Objective
We sought to examine if 17-alpha-hydroxyprogesterone caproate (17OHPC) effectiveness is dependent on the earliest gestational age (GA) at prior spontaneous preterm birth (SPTB) when administered in the clinical setting.
Study Design
Women enrolled for outpatient services with current singleton gestation and ≥1 prior SPTB between 20-36.9 weeks were identified. Data were divided into 3 groups according to earliest GA of prior SPTB (20-27.9, 28-33.9, and 34-36.9 weeks). We compared GA at delivery of current pregnancy and incidence of recurrent SPTB between women enrolled in outpatient 17OHPC administration program (n = 2978) and women receiving other outpatient services without 17OHPC (n = 1260).
Results
Rates of recurrent SPTB for those with and without 17OHPC prophylaxis, respectively, according to GA at earliest SPTB were: 20-27.9 weeks at earliest SPTB, 32.2% vs 40.7%, P = .025; 28-33.9 weeks at earliest SPTB, 34.1% vs 45.5%, P < .001; and 34-36.9 weeks at earliest SPTB, 29.3% vs 38.8%, P < .001.
Conclusion
17OHPC given to prevent recurrent SPTB is effective regardless of GA at earliest SPTB.
Despite ongoing prevention efforts, preterm birth (PTB) rates continue to rise in the United States with 12.8% of all births in 2006 considered preterm or <37 completed weeks of gestation. Women who have experienced a spontaneous PTB (SPTB) are at increased risk of delivering preterm in a subsequent pregnancy. The use of 17-alpha-hydroxyprogesterone caproate (17OHPC) has been shown to be effective in reducing the incidence of recurrent PTB in women with a current singleton pregnancy and a documented history of an SPTB.
A secondary analysis of women with a previous SPTB enrolled in a randomized placebo-controlled trial evaluating prophylactic use of 17OHPC vs placebo for the prevention of recurrent PTB questioned if the effectiveness of 17OHPC was dependent on the gestational age (GA) at the earliest prior PTB. Spong et al concluded that 17OHPC is associated with a prolongation of pregnancy overall but especially for those women whose previous SPTB occurred at <34 weeks. In their study, statistical significance was not reached for patients with and without 17OHPC prophylaxis whose earliest prior SPTB had occurred at 34-36.9 weeks’ gestation. The purpose of the present study is to examine if 17OHPC effectiveness is dependent on the earliest GA at prior SPTB when administered in the clinical setting.
Materials and Methods
We conducted a retrospective analysis of deidentified clinical data collected from high-risk pregnant women enrolled in outpatient perinatal services provided by Alere, formerly Matria Healthcare. The Women’s and Children’s Health Division of Alere provides physician-prescribed comprehensive home-based services to pregnant women throughout the United States who have medical or pregnancy-related problems that could harm their pregnancies including preterm labor, gestational diabetes, hypertensive conditions, coagulation disorders, and nausea and vomiting in pregnancy.
Clinical data were prospectively collected from the patient and her physician throughout provision of outpatient services and at conclusion of the pregnancy, and maintained in a relational database. All data were collected using standardized operating procedures, forms, and customized proprietary computer software. All women provided written consent for outpatient services and allowed for the use of their deidentified protected health information for research and reporting purposes.
Records from women with a current singleton gestation, a history of at least 1 SPTB with a documented GA between 20-36.9 weeks, and a documented pregnancy outcome of the current pregnancy were identified. Each record was labeled as to if weekly 17OHPC injections or other progestational agents were prescribed during the current pregnancy. Excluded were women reporting use of progestational agents other than 17OHPC in the current pregnancy, or who initiated 17OHPC at ≥25 weeks’ gestation. All decisions regarding use or nonuse of progestational agents were made by each patient’s individual health care provider. Pregnancy outcomes were compared between 2978 women who received 17OHPC and 1260 women with a history of SPTB receiving other outpatient services but no 17OHPC prophylaxis.
