Pregnancy outcomes of women receiving compounded 17 α-hydroxyprogesterone caproate for prophylactic prevention of preterm birth 2004 to 2011.

OBJECTIVE: To examine pregnancy outcomes of women receiving weekly compounded 17 α-hydroxyprogesterone caproate (17P) injections through a home nursing program compared with those reported in a multicenter trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Network. METHODS: The study sample was comprised of patients receiving compounded 17P through a home nurse administration care management program. Included were women with current singleton gestation and prior spontaneous preterm birth (SPTB) initiating 17P between 16 and 20 weeks. Maternal characteristics and pregnancy outcomes were compared between study group and NICHD Network trial patients. RESULTS: Women (n = 5493) received a mean of 16.9 ± 4.0 injections. Of the 92,700 injections, 98.4% were administered within the recommended 5- to 9-day interval. Recurrent SPTB occurred in 28.3%. The overall rate of SPTB at <37 weeks was similar for black and nonblack women (p = 0.592). Within black or nonblack groups, preterm birth rates at <37 weeks were similar regardless of gestational age at start of 17P (p = 0.894 and p = 0.374, respectively). These results were similar to those reported in the multicenter trial. Fetal and neonatal death occurred in 0.8% (46/5493). No significant difference was observed in rate of fetal or neonatal death by gestational age at initiation of 17P (p = 0.478). CONCLUSION: Home nurse administration of compounded 17P is safe and effective.

Elective delivery at 34°(/)7 to 366(/)7 weeks' gestation and its impact on neonatal outcomes in women with stable mild gestational hypertension.

OBJECTIVE: To examine the frequency of elective delivery and neonatal outcomes in women with stable mild gestational hypertension delivering late preterm. STUDY DESIGN: The frequency of elective delivery between 1995 and 2007 at gestational age of 34°(/)7-366(/)7 weeks (late preterm), 37°(/)7-376(/)7 weeks, and ≥38°(/)7 weeks, as well as neonatal outcomes, were studied in singleton gestation with mild gestational hypertension without proteinuria from a large national database. RESULTS: One thousand eight hundred fifty-eight patients were studied: 607 (33%) were delivered for maternal/fetal reasons and 1251 (67%) were electively delivered. Among the 1251 women delivered electively, 25.5% were late preterm, 24.4% at 37°(/)7-376(/)7 weeks and 50.1% at ≥38°(/)7 weeks' gestation. Neonatal intensive care unit admission, ventilatory assistance, and respiratory distress syndrome were more common in late-preterm infants. There was no maternal/perinatal mortality. CONCLUSION: We found that 25.5% of patients with stable mild gestational hypertension, without any maternal or fetal complication, had iatrogenic elective late-preterm delivery. This practice also was associated with increased rates of neonatal complications and neonatal length of stay.

Influence of gestational age and reason for prior preterm birth on rates of recurrent preterm delivery.

OBJECTIVE: We sought to compare rates of recurrent spontaneous preterm birth (SPTB) in women receiving 17-α-hydroxyprogesterone caproate (17P) with prior SPTB due to preterm labor (PTL) vs preterm premature rupture of membranes (PPROM). STUDY DESIGN: Women with singleton gestation having 1 prior SPTB enrolled at 16-24.9 weeks' gestation for weekly outpatient 17P administration were identified from a database. Rates of recurrent SPTB were compared between those with prior SPTB due to PTL or PPROM overall and by gestational age at prior SPTB. RESULTS: Records from 2123 women were analyzed. The prior PTL group vs the prior PPROM group experienced higher rates of recurrent SPTB at <37 weeks (29.7% vs 22.9%, P = .004), <35 weeks (14.0% vs 9.1%, P = .004), and <32 weeks (5.9% vs 3.3%, P = .024), respectively. CONCLUSION: Reason and gestational age of prior SPTB influence the likelihood of recurrent SPTB in women receiving 17P prophylaxis.

