Original Research
Home Cervical Ripening With Dinoprostone Gel in Nulliparous Women With Singleton Pregnancies Sarah J. Stock, PhD, Rebecca Taylor, MBChB, Rebecca Mairs, MBChB, Abdulhamid Azaghdani, Kahyee Hor, MBChB, Imogen Smith, MBChB, Kirsty Dundas, MBChB, Chris Kissack, MBChB, Jane E. Norman, MD, and Fiona Denison, MD OBJECTIVE: To evaluate whether home cervical ripening is safe and results in shorter hospital stay. METHODS: This was a retrospective cohort study of women with singleton pregnancies having induction of labor for postmaturity at a single center between January 2007 and June 2010. Women were offered home cervical ripening with 1 mg dinoprostone gel if they were nulliparous, had uncomplicated singleton pregnancies, and the indication for induction was postmaturity. RESULTS: Nine hundred seven of 1,536 (59.1%) nulliparous women having induction of labor for postmaturity were eligible for home cervical ripening. The median number of hours at home was 11.76 hours (range 0–24.82 hours). There were no cases of birth outside
From the Tommy’s Centre for Maternal and Fetal Health and MRC Centre for Reproductive Health, University of Edinburgh, Queen’s Medical Research Institute, and the Departments of Obstetrics and Gynaecology and Neonatology, Simpson Centre for Reproductive Health, Edinburgh Royal Infirmary, Edinburgh, United Kingdom. Supported by Tommy’s (registered charity Nos. 1060508 and SCO39280). Tommy’s had no involvement in study design, data collection, analysis, interpretation, or writing of the report or the decision to publish. Allyn Dick provided data from the maternity database systems and Vivek Varadarajan assisted with data formatting. Presented at the Perinatal Medicine 2014 Conference, June 9–11, 2014, Harrogate, United Kingdom. Corresponding author: Sarah J. Stock, PhD, MRC Centre for Reproductive Health, University of Edinburgh, Queen’s Medical Research Institute, Little France, Edinburgh EH16 4TJ, U.K.; e-mail: [email protected]. Financial Disclosure Dr. Dundas received funding from Ferring Pharmaceuticals to attend an educational course. Dr. Norman has received funding from charities and government bodies for investigating pregnancy problems, including the effects of induction of labor. She has received drug donations or partial donation of tests for noncommercially funded clinical trials. The other authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
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of the hospital, uterine rupture, or significant neonatal morbidity or neonatal death related to home cervical ripening. Eighty-five (5.5%) women who underwent hospital cervical ripening because of maternal preference or social issues formed a hospital cervical ripening comparison group. There was no significant difference in the total number of hours before delivery spent in the hospital between the two groups (26.25; 95% confidence interval [CI] 25.27–27.23 in home cervical ripening group compared with 24.28; 95% CI 22.5–26.0 in the hospital group; P5.26). CONCLUSIONS: Clinical outcomes are comparable in nulliparous women who receive a single dose of dinoprostone gel for home cervical ripening compared with those who undergo hospital cervical ripening. However, preadmission home cervical ripening with 1 mg dinoprostone does not decrease the number of hours women spend in the hospital. (Obstet Gynecol 2014;124:354–60) DOI: 10.1097/AOG.0000000000000394
LEVEL OF EVIDENCE: II
M
ore than 20% of pregnant women in developed countries undergo induction of labor.1 One of the most commonly used ways to induce labor is with vaginal prostaglandins, which ripen the cervix in preparation for labor. The most concerning potential side effect of prostaglandins is excessive uterine activity, termed uterine tachysystole, which can cause fetal hypoxemia.2 Cervical priming with prostaglandins has thus been traditionally performed as a hospital procedure, where fetal and maternal well-being can be monitored. There is increasing interest in performing cervical ripening as a home procedure, which may be preferable to women3 and may have cost benefits to health service providers.4 Home cervical ripening is performed in
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selected women undergoing induction of labor at the Simpson Centre for Reproductive Health in Edinburgh and is perceived in our unit to be preferable to women and safe. In January 2006, a protocol was introduced for offering home cervical ripening with 1 mg dinoprostone gel to all low-risk nulliparous women in whom induction of labor for postmaturity (between 41 and 42 weeks of gestation) was being performed. The protocol remained in place until 2010. We performed a retrospective cohort study of women having induction of labor for postmaturity. The primary objective of this study was to evaluate the clinical effectiveness of the policy when instituted on a busy maternity unit and to test the hypotheses that home cervical ripening would 1) be safe and 2) result in shorter hospital stay.
