Brian M. Mercer

The Preterm Prediction Study: Effect of gestational age and cause of preterm birth on subsequent obstetric outcome

OBJECTIVEnWe sought to evaluate the association between prior spontaneous preterm delivery and subsequent pregnancy outcome.nnnSTUDY DESIGNnA total of 1711 multiparous women with singleton gestations were prospectively evaluated at 23 to 24 weeks gestation. Prior pregnancies were coded for the presence or absence of a prior spontaneous preterm delivery. If a prior spontaneous preterm delivery had occurred, the gestation of the earliest prior delivery (13-22, 23-27, 28-34, and 35-36 weeks gestation) was recorded. Current gestations were categorized as spontaneous preterm delivery at <28, <30, <32, <35, or <37 weeks gestation. The risk of spontaneous preterm delivery in the current gestation was determined on the basis of the occurrence, gestational age, and cause of the earliest prior spontaneous preterm delivery.nnnRESULTSnThe incidences of spontaneous preterm delivery before 28, 30, 32, 35, and 37 weeks gestation were 0.8%, 1.1%, 1.9%, 5.1%, and 11.9%, respectively. Those with a prior spontaneous preterm delivery carried a 2.5-fold increase in the risk of spontaneous preterm delivery in the current gestation over those with no prior spontaneous preterm delivery (21. 7% vs 8.8%; P </=.001). Gravid women with an early prior spontaneous preterm delivery (23-27 weeks gestation) had a higher risk of recurrent spontaneous preterm delivery (27.1% vs 8.8%; P </=.001). Prior spontaneous preterm delivery was more closely associated with subsequent early spontaneous preterm delivery at <28 weeks gestation (relative risk, 10.6) than for spontaneous preterm delivery overall (relative risk, 2.5). An early prior spontaneous preterm delivery (23-27 weeks gestation) was most highly associated with early spontaneous preterm delivery (<28 weeks gestation) in the current gestation (relative risk, 22.1). The relationship between prior spontaneous preterm delivery and current outcome was not as strong for those with a very early spontaneous preterm delivery (13-22 weeks gestation). Prior spontaneous preterm delivery caused by preterm premature rupture of the membranes and preterm labor was significantly associated with similar outcomes in the current gestation (P <.001).nnnCONCLUSIONnPrior spontaneous preterm delivery is highly associated with recurrence in the current gestation. An early prior spontaneous preterm delivery is more predictive of recurrence and is most highly associated with subsequent early spontaneous preterm delivery.

The preterm prediction study: Fetal fibronectin testing and spontaneous preterm birth*

Objective To evaluate the presence of fetal fibronectin in the cervix and vagina as a screening test for spontaneous preterm birth. Methods Two thousand nine hundred twenty-nine women at ten centers were routinely screened every 2 weeks from 22–24 to 30 weeks for cervical and vaginal fetal fibronectin. A positive test was defined as a value equal to or greater than 50 ng/mL. The relation between a positive test at four gestational ages and spotaneous pretern birth at various intervals after the test was determined. Results In each testing period 3–4% of the fetal fibronectin tests were positive. The correlation between cervical and vaginal fetal firbonectin at the same visit was always approximately 0.7 (P < .001), and that between cervical or vaginal fetal fibronectin in consecutive visits was between 0.17 and 0.25 (P < .001). The sensitivity of fetal fibronectin at 22–24 weeks to predict spontaneous preterm birth at less than 28 weeks was 0.63, and the relative risk for a positive versus negative test was 59. The specificity was always 96–98%, whereas the positive predictive value rose from 13% to 36% as the upper limit of the definition of preterm birth was increased from less than 28 to less than 37 weeks. The relative risk for spontaneous preterm birth after a positive fetal fibronectin test compared with a negative fetal fibronectin test varied substantially by testing period and by the definition of spontaneous preterm birth, but always remained greater than 4 and statistically significant. Conclusion A positive cervical or vaginal fetal fibronectin test at 22–24 weeks predicted more than half of the spontaneous preterm births at less than 28 weeks (sensitivity 0.63). As the definition of spontaneous preterm birth was extended to include later gestational ages or when the fetal fibronectin test was performed later in pregnancy, the level of association between a positive fetal fibronectin test and spontaneous preterm birth, while remaining highly significant, tended to decrease. Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, we present no evidence that the use of this test will result in a reduction in spontaneous preterm birth.