Uterine activity in women receiving 17 alpha-hydroxyprogesterone caproate for the prevention of preterm birth: an observational study.

We evaluated uterine contraction frequency in women receiving 17 alpha-hydroxyprogesterone caproate (17-OHP-C) for the prevention of preterm delivery. Women with singleton pregnancies and receiving weekly 17-OHP-C and outpatient tococardiography were identified from a database. The mean and maximum contraction frequencies per hour were compared from 3 days before to 3 days after 17-OHP-C dosing. McNemar chi(2), Mann-Whitney U, and Friedman test statistics were used for analysis. Data were obtained from 388 women. Median contraction frequency was greater for women with subsequent preterm birth versus those delivering at term (1.5 [range 0, 14.5] versus 1.2 [range 0, 21.0] contractions per hour, P < 0.001). No reduction in contraction frequency was observed after 17-OHP-C administration, and in fact, the converse was observed for the average contractions 3 days prior compared with 3 days posttreatment ( P < 0.001). In the subgroup of women with a subsequent spontaneous preterm, the proportion who had an average contraction frequency of more than five per hour 1 day preinjection versus 1 day postinjection was not significantly different (2.6% versus 3.0%, P = 1.0). Administration of 17-OHP-C was not associated with a reduction in contraction frequency. To be effective, this drug likely has effects by mechanisms other than tocolysis. Although a statistically significant increase in contractions was identified posttherapy versus pretherapy, the clinical importance of this observation is unknown.

The impact of acute tocolysis on neonatal outcome in women hospitalized with preterm labor at 32 to 34 weeks' gestation.

We compared neonatal outcomes from singleton pregnancies in women hospitalized with preterm labor (PTL) at 32 0/7 to 34 6/7 weeks managed with and without acute tocolysis. Women enrolled for outpatient surveillance who were hospitalized and diagnosed with PTL between 32 0/7; to 34 6/7 weeks' gestation without conditions necessitating interventional delivery during hospitalization were identified ( N = 2921). Patients with contraindications to pregnancy prolongation were excluded ( N = 168). Data were compared between patients whose clinical management included tocolysis ( N = 2342) and patients in whom tocolysis was not utilized ( N = 411). The incidence of preterm birth (77.9% versus 48.1%), low birth weight (48.9% versus 16.7%), neonatal intensive care unit admission (41.4% versus 16.2%), and nursery length of stay > 7 days (28.0% versus 9.7%) were all higher in women not receiving acute tocolysis compared with the acute tocolysis group (all P < 0.001). Using acute tocolysis to prolong pregnancy in patients hospitalized with PTL at 32 0/7 to 34 6/7 weeks' gestation is associated with improved neonatal outcomes.

Preterm birth prevention by 17 alpha-hydroxyprogesterone caproate vs. daily nursing surveillance.

OBJECTIVE: To compare the incidence of spontaneous recurrent preterm delivery (SPTD) between women receiving 17 alpha-hydroxyprogesterone caproate (17P) and women receiving daily perinatal nursing surveillance (dPNS) with home uterine activity monitoring. STUDY DESIGN: Women enrolled for dPNS or weekly nursing visits with 17P injection were eligible. Included were singletons with previous SPTD, without preterm labor (PTL), cerclage or vaginal bleeding and < 27 weeks at enrollment. 17P and dPNS patients were matched 1:1 by race, marital status, tobacco use and number of SPTDs. Primary study outcome was incidence of spontaneous PTD. RESULTS: Data from 342 matched pairs were compared. Diagnosis of PTL (39.2% vs. 60.8%) and tocolytic use (12.9% vs. 49.7%) was decreased with 17P vs. dPNS (p < 0.001). The incidences of spontaneous PTD at < 32, 35 and 37 weeks were similar between the groups. CONCLUSION: There was no difference in recurrent SPTD between women treated with 17P and those receiving dPNS.

Management of recurrent preterm labor in twin gestations with nifedipine tocolysis.