MATERIALS AND METHODS The study was performed at the Simpson Centre for Reproductive Health, a university tertiary care referral center with more than 6,000 deliveries per year. The study period was January 2007 to June 2010. This period was chosen as one in which a uniform policy for home cervical ripening was embedded in obstetric practice (the policy was introduced in January 2006 and changed in July 2010). The study used routinely collected hospital data that were anonymized at the source. An opinion was sought from South East Scotland Research Ethics Service who found that the study did not need National Health Service ethical review under the terms of the Governance Arrangements for Research Ethics Committees and no formal ethical committee approval was required. Throughout the study period, the hospital policy was to offer women home cervical ripening if they were nulliparous, had singleton pregnancies with cephalic presentation, had no medical or obstetric complications, had body mass indexes (BMIs, calculated as weight (kg)/[height (m)]2) less than 40, had support and transportation available, lived within 30 minutes of the hospital and had a telephone at home, had a primary indication for induction of labor of postmaturity, and had a gestation of 41 3/7 to 42 weeks of gestation when induction was initiated. Additionally, women had to have an amniotic fluid index 5 cm or greater on ultrasound assessment and normal electronic fetal monitoring, both performed immediately before cervical ripening. Signs of labor (palpable or painful uterine activity, fluid loss or bleeding from the vagina) conferred ineligibility for cervical ripening. Cervical ripening was generally commenced in the evening with appointments between 4:30 PM and 7:00 PM. A vaginal examination was performed and
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1 mg dinoprostone was inserted to the posterior vaginal fornix if the Bishop’s score was less than 7. Women were asked to stay semirecumbent for at least 30 minutes postadministration of gel, after which time further electronic fetal monitoring was performed. If this was reassuring, women were allowed to go home with instructions to return the next morning for further assessment. Contact details and indicators to return to the hospital were provided (painful regular contractions or frequent contractions, pain, bleeding, membrane rupture). On return to the hospital, women were assessed for maternal and fetal well-being with routine clinical assessment and electronic fetal monitoring. Vaginal assessment was performed with artificial rupture of membranes if the cervix was ripened. If the Bishop’s score was less than 7, further prostaglandin was given as a hospital procedure. The study was a retrospective cohort study of women with singleton pregnancies having induction of labor for postmaturity. Women with singleton pregnancies having induction of labor at gestations greater than 41 weeks were identified from our hospital databases (Maternity Management Systems, InterSystems TrakCareÒ), which include data contemporaneously entered by midwives and doctors. Previous studies have used similar strategies, and data have been shown to be accurate in greater than 99% of cases.5 Case records were retrieved and reviewed by one of five investigators (R.M., A.A., R.T., I.S., K.H.). Women were included if they were nulliparous with live singleton pregnancies undergoing induction of labor for postmaturity and assessed with no medical or obstetric complications that would preclude home induction of labor. Women were excluded if they had prelabor rupture of membranes (suspected or confirmed), when the primary indication for induction of labor was not postmaturity, or if there was an antepartum stillbirth. We collected data on eligible women even if the home protocol was not actually initiated or completed as a result of the development of complications. This allowed us to perform a retrospective “intention-to-treat” analysis of safety outcomes and effectiveness. Data were extracted from the case records and entered onto standardized data collection sheets. Data were collected on women who were eligible for home cervical ripening but had hospital cervical ripening either because of maternal preference or social indication (eg, lack of support at home or transport to the hospital). These women formed a hospital cervical ripening comparison group. To make sure that no poor neonatal outcomes were missed, hospital perinatal mortality records
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(stillbirths and neonatal deaths up to 28 days) and neonatal unit admission records were searched for all cases at a gestational age of 41 0/7 weeks or greater. Maternal records relating to these births were crosschecked. Records for all cases were found, and no additional cases of induction of labor were identified. The primary outcome relating to safety of home cervical ripening was birth outside of the hospital. Other maternal adverse events recorded included emergency delivery as a result of suspected or confirmed fetal compromise within 8 hours of prostaglandin administration or 2 hours of readmission from home ripening; uterine tachysystole (as documented by the caregiver), uterine tachysystole requiring terbutaline and uterine tachysystole with electronic fetal monitoring changes indicating emergency delivery; uterine rupture; maternal death; antepartum hemorrhage; and postpartum hemorrhage greater than 1,000 mL. Other neonatal adverse events included meconium stained liquor; Apgar score less than 7 at 5 minutes after delivery; umbilical cord arterial pH less than 7.0; admission to neonatal unit within 24 hours of delivery for greater than 48 hours’ duration; neonatal encephalopathy defined as seizures within 24 hours of birth or requirement for cooling); and extended perinatal mortality (stillbirth or neonatal death within 28 days of delivery). The primary outcome relating to effectiveness was duration of hospital stay before delivery. We also determined the following secondary outcomes: the number of procedures initiated; the number of procedures completed at home; mode of delivery; epidural use; cesarean delivery for failed induction of labor (as documented by the caregiver); the proportion requiring subsequent prostaglandin doses; prostaglandin-to-delivery interval; and proportion of women delivering within 24 hours. We calculated that a total sample size of 968 with a ratio of 10 home cervical ripening (n5880) to one hospital cervical ripening (n588) would have 90% power to detect a difference of 4 hours in hospital stay with 95% confidence interval (CI) based on standard deviation of 11 hours. This sample size (n5880 in the home cervical ripening group) would have 80% power to detect adverse events with a rate of 0.2% (2/1,000) or more and 90% power to detect adverse events with a rate of 0.25% (2.5/1,000) or more. Data were analyzed using SPSS 19. Parametric data are presented as mean (standard deviation) and nonparametric data as median (range) unless otherwise stated. Unpaired Student’s t test was used to compare continuous parametric data (age, BMI, gestation at induction of labor, birth weight, Bishop’s score). Mann–Whitney U test was used to compare nonparametric data (number of
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doses of prostaglandin, time to delivery, time spent at home, postnatal stay). Fisher’s exact test was used to compare rates (modes of delivery; proportion who delivered within 24 hours; epidural use; proportion who required additional prostaglandin; failed induction of labor; neonatal outcomes). Missing fields were excluded from analysis. The number of missing fields for each outcome is stated in the “Results.” Significance was defined as P,.05.
RESULTS There were 23,112 deliveries over the study period, including 22,312 singleton pregnancies. One hundred fifty-eight (7.1%) were identified as being nulliparous women undergoing induction of labor and delivering at 41 weeks or more of gestation. Forty-four (2.8%) maternal case records were missing, leaving 1,536 cases for assessment of notes for inclusion criteria. Two hundred twenty-five of 1,536 (14.6%) participants were excluded as a result of a history of a medical or obstetric risk factor making them ineligible for home cervical ripening. A further 319 of 1,536 (20.8%) women were excluded because they had a contraindication identified on preinduction assessment (Fig. 1). This left a cohort of 907 (59.1%) who initiated cervical ripening with the intention of a home protocol being followed. Eighty-five of 1,536 (5.5%) women either expressed a preference for hospital cervical ripening or had a social risk factor such as inadequate support or lack of transport to and from the hospital, necessitating hospital cervical ripening. These women formed a comparison group for outcomes of induction of labor. Table 1 shows the characteristics of the home cervical ripening and hospital cervical ripening cohorts. Overall 597 of 907 (65.8%) women who were administered dinoprostone with the intention of having home cervical ripening completed the home induction of labor protocol, returning at the planned time for reassessment after dinoprostone administration. This represents 38.9% (597/1,536) of all nulliparous women with singleton pregnancies having induction of labor at greater than 41 weeks of gestation. Ninety-six of 907 (10.6%) women who were administered prostaglandin gel with the intention of having home cervical ripening were not discharged home. The reasons for this are summarized in Table 2. Of the 811 women discharged home after prostaglandin administration, 214 women returned before the scheduled readmission time (26.4% of women who were discharged after prostaglandin; 23.6% of the 907 women who received prostaglandin with the intention
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Fig. 1. Flow chart of participants. Stock. Home Cervical Ripening. Obstet Gynecol 2014.
