New labor curves of dilation and station to improve the accuracy of predicting labor progress.

BACKGROUND: The diagnosis of failure to progress, the most common indication for intrapartum cesarean delivery, is based on the assessment of cervical dilation and station over time. Labor curves serve as references for expected changes in dilation and fetal descent. The labor curves of Friedman, Zhang et al, and others are based on time alone and derived from mothers with spontaneous labor onset. However, labor induction is now common, and clinicians also consider other factors when assessing labor progress. Labor curves that consider the use of labor induction and other factors that influence labor progress have the potential to be more accurate and closer to clinical decision-making. OBJECTIVE: This study aimed to compare the prediction errors of labor curves based on a single factor (time) or multiple clinically relevant factors using two modeling methods: mixed-effects regression, a standard statistical method, and Gaussian processes, a machine learning method. STUDY DESIGN: This was a longitudinal cohort study of changes in dilation and station based on data from 8022 births in nulliparous women with a live, singleton, vertex-presenting fetus ≥35 weeks of gestation with a vaginal delivery. New labor curves of dilation and station were generated with 10-fold cross-validation. External validation was performed using a geographically independent group. Model variables included time from the first examination in the 20 hours before delivery; dilation, effacement, and station recorded at the previous examination; cumulative contraction counts; and use of epidural anesthesia and labor induction. To assess model accuracy, differences between each model's predicted value and its corresponding observed value were calculated. These prediction errors were summarized using mean absolute error and root mean squared error statistics. RESULTS: Dilation curves based on multiple parameters were more accurate than those derived from time alone. The mean absolute error of the multifactor methods was better (lower) than those of the single-factor methods (0.826 cm [95% confidence interval, 0.820-0.832] for the multifactor machine learning and 0.893 cm [95% confidence interval, 0.885-0.901] for the multifactor mixed-effects method and 2.122 cm [95% confidence interval, 2.108-2.136] for the single-factor methods; P<.0001 for both comparisons). The root mean squared errors of the multifactor methods were also better (lower) than those of the single-factor methods (1.126 cm [95% confidence interval, 1.118-1.133] for the machine learning [P<.0001] and 1.172 cm [95% confidence interval, 1.164-1.181] for the mixed-effects methods and 2.504 cm [95% confidence interval, 2.487-2.521] for the single-factor [P<.0001 for both comparisons]). The multifactor machine learning dilation models showed small but statistically significant improvements in accuracy compared to the mixed-effects regression models (P<.0001). The multifactor machine learning method produced a curve of descent with a mean absolute error of 0.512 cm (95% confidence interval, 0.509-0.515) and a root mean squared error of 0.660 cm (95% confidence interval, 0.655-0.666). External validation using independent data produced similar findings. CONCLUSION: Cervical dilation models based on multiple clinically relevant parameters showed improved (lower) prediction errors compared to models based on time alone. The mean prediction errors were reduced by more than 50%. A more accurate assessment of departure from expected dilation and station may help clinicians optimize intrapartum management.

Should case management be considered a component of obstetrical interventions for pregnancies at risk of preterm birth?

Preterm birth remains the leading cause of morbidity and mortality among nonanomalous neonates in the United States. Unfortunately, preterm birth rates remain high despite current medical interventions such as progestogen supplementation and cerclage placement. Case management, which encompasses coordinated care aimed at providing a more comprehensive and supportive environment, is a key component in improving health and reducing costs in other areas of medicine. However, it has not made its way into the general lexicon and practice of obstetrical care. Case management intended for decreasing prematurity or ameliorating its consequences may include specialty clinics, social services, coordination of specialty services such as nutrition counseling, home visits or frequent phone calls by specially trained personnel, and other elements described herein. It is not currently included in nor is it advocated for as a recommended prematurity prevention approach in the American College of Obstetricians and Gynecologists or Society for Maternal-Fetal Medicine guidelines for medically indicated or spontaneous preterm birth prevention. Our review of existing evidence finds consistent reductions or trends toward reductions in preterm birth with case management, particularly among individuals with high a priori risk of preterm birth across systematic reviews, metaanalyses, and randomized controlled studies. These findings suggest that case management has substantial potential to improve the environmental, behavioral, social, and psychological factors with patients at risk of preterm birth.

A double-blinded randomized controlled trial on the effects of increased intravenous hydration in nulliparas undergoing induction of labor.