We examined outcomes of twin pregnancies complicated by recurrent preterm labor receiving nifedipine tocolysis. In a retrospective study design, twin pregnancies receiving outpatient preterm labor surveillance services and oral nifedipine tocolysis following a diagnosis of preterm labor were identified from a database ( N = 1421). Eligible for inclusion were patients subsequently rehospitalized with recurrent preterm labor symptoms ( N = 862). Included were patients at < 35 weeks' gestation, having intact membranes, and remaining undelivered for > 48 hours after recurrent preterm labor ( N = 656). Pregnancy outcomes of women resuming nifedipine tocolysis ( N = 418) following hospitalization were compared with those having an alteration in treatment ( N = 238) to continuous subcutaneous terbutaline. Alteration of tocolytic treatment versus resuming nifedipine resulted in increased pregnancy prolongation (34.7 +/- 18.8 days versus 27.5 +/- 19.9 days, P < 0.001), with delivery of fewer low birth weight (67.2% versus 78.3%, P < 0.001) and very low birth weight infants (6.5% versus 15.0%, P < 0.001) and a decreased incidence of neonatal intensive care unit admission (44.7% versus 52.9%, P = 0.005). In twin pregnancies receiving nifedipine tocolysis, alteration of tocolytic treatment to subcutaneous terbutaline following hospitalization for recurrent preterm labor symptoms had a positive impact on pregnancy prolongation and neonatal outcomes.

Prophylaxis with 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm delivery: does gestational age at initiation of treatment matter?

OBJECTIVE: The purpose of this study was to determine effectiveness of 17 alpha-hydroxyprogesterone caproate (17 P) prophylaxis by gestational age (GA) at 17 P initiation. STUDY DESIGN: Singleton gestations with > or = 1 preterm birth (PTB) treated with 17 P prophylaxis for recurrent preterm birth before 27 weeks were identified from a data base. Data were stratified by GA at 17 P initiation (16-20.9 [n = 599] weeks and 21-26.9 [n = 307] weeks) and number of PTB (1, 2, > 2). Outcome variables were PTB at < 37, < 35, and < 32 weeks. RESULTS: No significant differences were found in gestational age at delivery or rates of recurrent PTB < 37, < 35, and < 32 weeks between those women initiating 17 P at 16-20.9 weeks or 21-26.9 weeks, or when stratified by number of prior preterm deliveries. CONCLUSION: Initiation of 17 P prophylaxis at 21-26.9 weeks is as effective as initiation at 16-20.9 weeks of gestation.

Increased recurrence of preterm delivery with early cessation of 17-alpha-hydroxyprogesterone caproate.

OBJECTIVE: The purpose of this study was to identify the effect of early cessation of 17-alpha-hydroxyprogesterone caproate (17P) on the incidence of spontaneous recurrent preterm delivery (PTD). STUDY DESIGN: Retrospective analysis of data from women who were enrolled for outpatient 17P administration between January 2004 and May 2006 included women with previous PTD and current singleton pregnancy who were beginning weekly 17P injections (250 mg intramuscularly) at 16-20.9 weeks. The study group was comprised of patients who were electively terminating 17P at <32.0 weeks and who delivered >10 days from the last injection. The control group consisted of patients who received weekly 17P injections until PTD or 36.9 weeks of gestation. The primary study outcome was the rate of recurrent spontaneous PTD. RESULTS: Study group patients were significantly more likely to have spontaneous recurrent PTD at <37 weeks of gestation (48.1% vs 33.3%; P = .011), at <35 weeks of gestation (30.9% vs 14.0%; P < .001), and at <32 weeks of gestation (16.0% vs 7.0%; P = .020). CONCLUSION: Early cessation of 17P treatment is associated with an increased risk for spontaneous recurrent PTD.

Gestational age at initiation of 17-hydroxyprogesterone caproate (17P) and recurrent preterm delivery.