of having home cervical ripening). In 204 women, this was the result of signs and symptoms of labor (contractions, pain, or rupture of membranes; 25.1% of women who were discharged after prostaglandin). In six patients (0.74% of women who were discharged after prostaglandin), it was the result of vaginal bleeding, and in four patients, the reason was not clearly documented. The median number of hours at home for the home cohort was 11.76 hours (range 0–24.82 hours). No women delivered outside the hospital. The shortest admission-to-delivery interval was 6 minutes. Seven women delivered within an hour of readmission, and a further 13 women delivered between 1 and 2 hours after readmission to the hospital after home cervical ripening. In one case, the neonate was admitted to the neonatal unit for observation. The 5-minute Apgar score was 9, and the cord pH was 7.25. In all other cases, there were no maternal or neonatal complications. Uterine tachysystole was documented in 25 of 907 cases of women having home cervical ripening overall
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but only related to the first dose of prostaglandin in 19 of these cases (2.1%; 95% CI 1.3–3.2 of all cases in home cervical ripening cohort). In the remaining six patients, tachysystole was related to subsequent doses of prostaglandin or oxytocin. There were no cases of uterine rupture or maternal deaths in either the home cervical ripening or the hospital cervical ripening groups. Six women were readmitted from home after initiating home cervical ripening with vaginal bleeding. This was thought to be “show” in all patients, and delivery was not expedited or management changed after clinical assessment. The incidence of postpartum hemorrhage greater than 1,000 mL was similar in the hospital and home cervical ripening groups (114/907; 12.6%; 95% CI 10.6–14.9 in the home cervical ripening group and 8/85; 9.4%; 95% CI 4.6–17.7 in the hospital cervical ripening group; P5.51). Neonatal outcomes are summarized in Table 3. No significant differences were found between home
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Table 1. Characteristics of the Cohort Administered Prostaglandin With the Intention of Undertaking Home Cervical Ripening and Comparison Group of Women Who Had Inpatient Cervical Ripening as a Result of Social Indication or Preference Home Ripening (n5907)
Characteristic Age (y) BMI (kg/m2) Gestation at induction of labor (d) Median Bishop’s score (range) Birth weight (g) Median no. of doses of prostaglandin E (range)
28.7 (28.3–29.1) 25.8 (25.4–26.2) 292.3 (292.2–292.4) 4 (1–7)
Missing 1 228 0 124
3,729 (3,700.1–3,737.9) 1 (1–6)
1 1
Inpatient Ripening Resulting From Preference or Social Reason (n585) 29.6 (28.1–31.2) 25.8 (24.4–27.2) 291.5 (291.0–292.0) 4 (1–7) 3,702 (3,618.0–3,786.0) 1 (1–5)
P
Missing
.29 .92 .003
0 19 0
.23
25
.55 .72
0 0
BMI, body mass index. Data are mean (95% confidence interval) unless otherwise specified. Means were compared using unpaired student t test. Medians were compared using Mann–Whitney U test.
and hospital cervical ripening groups, but the numbers of adverse events were small and the study was not adequately powered for comparison of these. There were no cases of intrauterine death in either group. There was one neonatal death in the home cervical ripening group and a further two cases of serious neonatal morbidity (one case of neonatal encephalopathy and one case of meconium aspiration leading to infant death at 3 months of age). All three cases followed long labors requiring subsequent doses
Table 2. Reasons for Actual Inpatient Cervical Ripening in Women Who Had Planned to Go Home for Home Cervical Ripening
Reason for Remaining Inpatient Signs of labor Contractions or pain Membrane rupture Abnormal electronic fetal monitoring Pyrexia Antepartum hemorrhage Workload issues Maternal preference Bad weather Wrong dose Not documented
Indications for Staying in the Hospital After Administration of Dinoprostone Gel in Women Eligible for Home Cervical Ripening (n596/907) (10.6% [95% CI 8.7–12.7]) 50 (5.5) 47 (5.2) 3 (0.3) 21 (2.3) 1 (0.1) 1 (0.1) 17 3 1 1 1
(1.9) (0.3) (0.1) (0.1) (0.1)
CI, confidence interval. Data are n (% of total home cervical ripening cohort).
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of dinoprostone and oxytocin augmentation and operative deliveries. Outcomes of women with planned home cervical ripening compared with women with a social indication for hospital cervical ripening are summarized in Table 4.
