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.

Pregnancy outcomes of managed Medicaid members prescribed home administration of 17 α-hydroxyprogesterone caproate.

OBJECTIVE: Examine adherence to treatment guidelines and rates of recurrent spontaneous preterm birth (SPTB) in managed Medicaid patients prescribed 17 α-hydroxyprogesterone caproate (17P). STUDY DESIGN: A retrospective observational study of women receiving 17P between July 2004 and May 2010 through one of Centene's managed Medicaid programs. Included for analysis were singleton pregnancies without cerclage having SPTB history and prescribed 17P by their physician. Compounded 17P was administered through an outpatient program inclusive of patient education, weekly home nurse visits, and 24-7 telephonic nurse access. A health plan-directed pregnancy management program, Start Smart for Your Baby(®), supported the therapy with case management activities. RESULTS: Of the 790 patients studied, 58.6% initiated 17P in the recommended 16- to 20.9-week gestational age window. Elective discontinuation of 17P occurred in 18.6%. Of the 10,583 17P injections administered, 97.5% were administered within the recommended injection interval of 6 to 10 days. Recurrent SPTB occurred in 28.2% of women studied. CONCLUSION: Managed Medicaid patients enrolled in an outpatient 17P administration program supported with maternal case management have high rates of treatment compliance. Their pregnancy outcomes compare favorably to previously published reports that include both Medicaid and commercially insured patients.

The effect of maternal obesity on pregnancy outcomes of women with gestational diabetes controlled with diet only, glyburide, or insulin.

OBJECTIVE: To examine the effect of obesity on maternal and neonatal outcomes in women diagnosed with gestational diabetes mellitus (GDM) and managed with diet only, glyburide, or insulin. STUDY DESIGN: Women with singleton gestations enrolled for outpatient services diagnosed with GDM and without history of pregnancy-related hypertension at enrollment or in a prior pregnancy were identified in a database. Women with GDM controlled by diet only (n = 3918), glyburide (n = 873), or insulin without prior exposure to oral hypoglycemic agents (n = 2229) were included. Pregnancy outcomes were compared for obese versus nonobese women within each treatment group and also compared across treatment groups within the obese and nonobese populations. RESULTS: Within each treatment group, obesity was associated with higher rates of cesarean delivery, pregnancy-related hypertension, macrosomia, and hyperbilirubinemia (all p < 0.05). Higher rates of pregnancy-related hypertension and hyperbilirubinemia were observed in women receiving glyburide. CONCLUSION: Obesity adversely affects pregnancy outcome in women with GDM. Higher rates of pregnancy-related hypertension and hyperbilirubinemia were observed in pregnant women receiving glyburide.

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.

The risk for preterm labor in women receiving 17 alpha-hydroxyprogesterone caproate prophylaxis for preterm birth prevention.

We sought to identify maternal or clinical characteristics of women likely to develop preterm labor (PTL) at <34 weeks' gestation while receiving 17 alpha-hydroxyprogesterone caproate (17P) prophylaxis. Current singleton gestations with prior preterm delivery enrolled for outpatient 17P administration at <27 weeks' gestation were identified ( N = 1177). Maternal and clinical characteristics were compared between women hospitalized and diagnosed with PTL at <34 weeks' gestation (PTL group, N = 270) and those without PTL (No PTL group, N = 660). PTL at <34 weeks' gestation occurred in 270/1177 (22.9%) of patients receiving 17P prophylaxis (mean gestational age at diagnosis was 28.3 +/- 4.0 weeks). Recurrent preterm delivery occurred in 73.3% of women with PTL at <34 weeks. Maternal age, marital status, race, tobacco use, cerclage, gestational age at start of 17P, and Medicaid status were similar between the groups. Women developing PTL at <34 weeks were more likely to have >1 prior preterm delivery than those without PTL (35.2% versus 25.9%, P = 0.006, odds ratio [95% confidence interval] 1.5 [1.1, 2.1]). Women receiving 17P prophylaxis remain at increased risk for PTL and preterm birth. Patient education and surveillance for PTL symptoms may be warranted in women with a history of more than one prior preterm delivery.

