Objective
We sought to compare rates of recurrent spontaneous preterm birth (PTB) and neonatal morbidity between women enrolled in a recurrent PTB prevention clinic compared to those receiving usual care.
Study Design
This was a retrospective cohort study of women with a single, nonanomalous fetus and ≥1 spontaneous PTB <35 weeks. Women enrolled in a recurrent PTB prevention clinic were compared to those receiving usual care. The recurrent PTB prevention clinic was consultative and included 3 standardized visits. Usual-care patients were treated by their primary provider. The primary outcome was recurrent spontaneous PTB <37 weeks.
Results
Seventy recurrent PTB prevention clinic and 153 usual-care patients were included. Both groups had similar pregnancy histories. Recurrent PTB prevention clinic patients had increased utilization of resources, had lower rates of recurrent spontaneous PTB (48.6% vs 63.4%, P = .04), delivered later (mean 36.1 vs 34.9 weeks, P = .02), and had lower rates of composite major neonatal morbidity (5.7% vs 16.3%, P = .03).
Conclusion
Women referred to a consultative recurrent PTB prevention clinic had reduced rates of recurrent spontaneous prematurity and major neonatal morbidity.
One in every 8 newborns in the United States is delivered <37 weeks’ gestation; prematurity is the leading cause of neonatal morbidity and mortality in this country. Spontaneous preterm birth (PTB) remains the leading cause of prematurity. Spontaneous PTB is a multifactorial process that remains difficult to treat; its etiology is unknown and there are few proven preventive measures.
A history of a prior spontaneous PTB remains the greatest risk factor for spontaneous PTB. These high-risk women have been the focus of recent trials for the prevention of recurrent prematurity. Several trials have shown a reduction in spontaneous PTB using various formulations of progesterone (intramuscular, vaginal, and oral). Offering progesterone supplementation to women with a prior spontaneous PTB is now recommended by American College of Obstetricians and Gynecologists. Owen et al recently reported that surveillance of high-risk women with serial cervical length measurements and placement of a cervical cerclage in those with cervical shortening reduces the risk of recurrent early spontaneous PTB and perinatal morbidity, and may prolong pregnancy. Despite these advances, further research suggests that the clinical use of these potentially beneficial interventions outside of controlled trials is inconsistent, and substantial variation in therapeutic recommendations and counseling occurs.
Other disciplines throughout medicine have successfully instituted prevention clinics or prevention programs to address major health problems such as pediatric dental caries and type 2 diabetes. Many of the most successful programs have educated patients and primary providers regarding available resources as well as the most recent prevention or treatment literature.
We established a recurrent PTB prevention clinic in an effort to provide consistent, evidence-based medical care and education to those women at highest risk for spontaneous PTB. We hypothesized that women followed up in a recurrent PTB prevention clinic would have lower rates of recurrent prematurity compared to those patients receiving usual care.
Materials and Methods
This is a retrospective cohort study of women with a single, nonanomalous fetus and at least 1 documented previous spontaneous PTB <35 weeks’ gestation. Patients were identified from a large database including all live births in the 17 Utah hospitals within the Intermountain Healthcare system. All women from this database with at least 1 documented spontaneous PTB <35 weeks’ gestation and with at least 1 subsequent singleton pregnancy (carried to at least 20 weeks’ gestation) were included. Women who delivered prematurely at <37 weeks’ gestation due to medical or fetal indications (eg, preeclampsia, fetal growth restriction) were excluded.
Women referred to our recurrent PTB prevention clinic were compared to women from the database who did not receive a consultation in the recurrent PTB clinic (usual-care patients). If a woman had >1 subsequent pregnancy following a documented spontaneous PTB, the last pregnancy in the study period was analyzed. Furthermore, women who had multiple deliveries and qualified for the usual-care group but then had a pregnancy during which they were cared for in the recurrent PTB clinic were included in the recurrent PTB clinic cohort only. Charts were manually verified following identification from the database.
The focus of the recurrent PTB clinic is on idiopathic preterm labor and spontaneous PTB. Because the clinical presentation, diagnosis, treatment, and outcomes for patients with cervical insufficiency are different from those for preterm labor, women were excluded from analysis if they had a history suggestive of incompetent cervix (painless cervical dilation <24 weeks’ gestation).
This study was approved by the Intermountain Healthcare Institutional Review Board.
The recurrent PTB prevention clinic was established in 2008 as a consultative-only clinic. The clinic was marketed to local obstetrics providers, offering a venue for patient counseling, a standard risk evaluation, and a source for recommendations regarding treatment of their patients with a prior PTB. The marketing included a visit to the office by one of the authors (M.S.E.), with a presentation regarding the potential patient and provider benefits of the recurrent PTB clinic, along with flyers and reminders soliciting referral. Patients were then referred to the recurrent PTB clinic solely at the discretion of the referring providers. No other organized educational programs are made available to referring providers that could serve as a direct template to replicate the recurrent PTB clinic protocol.
