parity, and patient demographic factors. A value of P < .05 was considered significant. RESULTS: Seventy-seven women with antenatal suspicion for placenta accreta were identified. Thirty-eight (49.4%) had an unscheduled delivery. Demographics were similar between groups. Unscheduled patients delivered earlier (mean 32.3 vs 35.7 weeks, P < .001) and were significantly more likely to have had vaginal bleeding (86.8% vs 35.9%, P < .001) and uterine activity (47.4% vs 2.6%, P < .001). Each episode of antenatal vaginal bleeding was associated with an increased risk of unscheduled delivery (adjusted odds ratio, 3.8; 95% confidence interval, 1.8-7.8). Risk of earlier delivery was even greater when associated with PPROM (P < .001). CONCLUSION: Among women with suspected placenta accreta, those with antenatal vaginal bleeding were more likely to require unscheduled delivery. This risk increases further in the setting of PPROM and/or uterine contractions. These clinical factors should be considered when determining the optimal delivery gestational age for women with placental accreta.

Tachysystole in term labor: incidence, risk factors, outcomes, and effect on fetal heart tracings.

OBJECTIVE: Recent recommendations called for obstetricians to abandon the terms of "hyperstimulation" and "hypercontractility" in favor of the more rigidly defined term, "tachysystole" (TS). The aim of the current study is to describe incidence of and risk factors for TS, describe fetal heart rate (FHR) changes associated with TS, and investigate maternal and neonatal outcomes associated with TS. STUDY DESIGN: For this retrospective cohort study, we reviewed and analyzed the intrapartum FHR and tocometric characteristics of all patients with a singleton, nonanomalous fetus in term labor in a single hospital system over a 28-month period. Univariate association testing was done using χ(2) and t tests, comparing demographics, pregnancy characteristics, outcomes, and TS events. Multivariable association testing between risk factors and TS events were tested using generalized estimating equations, adjusting for multiple pregnancies during the study period for the same woman. RESULTS: There were a total of 50,335 deliveries from 48,529 women during the 28-month period. Of these, there were a total of 7567 TS events in 5363 deliveries among 5332 women. Use of oxytocin or misoprostol, an epidural, hypertension, and induction of labor were associated with an increased risk of TS. We found a doubling of TS events with any oxytocin, a dose-response correlation between oxytocin and TS, FHR changes occurring in a quarter of TS events and, finally, that presence of TS increases the chance of composite neonatal morbidity. CONCLUSION: TS is associated with specific risk factors and impacts FHR and neonatal morbidity.

Survey of physicians' approach to severe fetal anomalies.

OBJECTIVE: Standards of care regarding obstetric management of life-threatening anomalies are not defined. It is hypothesised that physicians' management of these pregnancies is variable and influenced by demographic factors. DESIGN: A questionnaire was mailed to members of the Society of Maternal-Fetal Medicine with valid US addresses assessing obstetric management of both 'uniformly lethal' (eg, anencephaly, renal agenesis) and 'uniformly severe, commonly lethal' (eg, trisomy 13 and 18) anomalies. Respondents were asked to answer as if not limited by state/institutional restrictions. Fisher's exact or χ(2) tests were used as appropriate and correction made for multiple comparisons in analyses that were not prespecified. RESULTS: The response rate was 36% (732/2038). Nearly 100% of respondents discuss termination for both uniformly and commonly lethal anomalies. In continuing pregnancies, with patient request for obstetric non-intervention 99% of providers would comply for either uniformly or commonly lethal anomalies. The majority 'encourage' such management, but some were non-directive or discouraged this management. In continuing pregnancies, with patient request for full obstetric intervention the majority of respondents was willing to comply for both uniformly (71%) and commonly (82%) lethal anomalies. While most practitioners 'discouraged' full intervention, some were non-directive or encouraged this management. Demographics and severity of anomaly influenced counselling. CONCLUSION: Discrepancies exist regarding the management of life-threatening fetal anomalies. Patients may be offered different options based on practitioner demographics. The majority of physicians comply with patient wishes. Differences were noted when comparing the management of lethal with that of severe commonly lethal anomalies, suggesting that practitioners make a distinction when counselling patients.

