Journal of Obstetrics and Gynaecology, 2014; Early Online: 1–8 © 2014 Informa UK, Ltd. ISSN 0144-3615 print/ISSN 1364-6893 online DOI: 10.3109/01443615.2014.987114
ORIGINAL ARTICLE
Expectant management of PPROM and major complications before planned delivery: A retrospective cohort study J. M. Bendix1, H. K. Hegaard2, T. Bergholt1 & J. Langhoff-Roos3 1Department of Gynaecology & Obstetrics, Nordsjaellands Hospital, Hillerod, University of Copenhagen, Denmark, 2The Research Unit
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Women’s and Children’s Health, the Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Denmark and 3Department of Obstetrics, the Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Denmark
Women with pre-term pre-labour rupture of membranes (PPROM) 22–33 weeks’ gestation were included in a retrospective cohort study with a structured audit to identify risk factors of major complications following PPROM and to assess whether these complications are predictable. Of the 234 women analysed, 106 (45%) delivered within three days. Eighty-four women (36%) had at least one major complication and 45% of these complications occurred within three days. The complication rate was 64% in early PPROM before 28 weeks’ gestation and 11% in late PPROM at 28 weeks’ gestation or later. Nulliparous women had an increased risk of major complications (adjusted hazards ratio: 3.07 (95% confidence interval: 1.28–7.37)). The complication rates were highest in early PPROM and during the first three days after PPROM. Multiparous women with late PPROM, who do not deliver within the first three days, have the lowest risk of major complications and are suitable for home care. Keywords: Chorioamnionitis, cord prolapse, general obstetrics, PPROM, placental abruption, place of care
Although clinicians may find it easier to monitor the mother and her foetus in a hospital, a recent Cochrane review suggests that pregnant women might have different preferences and views (Abou El Senoun et al. 2010). The counselling of women with PPROM is based on clinical experience and considers flexibility according to patient wishes (Abou El Senoun et al. 2010; Sciscione 2010). The challenge is to advise hospitalisation for women at high risk for complications that require immediate attention and outpatient care for women at low risk of complications. However, little is known about the potential risk factors for major complications, such as infection, umbilical cord prolapse and placental abruption that necessitate immediate interventions including unplanned delivery. The objective of this study is to describe the course of pregnancies with PPROM between 22 and 33 weeks’ gestation that were managed expectantly in a hospital and to identify the clinical risk factors for major complications before planned delivery to assess whether these major complications are predictable.
Materials and methods Introduction
Study population
Pre-term pre-labour rupture of membranes (PPROM) before 37 weeks’ gestation complicates between 1 and 3% of all pregnancies and accounts for approximately 30% of all pre-term deliveries (Goldenberg et al. 2008; Buchanan et al. 2010). PPROM before 34 weeks’ gestation is associated with serious complications, such as chorioamnionitis, umbilical cord complications and placental abruption, and is an important cause of peri-natal morbidity and mortality (Mercer 2003; Goldenberg et al. 2008; Beck et al. 2010). Even when serious pregnancy complications are not present, PPROM has been demonstrated to be associated with a higher rate of adverse neonatal outcomes than spontaneous low-risk preterm deliveries (Melamed et al. 2011). In the management of women with PPROM, the objective is to maximise the benefits of foetal maturation while avoiding the potential harms of remaining in utero (Buchanan et al. 2010). Women with PPROM before 34 weeks’ gestation are typically managed expectantly in hospitals (Fox et al. 2009; Maloni 2011; Bendix et al. 2014). The optimal settings are unknown, whether hospital or outpatient, for detecting the early signs and symptoms of complications during PPROM (Abou El Senoun et al. 2010).
We conducted a retrospective cohort study with data from the medical records of women with PPROM between 22 and 33 weeks’ gestation (Figure 1) who were admitted to the Obstetric Clinic, a tertiary referral unit at Rigshospitalet, University of Copenhagen, from January 2006 to December 2010. All women with PPROM from the catchment area and women with PPROM before 28 weeks’ gestation from other hospitals in Eastern Denmark, Greenland and the Faroe Islands were admitted. PPROM was diagnosed by the presence of amniotic fluid at speculum examination and ultrasonographic signs of oligohydramnios. Gestational age was calculated from an early ultrasonographic estimation of crown–rump length.
Standard procedure for PPROM All included patients with PPROM received standard antibiotic treatment; three intravenous treatments with a combination of ampicillin and metronidazole within the first 24 h and subsequent oral treatment three times a day for six days.