After referral to the recurrent PTB clinic, women remain under the primary care of their referring provider. The recurrent PTB prevention clinic includes 3 prescribed visits, at 10-18 weeks’, 19-24 weeks’, and 28-32 weeks’ gestation, with additional visits as clinically indicated. A standard protocol is followed for screening, counseling, and intervention ( Table 1 ).
| Variable | Visit 1 (10-18 wk) | Visit 2 (19-24 wk) | Visit 3 (28-32 wk) |
|---|---|---|---|
| Detailed obstetric history and personal recurrence risk assessment | X | ||
| Screen for BV, treat if positive | X | X | X |
| Urinalysis | X | X | X |
| Urine culture | As indicated by urinalysis or symptoms | As indicated by urinalysis or symptoms | As indicated by urinalysis or symptoms |
| Transvaginal cervical length | X (≥16 wk) | X | X |
| Offer 17OHPC | X | a |
a Women with short cervix identified on transvaginal ultrasound through 24 wk’ gestation who previously declined 17OHPC treatment are again counseled regarding 17OHPC.
At the initial visit, all women are interviewed to obtain a detailed obstetric history. Women with a history consistent with cervical insufficiency (previous pregnancy loss at <24 weeks with asymptomatic cervical dilation) are offered prophylactic cerclage; patients with such a history were not included in the current report. The remaining women are given a personal recurrence risk based on the number and severity of their previous PTBs.
Patients are screened for infection at each visit. A vaginal examination to assess for bacterial vaginosis is performed at each visit; all women found to be positive are treated with oral metronidazole (500 mg twice daily for 7 days). Urinalysis is performed at each visit; a urine culture is performed if indicated by urinalysis results or based on patient symptoms. Patients with a positive urine culture are treated with antibiotics.
All patients are offered prophylactic 17-alpha hydroxyprogesterone caproate (17OHPC). When accepted, 250 mg of 17OHPC is given weekly as an intramuscular injection beginning at 16-20 weeks’ gestation and continuing through 36 weeks’ gestation. Women who initially decline 17OHPC at visit 1 are offered treatment again (until 24 weeks’ gestation) if cervical shortening is noted.
A transvaginal ultrasound for cervical length is performed at each study visit beginning at 16 weeks. A cervical length <2.5 cm is considered abnormal. When cervical shortening to a functional (closed) canal length of <2.5 cm is noted <22 weeks’ gestation, an “ultrasound-indicated” cervical cerclage is offered. If cervical shortening is noted >22 weeks’ gestation, women are admitted to the hospital for observation and monitored with external tocometry for contractions for at least 2 hours. Women without contractions are then managed as outpatients on home bedrest and are seen in clinic more frequently (every 1-2 weeks). Women with uterine contractions at >20 and <32 weeks’ gestation are treated inhospital with indomethacin tocolysis (50 mg oral loading dose followed by 25 mg orally every 6 hours to complete a 48-hour course), followed by modified bedrest (either at home or inhospital) and increased surveillance. Women with cervical shortening and continuing uterine activity are given maintenance tocolysis (nifedipine 10-20 mg orally every 6 hours) until 34 weeks. All women with cervical shortening noted >24 weeks’ gestation are treated with betamethasone (2 doses of 12 mg intramuscularly 24 hours apart). Digital cervical examinations and fetal fibronectin were used only in the assessment of acute labor symptoms. A perinatologist is also immediately available to each woman’s primary obstetrician for further consultation as necessary.
All usual-care patients were managed throughout pregnancy by their primary obstetrician, without referral to the recurrent PTB clinic. Given the variety of providers caring for these women, recommendations regarding activity restriction, prophylactic 17OHPC, cervical length screening, cervical cerclage placement, perinatology consultation, and other interventions varied widely.
Inpatient hospital costs for care of the mother and the neonate were also compiled and compared between groups. Due to patients receiving prenatal care from a variety of providers, outpatient costs were not available. The primary outcome was recurrent spontaneous PTB <37.0 weeks’ gestation. This cutoff, rather than the 35.0 weeks utilized for the prior PTB inclusion criterion, was used in recognition of the increased morbidities associated with late PTB. Secondary outcomes included spontaneous PTB <32.0 weeks’ gestation; neonatal intensive care unit admission; neonatal length of stay; hospital charges associated with outpatient, inpatient, and neonatal care; and composite major neonatal morbidity (defined as diagnosis of ≥1 of the following prior to hospital discharge: necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage, neonatal sepsis, or death).
Data were analyzed using software (STATA 10.0; StataCorp, College Station, TX). Student t test and χ 2 were used as appropriate. Multivariable Poisson regression assessed factors associated with recurrent PTB.
Results
A total of 223 patients (70 recurrent PTB prevention clinic and 153 usual-care patients) met inclusion criteria. Recurrent PTB clinic patients were delivered from 2008 through 2010; usual-care patients identified in the database were delivered from June 2002 through June 2010. Groups had similar demographic and previous pregnancy characteristics, although recurrent PTB clinic patients were more likely to have private insurance ( Table 2 ). Recurrent PTB prevention clinic patients had more cervical length ultrasounds, had higher rates of use of prophylactic 17OHPC, and delivered at later gestational ages ( Table 3 ). There were a total of 4 cervical cerclages placed in the usual-care group (3 placed prophylactically due to a history of spontaneous PTB, 1 placed at 22.5 weeks due to cervical shortening), and 3 placed in the recurrent PTB prevention clinic cohort (2 placed due to cervical shortening [at 19 weeks and 22 weeks], and 1 placed at 22 weeks due to advanced cervical dilation).