OBJECTIVE: To compare rates of recurrent preterm birth between women starting treatment with 17alpha-hydroxyprogesterone caproate (17P) at 16-20.9 weeks of gestation versus 21-26.9 weeks. METHODS: Women enrolled in an outpatient program of education, nursing assessment and weekly 17P injections beginning at 16-26.9 weeks were eligible. Included were patients with singleton pregnancies and a history of preterm delivery (PTD). Pregnancy outcome was compared between women starting 17P at 16-20.9 weeks (n=156) and those starting 17P at 21-26.9 weeks (n=119) using Fisher's exact and Mann-Whitney U test statistics (p<0.05 considered significant). RESULTS: Mean gestational age at delivery (36.8 +/- 3.0 vs. 36.7 +/- 2.5) and rates of PTD at <37 weeks (40.4% vs. 48.7%), <35 weeks (16.7% vs. 16.8%) and <32 weeks (5.1% vs. 5.0%) were similar between the groups; all p > 0.05. CONCLUSIONS: Rates of preterm delivery were similar in patients initiating 17P at 16-20.9 or 21-26.9 weeks. A larger sample size is warranted in order to confirm our findings.

Cost-savings analysis of an outpatient management program for women with pregnancy-related hypertensive conditions.

The aim of this study was to evaluate the cost savings of outpatient management services for women with pregnancy-related hypertensive conditions. The outpatient management program included verbal and written patient education related to the hypertensive disease process during pregnancy as well as self-care procedures. Biometric data (ie, automated blood pressure measurement, qualitative urine protein) were collected at least daily by the patient and transmitted telephonically to a nursing call center. Data were evaluated and subjective symptoms assessed daily. Electronic records were maintained and reports provided to the prescribing physician and case manager. Included for analysis were: patients with pregnancy-related hypertensive conditions receiving outpatient services between January 1999 and November 2003, singleton gestation, no history of chronic hypertension, and gestational age of 20.0-36.9 weeks at start of outpatient program (n = 1,140). Maternal characteristics, antenatal hospitalization and length of stay, progression of disease, and neonatal outcome were analyzed. To evaluate cost-effectiveness, a model was developed to compare the cost of the program plus adjunctive antenatal hospitalization, to control data. The mean gestational age at program start was 32.6 weeks. Antenatal hospital admission was required for 24.8% of patients, with a mean length of stay of 2.3 days per admission. Progression to severe preeclampsia occurred in 14.3% of patients. Mean gestational age at delivery was 37.0 weeks. Antepartum charges averaged 10,327 US dollars per control patient and 4,888 US dollars per program patient, a difference of 5,439 US dollars. For each dollar spent on outpatient management, an average of 2.50 US dollars was saved. Utilizing outpatient management services for women with pregnancy-related hypertension reduces the need for inpatient care and is cost-effective.

A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.

Excessive uterine contractions: effect on the incidence of preterm delivery in twin gestation.

OBJECTIVE: To evaluate the effect of uterine contractions on the incidence of preterm delivery within 7 and 14 days in twin pregnancies. STUDY DESIGN: Study patients were identified from a large database composed of women receiving outpatient surveillance with home uterine contraction monitoring. We included tracings collected on a routine or acute basis from twin pregnancies without cerclage at 24.0-36.0 weeks. Tracings from patients with indicated delivery were excluded. Fisher's exact and Pearson's X2 tests were used. RESULTS: Datafrom 2,423 patients who recorded 8,291 acute tracings and 12,649 routine tracings were analyzed. Preterm delivery within 7 days followed 1.4% of routine vs. 6.6% of acute tracings (p < 0.001). Preterm delivery within 14 days followed 5.1% of routine vs. 16.8% of acute tracings (p < 0.001). CONCLUSION: Preterm uterine contractions affect pregnancy prolongation and outcome in twin pregnancies utilizing outpatient surveillance. Evaluation of patients exhibiting elevated preterm uterine contractions is warranted.

Consequences of nonindicated preterm delivery in singleton gestations.