Correspondence: Dr Jane Marie Bendix, RM, MHS, Department of Gynecology and Obstetrics, Nordsjaellands Hospital, University of Copenhagen, Dyrehavevej 29, Hillerod 3400, Denmark. E-mail: [email protected]
2 J. M. Bendix et al.
Audit of cases with major complications We conducted a structured qualitative audit of the major complications before planned delivery to assess whether prediction of these complications was possible. The time intervals between the displays of signs or symptoms to the diagnoses of any major complications were recorded. Furthermore, we recorded whether the maternal subjective symptoms predicted the major complication. Pregnancy-related physical complaints or discomfort that resulted in specific notes in the medical records for which treatment was not initiated were registered as women’s needs for assessment. Less serious complications that were treated medically but did not necessitate unplanned delivery were registered as supplemental medical treatments.
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Statistical analyses
Figure 1. Flowchart of included women with PPROM GA 22-33.
A single course of corticosteroids was administered intramuscularly twice at a 24-h interval from gestational age of 24 0 weeks (Crowley 1996). The women with PPROM were managed expectantly as inpatients with strict activity restriction (Sciscione 2010). They received a DVD with specific instructions for physical exercise during bed rest. Daily cardiotocography (CTG) was performed and rectal temperature was monitored twice daily. The recommendations of strict activity restriction and daily CTG were based on traditionbased best clinical practice. Tocolysis with atosiban or indomethacin was administered only to gain effect from corticosteroid treatment or in cases of pre-term labour at very early gestational ages. Planned delivery was recommended at 34 weeks’ gestation.
Data collection From the medical records, we retrieved information about the date and time of PPROM, admission, onset of major complications, labour and delivery. We had specific information about tocolysis following PPROM, the mode of delivery, the gestational age at delivery, the birth weight, the Apgar score, stillbirth and neonatal death. We retrieved information about potential risk factors for major complications: gestational age at PPROM, maternal age, parity, plurality, infertility treatment, transferral, vaginal bleeding before PPROM, the ‘women’s calls for immediate medical assessment’, supplemental medical treatment, smoking, partner status and body mass index kg/m2.
Major complications before planned delivery Major complications were defined as conditions that necessitated unplanned delivery. Major complications included acute placental abruption, chorioamnionitis, umbilical cord prolapse, pathological foetal heart rate, prolapse of foetal extremities in the vagina, severe vaginal bleeding without a specific origin, abnormal umbilical flow, foetal death, incomplete twin delivery, maternal lung oedema and maternal appendicitis.
The rates of the maternal, obstetrical and neonatal characteristics were calculated as percentages or medians or mean values with standard deviations and stratified by gestational age at PPROM (22–23, 24–27, 28–31, 32–33 weeks’ gestation). The Pearson’s chi-squared test was used to examine independence within the contingency tables. The hazard ratios (HRs) for major complications before labour were estimated according to the potential risk factors using a Cox regression model. The potential risk factors were all considered in a multivariable Cox regression analysis. The unadjusted and the mutually adjusted associations between the potential risk factors are presented as HRs with 95% confidence intervals (CIs). Statistical significance was defined as a two-sided P value less than 0.05. All analyses were performed using SPSS statistical software version 20.0 (IBM SPSS Statistics). The Danish Data Protection Agency (J.nr. 2011-41-7010) and the Danish Health and Medicines Authority (J.nr. 3–3013-8/1/ EHE) approved the study. We notified a regional committee on biomedical research ethics about this study, and approval is not required for studies based on registries and medical records in Denmark (P.nr. H-2-2011-130).
Results Overall, 234 women with PPROM between 22 and 33 weeks’ gestation were included. The mean gestational age at PPROM was 27.6 weeks’ gestation (SD 4.4). The maternal and obstetric characteristics by gestational age at PPROM are summarised in Table I.
Obstetrical and peri-natal outcomes One hundred and six women (45%) gave birth within three days of PPROM. Forty-two women (18%) reached 34 weeks’ gestation and were induced or delivered by elective caesarean section. Overall, 102 (44%) women had emergency caesarean sections and 35 (15%) had emergency caesarean sections before the onset of labour. The maternal and neonatal outcomes are shown in Table II.
Major complications Overall, 84 women (36%) encountered one or more major complications. Among the 111 women with PPROM before 28 weeks’ gestation, there were 71 major complications (64%), and among the 123 women with PPROM at 28 weeks’ gestation or later, there were 13 major complications (11%). Of the major complications, 38 (45%) occurred within 3 days after PPROM, whereas 21 (25%) occurred 12 days or more after PPROM. The types of complications by gestational age at PPROM are illustrated in Table III.