BACKGROUND: Rates of labor induction are increasing, raising concerns related to increased healthcare utilization costs. High-dose intravenous fluid (250 cc/h) has been previously demonstrated to shorten the time to delivery in nulliparous individuals in spontaneous labor. Whether or not this relationship exists among individuals undergoing induction of labor is unknown. OBJECTIVE: Our study aimed to evaluate the effect of high-dose intravenous hydration on time to delivery among nulliparous individuals undergoing induction of labor. STUDY DESIGN: Nulliparous individuals presenting for induction of labor with a Bishop score of ≤6 (with and without rupture of membranes) were randomized to receive either 125 cc/h or 250 cc/h of normal saline. The primary outcome was length of labor (defined as time from initiation of study fluids to delivery). Both time to overall delivery and vaginal delivery were evaluated. Secondary outcomes included the lengths of each stage of labor, the percentage of individuals delivering within 24 hours, and maternal and neonatal outcomes, including cesarean delivery rate. RESULTS: A total of 180 individuals meeting inclusion criteria were enrolled and randomized. Baseline demographic characteristics were similar between groups; however, there was a higher incidence of diabetes mellitus in the group receiving 125 cc/h. Average length of labor was similar between groups (27.6 hours in 250 cc/h and 27.8 hours in 125 cc/h), as was the length of each stage of labor. Cox regression analysis did not demonstrate an effect of fluid rate on time to delivery. Neither the admission Bishop score, body mass index, nor other demographic characteristics affected time to delivery or vaginal delivery. There were no differences in maternal or neonatal outcomes, including overall cesarean delivery rate, clinically apparent iatrogenic intraamniotic infection, Apgar scores, need for neonatal phototherapy, or neonatal intensive care unit stay. CONCLUSION: There were no observed differences in the length of labor or maternal or neonatal outcomes with the administration of an increased rate of intravenous fluids among nulliparous individuals undergoing induction of labor.

Is Exposure to Intrapartum Prostaglandins for Labor Induction Associated with a Lower Incidence of Neonatal Respiratory Distress Syndrome?

OBJECTIVE: Respiratory distress syndrome (RDS) is implicated in 30% of neonatal deaths. Since prostaglandins promote surfactant secretion and labor is associated with a lower risk of RDS in term neonates, it is plausible that synthetic prostaglandin (sPG) exposure is associated with a lower risk of RDS. Thus, we evaluated the association between sPG exposure and RDS in neonates born after the induction of labor (IOL). STUDY DESIGN: Secondary analysis of women with singleton pregnancies undergoing IOL at 340/7 to 420/7 weeks in the nuMoM2b study, a multicenter prospective cohort of nulliparous women. RDS rates and secondary neonatal outcomes in neonates with intrapartum sPG exposure were compared with those who had IOL with non-sPG methods (e.g., balloon catheter, amniotomy, oxytocin, and laminaria). Logistic regression models estimated the association of sPG with RDS and with secondary outcomes after adjustment for clinical and demographic factors (including gestational age). A sensitivity analysis was performed in which analysis was restricted to those with an admission cervical dilation ≤2 cm. RESULTS: Of 10,038 women in the total cohort, 3,071 met inclusion criteria; 1,444 were exposed and 1,627 were unexposed to sPGs. Antenatal corticosteroid exposure rates were low (3.0%) and similar between groups. In univariable analysis, neonates with sPG exposure had higher rates of RDS (3.2 vs. 2.0%, odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.01-2.50). This relationship was similar by gestational age at delivery (term vs. preterm, interaction p = 0.14). After adjustment, the association between sPG and RDS was no longer significant (adjusted odds ratio: 1.4, 95% CI: 0.9-2.3). When analysis was restricted to subjects with admission cervical dilation of ≤2 cm, there was also no association between sPG exposure and RDS. CONCLUSION: In pregnancies between 34 and 42 weeks of gestation, exposure to sPG for cervical ripening or labor induction was not associated with newborn RDS. KEY POINTS: · RDS is implicated in 30% of neonatal deaths.. · sPG exposure was not associated with RDS.. · Avoiding preterm birth remains crucial in RDS prevention..

Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis.