DISCUSSION Our study of more than 1,000 cases of induction of labor for postmaturity supports the growing body of evidence that suggests that home ripening may be a reasonable alternative to hospital cervical ripening if desired by the woman and her family for induction of labor at term, although using one dose of dinoprostone for home cervical ripening does not appear to reduce the hospital stay. The findings of our study are supported by a recent Cochrane review.6 Because this was a retrospective study, it was dependent on the quality of the recorded data. In an attempt to maximize accuracy, we performed systematic and careful review of medical records collecting predefined data. We used electronic maternity records to collect all maternal clinical outcomes. The proportion of missing data was very low for the majority of key clinical outcomes as a result of entry of these fields being mandatory in the electronic maternity record. In addition, multiple sources of neonatal outcome data were used to increase confidence that no cases of significant morbidity or perinatal mortality were missed. Our study was significantly larger than published studies, which increases our confidence in the study’s findings. Furthermore, women eligible for home induction of labor were managed according to a uniform policy that was embedded in the clinical practice of a busy tertiary care centre maternity unit. This means that the results are relevant to
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Table 3. Neonatal Complications of the Cohort Administered Prostaglandin With the Intention of Undertaking Home Cervical Ripening and the Comparison Group of Women Who Had Inpatient Cervical Ripening as a Result of Social Indication or Preference Inpatient Ripening as a Result of Preference or Social Reason (n585)
Home Ripening (n5907) n
Complication Meconium Apgar score less than 7 at 5 min Arterial cord pH less than 7.00 Neonatal unit admission longer than 48 h Perinatal mortality Severe perinatal morbidity
263 21 6 8 1 2
% (95% CI) 30.1 2.3 3.2 0.88 0.11 0.22
Missing
n
% (95% CI)
P
Missing
39 5 277 0 0
26 1 0 1 0 0
37.7 (26.9–49.5) 1.2 (0.1–5.9) — 1.2 (0.06–5.7) — —
.29 .89 1.00 .39 1.00 1.00
6 2 24 0 0
(27.1–33.2) (1.5–3.5) (2.0–4.7) (0.45–1.7) (0.01–0.54) (0.03–0.73)
CI, confidence interval. Proportions were compared with Fisher’s exact test.
contemporary clinical practice and not just within the “ideal” conditions of a clinical trial. As a result of the design of the study, the study was not powered for all clinical outcomes, specifically rare adverse neonatal outcomes. However, the cohort was large enough to have more than 80% power to detect an adverse event rate of 2 per 1,000 or more and 90% power to detect an event rate of 2.5 per 1,000 or more. It is therefore reassuring that no cases of birth outside the hospital, uterine rupture, or significant neonatal morbidity of neonatal death likely to relate to the setting of cervical ripening were seen. We accept that our comparison group has limitations in that it may be higher risk as a result of increased social risk factors, and it is also
relatively small (because most women accept to undergo home cervical ripening). However, both groups were matched for maternal age and BMI, which are important predictors of risk of intrapartum intervention and adverse perinatal outcome. We therefore believe that within the constraints of our study design and with appropriate caveats, it is valid to compare outcomes between women having hospital as opposed to home cervical ripening. In conclusion, our study suggests that clinical outcomes are comparable in nulliparous women who receive a single dose of dinoprostone gel for home cervical ripening compared with those who undergo hospital cervical ripening and that adverse outcomes are rare. However, home ripening does not decrease
Table 4. Outcomes of Women Who Were Administered Prostaglandin With the Intention of Undertaking Home Cervical Ripening and the Comparison Group of Women Who Had Inpatient Cervical Ripening As a Result of Social Indication or Preference Inpatient Ripening as a Result of Preference or Social Reason (n585)
Home Ripening (n5907) Outcome Mode of delivery Spontaneous vaginal Operative vaginal Cesarean Epidural use in labor Proportion requiring further prostaglandin Failed induction of labor Proportion delivered in 24 h Mean prostaglandin-to-delivery time (h) Mean time in hospital until delivery (h)
n
% (95% CI)
Missing
n
% (95% CI)
P
Missing
1 263 325 319 606 444 18 207 35.45 26.25
29.0 35.8 35.2 69.8 49.0 2.1 22.8
(26.1–32.0) (32.8–39.0) (32.1–38.3) (66.7–72.8) (45.8–52.3) (1.3–3.2) (20.2–25.7) (34.4–36.5) (25.3–27.2)
50 1 5 14 14 35
0 26 23 36 52 41 4 23 22.5 24.28
30.6 27.0 42.4 75.4 48.2 5.1 27.1
(21.5–41.0) (18.4–37.2) (32.2–53.0) (64.2–84.4) (37.8–58.8) (1.6–11.8) (18.4–37.2) (21.1–23.9) (22.5–26.0)
.80 .12 .19 .41 .91 .12 .42 ,.001 .26
5 0 1 2 2 4
CI, confidence interval. Proportions were compared with Fisher’s exact test. Means were compared with unpaired Student’s t test.
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the number of hours women spend in the hospital before delivery and further research needs to be undertaken to evaluate resource use, costeffectiveness, and women’s preferences for home compared with hospital cervical ripening. REFERENCES
3. Reid M, Lorimer K, Norman JE, Bollapragada SS, Norrie J. The home as an appropriate setting for women undertaking cervical ripening before the induction of labour. Midwifery 2011;27:30–5. 4. Farmer KC, Schwartz WJ III, Rayburn WF, Turnbull G. A costminimization analysis of intracervical prostaglandin E2 for cervical ripening in an outpatient versus inpatient setting. Clin Ther 1996;18:747–56.
1. Keirse MJ. Natural prostaglandins for induction of labor and preinduction cervical ripening. Clin Obstet Gynecol 2006;49: 609–26.
5. Stock SJ, Josephs K, Farquharson S, Love C, Cooper SE, Kissack C, et al. Maternal and neonatal outcomes of successful Kielland’s rotational forceps delivery. Obstet Gynecol 2013;121: 1032–9.
2. Intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. ACOG Practice Bulletin No. 106. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114:192–202.
6. Kelly AJ, Malik S, Smith L, Kavanagh J, Thomas J. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term. The Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD003101. DOI: 10.1002/14651858.CD003101.pub2.