PPROM and major complications before planned delivery 3 Table I. Maternal and obstetrical characteristics by gestational age at PPROM. Gestational age in weeks at PPROM
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Overall Maternal age (years) 24 25–29 30–34 35 Nulliparious Singleton pregnancy Infertility treatment*
Vaginal bleeding prior to PPROM* Transferrals Body Mass Index kg/m2,* 25 25–29.9 30 Smoking during pregnancy* Cohabitant with partner*
Total
22 23 n (%)
24 27 n (%)
28 31 n (%)
32 33 n (%)
22 33 n (%)
37 (16)
74 (32)
50 (21)
73 (31)
234 (100)
1 (3) 5 (14) 15 (41) 16 (43) 13 (36) 31 (84) 5 (14) 14 (38) 27 (73)
10 (13) 13 (18) 26 (35) 25 (34) 38 (51) 58 (78) 10 (14) 21 (28) 51 (69)
4 (8) 17 (34) 13 (26) 16 (32) 37 (74) 33 (66) 15 (31) 6 (12) 16 (32)
4 (6) 19 (26) 28 (38) 22 (30) 48 (67) 51 (71) 14 (19) 3 (4) 25 (34)
19 (8) 54 (23) 82 (35) 79 (34) 136 (59) 173 (74) 44 (19) 44 (19) 119 (51)
18 (49) 12 (35) 4 (12) 4 (12) 26 (87)
47 (64) 18 (25) 6 (9) 18 (26) 55 (89)
35 (70) 8 (17) 5 (10) 6 (13) 35 (85)
53 (73) 15 (21) 3 (4) 8 (11) 59 (91)
153 (65) 53 (24) 18 (8) 36 (16) 175 (88)
*Totals may vary as data were missing for some categories.
Overall, there were 38 cases (16%) of chorioamnionitis, 29 cases (12%) of foetal distress, 9 cases (4%) of placental abruption and 6 cases (3%) of cord prolapse (Table III). Some women encountered more than one specific major complication. One
woman declined induction of labour at 34 weeks’ gestation and sustained severe chorioamnionitis at 35 weeks’ gestation. There were no cases of deep vein thrombosis or maternal deaths before delivery. However, a woman with serious drug abuse died from
Table II. Maternal and neonatal outcomes by gestational age of PPROM. Gestational age in weeks at PPROM
Overall Tocolysis after PPROM Supplemental medical treatment Latency time from PPROM to delivery 24 h 1–2 days 3–5 days 6–8 days 9–11 days 12 days Onset of labour Spontaneous Induction Emergency caesarean before labour Mode of delivery* Vaginal Caesarean section Emergency Elective Deliveries at 34 weeks Deliveries with adverse neonate outcome€ GA at delivery (weeks) mean SD Neonatal outcome Newborns Birth weight (g) mean SD Neonates with adverse outcome € Apgar score, 7 at 5 min# UApH 7.15§ Antenatal deaths Peri- and neonatal deaths
Total
22 23 n (%)
24 – 27 n (%)
28 – 31 n (%)
32 – 33 n (%)
22 – 33 n (%)
37 (16) 14 (38) 12 (32)
74 (32) 39 (53) 13 (18)
50 (21) 21 (42) 4 (8)
73 (31) 33 (45) 1 (1)
234 (100) 107 (46) 30 (13)
2 (5) 5 (14) 4 (11) 3 (8) 3 (8) 20 (54)
13 (17) 10 (14) 11 (15) 9 (12) 10 (14) 21 (28)
14 (28) 10 (20) 4 (8) 5 (10) 2 (4) 15 (30)
37 (51) 15 (20) 11 (15) 6 (8) 2 (3) 2 (3)
66 (28) 40 (17) 30 (13) 23 (10) 17 (7) 58 (25)
29 (78) 4 (11) 5 (14)
50 (68) 3 (4) 18 (24)
40 (80) 3 (6) 4 (8)
46 (63) 14 (19) 8(11)
165 (71) 24 (10) 35 (15)
20 (54)
32 (43)
31 (62)
44 (60)
127 (54)
17 (46) 0 0 18 (49) 25.3 2.3
43(58) 2 (3) 4 (5) 17 (23) 26.9 2.5
17(34) 3 (6) 6 (12) 2 (4) 31.1 1.6
26 (36) 4 (6) 32 (44) 7 (10) 32.9 0.7
102 (44) 9 (4) 42 (18) 44 (19) 29.4 3.5
43 (100) 675 220 21 (49) 18 (42) . 4 (9) 9 (21)
91 (100) 963 298 18 (20) 11 (12) 5 (6) 3 (3) 5 (5)
68 (100) 1717 349 2 (3) 0 2 (3) 0 0
95 (100) 1854 322 8 (8) 0 7 (7) 0 1 (1)
297 (100) 1411 573 49 (17) 29 (10) 15 (5) 7 (2) 15 (5)
* Five women delivered first twin vaginally and the second twin by caesarean. #Apgar score were missing for 30 neonates. §Umbilical cord arterial pH were missing for 73 neonates. €Adverse neonatal outcome; low apgar score ( 7 at 5 min.), low umbilical cord arterial pH ( 7.15), ante-, peri- or neonatal death.