BACKGROUND: Infants born preterm compared with infants born at term are at an increased risk of dying and of serious morbidities in early life, and those who survive have higher rates of neurological impairments. It remains unclear whether exposure to repeat courses of prenatal corticosteroids can reduce these risks. This individual participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal corticosteroid treatment given to women at ongoing risk of preterm birth in order to benefit their infants is modified by participant or treatment factors. METHODS AND FINDINGS: Trials were eligible for inclusion if they randomised women considered at risk of preterm birth who had already received an initial, single course of prenatal corticosteroid seven or more days previously and in which corticosteroids were compared with either placebo or no placebo. The primary outcomes for the infants were serious outcome, use of respiratory support, and birth weight z-scores; for the children, they were death or any neurosensory disability; and for the women, maternal sepsis. Studies were identified using the Cochrane Pregnancy and Childbirth search strategy. Date of last search was 20 January 2015. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. IPD were analysed using a one-stage approach. Eleven trials, conducted between 2002 and 2010, were identified as eligible, with five trials being from the United States, two from Canada, and one each from Australia and New Zealand, Finland, India, and the United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants contributing data. The mean gestational age at trial entry for the trials was between 27.4 weeks and 30.2 weeks. There was no significant difference in the proportion of infants with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to 1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the use of respiratory support in infants exposed to repeat prenatal corticosteroids compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10 trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21 (95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support. Birth weight z-scores were lower in the repeat corticosteroid group (mean difference -0.12, 95%CI -0.18 to -0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No statistically significant differences were seen for any of the primary outcomes for the child (death or any neurosensory disability) or for the woman (maternal sepsis). The treatment effect varied little by reason the woman was considered to be at risk of preterm birth, the number of fetuses in utero, the gestational age when first trial treatment course was given, or the time prior to birth that the last dose was given. Infants exposed to between 2-5 courses of repeat corticosteroids showed a reduction in both serious outcome and the use of respiratory support compared with infants exposed to only a single repeat course. However, increasing numbers of repeat courses of corticosteroids were associated with larger reductions in birth z-scores for weight, length, and head circumference. Not all trials could provide data for all of the prespecified subgroups, so this limited the power to detect differences because event rates are low for some important maternal, infant, and childhood outcomes. CONCLUSIONS: In this study, we found that repeat prenatal corticosteroids given to women at ongoing risk of preterm birth after an initial course reduced the likelihood of their infant needing respiratory support after birth and led to neonatal benefits. Body size measures at birth were lower in infants exposed to repeat prenatal corticosteroids. Our findings suggest that to provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited to a maximum of three and the total dose to between 24 mg and 48 mg.

"Doing something" about the cesarean delivery rate.

There is a general consensus that the cesarean delivery rate in the United States is too high, and that practice patterns of obstetricians are largely to blame for this situation. In reality, the US cesarean delivery rate is the result of 3 forces largely beyond the control of the practicing clinician: patient expectations and misconceptions regarding the safety of labor, the medical-legal system, and limitations in technology. Efforts to "do something" about the cesarean delivery rate by promulgating practice directives that are marginally evidence-based or influenced by social pressures are both ineffective and potentially harmful. We examine both the recent American Congress of Obstetricians and Gynecologists (ACOG)/Society for Maternal-Fetal Medicine Care Consensus Statement "Safe Prevention of Primary Cesarean Delivery" document and the various iterations of the ACOG guidelines for vaginal birth after cesarean delivery in this context. Adherence to arbitrary time limits for active phase or second-stage arrest without incorporating other clinical factors into the decision-making process is unwise. In a similar manner, ever-changing practice standards for vaginal birth after cesarean driven by factors other than changing data are unlikely to be effective in lowering the cesarean delivery rate. Whether too high or too low, the current US cesarean delivery rate is the expected result of the unique demographic, geographic, and social forces driving it and is unlikely to change significantly given the limitations of current technology to otherwise satisfy the demands of these forces.

A randomized, double-blinded, controlled trial of the effects of fluid rate and/or presence of dextrose in intravenous fluids on the labor course of nulliparas.

BACKGROUND: Prolonged labor has been demonstrated to increase adverse maternal and neonatal outcome. A practice that may decrease the risk of prolonged labor is the modification of fluid intake during labor. OBJECTIVE: Several studies demonstrated that increased hydration in labor as well as addition of dextrose-containing fluids may be associated with a decrease in length of labor. The purpose of our study was to characterize whether high-dose intravenous fluids, standard-dose fluids with dextrose, or high-dose fluids with dextrose show a difference in the duration of labor in nulliparas. STUDY DESIGN: Nulliparous subjects with singletons who presented in active labor were randomized to 1 of 3 groups of intravenous fluids: 250 mL/h of normal saline, 125 mL/h of 5% dextrose in normal saline, or 250 mL/h of 2.5% dextrose in normal saline. The primary outcome was total length of labor from initiation of intravenous fluid in vaginally delivered subjects. Secondary outcomes included cesarean delivery rate and length of second stage of labor, among other maternal and neonatal outcomes. RESULTS: In all, 274 subjects who met inclusion criteria were enrolled. There were no differences in baseline characteristics among the 3 groups. There was no difference in the primary outcome of total length of labor in vaginally delivered subjects among the 3 groups. First stage of labor duration, second stage of labor duration, and cesarean delivery rates were also equivalent. There were no differences identified in other secondary outcomes including clinical chorioamnionitis, postpartum hemorrhage, blood loss, Apgar scores, or neonatal intensive care admission. CONCLUSION: There is no difference in length of labor or delivery outcomes when comparing high-dose intravenous fluids, addition of dextrose, or use of high-dose intravenous fluids with dextrose in nulliparous women who present in active labor.

The limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia.