Serve As a Reviewer for Obstetrics & Gynecology The Editors of Obstetrics & Gynecology are looking for new peer reviewers.* Sign up to become a peer reviewer by going to ong.editorialmanager.com and downloading the “Reviewer Contact Information Update Form” (located under“Files & Resources”). Please fill the form out electronically and submit it by e-mail to the editorial office ([email protected]). *In recognition of their time, effort, and expertise expended, reviewers of manuscripts for Obstetrics & Gynecology are eligible to receive continuing medical education credits. ACCME Accreditation The American College of Obstetricians and Gynecologists is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. AMA PRA Category 1 Credit(s)™ The American College of Obstetricians and Gynecologists designates this manuscript review activity for a maximum of 3 AMA PRA Category 1 C redits.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity. College Cognate Credit(s) The American College of Obstetricians and Gynecologists designates this manuscript review activity for a maximum of 3 Category 1 College Cognate Credits. The College has a reciprocity agreement with the AMA that allows AMA PRA Category 1 Credits™ to be equivalent to College Cognate Credits. College Fellows will be awarded credit for a maximum of five reviews yearly. Those who are not College Fellows will receive e-mail documentation approximately1 month after completion of the review, which can be submitted to an accrediting body for credits. rev 7/2013
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Home Cervical Ripening With Dinoprostone Gel in Nulliparous Women With Singleton Pregnancies Sarah J. Stock, PhD, Rebecca Taylor, MBChB, Rebecca Mairs, MBChB, Abdulhamid Azaghdani, Kahyee Hor, MBChB, Imogen Smith, MBChB, Kirsty Dundas, MBChB, Chris Kissack, MBChB, Jane E. Norman, MD, and Fiona Denison, MD OBJECTIVE: To evaluate whether home cervical ripening is safe and results in shorter hospital stay. METHODS: This was a retrospective cohort study of women with singleton pregnancies having induction of labor for postmaturity at a single center between January 2007 and June 2010. Women were offered home cervical ripening with 1 mg dinoprostone gel if they were nulliparous, had uncomplicated singleton pregnancies, and the indication for induction was postmaturity. RESULTS: Nine hundred seven of 1,536 (59.1%) nulliparous women having induction of labor for postmaturity were eligible for home cervical ripening. The median number of hours at home was 11.76 hours (range 0–24.82 hours). There were no cases of birth outside
From the Tommy’s Centre for Maternal and Fetal Health and MRC Centre for Reproductive Health, University of Edinburgh, Queen’s Medical Research Institute, and the Departments of Obstetrics and Gynaecology and Neonatology, Simpson Centre for Reproductive Health, Edinburgh Royal Infirmary, Edinburgh, United Kingdom. Supported by Tommy’s (registered charity Nos. 1060508 and SCO39280). Tommy’s had no involvement in study design, data collection, analysis, interpretation, or writing of the report or the decision to publish. Allyn Dick provided data from the maternity database systems and Vivek Varadarajan assisted with data formatting. Presented at the Perinatal Medicine 2014 Conference, June 9–11, 2014, Harrogate, United Kingdom. Corresponding author: Sarah J. Stock, PhD, MRC Centre for Reproductive Health, University of Edinburgh, Queen’s Medical Research Institute, Little France, Edinburgh EH16 4TJ, U.K.; e-mail: [email protected]. Financial Disclosure Dr. Dundas received funding from Ferring Pharmaceuticals to attend an educational course. Dr. Norman has received funding from charities and government bodies for investigating pregnancy problems, including the effects of induction of labor. She has received drug donations or partial donation of tests for noncommercially funded clinical trials. The other authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
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of the hospital, uterine rupture, or significant neonatal morbidity or neonatal death related to home cervical ripening. Eighty-five (5.5%) women who underwent hospital cervical ripening because of maternal preference or social issues formed a hospital cervical ripening comparison group. There was no significant difference in the total number of hours before delivery spent in the hospital between the two groups (26.25; 95% confidence interval [CI] 25.27–27.23 in home cervical ripening group compared with 24.28; 95% CI 22.5–26.0 in the hospital group; P5.26). CONCLUSIONS: Clinical outcomes are comparable in nulliparous women who receive a single dose of dinoprostone gel for home cervical ripening compared with those who undergo hospital cervical ripening. However, preadmission home cervical ripening with 1 mg dinoprostone does not decrease the number of hours women spend in the hospital. (Obstet Gynecol 2014;124:354–60) DOI: 10.1097/AOG.0000000000000394
LEVEL OF EVIDENCE: II
M
ore than 20% of pregnant women in developed countries undergo induction of labor.1 One of the most commonly used ways to induce labor is with vaginal prostaglandins, which ripen the cervix in preparation for labor. The most concerning potential side effect of prostaglandins is excessive uterine activity, termed uterine tachysystole, which can cause fetal hypoxemia.2 Cervical priming with prostaglandins has thus been traditionally performed as a hospital procedure, where fetal and maternal well-being can be monitored. There is increasing interest in performing cervical ripening as a home procedure, which may be preferable to women3 and may have cost benefits to health service providers.4 Home cervical ripening is performed in
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selected women undergoing induction of labor at the Simpson Centre for Reproductive Health in Edinburgh and is perceived in our unit to be preferable to women and safe. In January 2006, a protocol was introduced for offering home cervical ripening with 1 mg dinoprostone gel to all low-risk nulliparous women in whom induction of labor for postmaturity (between 41 and 42 weeks of gestation) was being performed. The protocol remained in place until 2010. We performed a retrospective cohort study of women having induction of labor for postmaturity. The primary objective of this study was to evaluate the clinical effectiveness of the policy when instituted on a busy maternity unit and to test the hypotheses that home cervical ripening would 1) be safe and 2) result in shorter hospital stay.