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 maternal obesity on the incidence of adverse pregnancy outcomes in high-risk term pregnancies.

We investigated the impact of maternal obesity on pregnancy outcomes. Women with normal or obese body mass index (BMI) who delivered singleton infants at term were identified from a perinatal database. Rates of pregnancy complications and neonatal outcomes were compared between women with normal prepregnancy BMI (20 to 24.9 kg/m (2), N = 9171) and those with an obese prepregnancy BMI (> or = 30, N = 3744). Rates of pregnancy complications and neonatal outcomes were also evaluated by the level of obesity (obese [30 to 34.9 kg/m (2), N = 2106], severe obesity [35 to 39.9 kg/m (2), N = 953], and morbid obesity [> or = 40 kg/m (2), N = 685]). Rates of gestational diabetes (12.0% versus 3.7%, P < 0.001, odds ratio [95% confidence interval] = 3.5 [3.0, 4.1]) and gestational hypertension (30.9% versus 9.0%, P < 0.001, odds ratio [95% confidence interval] = 4.5 [4.1, 5.0]) were higher for obese versus normal BMI gravidas, respectively. Women with morbid or severe obesity had a greater incidence of gestational diabetes than women with an obese (30 to 34.9 kg/m (2)) or normal BMI (14.1%, 16.4%, 9.6%, and 3.7%, respectively; P < 0.05). The incidence of gestational hypertension increased with maternal BMI (9.0% normal, 25.5% obese, 33.7% severe, 43.4% morbid; all pairwise comparisons P < 0.05). Obese versus normal BMI was associated with more higher-level nursery admissions (8.2% versus 5.8%) and large-for-gestational age infants (12.3% versus 6.5%; P < 0.001). Obesity places a term pregnancy at risk for adverse maternal and neonatal outcomes.

The association of elective cessation of tocolysis and preterm birth in singleton gestations.

We evaluated outcomes following tocolysis discontinuation in singleton pregnancies between 33.0 and 36.9 weeks' gestation. We performed a retrospective analysis of singleton pregnancies prescribed continuous subcutaneous terbutaline tocolysis. Patients without indicated preterm delivery discontinuing treatment between 33.0 and 36.9 weeks were evaluated ( N = 4253). Data were grouped by week at treatment discontinuation. Outcomes were compared for each week. Approximately 55% (2316/4253) delivered preterm (< 37 weeks). After treatment discontinuation, 58.1% (2472/4253) of patients delivered within 7 days and 41.2% (1752/4253) within 3 days. Median number of days from discontinuation to delivery was 5 (range, 0 to 65). Incidence of low birth weight (< or = 2500 g), neonatal intensive care unit admissions, days in nursery, and estimated charges decreased with each additional week of tocolysis (all P < 0.05, adjusted for multiple comparisons). Tocolysis discontinuation prior to term is associated with late-preterm birth, adverse neonatal outcomes, and increased estimated health care costs.

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.

Women receiving 17-alpha-hydroxyprogesterone caproate hospitalized for preterm labor at less than 34 weeks benefit from daily perinatal nursing surveillance.

OBJECTIVE: The objective of the study was to compare pregnancy outcomes of women receiving 17-alpha-hydroxyprogesterone caproate (17P) prophylaxis for the prevention of recurrent spontaneous preterm delivery (SPTD) hospitalized for preterm labor (PTL) less than 34 weeks' gestation prescribed daily vs weekly perinatal nursing surveillance. STUDY DESIGN: Singleton gestations with prior SPTD enrolled for outpatient 17P administration at less than 27 weeks' gestation were eligible. Women hospitalized for PTL at less than 34 weeks (n = 379) were identified. Women receiving daily perinatal nursing surveillance (dPNS) (n = 99) following PTL were matched by Medicaid status and gestational age at onset of PTL to women receiving weekly surveillance (n = 280), yielding 83 matched pairs. RESULTS: Among patients receiving 17P who were hospitalized for PTL, the addition of dPNS following hospitalization resulted in lower rates of SPTD less than 32 weeks (odds ratio [OR], 0.29, 95% confidence interval [CI], 0.21-0.38) and less than 35 weeks (OR, 0.25, 95% CI, 0.17-0.33), whereas the rates of SPTD less than 37 weeks were similar. CONCLUSION: Women receiving prophylactic 17P hospitalized for PTL before 34 weeks benefit from the addition of daily perinatal nursing surveillance.