BACKGROUND: Despite intensive efforts directed at initial training in fetal heart rate interpretation, continuing medical education, board certification/recertification, team training, and the development of specific protocols for the management of abnormal fetal heart rate patterns, the goals of consistently preventing hypoxia-induced fetal metabolic acidemia and neurologic injury remain elusive. OBJECTIVE: The purpose of this study was to validate a recently published algorithm for the management of category II fetal heart rate tracings, to examine reasons for the birth of infants with significant metabolic acidemia despite the use of electronic fetal heart rate monitoring, and to examine critically the limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia. STUDY DESIGN: The potential performance of electronic fetal heart rate monitoring under ideal circumstances was evaluated in an outcomes-blinded examination fetal heart rate tracing of infants with metabolic acidemia at birth (base deficit, >12) and matched control infants (base deficit, <8) under the following conditions: (1) expert primary interpretation, (2) use of a published algorithm that was developed and endorsed by a large group of national experts, (3) assumption of a 30-minute period of evaluation for noncritical category II fetal heart rate tracings, followed by delivery within 30 minutes, (4) evaluation without the need to provide patient care simultaneously, and (5) comparison of results under these circumstances with those achieved in actual clinical practice. RESULTS: During the study period, 120 infants were identified with an arterial cord blood base deficit of >12 mM/L. Matched control infants were not demographically different from subjects. In actual practice, operative intervention on the basis of an abnormal fetal heart rate tracings occurred in 36 of 120 fetuses (30.0%) with metabolic acidemia. Based on expert, algorithm-assisted reviews, 55 of 120 patients with acidemia (45.8%) were judged to need operative intervention for abnormal fetal heart rate tracings. This difference was significant (P=.016). In infants who were born with a base deficit of >12 mM/L in which blinded, algorithm-assisted expert review indicated the need for operative delivery, the decision for delivery would have been made an average of 131 minutes before the actual delivery. The rate of expert intervention for fetal heart rate concerns in the nonacidemic control group (22/120; 18.3%) was similar to the actual intervention rate (23/120; 19.2%; P=1.0) Expert review did not mandate earlier delivery in 65 of 120 patients with metabolic acidemia. The primary features of these 65 cases included the occurrence of sentinel events with prolonged deceleration just before delivery, the rapid deterioration of nonemergent category II fetal heart rate tracings before realistic time frames for recognition and intervention, and the failure of recognized fetal heart rate patterns such as variability to identify metabolic acidemia. CONCLUSIONS: Expert, algorithm-assisted fetal heart rate interpretation has the potential to improve standard clinical performance by facilitating significantly earlier recognition of some tracings that are associated with metabolic acidemia without increasing the rate of operative intervention. However, this improvement is modest. Of infants who are born with metabolic acidemia, only approximately one-half potentially could be identified and have delivery expedited even under ideal circumstances, which are probably not realistic in current US practice. This represents the limits of electronic fetal heart rate monitoring performance. Additional technologies will be necessary if the goal of the prevention of neonatal metabolic acidemia is to be realized.

A multicenter prospective study of neonatal outcomes at less than 32 weeks associated with indications for maternal admission and delivery.

BACKGROUND: Counseling for patients with impending premature delivery traditionally has been based primarily on the projected gestational age at delivery. There are limited data regarding how the indications for the preterm birth affect the neonatal outcome and whether this issue should be taken into account in decisions regarding management and patient counseling. OBJECTIVE: We performed a prospective study of pregnancies resulting in premature delivery at less than 32 weeks to determine the influence of both the indications for admission and their associated indications for delivery on neonatal mortality and complications of prematurity. STUDY DESIGN: This is a multicenter, prospective study in 10 hospitals where all data from the neonatal intensive care unit routinely was imported to a deidentified data warehouse. Maternal data were collected prospectively at or near the time of delivery. Eligible subjects included singleton deliveries in these hospitals between 23 0/7 and 31 6/7 weeks. The primary hypothesis of the study was to determine whether there was a difference in the primary outcome, which was defined as neonatal composite morbidity, between those neonates delivered after admission for premature labor vs premature rupture of membranes, because these were expected to be the 2 most frequent diagnoses leading to premature birth. The sample size was calculated based on a 10% difference in outcomes for these 2 entities. We based this hypothesis on the knowledge that premature rupture of membranes has a greater incidence of intra-amniotic infection and inflammation than premature labor and that outcomes for premature neonates are worse when delivery is associated with intra-amniotic infection. Additional outcomes were analyzed for all other indications for admission and delivery. Composite morbidity was defined as ≥1 of the following: respiratory distress syndrome (oxygen requirement, clinical diagnosis, and consistent chest radiograph), bronchopulmonary dysplasia (requirement for oxygen support at 28 days of life), severe intraventricular hemorrhage (grades 3 or 4), periventricular leukomalacia, blood culture-proven sepsis present within 72 hours of birth, necrotizing enterocolitis, or neonatal death before discharge from the hospital. A secondary composite of serious neonatal morbidity also was defined prospectively. RESULTS: The study included 1089 mother/baby pairs. Composite morbidity between those with premature labor (77.2%) and premature rupture of membranes (73.2%) was not significantly different (P = .29). A few neonatal complications were associated with indications for admission and delivery, but on logistic regression adjusting for gestational age and other confounders, suspected intrauterine growth restriction was the only indication for admission or delivery associated with an increase in serious morbidity (odds ratio 4.5, [2.1 to 9.8], P < .003). Other factors not related to the indications for admission including cesarean delivery, and low 5-minute Apgar were associated with an increase in morbidity. CONCLUSION: Studies of many single factors related to the indications for preterm delivery have been shown to be associated with adverse neonatal outcome. In this study evaluating all of the most frequent indications, however, we found only suspected intrauterine growth restriction as an indication for admission and delivery was found to be so. Thus, it seems that in almost all situations counseling patients can be based primarily on gestational age along with other factors including estimated fetal weight, sex, race, plurality, and completion of a course of antenatal corticosteroids.