MATERIALS AND METHODS The study was performed at the Simpson Centre for Reproductive Health, a university tertiary care referral center with more than 6,000 deliveries per year. The study period was January 2007 to June 2010. This period was chosen as one in which a uniform policy for home cervical ripening was embedded in obstetric practice (the policy was introduced in January 2006 and changed in July 2010). The study used routinely collected hospital data that were anonymized at the source. An opinion was sought from South East Scotland Research Ethics Service who found that the study did not need National Health Service ethical review under the terms of the Governance Arrangements for Research Ethics Committees and no formal ethical committee approval was required. Throughout the study period, the hospital policy was to offer women home cervical ripening if they were nulliparous, had singleton pregnancies with cephalic presentation, had no medical or obstetric complications, had body mass indexes (BMIs, calculated as weight (kg)/[height (m)]2) less than 40, had support and transportation available, lived within 30 minutes of the hospital and had a telephone at home, had a primary indication for induction of labor of postmaturity, and had a gestation of 41 3/7 to 42 weeks of gestation when induction was initiated. Additionally, women had to have an amniotic fluid index 5 cm or greater on ultrasound assessment and normal electronic fetal monitoring, both performed immediately before cervical ripening. Signs of labor (palpable or painful uterine activity, fluid loss or bleeding from the vagina) conferred ineligibility for cervical ripening. Cervical ripening was generally commenced in the evening with appointments between 4:30 PM and 7:00 PM. A vaginal examination was performed and
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1 mg dinoprostone was inserted to the posterior vaginal fornix if the Bishop’s score was less than 7. Women were asked to stay semirecumbent for at least 30 minutes postadministration of gel, after which time further electronic fetal monitoring was performed. If this was reassuring, women were allowed to go home with instructions to return the next morning for further assessment. Contact details and indicators to return to the hospital were provided (painful regular contractions or frequent contractions, pain, bleeding, membrane rupture). On return to the hospital, women were assessed for maternal and fetal well-being with routine clinical assessment and electronic fetal monitoring. Vaginal assessment was performed with artificial rupture of membranes if the cervix was ripened. If the Bishop’s score was less than 7, further prostaglandin was given as a hospital procedure. The study was a retrospective cohort study of women with singleton pregnancies having induction of labor for postmaturity. Women with singleton pregnancies having induction of labor at gestations greater than 41 weeks were identified from our hospital databases (Maternity Management Systems, InterSystems TrakCareÒ), which include data contemporaneously entered by midwives and doctors. Previous studies have used similar strategies, and data have been shown to be accurate in greater than 99% of cases.5 Case records were retrieved and reviewed by one of five investigators (R.M., A.A., R.T., I.S., K.H.). Women were included if they were nulliparous with live singleton pregnancies undergoing induction of labor for postmaturity and assessed with no medical or obstetric complications that would preclude home induction of labor. Women were excluded if they had prelabor rupture of membranes (suspected or confirmed), when the primary indication for induction of labor was not postmaturity, or if there was an antepartum stillbirth. We collected data on eligible women even if the home protocol was not actually initiated or completed as a result of the development of complications. This allowed us to perform a retrospective “intention-to-treat” analysis of safety outcomes and effectiveness. Data were extracted from the case records and entered onto standardized data collection sheets. Data were collected on women who were eligible for home cervical ripening but had hospital cervical ripening either because of maternal preference or social indication (eg, lack of support at home or transport to the hospital). These women formed a hospital cervical ripening comparison group. To make sure that no poor neonatal outcomes were missed, hospital perinatal mortality records
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(stillbirths and neonatal deaths up to 28 days) and neonatal unit admission records were searched for all cases at a gestational age of 41 0/7 weeks or greater. Maternal records relating to these births were crosschecked. Records for all cases were found, and no additional cases of induction of labor were identified. The primary outcome relating to safety of home cervical ripening was birth outside of the hospital. Other maternal adverse events recorded included emergency delivery as a result of suspected or confirmed fetal compromise within 8 hours of prostaglandin administration or 2 hours of readmission from home ripening; uterine tachysystole (as documented by the caregiver), uterine tachysystole requiring terbutaline and uterine tachysystole with electronic fetal monitoring changes indicating emergency delivery; uterine rupture; maternal death; antepartum hemorrhage; and postpartum hemorrhage greater than 1,000 mL. Other neonatal adverse events included meconium stained liquor; Apgar score less than 7 at 5 minutes after delivery; umbilical cord arterial pH less than 7.0; admission to neonatal unit within 24 hours of delivery for greater than 48 hours’ duration; neonatal encephalopathy defined as seizures within 24 hours of birth or requirement for cooling); and extended perinatal mortality (stillbirth or neonatal death within 28 days of delivery). The primary outcome relating to effectiveness was duration of hospital stay before delivery. We also determined the following secondary outcomes: the number of procedures initiated; the number of procedures completed at home; mode of delivery; epidural use; cesarean delivery for failed induction of labor (as documented by the caregiver); the proportion requiring subsequent prostaglandin doses; prostaglandin-to-delivery interval; and proportion of women delivering within 24 hours. We calculated that a total sample size of 968 with a ratio of 10 home cervical ripening (n5880) to one hospital cervical ripening (n588) would have 90% power to detect a difference of 4 hours in hospital stay with 95% confidence interval (CI) based on standard deviation of 11 hours. This sample size (n5880 in the home cervical ripening group) would have 80% power to detect adverse events with a rate of 0.2% (2/1,000) or more and 90% power to detect adverse events with a rate of 0.25% (2.5/1,000) or more. Data were analyzed using SPSS 19. Parametric data are presented as mean (standard deviation) and nonparametric data as median (range) unless otherwise stated. Unpaired Student’s t test was used to compare continuous parametric data (age, BMI, gestation at induction of labor, birth weight, Bishop’s score). Mann–Whitney U test was used to compare nonparametric data (number of
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doses of prostaglandin, time to delivery, time spent at home, postnatal stay). Fisher’s exact test was used to compare rates (modes of delivery; proportion who delivered within 24 hours; epidural use; proportion who required additional prostaglandin; failed induction of labor; neonatal outcomes). Missing fields were excluded from analysis. The number of missing fields for each outcome is stated in the “Results.” Significance was defined as P,.05.