4 J. M. Bendix et al. Table III. Major complications by gestational age at PPROM.
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Gestational age in weeks at PPROM
Women with major complications Placental abruption Chorioamnionit Cord prolapse Foetal distress Vaginal bleeding (abruption not suspected) Prolapse of extremities Other complications* Diagnosis of major complication initiated by Symptoms, subjective Signs, objective Unknown Latency time from PPROM to major complication 24 h 1–2 days 3–5 days 6–8 days 9–11 days 12 days Time interval from symptoms to diagnosis Immediate ( 1 h) Hours ( 1 h) Days Time from diagnosis to delivery 1 h 1 – 2 h 2 h
Total
22 – 23 n (%)
24 – 27 n (%)
28 – 31 n (%)
32 – 33 n (%)
22 – 33 n (%)
28 (33) 3 (11) 16 (57) 0 9 (32) 2 (7) 1 (4) 3 (11)
43 (51) 5 (12) 18 (42) 5 (12) 10 (23) 5 (12) 4 (9) 6 (14)
7 (8) 1 (14) 4 (57) 0 6 (86) 0 0 0
6 (7) 0 0 1 (17) 4 (67) 0 0 1 (17)
84 (100) 9 (11) 38 (45) 6 (7) 29 (35) 7 (8) 5 (6) 10 (12)
21 (78) 6 (21) 1 (4)
35 (81) 8 (19) 0
4 (57) 2 (29) 1 (14)
2 (33) 4 (67) 0
62 (74) 20 (24) 2 (2)
5 (18) 1 (3) 4 (14) 3 (11) 1 (4) 14 (50)
15 (35) 8 (18) 3 (7) 6 (14) 6 (14) 5 (12)
1 (13) 2 (29) 0 2 (29) 0 2 (29)
3 (50) 3 (50) 0 0 0 0
24 (29) 14 (17) 7 (8) 11 (13) 7 (8) 21 (25)
16 (59) 6 (22) 5 (19)
24 (60) 5 (12) 11 (28)
4 (67) 2 (33) 0
5 (83) 1 (17) 0
49 (62) 14 (18) 16 (20)
4 (14) 5 (18) 19 (68)
5 (12) 9 (21) 29 (67)
0 2 (29) 5 (71)
2 (33) 1 (17) 3 (50)
11 (13) 17 (20) 56 (67)
omen may encounter more than one complication, hence the sum of the different complications may exceed the number of women W with major complications. *Other complications, abnormal umbilical flow, foetal death, maternal lung oedema and appendicitis.
multiple organ failure on the first day after delivery following severe chorioamnionitis and intrauterine foetal death. The interval between the occurrence of symptoms and the diagnosis of major complications was less than 1 h for 49 patients (62%), and 11 patients (13%) delivered within 1 h of the occurrence of symptoms (Table III). Sixty-two of these complications (74%) were detected as subjective symptoms. Fifty-six women (67%) had latencies of more than 2 h from the diagnosis of a major complication to delivery (Table III).
Potential risks of major complications Table IV shows crude and mutually adjusted HRs for major complications. Nulliparous women (adjusted HR: 2.76; 95% CI: 1.15–6.64) had a significantly increased risk of major complications. The incidence rates (IR) of major complications by gestational age at PPROM were high in the first three days after PPROM and decreased with latency from PPROM. Overall, the IR was 5%, and this rate was higher when PPROM occurred before 28 weeks (Table V). Therefore, we compared the incidences of major complications between the women with PPROM before 28 weeks’ gestation and those with PPROM at 28 weeks’ gestation or later (Table VI). The rate of precipitated deliveries (less than 2 h from diagnosis of a major complication or the onset of labour) was higher among the women with PPROM before 28 weeks’ gestation (Table VI). The crude risk factors for major complications among the 116 women who did not deliver within 3 days following PPROM are shown in Table VII. Only PPROM before 28 weeks’ gestation
(OR: 9.7, 95% CI: 1.7–54.1) remained a significant risk factor for major complications after mutual adjustment for all risk factors (Table VII). For all women with major complications the risk of their neonates having an adverse outcome was significantly raised (OR: 5.4; 95% CI: 2.7–10.9); when we stratified the gestational age at PPROM earlier or later than 28 weeks’ gestation the risk remained significantly raised for the early PPROM with (OR: 3.9, range: 1.5–10.5), but not for the late PPROM (data not shown).
Discussion Our study describes the courses of pregnancies with PPROM between 22 and 33 weeks’ gestation that were managed expectantly in a tertiary hospital setting until 34 weeks’ gestation. We identified clinical risk factors for major complications before planned delivery. The present study offers new insights into major maternal and foetal complications in the latency following PPROM, which are the main reason for hospitalisation of women with PPROM. The majority of other related studies have focused on the effect of PPROM duration on neonatal outcomes (Manuck et al. 2009; Melamed et al. 2011; Nayot et al. 2012; Frenette et al. 2013; van der Heyden et al. 2013). Our study population was treated according to standard guidelines, which were unchanged during the study period. One limitation is that this observational study was based on a consecutive sample of cases from a tertiary hospital that included
PPROM and major complications before planned delivery 5 Table IV. Risk factors of major complications in pregnancies with PPROM.