Pregnancy outcomes with weight gain above or below the 2009 institute of medicine guidelines

OBJECTIVE: To evaluate pregnancy outcomes according to 2009 Institute of Medicine (IOM) gestational weight gain guidelines. METHODS: This study is a secondary analysis of a preeclampsia prevention trial among nulliparas carrying singletons. Odds ratios and 95% confidence intervals (adjusted for maternal age, race, smoking, and treatment group) were calculated based on total weight gain below or above the IOM guidelines stratified by prepregnancy body mass index (BMI). The referent group was weight gain within the guidelines. RESULTS: Of 8,293 pregnancies, 9.5% had weight gain below, 17.5% within, and 73% above IOM guidelines. With excess weight gain, all BMI categories had an increased risk of hypertensive disorders; normal weight and overweight women also had increased risk of cesarean delivery and neonatal birth weight at or above the 90th centile but a decreased risk of weight below the 10th centile. There were no consistent associations with insufficient weight gain and adverse outcomes. CONCLUSION: Excess weight gain was prevalent and associated with an increased risk of hypertensive disorders, cesarean delivery, and large-for-gestational-age neonates.

The preterm prediction study: Patterns of cervicovaginal fetal fibronectin as predictors of spontaneous preterm delivery

OBJECTIVEnOur purpose was to determine how various temporal patterns of fetal fibronectin positivity from 24 to 30 weeks predict subsequent fetal fibronectin test results and spontaneous preterm delivery.nnnSTUDY DESIGNnA total of 2929 women had vaginal and cervical fetal fibronectin tests obtained at least once at 24, 26, 28, or 30 weeks, and 1870 women had tests performed at all four gestational ages. Fetal fibronectin values > or = 50 ng/ml were considered positive. Various patterns of positive and negative tests were evaluated for prediction of (1) whether the next fetal fibronectin test would be positive or negative and (2) the percent of women with a spontaneous preterm delivery > or = 4 weeks after the last fetal fibronectin test at < 30, < 32, < 35, and < 37 weeks gestational age.nnnRESULTSnWomen with previous negative test results had only a 3% chance of a subsequent positive test result; however, if the last test result was positive, 29% of the next tests were positive. Of the 1870 women with tests at 24, 26, 28, and 30 weeks, 89% had all negative results, 8.4% had one positive result, 1.8% had two positive results, and 0.8% had three or four positive results. The higher the percent of positive tests at 24 to 26 weeks, at 28 to 30 weeks, or at 24 to 30 weeks, the greater the risk of subsequent spontaneous preterm birth. As an example, the risk of spontaneous preterm birth at < 30 weeks for women with two negative fetal fibronectin test results at 24 and 26 weeks was 0.3% versus 16% for women with two positive results.nnnCONCLUSIONnThe presence of a positive cervical or vaginal fetal fibronectin test result predicts subsequent positive fetal fibronectin positivity and subsequent spontaneous preterm birth. The greater the percent of positive results, the higher is the risk of spontaneous preterm birth. After a positive test result, two negative results are required before the risk of spontaneous preterm birth returns to baseline.

Timing of Elective Repeat Cesarean Delivery at Term and Maternal Perioperative Outcomes

OBJECTIVE: Elective repeat cesarean delivery at 37 or 38 weeks compared with 39 completed weeks of gestation is associated with adverse neonatal outcomes. We assessed whether delivery before 39 weeks is justifiable on the basis of decreased adverse maternal outcomes. METHODS: We conducted a cohort study of women with live singleton pregnancies delivered by prelabor elective repeat cesarean delivery from 1999 through 2002 at 19 U.S. academic centers. Gestational age was examined by completed weeks (eg, 37 completed weeks=37 0/7–37 6/7 weeks). Maternal outcomes included a primary composite of death, hysterectomy, uterine rupture or dehiscence, blood transfusion, uterine atony, thromboembolic complications, anesthetic complications, surgical injury or need for arterial ligation, intensive care unit admission, wound complications, or endometritis. RESULTS: Of 13,258 elective repeat cesareans performed at 37 weeks of gestation or later, 11,255 (84.9%) were between 37 0/7 and 39 6/7 weeks (6.3% at 37, 29.5% at 38, and 49.1% at 39 completed weeks), and 15.1% were at 40 0/7 weeks or more. The primary outcome occurred in 7.43% at 37 weeks, 7.47% at 38 weeks and 6.56% at 39 weeks (P for trend test=.09). Delivery before 39 weeks was not associated with a decrease in the primary outcome when compared with delivery at 39 weeks (adjusted odds ratio 1.16; 95% confidence interval 1.00–1.34). Early delivery was associated with increased maternal hospitalization of 5 days or more [1.96 (1.54, 2.49)] but not with a composite of death or hysterectomy or with individual maternal morbidities. CONCLUSION: Elective repeat cesarean delivery at 37 or 38 weeks is not associated with decreased maternal morbidity. LEVEL OF EVIDENCE: II

Timing of Delivery and Adverse Outcomes in Term Singleton Repeat Cesarean Deliveries