OBJECTIVE: To determine the neonatal and economic consequences of nonindicated preterm delivery in singleton gestations. STUDY DESIGN: From a database of women with high-risk pregnancies enrolled for outpatient nursing services between October 1995 and February 2000, singleton gestations with induced labor or scheduled cesarean delivery and a gestational age at delivery of 34-36 weeks were identified. Excluded were women with preterm premature rupture of the membranes or medically indicated delivery. We compared infant neonatal intensive care unit (NICU) admission rates and ventilator use for consecutive weeks and applied a cost model to determine potential savings of delaying delivery. RESULTS: A total of 1,538 pregnancies were analyzed. Risk of NICU admission declined significantly with each advancing week (by > 50%, P <.05). NICU length of stay and total nursery costs decreased significantly between weeks 35 and 36 and weeks 34 and 35. Need for ventilatory assistance increased significantly for infants admitted to the NICU between weeks 34 and 35. The incidence of respiratory distress syndrome decreased 49% between 35 and 36 weeks. CONCLUSION: Prolonging gestation 1 week beyond weeks 34 and 35 has a significant impact on improving neonatal outcome and decreasing associated costs. These factors should be considered when electing to deliver at 34 and 35 weeks.

Managing perinatal outcomes: the clinical benefit and cost-effectiveness of pharmacologic treatment of recurrent preterm labor.

PURPOSE: To compare the clinical benefit and cost-effectiveness of utilizing continuous subcutaneous terbutaline versus oral tocolytics following recurrent preterm labor. DESIGN: Retrospective, 1:1 matched cohort. METHODOLOGY: From prospectively collected data in a nationwide, perinatal database of women receiving outpatient services, we identified singleton gestations having recurrent preterm labor, stabilized during hospitalization, and subsequently treated with oral tocolytics (PO group) or continuous subcutaneous terbutaline infusion (SQ group). Those without medically indicated delivery were eligible for inclusion. Each woman in the PO group was matched 1:1 by gestational age at recurrent preterm labor to a woman in the SQ group. A standardized cost model was applied to compare total antepartum hospital, nursery, and outpatient charges. Wilcoxon Signed Rank, paired t, and McNemar's C2 test statistics were used for comparisons. PRINCIPAL FINDINGS: 558 women were studied (279 per group). The PO group had less gestational gain following recurrent preterm labor than the SQ group (28.4 +/- 19.8 days vs. 33.9 +/- 19.0 days, respectively, P < .001). The SQ group had less per patient charges ($) for antepartum hospitalization (3,986 +/- 6,895 vs. 5,495 +/- 7,131, P = .009), and nursery (7,143 +/- 20,048 vs. 15,050 +/- 32,648, P < .001). Outpatient charges were less for the PO group (1,390 +/- 1,152 vs. 5,520 +/- 3,292, P < .001). Overall costs for those in the SQ group were $5,286 less per pregnancy compared to the PO group. CONCLUSION: In this population, continuous subcutaneous terbutaline infusion was both a clinically beneficial and cost-effective treatment following recurrent preterm labor.

Using 17 α-hydroxyprogesterone caproate to impact rates of recurrent preterm delivery in clinical practice.

OBJECTIVE: Evaluation of an outpatient 17 α-hydroxyprogesterone caproate (17P) administration programme. METHODS: A retrospective analysis of data collected from patients with a history of preterm birth (PTB) and current singleton gestation enrolled between 16.0 and 20.9 weeks' gestational age (GA) for weekly outpatient 17P administration and nursing assessment between 7/2004 and 12/2007 was conducted (n=3139). RESULTS: The population was mostly white (50.3%), 18-35 years old (77.7%), and married (67.0%). Median GA at 17P initiation and stop was 17.4 (16.0, 20.9) weeks and 35.1 (18.6, 37.4) weeks. Mean injections per patient were 16.5±4.9, at an interval of 7.2 days. Median GA at delivery was 37.3 (18.6, 44.0) weeks. Rate of recurrent spontaneous PTB was 29.8%, with 15.5% and 7.0% with PTB at <35 and <32 weeks. CONCLUSIONS: This represents the largest cohort reported to date of patients prescribed 17P therapy in clinical practice to prevent recurrent spontaneous PTB.