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No major complication n (%) Total PPROM (Gestational age in weeks) 22–23 24–27 28–31 32–33 Maternal age (years) 24 25–29 30–34 35 Parity* Nulliparous Multiparous Pregnancy* Singleton Multiple Infertility treatment* No Yes Transferral No Yes Vaginal bleeding prior to PPROM No Yes Women’s need of assessment* None 1–2 3–4 5 Supplemental medical treatment* None 1–3 Smoking status* Non-smokers Smokers Partner status* Cohabitant Single status Body Mass Index kg/m2* 25 25–29.9 30
Major complication n (%)
Crude hazard ratio (95%CI)
Ajusted hazard ratio (95%CI)
150 (64)
84 (36)
9 (24) 31 (42) 43 (86) 67 (92)
28 (76) 43 (58) 7 (14) 6 (8)
2.43 (0.90–6.53) 2.88 (1.11–7.46) 0.85 (0.26–2.71) 1
1.73 (0.47–6.35) 2.22 (0.68–7.27) 0.75 (0.18–3.10) 1
12 (63) 38 (70) 58 (71) 42 (53)
7 (37) 16 (30) 24 (29) 37 (47)
0.95 (0.38–2.35) 1 0.95 (0.48–1.85) 1.12 (0.60–2.09)
0.38 (0.09–1.8) 1 0.48 (0.18–1.31) 1.45 (0.56–3.76)
100 (74) 49 (51)
36 (26) 47 (49)
1.05 (0.66–1.58) 1
2.76 (1.15–6.64) 1
105 (61) 44 (73)
68 (39) 16 (27)
1 1.50 (0.81–2.78)
1 2.50 (0.87–7.16)
117 (63) 32 (73)
69 (37) 12 (27)
1 0.85 (0.45–1.61)
1 0.49 (0.19–1.24)
90 (78) 60 (50)
25 (22) 59 (50)
1 1.80 (1.08–3.02)
1 1.88 (0.84–4.20)
134 (71) 16 (36)
56 (29) 28 (64)
1 1.21 (0.75–1.95)
1 1.84 (0.84–4.20)
93 (71) 32 (64) 11 (39) 7 (47)
38 (29) 18 (36) 17 (61) 8 (53)
1 0.58 (0.32–1.05) 0.85 (0.47–1.55) 0.43 (0.19–1.00)
1 0.61 (0.25–1.45) 1.55 (0.57–4.08) 0.59 (0.19–1.83)
131 (68) 12 (40)
63 (32) 18 (60)
1 0.66 (0.38–1.17)
1 0.50 (0.21–1.20)
128 (68) 19 (53)
59 (32) 17 (47)
1 1.86 (1.05–3.31)
1 1.35 (0.48–3.78)
116 (66) 13 (57)
59 (34) 10 (43)
1 1.38 (0.68–2.80)
1 1.79 (0.53–6.03)
112 (71) 23(47) 10 (56)
45 (29) 26 (53) 8 (44)
1 1.42 (0.86–2.35) 1.45 (0.65–3.24)
1 1.37 (0.63–2.96) 0.58 (0.15–2.67)
*Totals may vary as data were missing for some categories. Ajusted HR, mutually ajusted.
women from the local catchment area and transferrals from other hospitals. We identified PPROM before 28 weeks’ gestation as the adjusted risk factor for major complications. The accumulation of major complications before 28 weeks’ gestation, mainly chorioamnionitis, may indicate that choriodecidual infection or inflammation play more important roles (Mercer 2003) in women with early PPROM than those with late PPROM and that the prescribed standard treatment with antibiotics is insufficient in early PPROM. The risk factors may be useful for individual management and for choosing the optimal place of care during latency. Hospitalisation during the expectant management of PPROM is recommended by the American College of Obstetricians and Gynecologists (ACOG 2013), whereas The Royal College of Obstetricians and Gynaecologists guidelines are equivocal regarding a recommendation for the place of care, however without providing specific criteria (RCOG 2010).