OBJECTIVE: To compare the maternal and neonatal risks of elective repeat cesarean delivery compared with pregnancy continuation at different gestational ages, starting from 37 weeks. METHODS: We analyzed the composite maternal and neonatal outcomes of repeat cesarean deliveries studied prospectively over 4 years at 19 U.S. centers. Maternal outcome was a composite of pulmonary edema, cesarean hysterectomy, pelvic abscess, thromboembolism, pneumonia, transfusion, or death. Composite neonatal outcome consisted of respiratory distress, transient tachypnea, necrotizing enterocolitis, sepsis, ventilation, seizure, hypoxic–ischemic encephalopathy, neonatal intensive care unit admission, 5-minute Apgar of 3 or lower, or death. Outcomes after elective repeat cesarean delivery without labor at each specific gestational age were compared with outcomes for all who were delivered later as a result of labor onset, specific obstetric indications, or both. RESULTS: Twenty-three thousand seven hundred ninety-four repeat cesarean deliveries were included. Elective delivery at 37 weeks of gestation had significantly higher risks of adverse maternal outcome (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.06–2.31), whereas elective delivery at 39 weeks of gestation was associated with better maternal outcome when compared with pregnancy continuation (OR 0.51, 95% CI 0.36–0.72). Elective repeat cesarean deliveries at 37 and 38 weeks of gestation had significantly higher risks of adverse neonatal outcome (37 weeks OR 2.02, 95% CI 1.73–2.36; 38 weeks OR 1.39 95% CI 1.24–1.56), whereas delivery at 39 and 40 weeks of gestation presented better neonatal outcome as opposed to pregnancy continuation (39 weeks OR 0.79, 95% CI 0.68–0.92; 40 weeks OR 0.57, 95% CI 0.43–0.75). CONCLUSION: In women with prior cesarean delivery, 39 weeks of gestation is the optimal time for repeat cesarean delivery for both mother and neonate. LEVEL OF EVIDENCE: II

Failed Labor Induction Toward an Objective Diagnosis

OBJECTIVE: To evaluate maternal and perinatal outcomes in women undergoing labor induction with an unfavorable cervix according to duration of oxytocin administration in the latent phase of labor after ruptured membranes. METHODS: This was a secondary analysis of a randomized multicenter trial in which all cervical examinations from admission were recorded. Inclusion criteria: nulliparas at or beyond 36 weeks of gestation undergoing induction with a cervix of 2 cm or less dilated and less than completely effaced. The latent phase of labor was defined as ending at a cervical dilation of 4 cm and effacement of at least 90%, or at a cervical dilation of 5 cm regardless of effacement. RESULTS: A total of 1,347 women were analyzed. The overall vaginal delivery rate was 63.2%. Most women had exited the latent phase after 6 hours of oxytocin and membrane rupture (n=939; 69.7%); only 5% remained in the latent phase after 12 hours. The longer the latent phase, the lower the vaginal delivery rate. Even so, 39.4% of the 71 women who remained in the latent phase after 12 hours of oxytocin and membrane rupture were delivered vaginally. Chorioamnionitis, endometritis, or both, and uterine atony were the only maternal adverse outcomes related to latent-phase duration: adjusted odds ratios (95% confidence intervals) of 1.12 (1.07, 1.17) and 1.13 (1.06, 1.19), respectively, for each additional hour. Neonatal outcomes were not related to latent-phase duration. CONCLUSION: Almost 40% of the women who remained in the latent phase after 12 hours of oxytocin and membrane rupture were delivered vaginally. Therefore, it is reasonable to avoid deeming labor induction a failure in the latent phase until oxytocin has been administered for at least 12 hours after membrane rupture. LEVEL OF EVIDENCE: III

Indicated versus spontaneous preterm delivery: An evaluation of neonatal morbidity among infants weighing ≤1000 grams at birth

OBJECTIVEnThe aim of the study was to determine whether infants weighing </=1000 g after birth who are born to women who undergo indicated preterm delivery have different neonatal outcomes than do those born as a result of either spontaneous preterm labor or preterm premature rupture of membranes.nnnSTUDY DESIGNnIn a 1-year observational study (1992-1993) the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network collected outcome data for 799 infants whose birth weights were </=1000 g. Only singleton infants with gestational age >20 weeks who were not produced as the result of an induced abortion were included. Our analysis was further limited to infants without major congenital anomalies who survived >2 days, were deemed potentially viable by the obstetrician, and would have undergone a cesarean delivery for fetal indications (N = 411). The primary reason for delivery was categorized as indicated delivery, spontaneous preterm labor, or spontaneous preterm premature rupture of membranes. Selected neonatal outcomes were evaluated among infants born to women in each of these groups. Logistic regression analyses were used to control for the effects of other potentially confounding variables.nnnRESULTSnA total of 156 of the 411 infants were born to women who underwent an indicated preterm delivery, whereas 160 were born after spontaneous preterm labor and 95 were delivered after preterm premature rupture of membranes. Univariate analyses revealed significantly lower incidences of grade III or IV intraventricular hemorrhage, grade III or IV retinopathy of prematurity, and seizure activity among infants born in an indicated preterm delivery than among those born after spontaneous preterm labor or preterm premature rupture of membranes. However, infants of women who underwent indicated preterm delivery had a more advanced mean gestational age at birth than did those born after spontaneous preterm labor or preterm premature rupture of membranes (28 +/- 2 weeks, 26 +/- 2 weeks, and 26 +/- 1 weeks, respectively, P <.001). Multiple logistic regression analysis was therefore used to control for the disparity in gestational age. Multivariate analyses did not confirm the apparent improvement in neonatal outcome in the indicated delivery group.nnnCONCLUSIONnIn this population of infants weighing </=1000 g, selected neonatal outcomes did not differ according to birth by indicated preterm delivery, spontaneous preterm labor, or preterm premature rupture of membranes.