A case-control study of membrane cofactor protein mutations in two populations of patients with early pregnancy loss.

Mouse models have demonstrated a strong link between complement activation and pregnancy loss. The purpose of this study was to assess if mutations or polymorphisms in the complement regulatory gene membrane cofactor protein (MCP) are associated with recurrent miscarriage (RM) or sporadic fetal loss (FL). This was a case-control study comprising two different populations of cases and controls: subjects with recurrent miscarriage (RM) and controls and maternal-fetal pairs with early fetal loss (at 10-20 weeks' gestation) and controls. In the RM cases and controls, we studied maternal DNA extracted from either whole blood or saliva samples. In the FL cases and controls, fetal DNA was obtained from evacuated products of conception (cases) or cord blood (controls). Exons from the MCP gene, previously identified as having functional mutations, were amplified with flanking primers, purified, and sequenced. Sequences were analyzed against the published reference sequence, the presence of known mutations and polymorphisms and novel polymorphisms. We enrolled and obtained maternal DNA from 75 women with RM and 115 controls. In the FL group, we identified 33 cases and 37 controls. We detected the previously described A304V variant, but neither genotype nor allele frequencies differed significantly between cases and controls in any of the populations (RM, FL (maternal) or FL (fetal)). Although other variants and mutations in MCP were identified, no significant differences were found between the groups. Thus, we conclude that the A304V mutation in the MCP gene is not strongly associated with RM or FL.

Assessing the role of magnetic resonance imaging in the management of gravid patients at risk for placenta accreta.

RATIONALE AND OBJECTIVES: The role of magnetic resonance imaging (MRI) in the diagnosis of placenta accreta remains uncertain. The purpose of this study was to evaluate the incremental benefit of MRI after ultrasound (US) for a large cohort of gravid patients at risk for a placenta accreta. MATERIALS AND METHODS: A retrospective review of outcomes in women with risk factors for a placenta accreta between November 1995 and February 2008 was performed. Inclusion criteria were high-risk women with abnormal placenta implantation on US or operative diagnosis of placenta accreta, with or without a prenatal MRI. Delivery mode, diagnosis, and transfusion requirements were compared. RESULTS: Ranging in age from 19 to 43 years, with zero to five prior cesarean sections, 139 women met inclusion criteria. The MRI was performed in 28.7% (40/139). US, MRI, and operative diagnoses were highly correlated (P < .001). Women who underwent both US and MRI were more likely to deliver by cesarean hysterectomy (P < .001). When the cohort is stratified by outcome diagnosis (normal, previa, accreta), no difference in delivery mode is found; regardless of whether subjects were imaged by US alone or US and MRI. Transfusion requirements were highest in the US and MRI group (mean of 3.9 units vs. 0.9 units in the US only group, P < .001). CONCLUSION: This study fails to demonstrate that the incremental use of MRI for placenta accreta changes delivery mode in stratified analysis. Patients who underwent both US and MRI were most likely to have a cesarean hysterectomy delivery, and required more blood products, suggesting that undergoing tests may be indicative of an abnormal and at risk patient population.

Maternal morbidity in cases of placenta accreta managed by a multidisciplinary care team compared with standard obstetric care.