Twenty-one years ago, Carlan et al. (1993) randomised women with PPROM before 37 weeks’ gestation to outpatient (n 28) versus hospital (n 27) management and found no difference in latencies or neonatal outcomes. Similarly, a non-randomised retrospective cohort study of selected women with PPROM before 34 weeks’ gestation who had not delivered after 72 h revealed no differences in major adverse maternal or peri-natal outcomes between those who were cared for in hospital (n 91) and those in an outpatient setting (n 53) (Beckmann and Gardener 2013). We performed an audit to examine whether the major complications that occur during hypothetical home care are predictable. To assess the risk of home care, we estimated the reduction in complications rates using several cut-offs that are based on gestational age at PPROM and latency (Table VI). We found that major complications occurred more often in the first days after PPROM and that the rate was higher in early than in late PPROM. If home care were introduced to women with PPROM before 28 weeks’ gestation with
5 (84/1866.8) 99 (24/24.2) 25 (14/56.6) 8 (7/92.8) 7 (11/166.5) 6 (7/116.1) 1 (21/1410.6) 2 (1/59.7) 0 (0/7.8) 11 (1/9.1) 0 (0/20.6) 0 (0/22.2) 0 (0/0) 0 (0/0) 6 (5/87.4) 41 (3/7.4) 33 (2/6.0) 0 (0/16.2) 0 (0/14.1) 0 (0/17.6) 0 (0/26.1)
Table VI. Major complications according to latency from PPROM to onset of major complications or labour. Major Precipitated Total GA at Days after Overall complications deliveries* latency Incidence 2 h n (%) (days) PPROM PPROM (n) n (%) rate 22–27
28–33
1 (2/150.5) 0 (0/1.2) 11 (1/9.1) 0 (0/8.3) 6 (1/17.9) 0 (0/8.1) 0 (0/105.9)
Total 33
All 1 3 6 9 12 All 1 3 6 9 12
111 85 71 60 45 37 123 64 45 32 21 17
71 (64) 51 (60) 42 (59) 35 (58) 26 (58) 19 (51) 13 (11) 9 (14) 4 (9) 4 (13) 2 (10) 2 (12)
23 (21) 16 (19) 15 (21) 13 (22) 9 (20) 7 (19) 11 (10) 4 (6) 2 (4) 2 (6) 2 (10) 1 (6)
1306.3 1308.4 1283.3 1239.1 1139.8 1059.1 542.3 524.6 492.9 444.4 377.0 341.5
5% 4% 3% 3% 2% 2% 2% 2% 1% 1% 1% 1%
3 (7/202.1) 400 (2/0.5) 24 (1/4.2) 0 (0/3.8) 4 (2/26.5) 9 (1/10.8) 1 (1/156.3)
1 (1/110.9) 0 (0/0.4) 0 (0/3.0) 0 (0/0) 0 (0/6.0) 0 (0/0) 1 (1/101.5)
2 (3/105.8) 0 (0/1.1) 34 (1/2.9) 0 (0/0) 14 (1/7.2) 0 (0/0) 1 (1/94.6)
3 (1/39.0) 133 (1/0.8) 0 (0/1.5) 0 (0/3.6) 0 (0/0) 0 (0/9.7) 0 (0/23.4)
* Precipitated deliveries less than 2 h from onset of major complication or labour.
acency time from PPROM to onset of major complication or labour. L Incidence rate (IR) (number of major complications/accumulated latency time in days).
10 (10/102.1) 222 (2/0.9) 80 (2/2.5) 8 (1/11.9) 9 (1/11.0) 10 (2/19.5) 4 (2/56.3) 7 (13/180.0) 563 (9/1.6) 33 (1/3.0) 0 (0/0) 9 (2/22.1) 9 (1/11.0) 0 (0/142.3) 5 (18/341.5) 6 (13/208.7) 800 (4/0.5) 200 (2/1.0) 0 (0/1.0) 34 (4/11.8) 25 (4/15.9) 16 (2/12.5) 11 (3/26.9) 20 (1/5.0) 12 (1/8.5) 6 (2/30.9) 2 (6/288.7) 1 (2/147.5) 4 (10/279.1) 100 (1/1.0) 40 (1/2.5) 0 (0/0) 0 (0/7.6) 0 (0/0) 3 (8/268.0) Overall IR % Latency time 24 h, IR 1–2 days, IR 3–5 days, IR 6–8 days, IR 9–11 days, IR 12 days, IR
30 29 28 27 22
23
24
25
26
Gestational age at PPROM
Table V. Incidence rate of major complications according to gestational age at PPROM.
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32
6 J. M. Bendix et al.
latency of nine days or more and to women with PPROM between 28 and 33 weeks’ gestation with latency of 3 days or more, a total of 1633 days would be spent at home. This home care would also result in 30 major complications at home (1 per 54 days). However, even with the low incidence of 2% in the PPROM before 28 weeks’ gestation with latencies of 9 days or more, there would still be 26 (58%) major complications (1 per 44 days) at home and 9 (20%) precipitated deliveries below 2 h. In contrast, among the cases of PPROM at 28 weeks’ gestation or later, only 4 (9%) major complications (1 per 123 days) and 2 (4%) precipitated deliveries would have occurred at home. The questions arise of how many major complications at home are acceptable and the extent to which the results and prognoses of these cases would have been better had the mothers been cared for in a hospital. To minimise the number of major complications in PPROM cases before 28 weeks’ gestation, inpatient care should last for 8 days or more, and the risk factors for major complications should be considered. Alternatively, women with PPROM before 28 weeks’ gestation should remain hospitalised until delivery. For women with PPROM at 28 weeks’ gestation or later, home care seems to be quite safe after 3 days of inpatient care regardless of the risk factors. Several studies have shown that women who are hospitalised during labour are exposed to a greater number of interventions than women who experience labour and delivery at home (Janssen et al. 2009; Blix et al. 2012). The interventions due to complications in our study might have been needed and appropriate, but we cannot be certain that they were all necessary or would have been performed if the women had been cared for at home. An additional concern regarding outpatient management is that treatments for major complications might be delayed if the patient is at home (Ellestad et al. 2008; Abou El Senoun et al. 2010). However, Carlan and colleagues argue that emergency conditions occur at a reasonable level in carefully selected patients (Carlan et al. 1993; Bartfield and Carlan 1998).