Risk of uterine rupture and placenta accreta with prior uterine surgery outside of the lower segment

OBJECTIVE: Women with a prior myomectomy or prior classical cesarean delivery often have early delivery by cesarean because of concern for uterine rupture. Although theoretically at increased risk for placenta accreta, this risk has not been well-quantified. Our objective was to estimate and compare the risks of uterine rupture and placenta accreta in women with prior uterine surgery. METHODS: Women with prior myomectomy or prior classical cesarean delivery were compared with women with a prior low-segment transverse cesarean delivery to estimate rates of both uterine rupture and placenta accreta. RESULTS: One hundred seventy-six women with a prior myomectomy, 455 with a prior classical cesarean delivery, and 13,273 women with a prior low-segment transverse cesarean delivery were evaluated. Mean gestational age at delivery differed by group (P<.001), prior myomectomy (37.3 weeks), prior classical cesarean delivery (35.8 weeks), and low-segment transverse cesarean delivery (38.6 weeks). The frequency of uterine rupture in the prior myomectomy group (P-MMX group) was 0% (95% confidence interval [CI] 0–1.98%). The frequency of uterine rupture in the low-segment transverse cesarean delivery group (LTC group) (0.41%) was not statistically different from the risk in the P-MMX group (P>.99) or in the prior classical cesarean delivery group (PC group) (0.88%; P=.13). Placenta accreta occurred in 0% (95% CI 0–1.98%) of the P-MMX group compared with 0.19% in the LTC group (P>.99) and 0.88% in the PC group (P=.01 relative to the LTC group). The adjusted odds ratio for the PC group (relative to LTC group) was 3.23 (95% CI 1.11–9.39) for uterine rupture and 2.09 (95% CI 0.69–6.33) for accreta. The frequency of accreta for those with previa was 11.1% for the PC group and 13.6% for the LTC group (P>.99). CONCLUSION: A prior myomectomy is not associated with higher risks of either uterine rupture or placenta accreta. The absolute risks of uterine rupture and accreta after prior myomectomy are low.

Association between Sleep-Disordered Breathing and Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus

OBJECTIVEnTo estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM).nnnMETHODSnIn this prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results. An apnea-hypopnea index of 5 or greater was used to define sleep-disordered breathing. Exposure-response relationships were examined, grouping participants into four apnea-hypopnea index groups: 0, greater than 0 to less than 5, 5 to less than 15, and 15 or greater. The study was powered to test the primary hypothesis that sleep-disordered breathing occurring in pregnancy is associated with an increased incidence of preeclampsia. Secondary outcomes were rates of hypertensive disorders of pregnancy, defined as preeclampsia and antepartum gestational hypertension, and GDM. Crude and adjusted odds ratios and 95% confidence intervals (CIs) were calculated from univariate and multivariate logistic regression models.nnnRESULTSnThree thousand seven hundred five women were enrolled. Apnea-hypopnea index data were available for 3,132 (84.5%) and 2,474 (66.8%) women in early and midpregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%. The prevalence of preeclampsia was 6.0%, hypertensive disorders of pregnancy 13.1%, and GDM 4.1%. In early and midpregnancy the adjusted odds ratios for preeclampsia when sleep-disordered breathing was present were 1.94 (95% CI 1.07-3.51) and 1.95 (95% CI 1.18-3.23), respectively; hypertensive disorders of pregnancy 1.46 (95% CI 0.91-2.32) and 1.73 (95% CI 1.19-2.52); and GDM 3.47 (95% CI 1.95-6.19) and 2.79 (95% CI 1.63-4.77). Increasing exposure-response relationships were observed between apnea-hypopnea index and both hypertensive disorders and GDM.nnnCONCLUSIONnThere is an independent association between sleep-disordered breathing and preeclampsia, hypertensive disorders of pregnancy, and GDM.