At the start of outpatient services, all women received an initial in-home patient education session with an experienced perinatal nurse. Verbal instruction and written patient education materials were provided to each patient related to pregnancy and the specific condition that placed their pregnancy at risk. In addition, women enrolled in the 17OHPC administration program received weekly skilled perinatal nursing visits for maternal assessment and administration of 250-mg intramuscular injections of 17OHPC given via the Z-track method until 36 completed weeks or preterm delivery. The 17OHPC was compounded at a qualified pharmacy using US Pharmacopeia Reference standards in an International Organization Standardization class 5 clean room with adequate quality control procedures and documentation to ensure sterility and potency of each vial. Arrangements were made for home delivery of unit dose, preservative-free vials of 17OHPC using the specifications and formulation of the 17OHPC used in the Meis et al network study including the vehicle (castor oil). A nurse and pharmacist were available by telephone for questions and concerns 24 hours a day, 7 days a week. Perinatal nurses provided clinical communication and care coordination with the patient’s physician and case manager as needed.
For this study, records were divided into 3 groups according to their earliest GA of prior SPTB (20-27.9, 28-33.9, and 34-36.9 weeks). The GAs and reasons for all past deliveries were captured during the enrollment process and were patient reported. If the woman was unsure, the space for that information was left blank. Within each group, we compared the GA at delivery of the current pregnancy and incidence of recurrent SPTB between the study group of women who received 17OHPC and controls who did not receive 17OHPC. Comparisons were made using Pearson χ 2 , Kruskal-Wallis H, and Mann-Whitney U test statistics. Logistic regression models were used to test relative associations for significant univariate factors within each of the 3 GAs at earliest SPTB groups. All P values reported were 2-sided and considered statistically significant if < .05.
Results
A total of 4238 records were included in the analysis. Maternal characteristics according to the earliest GA of prior SPTB subgroups are reported in Table 1 . Overall, 2978 (70.3%) women received weekly prophylactic 17OHPC injections in the current pregnancy: 692 in the 20-27.9 weeks’ subgroup, 1148 in the 28-33.9 weeks’ subgroup, and 1138 in the 34-36.9 weeks’ subgroup. The 1260 women not receiving 17OHPC were enrolled for daily outpatient perinatal nursing surveillance: 957 (75.9%) received twice-daily uterine monitoring and telephonic assessment of subjective signs and symptoms of preterm labor, 180 (14.3%) received outpatient treatment for nausea and vomiting of pregnancy, and 123 (9.8%) received services related to diabetes, hypertension, or anticoagulation. Tocolytic use was more common in women not receiving 17OHPC than those prescribed 17OHPC (75.0% vs 13.9%, respectively; P < .001).
| 20-27.9 wk | 28-33.9 wk | 34-36.9 wk | ||
|---|---|---|---|---|
| Characteristic | (n = 896) | (n = 1493) | (n = 1849) | P value |
| No. of women receiving 17OHPC | 692 (77.2%) | 1148 (76.9%) | 1138 (61.5%) | < .001 |
| Mean GA at 17OHPC start, wk | 18.7 ± 2.4 | 18.7 ± 2.5 | 18.8 ± 2.5 | .900 |
| 17.9 (15.7, 24.9) | 17.9 (14.6, 24.9) | 18 (15.6, 24.9) | ||
| Maternal age, y | 29.9 ± 5.7 | 30.5 ± 5.5 | 30.5 ± 5.2 | .010 |
| 30 (17, 49) | 31 (16, 45) | 31 (17, 46) | ||
| Black race | 338 (37.7%) | 335 (22.4%) | 263 (14.2%) | < .001 |
| Smoking | 51 (5.7%) | 102 (6.8%) | 88 (4.8%) | .037 |
| >1 PPTB | 273 (30.5%) | 427 (28.6%) | 347 (18.8%) | < .001 |
| Not married | 362 (40.4%) | 465 (31.1%) | 424 (22.9%) | < .001 |
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