Conclusion More than half of the women delivered more than three days after PPROM, and this proportion decreased with gestational age at PPROM. One-third of the women experienced one or more major complications before planned delivery. The complication rate was 64% in the women with PPROM before 28 weeks’ gestation compared with a rate of 11% in the women with PPROM at 28 weeks’ gestation or later. Women with late PPROM who do not deliver within the first few days had a reduced risk of major complications.
PPROM and major complications before planned delivery 7 Table VII. Risk factors of major complications in PPROM GA 22–33 and latency 2days.
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No major complication n (%) Total PPROM (Gestational age in weeks) 22–27 28–33 Maternal age (years) 24 25–29 30–34 35 Parity* Nulliparous Multiparous Pregnancy Singleton Multiple Infertility treatment* No Yes Transferral No Yes Vaginal bleeding prior to PPROM No Yes Women’s need of assessment* None 1 – 2 3 – 4 5 Supplemental medical treatment* None 1–3 Smoking status* Non-smokers Smokers Partner status* Cohabitant Single status Body Mass Index kg/m2* 25 25
Major complication n (%)
Crude OR (95%CI)
Ajusted OR (95%CI)
70 (60)
46 (40)
29 (41) 41 (91)
42 (59) 4 (9)
8 (57) 12 (63) 28 (74) 22 (49)
6 (43) 7 (37) 10 (26) 23 (51)
NS 1 NS NS
NS 1 NS NS
39 (72) 30 (50)
15 (28) 30 (50)
NS 1
NS 1
59 (59) 11 (69)
41 (41) 5 (31)
1 NS
1 NS
58 (60) 12 (71)
38 (40) 5 (29)
1 NS
1 NS
37 (76) 33 (49)
12 (24) 34 (51)
1 3.18 (1.42–7.13)
1 NS
57 (69) 13 (39)
26 (31) 20 (61)
1 3.37 (1.46–7.80)
1 NS
29 (63) 24 (71) 8 (36) 6 (55)
17 (37) 10 (29) 14 (64) 5 (45)
1 NS 0.71 (0.28–1.84) 2.99 (1.04–8.57) NS 1.42 (0.38–8.57)
1 NS NS NS
56 (64) 11 (42)
31 (36) 15 (58)
1 2.46 (1.01–6.02)
1 NS
58 (65) 9 (47)
31 (35) 10 (53)
1 NS
1 NS
51 (59) 5 (63)
36 (31) 3 (43)
1 NS
1 NS
48 (71) 20 (48)
20 (29) 22 (52)
14.85 (4.79–45.98) 1
1 2.64 (1.19–5.87)
9.69 (1.73–54.11) 1
1 NS
justed OR, mutually ajusted. A NS, not statsitically significant. *Totals may vary as data were missing for some categories.
In clinical practice these women might be offered home care. Large pragmatic controlled trials are required to evaluate whether home care is a superior alternative to hospital care for women with late PPROM who did not deliver within the first few days. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper. The study was supported by grants from the Nordsjaellands Hospital, Hillerod, University of Copenhagen, Denmark; TrygFonden; Lundbeckfonden and the Danish Association of Midwives.
References Abou El Senoun G, Dowswell T, Mousa HA. 2010. Planned home versus hospital care for preterm prelabour rupture of the membranes (PPROM) prior to 37 weeks’ gestation. The Cochrane Database of Systematic Reviews 4:CD008053.