Assessing first-stage labor progression and its relationship to complications.

BACKGROUND: New labor curves have challenged the traditional understanding of the general pattern of dilation and descent in labor. They also revealed wide variation in the time to advance in dilation. An interval of arrest such as 4 hours did not fall beyond normal limits until dilation had reached 6 cm. Thus, the American College of Obstetricians and Gynecologists/Society for Maternal-Fetal Medicine first-stage arrest criteria, based in part on these findings, are applicable only in late labor. The wide range of time to dilate is unavoidable because cervical dilation has neither a precise nor direct relationship to time. Newer statistical techniques (multifactorial models) can improve precision by incorporating several factors that are related directly to labor progress. At each examination, the calculations adapt to the mother's current labor conditions. They produce a quantitative assessment that is expressed in percentiles. Low percentiles indicate potentially problematic labor progression. OBJECTIVE: The purpose of this study was to assess the relationship between first-stage labor progress- and labor-related complications with the use of 2 different assessment methods. The first method was based on arrest of dilation definitions. The other method used percentile rankings of dilation or station based on adaptive multifactorial models. STUDY DESIGN: We included all 4703 cephalic-presenting, term, singleton births with electronic fetal monitoring and cord gases at 2 academic community referral hospitals in 2012 and 2013. We assessed electronic data for route of delivery, all dilation and station examinations, newborn infant status, electronic fetal monitoring tracings, and cord blood gases. The labor-related complication groups included 272 women with cesarean delivery for first-stage arrest, 558 with cesarean delivery for fetal heart rate concerns, 178 with obstetric hemorrhage, and 237 with neonatal depression, which left 3004 women in the spontaneous vaginal birth group. Receiver operating characteristic curves were constructed for each assessment method by measurement of the sensitivity for each complication vs the false-positive rate in the normal reference group. RESULTS: The duration of arrest at ≥6 cm dilation showed poor levels of discrimination for the cesarean delivery interventions (area under the curve, 0.55-0.65; P < .01) and no significant relationship to hemorrhage or neonatal depression. The dilation and station percentiles showed high discrimination for the cesarean delivery-related outcomes (area under the curve, 0.78-0.93; P < .01) and low discrimination for the clinical outcomes of hemorrhage and neonatal depression (area under the curve, 0.58-0.61; P < .01). CONCLUSIONS: Duration of arrest of dilation at ≥6 cm showed little or no discrimination for any of the complications. In comparison, percentile rankings that were based on the adaptive multifactorial models showed much higher discrimination for cesarean delivery interventions and better, but low discrimination for hemorrhage. Adaptive multifactorial models present a different method to assess labor progress. Rather than "pass/fail" criteria that are applicable only to dilation in late labor, they produce percentile rankings, assess 2 essential processes for vaginal birth (dilation and descent), and can be applied from 3 cm onward. Given the limitations of labor-progress assessment based solely on the passage of time and because of the extreme variation in decision-making for cesarean delivery for labor disorders, the types of mathematic analyses that are described in this article are logical and promising steps to help standardize labor assessment.

Descent of the fetal head (station) during the first stage of labor.