OBJECTIVE: To compare maternal morbidity in cases of placenta accreta managed by a multidisciplinary care team with similar cases managed by standard obstetric care. METHODS: This was a retrospective cohort study of all cases of placenta accreta identified in the State of Utah from 1996 to 2008. Cases of placenta accreta were identified using International Classification of Diseases (ICD-9) codes for placenta accreta, placenta previa, and cesarean hysterectomy. Maternal morbidity was compared for cases managed by a multidisciplinary care team in two tertiary care centers and similar cases managed at 26 other hospitals using multivariable logistic regression analysis. RESULTS: One-hundred forty-one cases of placenta accreta were identified including 79 managed by a multidisciplinary care team and 62 cases managed by standard obstetric care. Women managed by a multidisciplinary care team were less likely to require large-volume blood transfusion (4 or more units of packed red blood cells) (43% compared with 61%, P=.031) and reoperation within 7 days of delivery for bleeding complications (3% compared with 36%, P<.001) compared with women managed by standard obstetric care. Women with suspected placenta accreta managed by a multidisciplinary team were less likely to experience composite early morbidity (prolonged maternal admission to the intensive care unit, large-volume blood transfusion, coagulopathy, ureteral injury, or early reoperation) than women managed by standard obstetric care (47% compared with 74%, P=.026). The odds ratio of composite early morbidity in women managed by a multidisciplinary team was 0.22, (95% confidence interval, 0.07- 0.70) in the multivariable model. CONCLUSION: Maternal morbidity is reduced in women with placenta accreta who deliver in a tertiary care hospital with a multidisciplinary care team. LEVEL OF EVIDENCE: II

Vascular endothelial growth factor-A gene polymorphisms in women with recurrent pregnancy loss.

Vascular endothelial growth factor-A (VEGFA) is normally expressed at high levels in the human placenta, and lower levels have been observed in placental tissue of women with recurrent pregnancy loss. The objective of this study was to determine if genetic polymorphisms in the VEGFA gene associated with altered gene expression play a role in some cases of recurrent pregnancy loss (RPL). A case-control study of 99 women with RPL and 181 fertile controls was performed evaluating four common VEGFA polymorphisms associated with altered gene expression (-2578 C/A, -1154 G/A, -634 G/C, and +936 C/T). The allele frequency of the -2578 A allele was lower among women with RPL compared to fertile controls (0.39 vs. 0.48, p=0.049), while the allele frequency of the -634 C allele was higher among women with RPL compared to fertile controls (0.39 vs. 0.29, p=0.020). Women with RPL and controls had similar allele frequencies for the -1154 and +936 minor alleles. We conclude that some allelic polymorphisms associated with altered expression of VEGFA are more common among women with RPL compared to fertile controls.

Outcomes of expectantly managed preterm premature rupture of membranes occurring before 24 weeks of gestation.

OBJECTIVE: To assess contemporary outcomes in expectantly managed preterm premature rupture of membranes (PROM) before 24 weeks of gestation. METHODS: We analyzed all patients with singleton pregnancies and preterm PROM before 24 weeks of gestation from 2001 to 2007. Patients immediately electing delivery, delivering within 12 hours of preterm PROM, carrying anomalous fetus(es), or multiple gestations were excluded. Neonatal survival without major morbidities was the primary outcome. Data were analyzed with multivariable logistic regression and Cox regression models. Week-specific probability estimates for neonatal morbidity and mortality were calculated based on gestational age at the time of preterm PROM. RESULTS: One hundred fifty-nine women fulfilled study criteria. Median gestational age at preterm PROM for all patients was 21.4 (range 14.0-23.9) weeks of gestation. Median delivery gestational age was 24.7 (range 15.4-34.1) weeks. Forty-seven patients experienced either an intrauterine fetal demise, elected delivery after initial expectant management, or delivered before planned resuscitation. Of 112 newborns admitted to neonatal intensive care, 89 (56.0% of all neonates) survived; 43 (48.3% of survivors, 27.0% of all neonates) had no major neonatal morbidities. Morbidity probabilities decreased with increasing gestational age at the time of preterm PROM. Delivery gestational age was predictive of both neonatal morbidity and mortality. CONCLUSION: More than one half of women who achieved at least 12 hours of latency and elected expectant management had a surviving infant; nearly 50% of survivors had no major neonatal morbidity. These contemporary outcomes are valuable in counseling women with early preterm PROM. LEVEL OF EVIDENCE: III.