The reliability of patient-reported pregnancy outcome data.

Pregnancy and neonatal outcome information is frequently used in disease management to evaluate the cost-effectiveness of prenatal interventions and for other research and reporting activities. The purpose of this study was to determine if a telephone interview process is a reliable methodology for collecting pregnancy outcomes. High-risk patients from a large maternal-fetal medicine practice who received outpatient preterm labor management services from January 1996 to June 2001 were identified. Patient-reported pregnancy outcome data for 285 mothers and 478 infants were collected via a telephone interview by a perinatal nurse and compared to pregnancy outcome data abstracted from the maternal and infant hospital records. Overall, concordance and/or Kappa coefficients between maternal report and the medical record were high for delivery date (96.4%), birth weight within 100 grams (88.9%), Cesarean delivery (99.0%, Kappa = 0.98), and high-level nursery admission (91.2%, Kappa = 0.82). Both singleton and multiple gestation types accurately reported pregnancy outcome information. A telephone interview with a skilled nurse can be a reliable methodology for collection of valuable clinical and research data related to pregnancy outcome. Data collected in this manner and maintained in a database may be used with a high level of confidence by health care providers, payers, and researchers.

Antenatal factors predicting subsequent need for insulin treatment in women with gestational diabetes.

OBJECTIVE: To identify characteristics indicative of subsequent requirement of insulin in patients with gestational diabetes (GDM). METHODS: Identified from a database were patients with GDM not receiving insulin or oral hypoglycemic agents at enrollment for outpatient education and surveillance. Maternal characteristics were compared between patients achieving glycemic control with diet and those requiring insulin. Cox proportional hazards regression was used to assess multiple effects of significant univariate factors. RESULTS: Data from 2365 patients were analyzed. Patients requiring insulin were more likely to be multiparous, obese, have a history of GDM, be diagnosed at <28 weeks of gestation, and have a fasting blood glucose of >95 mg/dL, a glucose tolerance test 3-hour blood glucose of >140 mg/dL, and a glycosylated hemoglobin (A1c) of >or=6% at diagnosis of GDM. CONCLUSIONS: Laboratory values at diagnosis of GDM were the strongest indicators of subsequent need for insulin treatment. Patients with fasting blood glucose of >95 mg/dL and A1c values >or=6% at diagnosis of GDM should receive close surveillance of daily blood glucose.

Increased incidence of gestational diabetes in women receiving prophylactic 17alpha-hydroxyprogesterone caproate for prevention of recurrent preterm delivery.

OBJECTIVE: Progesterone has a known diabetogenic effect. We sought to determine whether the incidence of gestational diabetes mellitus (GDM) is altered in women receiving weekly 17alpha-hydroxyprogesterone caproate (17P) prophylaxis for the prevention of recurrent preterm birth. RESEARCH DESIGN AND METHODS: Singleton gestations in women having a history of preterm delivery were identified from a database containing prospectively collected information from women receiving outpatient nursing services related to a high-risk pregnancy. Included were patients enrolled for outpatient management at <27 weeks' gestation with documented pregnancy outcome and delivery at >28 weeks. Patients with preexisting diabetes were excluded. The incidence of GDM was compared between patients who received prophylactic intramuscular 17P (250-mg weekly injection initiated between 16.0 and 20.9 weeks' gestation) and those who did not. RESULTS: Maternal BMI and age were similar. The incidence of GDM was 12.9% in the 17P group (n = 557) compared with 4.9% in control subjects (n = 1,524, P < 0.001; odds ratio 2.9 [95% CI 2.1-4.1]). CONCLUSIONS: The use of 17P for the prevention of recurrent preterm delivery is associated with an increased risk of developing GDM. Early GDM screening is appropriate for women receiving 17P prophylaxis.