BACKGROUND: High station at specific points in the first stage of labor, such as a floating head on admission, or at 4-cm dilation or when arrest of dilation occurs, is associated with higher rates of failure to deliver vaginally. Therefore it could be useful to know if station is within an expected range at a given dilation during first stage. Arrest of descent disorders have been defined thus far on criteria applicable in the second stage. Statistical modeling is an attractive methodology to characterize the relationship between station and dilation because the resulting mathematical expressions could be used as a reference for comparison in the future. In addition, they can be used to produce a finely graded assessment of descent using numerical terms such as percentile rankings. A 2-step approach to potentially improving the assessment of station could be to develop a statistical model that describes the general relationship between station and dilation in the first stage of uncomplicated births and then determine if such a model would have identified births with complications related to poor labor progress. Given the complex nature of labor data, especially the imprecision of dilation and station measurement, it is not immediately evident that such a model is identifiable or what its precision would be. OBJECTIVE: We sought to characterize in mathematical terms the relationship of station to dilation during the first stage of labor for nulliparous and multiparous women with spontaneous vaginal births. STUDY DESIGN: This retrospective cohort study included 28,121 exams from 5555 women with singleton cephalic presentations at ≥37 weeks' gestation with electronic fetal monitoring tracings, who delivered vaginally without instrumentation and had 5-minute Apgar scores >6 at 2 academic community referral hospitals in 2012 through 2013. Women with a previous cesarean birth were excluded. We used longitudinal statistical techniques suitable to biological data that were irregularly sampled with repeated measures over time. RESULTS: A linear relationship was observed between station and dilation. For both nulliparous and multiparous women the final model was a linear regression with random effects for intercept and slope and a first-order autoregressive correlation structure. The 5th-95th range of station at any given dilation spanned about 3-4 cm. CONCLUSION: Our results demonstrate a general trend of increasing descent of the presenting part as dilation advances during the first stage of labor in women who delivered vaginally without instrumentation. We propose that the mathematical expressions describing this relationship may be valuable in the assessment of first-stage labor progression.

Vasa previa: diagnosis and management.

BACKGROUND: Vasa previa is a rare condition that is associated with a high rate of fetal or neonatal death when not diagnosed antenatally. The majority of available studies are either small, do not include antepartum data, limited to single institutions, or are biased by inclusion of patients from registries and online vasa previa support groups. OBJECTIVE: The purpose of this study was to investigate the diagnostic and management strategies for this potentially catastrophic entity and to describe further maternal and placental risk factors that may aid in the establishment of a screening protocol for vasa previa. STUDY DESIGN: This was a retrospective multicenter descriptive study that included all pregnancies that were complicated by vasa previa that delivered between January 1, 2000, and December 31, 2012. Nine maternal fetal medicine practices and the hospitals in which they practice participated in data collection of diagnosis, treatment, and maternal-neonatal outcomes. RESULTS: Sixty-eight pregnancies were identified that included the diagnosis of vasa previa or "possible vasa previa" either in the ultrasound record or in the hospital record at the time of delivery. Four cases (5.8%) appeared to resolve on repeat ultrasound examination. Fifteen of the 64 cases that were suspected of having vasa previa could not be verified or were not documented at delivery. Of the remaining 49 cases, where vasa previa was documented, 47 cases (96%) were diagnosed by ultrasound scanning antenatally. Known risk factors for vasa previa were present in 41 of 47 cases (87%). Of the 49 cases, 41 were delivered by planned cesarean delivery at a mean gestational age of 34.7 weeks, and 8 cases required emergent cesarean delivery at a mean gestational age of 34.6 weeks (range, 32.4-36.0 weeks gestation). Seven of these emergent cesarean deliveries had been diagnosed previously; 1 case had not. All of the emergent cesarean deliveries were for vaginal bleeding; 1 case was also for a concerning fetal heart rate, but only 1 of the known cases had a documented ruptured fetal vessel. None of these cases were found to have cervical shortening before the onset of bleeding. One of the undiagnosed cases resulted in a ruptured fetal vessel and a baby with no heart beat at birth who survived but had periventricular leukomalacia at 1 month of age with mild white-matter atrophy. Of the remaining neonates in this group, there were no deaths and no major complications beyond mild respiratory distress syndrome in 9 cases. There were no other major neonatal complications, which included no cases of periventricular leukomalacia, neonatal sepsis, necrotizing enterocolitis, or any grade of intraventricular hemorrhage in the confirmed cases of vasa previa. CONCLUSION: This study confirms most current recommendations that include risk-based ultrasound screening, early hospitalization at 30-34 weeks gestation, antenatal corticosteroids at 30-32 weeks gestation, and elective delivery at 33-34 weeks gestation. Thus, with these recommendations for current identification and management of vasa previa in this series of geographically diverse mostly private practice maternal fetal medicine practices, we have confirmed recent reports that show a dramatic improvement in neonatal survival and complications compared with earlier reports.

Role of the Hospitalist and Maternal Fetal Medicine Physician in Obstetrical Inpatient Care.