Antepartum uterine contraction patterns in twin pregnancies with and without preterm labor and delivering before or after 36 weeks.

OBJECTIVE: The purpose of this study was to identify differences in antepartum uterine contraction frequency (UCF) in twin pregnancies with and without preterm labor (PTL). STUDY DESIGN: Twin gestations enrolled for outpatient surveillance with twice daily electronic uterine activity monitoring and telephonic nursing assessment, without interventional delivery were identified. Mean UCF for each gestational week was compared between women without PTL or preterm delivery (PTD) < 36 weeks (controls) and those with a PTL diagnosis delivering at < 36 weeks (PTL/PTD group), and those with PTL with delivery > or = 36 weeks (PTL/GAD > or = 36 group). RESULTS: Data from 7891 patients with 267,840 monitored hours were analyzed. UCF at each gestational week was significantly higher for patients experiencing PTL with or without PTD compared to control. UCF was similar for patients with PTL with or without PTD < 36. CONCLUSION: Twin pregnancies complicated with PTL have a higher UCF than those that do not experience PTL. Outpatient surveillance may be beneficial in this population.

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.

The impact of maternal body mass on the effectiveness of 17 alpha-hydroxyprogesterone caproate.

OBJECTIVE: To examine the impact of maternal prepregnancy body mass index (BMI) on rates of recurrent preterm delivery (PTD) in women receiving 17alpha-hydroxyprogesterone caproate (17P) prophylaxis. STUDY DESIGN: The study population was identified from a large perinatal database containing prospectively collected information from women at high risk for PTD. We included patients with a current singleton pregnancy and a history of PTD who received weekly nursing visits and 17P 250 mg intramuscular injections beginning at 16.0 to 20.9 weeks' gestation. The data were stratified by number of prior PTDs (1 or >1) and maternal prepregnancy BMI (lean, normal, overweight and obese). Primary study outcomes included the rates of recurrent PTD at <35 and 32 weeks' gestation, and pregnancy loss at <24 weeks' gestation. RESULTS: Delivery outcomes for 606 women receiving 17P were analyzed. There were no significant differences found in the incidence of preterm labor, the rates of recurrent PTD or pregnancy loss at <35, 32 or 24 weeks between the BMI groups. CONCLUSION: Maternal prepregnancy BMI does not appear to influence the rates of recurrent PTD in women with singleton gestation receiving 17P prophylaxis. Larger studies are needed to confirm our findings.

Clinical characteristics of women prescribed 17 alpha-hydroxyprogesterone caproate in the community setting.

OBJECTIVE: The objective of the study was to describe clinical characteristics and pregnancy outcomes of women in a community setting prescribed 17 alpha-hydroxyprogesterone caproate (17P) prophylaxis for prevention of preterm delivery (PTD). STUDY DESIGN: A retrospective review was conducted of data collected from patients enrolled for weekly outpatient 17P administration and nursing assessment between April 2004 and January 1, 2006 (n = 1979). Pregnancy history, referral indication, labor/delivery onset (spontaneous or indicated), and gestational duration were identified. RESULTS: Almost 80% of women prescribed 17P had a prior preterm delivery, although only 711 of the study population (35.9%) met National Institute of Child Health and Human Development (NICHD) study criteria for 17P including initiation of treatment at 16 to 20.9 weeks. Spontaneous PTD occurred in 37.3%; 22.1% delivered less than 35 weeks; and 9.0% less than 32 weeks. More than one quarter of patients (26.9%) discontinued 17P at less than 34 weeks and prior to delivery. CONCLUSION: In community practice, only one third of patients receiving 17P met strict NICHD study criteria. Early initiation and adherence to completion of therapy are clinical issues related to 17P prophylaxis.

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.