RESULTS There were 23,112 deliveries over the study period, including 22,312 singleton pregnancies. One hundred fifty-eight (7.1%) were identified as being nulliparous women undergoing induction of labor and delivering at 41 weeks or more of gestation. Forty-four (2.8%) maternal case records were missing, leaving 1,536 cases for assessment of notes for inclusion criteria. Two hundred twenty-five of 1,536 (14.6%) participants were excluded as a result of a history of a medical or obstetric risk factor making them ineligible for home cervical ripening. A further 319 of 1,536 (20.8%) women were excluded because they had a contraindication identified on preinduction assessment (Fig. 1). This left a cohort of 907 (59.1%) who initiated cervical ripening with the intention of a home protocol being followed. Eighty-five of 1,536 (5.5%) women either expressed a preference for hospital cervical ripening or had a social risk factor such as inadequate support or lack of transport to and from the hospital, necessitating hospital cervical ripening. These women formed a comparison group for outcomes of induction of labor. Table 1 shows the characteristics of the home cervical ripening and hospital cervical ripening cohorts. Overall 597 of 907 (65.8%) women who were administered dinoprostone with the intention of having home cervical ripening completed the home induction of labor protocol, returning at the planned time for reassessment after dinoprostone administration. This represents 38.9% (597/1,536) of all nulliparous women with singleton pregnancies having induction of labor at greater than 41 weeks of gestation. Ninety-six of 907 (10.6%) women who were administered prostaglandin gel with the intention of having home cervical ripening were not discharged home. The reasons for this are summarized in Table 2. Of the 811 women discharged home after prostaglandin administration, 214 women returned before the scheduled readmission time (26.4% of women who were discharged after prostaglandin; 23.6% of the 907 women who received prostaglandin with the intention
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Fig. 1. Flow chart of participants. Stock. Home Cervical Ripening. Obstet Gynecol 2014.
of having home cervical ripening). In 204 women, this was the result of signs and symptoms of labor (contractions, pain, or rupture of membranes; 25.1% of women who were discharged after prostaglandin). In six patients (0.74% of women who were discharged after prostaglandin), it was the result of vaginal bleeding, and in four patients, the reason was not clearly documented. The median number of hours at home for the home cohort was 11.76 hours (range 0–24.82 hours). No women delivered outside the hospital. The shortest admission-to-delivery interval was 6 minutes. Seven women delivered within an hour of readmission, and a further 13 women delivered between 1 and 2 hours after readmission to the hospital after home cervical ripening. In one case, the neonate was admitted to the neonatal unit for observation. The 5-minute Apgar score was 9, and the cord pH was 7.25. In all other cases, there were no maternal or neonatal complications. Uterine tachysystole was documented in 25 of 907 cases of women having home cervical ripening overall
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but only related to the first dose of prostaglandin in 19 of these cases (2.1%; 95% CI 1.3–3.2 of all cases in home cervical ripening cohort). In the remaining six patients, tachysystole was related to subsequent doses of prostaglandin or oxytocin. There were no cases of uterine rupture or maternal deaths in either the home cervical ripening or the hospital cervical ripening groups. Six women were readmitted from home after initiating home cervical ripening with vaginal bleeding. This was thought to be “show” in all patients, and delivery was not expedited or management changed after clinical assessment. The incidence of postpartum hemorrhage greater than 1,000 mL was similar in the hospital and home cervical ripening groups (114/907; 12.6%; 95% CI 10.6–14.9 in the home cervical ripening group and 8/85; 9.4%; 95% CI 4.6–17.7 in the hospital cervical ripening group; P5.51). Neonatal outcomes are summarized in Table 3. No significant differences were found between home
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Table 1. Characteristics of the Cohort Administered Prostaglandin With the Intention of Undertaking Home Cervical Ripening and Comparison Group of Women Who Had Inpatient Cervical Ripening as a Result of Social Indication or Preference Home Ripening (n5907)
Characteristic Age (y) BMI (kg/m2) Gestation at induction of labor (d) Median Bishop’s score (range) Birth weight (g) Median no. of doses of prostaglandin E (range)
28.7 (28.3–29.1) 25.8 (25.4–26.2) 292.3 (292.2–292.4) 4 (1–7)
Missing 1 228 0 124
3,729 (3,700.1–3,737.9) 1 (1–6)
1 1
Inpatient Ripening Resulting From Preference or Social Reason (n585) 29.6 (28.1–31.2) 25.8 (24.4–27.2) 291.5 (291.0–292.0) 4 (1–7) 3,702 (3,618.0–3,786.0) 1 (1–5)
P
Missing
.29 .92 .003
0 19 0
.23
25
.55 .72
0 0
BMI, body mass index. Data are mean (95% confidence interval) unless otherwise specified. Means were compared using unpaired student t test. Medians were compared using Mann–Whitney U test.
and hospital cervical ripening groups, but the numbers of adverse events were small and the study was not adequately powered for comparison of these. There were no cases of intrauterine death in either group. There was one neonatal death in the home cervical ripening group and a further two cases of serious neonatal morbidity (one case of neonatal encephalopathy and one case of meconium aspiration leading to infant death at 3 months of age). All three cases followed long labors requiring subsequent doses
Table 2. Reasons for Actual Inpatient Cervical Ripening in Women Who Had Planned to Go Home for Home Cervical Ripening
Reason for Remaining Inpatient Signs of labor Contractions or pain Membrane rupture Abnormal electronic fetal monitoring Pyrexia Antepartum hemorrhage Workload issues Maternal preference Bad weather Wrong dose Not documented
Indications for Staying in the Hospital After Administration of Dinoprostone Gel in Women Eligible for Home Cervical Ripening (n596/907) (10.6% [95% CI 8.7–12.7]) 50 (5.5) 47 (5.2) 3 (0.3) 21 (2.3) 1 (0.1) 1 (0.1) 17 3 1 1 1
(1.9) (0.3) (0.1) (0.1) (0.1)
CI, confidence interval. Data are n (% of total home cervical ripening cohort).
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of dinoprostone and oxytocin augmentation and operative deliveries. Outcomes of women with planned home cervical ripening compared with women with a social indication for hospital cervical ripening are summarized in Table 4.