OBJECTIVE: The objective of this study was to evaluate the role of hospitalists and Maternal Fetal Medicine (MFM) subspecialists in obstetrical inpatient care. STUDY DESIGN: This electronic survey study was offered to members of the American College of Obstetrics & Gynecology (ACOG; n = 1,039) and the Society for Maternal-Fetal Medicine (SMFM; n = 1,813). RESULTS: Overall, 607 (21%) respondents completed the survey. Overall, 35% reported that hospitalists provided care in at least one of their hospitals. Compared with ACOG respondents, a higher frequency of SMFM respondents reported comfort with hospitalists providing care for all women on labor and delivery (74.4 vs. 43.5%, p = 0.005) and women with complex issues (56.4 vs. 43.5%, p = 0.004). The majority of ACOG respondents somewhat/completely agreed that hospitalists were associated with decreased adverse events (69%) and improved safety/safety culture (70%). Overall, 35% of ACOG respondents have MFM consultation available with 53% having inpatient coverage. Of these, 85% were satisfied with MFM availability. CONCLUSION: Over one-third of respondents work in units staffed with hospitalists and more than half have inpatient MFM coverage. It is important to evaluate if and how hospitalists can improve maternal and perinatal outcomes, and the types of hospitals that are best served by them.

Should we really avoid giving oxygen to mothers with concerning fetal heart rate patterns?

We challenge a provocative article entitled "Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful" by Hamel et al in the August issue of the Journal. The authors contend there is no good evidence that oxygen administration to the mother of a fetus with a concerning fetal heart rate pattern prevents acidosis and that in theory such oxygen administration may actually or potentially do harm to the fetus. It is clear that oxygen is administered quite often to women in labor, especially to those with category II fetal heart rate patterns and, because more than 80% of women in labor have these patterns and the majority of these patterns are unlikely to be associated with significant fetal hypoxia, that such oxygen administration is greatly overused. We describe in this article evidence that oxygen given to the mother actually does improve fetal oxygenation, especially in hypoxemic fetuses, and make arguments that there really is no substantial evidence that, except in theory, maternal oxygen administration causes any harm to the fetus.

17-hydroxyprogesterone caproate for preterm rupture of the membranes: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Preterm rupture of membranes (PROM) is associated with an increased risk of preterm birth and neonatal morbidity. Prophylactic 17-hydroxyprogesterone caproate (17OHP-C) reduces the risk of preterm birth in some women who are at risk for preterm birth. We sought to test whether 17OHP-C would prolong pregnancy or improve perinatal outcome when given to mothers with preterm rupture of the membranes. STUDY DESIGN: This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. The study included singleton pregnancies with gestational ages from 23(0/7) to 30(6/7) weeks at enrollment, documented PROM, and no contraindication to expectant management. Consenting women were assigned randomly to receive weekly intramuscular injections of 17OHP-C (250 mg) or placebo. The primary outcome was continuation of pregnancy until a favorable gestational age, which was defined as either 34(0/7) weeks of gestation or documentation of fetal lung maturity at 32(0/7) to 33(6/7) weeks of gestation. The 2 prespecified secondary outcomes were interval from randomization to delivery and composite adverse perinatal outcome. The planned sample size was 222 total women. RESULTS: From October 2011 to April 2014, 152 women were enrolled; 74 women were allocated randomly to 17OHP-C, and 78 were allocated randomly to placebo. The trial was stopped when results of a planned interim analysis suggested that continuation was futile. The primary outcome was achieved in 3% of the 17OHP-C group and 8% of the placebo group (P = .18). There was no significant between-group difference in the prespecified secondary outcomes, randomization-to-delivery interval (17.1 ± 16.1 vs 17.0 ± 15.8 days, respectively; P = .76) or composite adverse perinatal outcome (63% vs 61%, respectively; P = .93). No significant differences were found in other outcomes, which included rates of chorioamnionitis, postpartum endometritis, cesarean delivery, individual components of the composite outcome, or prolonged neonatal length of stay. CONCLUSION: Compared with placebo, weekly 17OHP-C injections did not prolong pregnancy or reduce perinatal morbidity in patients with PROM in this trial.

Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA.

OBJECTIVE: The objective of this study was to validate the clinical performance of massively parallel genomic sequencing of cell-free deoxyribonucleic acid contained in specimens from pregnant women at high risk for fetal aneuploidy to test fetuses for trisomies 21, 18, and 13; fetal sex; and the common sex chromosome aneuploidies (45, X; 47, XXX; 47, XXY; 47, XYY). STUDY DESIGN: This was a prospective multicenter observational study of pregnant women at high risk for fetal aneuploidy who had made the decision to pursue invasive testing for prenatal diagnosis. Massively parallel single-read multiplexed sequencing of cell-free deoxyribonucleic acid was performed in maternal blood for aneuploidy detection. Data analysis was completed using sequence reads unique to the chromosomes of interest. RESULTS: A total of 3430 patients were analyzed for demographic characteristics and medical history. There were 137 fetuses with trisomy 21, 39 with trisomy 18, and 16 with trisomy 13 for a prevalence rate of the common autosomal trisomies of 5.8%. There were no false-negative results for trisomy 21, 3 for trisomy 18, and 2 for trisomy 13; all 3 false-positive results were for trisomy 21. The positive predictive values for trisomies 18 and 13 were 100% and 97.9% for trisomy 21. A total of 8.6% of the pregnancies were 21 weeks or beyond; there were no aneuploid fetuses in this group. All 15 of the common sex chromosome aneuploidies in this population were identified, although there were 11 false-positive results for 45,X. Taken together, the positive predictive value for the sex chromosome aneuploidies was 48.4% and the negative predictive value was 100%. CONCLUSION: Our prospective study demonstrates that noninvasive prenatal analysis of cell-free deoxyribonucleic acid from maternal plasma is an accurate advanced screening test with extremely high sensitivity and specificity for trisomy 21 (>99%) but with less sensitivity for trisomies 18 and 13. Despite high sensitivity, there was modest positive predictive value for the small number of common sex chromosome aneuploidies because of their very low prevalence rate.

Advancing research transdisciplinarity within our discipline.

Advancing biomedical knowledge is crucial to the understanding of disease pathophysiology, diagnosis, treatment, and the maintenance of health. Whereas collaborative pursuits among basic and translational scientists, clinical researchers, and clinicians should advance biomedical progress and its translation to better medicine. The field of obstetrics and gynecology and its subspecialties has not escaped this problem. Obstetrics and gynecology specialists and subspecialists have limited opportunities to interact with translational or basic investigators, and cross-fertilization and collaborations are further challenged by the current healthcare and funding climate. This opinion manuscript focuses on the field of maternal-fetal medicine, serving as an example that illustrates the risks and opportunities that might exist within our obstetrics and gynecology academic community. A Pregnancy Task Force recently sought to identify ways to overcome hurdles related to research training, and ensure a sufficient pool of physician-scientists pursuing pertinent questions in the field. The group discussed strategies to promote a culture of intellectual curiosity and research excellence, securing additional resources for trainees, and attracting current and next generation basic, translational, and clinical scholars to our field. Recommendations encompassed activities within annual academic meetings, training initiatives, and additional funding opportunities. Inferences from these discussions can be made to all obstetrics and gynecology subspecialty areas.

Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes.

OBJECTIVE: The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes. STUDY DESIGN: Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). RESULTS: The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5, respectively). CONCLUSION: We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.

Removal versus retention of cerclage in preterm premature rupture of membranes: a randomized controlled trial.

OBJECTIVE: The decision of whether to retain or remove a previously placed cervical cerclage in women who subsequently rupture fetal membranes in a premature gestation is controversial and all studies to date are retrospective. We performed a multicenter randomized controlled trial of removal vs retention of cerclage in these patients to determine whether leaving the cerclage in place prolonged gestation and/or increased the risk of maternal or fetal infection. STUDY DESIGN: A prospective randomized multicenter trial of 27 hospitals was performed. Patients included were those with cerclage placement at ≤23 weeks 6 days in singleton or twin pregnancies, with subsequent spontaneous rupture of membranes between 22 weeks 0 days and 32 weeks 6 days. Patients were randomized to retention or removal of cerclage. Patients were then expectantly managed and delivered only for evidence of labor, chorioamnionitis, fetal distress, or other medical or obstetrical indications. Management after 34 weeks was at the clinician's discretion. RESULTS: The initial sample size calculation determined that a total of 142 patients should be included but after a second interim analysis, futility calculations determined that the conditional power for showing statistical significance after randomizing 142 patients for the primary outcome of prolonging pregnancy was 22.8%. Thus the study was terminated after a total of 56 subjects were randomized with complete data available for analysis, 32 to removal and 24 to retention of cerclage. There was no statistical significance in primary outcome of prolonging pregnancy by 1 week comparing the 2 groups (removal 18/32, 56.3%; retention 11/24, 45.8%) P = .59; or chorioamnionitis (removal 8/32, 25.0%; retention 10/24, 41.7%) P = .25, respectively. There was no statistical difference in composite neonatal outcomes (removal 16/33, 50%; retention 17/30, 56%), fetal/neonatal death (removal 4/33, 12%; retention 5/30, 16%); or gestational age at delivery (removal mean 200 days; retention mean 198 days). CONCLUSION: Statistically significant differences were not seen in prolongation of latency, infection, or composite neonatal outcomes. However, there was a numerical trend in the direction of less infectious morbidity, with immediate removal of cerclage. These findings may not have met statistical significance if the original sample size of 142 was obtained, however they provide valuable data suggesting that there may be no advantage to retaining a cerclage after preterm premature rupture of membranes and a possibility of increased infection with cerclage retention.