DISCUSSION Our study of more than 1,000 cases of induction of labor for postmaturity supports the growing body of evidence that suggests that home ripening may be a reasonable alternative to hospital cervical ripening if desired by the woman and her family for induction of labor at term, although using one dose of dinoprostone for home cervical ripening does not appear to reduce the hospital stay. The findings of our study are supported by a recent Cochrane review.6 Because this was a retrospective study, it was dependent on the quality of the recorded data. In an attempt to maximize accuracy, we performed systematic and careful review of medical records collecting predefined data. We used electronic maternity records to collect all maternal clinical outcomes. The proportion of missing data was very low for the majority of key clinical outcomes as a result of entry of these fields being mandatory in the electronic maternity record. In addition, multiple sources of neonatal outcome data were used to increase confidence that no cases of significant morbidity or perinatal mortality were missed. Our study was significantly larger than published studies, which increases our confidence in the study’s findings. Furthermore, women eligible for home induction of labor were managed according to a uniform policy that was embedded in the clinical practice of a busy tertiary care centre maternity unit. This means that the results are relevant to
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Table 3. Neonatal Complications of the Cohort Administered Prostaglandin With the Intention of Undertaking Home Cervical Ripening and the Comparison Group of Women Who Had Inpatient Cervical Ripening as a Result of Social Indication or Preference Inpatient Ripening as a Result of Preference or Social Reason (n585)
Home Ripening (n5907) n
Complication Meconium Apgar score less than 7 at 5 min Arterial cord pH less than 7.00 Neonatal unit admission longer than 48 h Perinatal mortality Severe perinatal morbidity
263 21 6 8 1 2
% (95% CI) 30.1 2.3 3.2 0.88 0.11 0.22
Missing
n
% (95% CI)
P
Missing
39 5 277 0 0
26 1 0 1 0 0
37.7 (26.9–49.5) 1.2 (0.1–5.9) — 1.2 (0.06–5.7) — —
.29 .89 1.00 .39 1.00 1.00
6 2 24 0 0
(27.1–33.2) (1.5–3.5) (2.0–4.7) (0.45–1.7) (0.01–0.54) (0.03–0.73)
CI, confidence interval. Proportions were compared with Fisher’s exact test.
contemporary clinical practice and not just within the “ideal” conditions of a clinical trial. As a result of the design of the study, the study was not powered for all clinical outcomes, specifically rare adverse neonatal outcomes. However, the cohort was large enough to have more than 80% power to detect an adverse event rate of 2 per 1,000 or more and 90% power to detect an event rate of 2.5 per 1,000 or more. It is therefore reassuring that no cases of birth outside the hospital, uterine rupture, or significant neonatal morbidity of neonatal death likely to relate to the setting of cervical ripening were seen. We accept that our comparison group has limitations in that it may be higher risk as a result of increased social risk factors, and it is also
relatively small (because most women accept to undergo home cervical ripening). However, both groups were matched for maternal age and BMI, which are important predictors of risk of intrapartum intervention and adverse perinatal outcome. We therefore believe that within the constraints of our study design and with appropriate caveats, it is valid to compare outcomes between women having hospital as opposed to home cervical ripening. In conclusion, our study suggests that clinical outcomes are comparable in nulliparous women who receive a single dose of dinoprostone gel for home cervical ripening compared with those who undergo hospital cervical ripening and that adverse outcomes are rare. However, home ripening does not decrease
Table 4. Outcomes of Women Who Were Administered Prostaglandin With the Intention of Undertaking Home Cervical Ripening and the Comparison Group of Women Who Had Inpatient Cervical Ripening As a Result of Social Indication or Preference Inpatient Ripening as a Result of Preference or Social Reason (n585)
Home Ripening (n5907) Outcome Mode of delivery Spontaneous vaginal Operative vaginal Cesarean Epidural use in labor Proportion requiring further prostaglandin Failed induction of labor Proportion delivered in 24 h Mean prostaglandin-to-delivery time (h) Mean time in hospital until delivery (h)
n
% (95% CI)
Missing
n
% (95% CI)
P
Missing
1 263 325 319 606 444 18 207 35.45 26.25
29.0 35.8 35.2 69.8 49.0 2.1 22.8
(26.1–32.0) (32.8–39.0) (32.1–38.3) (66.7–72.8) (45.8–52.3) (1.3–3.2) (20.2–25.7) (34.4–36.5) (25.3–27.2)
50 1 5 14 14 35
0 26 23 36 52 41 4 23 22.5 24.28
30.6 27.0 42.4 75.4 48.2 5.1 27.1
(21.5–41.0) (18.4–37.2) (32.2–53.0) (64.2–84.4) (37.8–58.8) (1.6–11.8) (18.4–37.2) (21.1–23.9) (22.5–26.0)
.80 .12 .19 .41 .91 .12 .42 ,.001 .26
5 0 1 2 2 4
CI, confidence interval. Proportions were compared with Fisher’s exact test. Means were compared with unpaired Student’s t test.
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the number of hours women spend in the hospital before delivery and further research needs to be undertaken to evaluate resource use, costeffectiveness, and women’s preferences for home compared with hospital cervical ripening. REFERENCES
3. Reid M, Lorimer K, Norman JE, Bollapragada SS, Norrie J. The home as an appropriate setting for women undertaking cervical ripening before the induction of labour. Midwifery 2011;27:30–5. 4. Farmer KC, Schwartz WJ III, Rayburn WF, Turnbull G. A costminimization analysis of intracervical prostaglandin E2 for cervical ripening in an outpatient versus inpatient setting. Clin Ther 1996;18:747–56.
1. Keirse MJ. Natural prostaglandins for induction of labor and preinduction cervical ripening. Clin Obstet Gynecol 2006;49: 609–26.
5. Stock SJ, Josephs K, Farquharson S, Love C, Cooper SE, Kissack C, et al. Maternal and neonatal outcomes of successful Kielland’s rotational forceps delivery. Obstet Gynecol 2013;121: 1032–9.
2. Intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. ACOG Practice Bulletin No. 106. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114:192–202.
6. Kelly AJ, Malik S, Smith L, Kavanagh J, Thomas J. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term. The Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD003101. DOI: 10.1002/14651858.CD003101.pub2.
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