ACOG. 2013. Practice bulletins No. 139: premature rupture of membranes. Obstetrics & Gynecology 122:918–930. Bartfield MC, Carlan SJ. 1998. The home management of preterm premature ruptured membranes. Clinical Obstetrics and Gynecology 41:503–514. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH et al. 2010. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bulletin of the World Health Organization 88:31–38. Beckmann M, Gardener G. 2013. Hospital versus outpatient care for preterm pre-labour rupture of membranes. The Australian & New Zealand Journal of Obstetrics & Gynaecology 53:119–124. Bendix J, Hegaard HK, Bergholt T, Langhoff-Roos J. 2014. Recommendations of activity restriction in high-risk pregnancy scenarios: a Danish national survey. J Perinat Med. 2014 Apr 1. pii: /j/jpme.ahead-of-print/ jpm-2013-0347/jpm-2013-0347.xml. doi: 10.1515/jpm-2013-0347. [Epub ahead of print]. Blix E, Huitfeldt AS, Oian P, Straume B, Kumle M. 2012. Outcomes of planned home births and planned hospital births in low-risk women in Norway between 1990 and 2007: a retrospective cohort study. Sexual & Reproductive Healthcare: Official Journal of the Swedish Association of Midwives 3:147–153.
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8 J. M. Bendix et al. Buchanan SL, Crowther CA, Levett KM, Middleton P, Morris J. 2010. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks’ gestation for improving pregnancy outcome. The Cochrane Database of Systematic Reviews 3:CD004735. Carlan SJ, O’Brien WF, Parsons MT, Lense JJ. 1993. Preterm premature rupture of membranes: a randomized study of home versus hospital management. Obstetrics and Gynecology 81:61–64. Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database of Systematic Reviews 1996, Issue 1. Art. No.: CD000065. DOI: 10.1002/14651858.CD000065. Ellestad SC, Swamy GK, Sinclair T, James AH, Heine RP, Murtha AP. 2008. Preterm premature rupture of membrane management–inpatient versus outpatient: a retrospective review. American Journal of Perinatology 25:69–73. Fox NS, Gelber SE, Kalish RB, Chasen ST. 2009. The recommendation for bed rest in the setting of arrested preterm labor and premature rupture of membranes. American Journal of Obstetrics and Gynecology 200:165.e1–165.e6. Frenette P, Dodds L, Armson BA, Jangaard K. 2013. Preterm prelabour rupture of membranes: effect of latency on neonatal and maternal outcomes. Journal of Obstetrics and Gynaecology Canada 35:710–717. Goldenberg RL, Culhane JF, Iams JD, Romero R. 2008. Epidemiology and causes of preterm birth. Lancet 371:75–84. Janssen PA, Saxell L, Page LA, Klein MC, Liston RM, Lee SK. 2009. Outcomes of planned home birth with registered midwife versus planned hospital birth with midwife or physician. Canadian Medical Association Journal 181:377–383.
Maloni JA. 2011. Lack of evidence for prescription of antepartum bed rest. Expert Review of Obstetrics & Gynecology 6:385–393. Manuck TA, Maclean CC, Silver RM, Varner MW. 2009. Preterm premature rupture of membranes: does the duration of latency influence perinatal outcomes? American Journal of Obstetrics and Gynecology 201:414. e1–414.e6. Melamed N, Ben-Haroush A, Pardo J, Chen R, Hadar E, Hod M, Yogev Y. 2011. Expectant management of preterm premature rupture of membranes: is it all about gestational age? American Journal of Obstetrics and Gynecology 204:48.e1–48.e8. Mercer BM. 2003. Preterm premature rupture of the membranes. Obstetrics and Gynecology 101:178–193. Nayot D, Penava D, Da Silva O, Richardson BS, De Vrijer B. 2012. Neonatal outcomes are associated with latency after preterm premature rupture of membranes. Journal of Perinatology 32:970–977. RCOG. 2010. Green-top Guideline No. 44. Available from: http://www. rcog.org.uk/womens-health/clinical-guidance/preterm-prelabourrupture-membranes-green-top-44. [15 May 2014]. Sciscione AC. 2010. Maternal activity restriction and the prevention of preterm birth. American Journal of Obstetrics and Gynecology 202:232. e1–232.e5. van der Heyden JL, van der Ham DP, van Kuijk S, Notten KJ, Janssen T, Nijhuis JG et al. 2013. Outcome of pregnancies with preterm prelabor rupture of membranes before 27 weeks’ gestation: a retrospective cohort study. European Journal of Obstetrics, Gynecology, and Reproductive Biology 170:125–130.
ORIGINAL ARTICLE
Expectant management of PPROM and major complications before planned delivery: A retrospective cohort study J. M. Bendix1, H. K. Hegaard2, T. Bergholt1 & J. Langhoff-Roos3 1Department of Gynaecology & Obstetrics, Nordsjaellands Hospital, Hillerod, University of Copenhagen, Denmark, 2The Research Unit
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Women’s and Children’s Health, the Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Denmark and 3Department of Obstetrics, the Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Denmark
Women with pre-term pre-labour rupture of membranes (PPROM) 22–33 weeks’ gestation were included in a retrospective cohort study with a structured audit to identify risk factors of major complications following PPROM and to assess whether these complications are predictable. Of the 234 women analysed, 106 (45%) delivered within three days. Eighty-four women (36%) had at least one major complication and 45% of these complications occurred within three days. The complication rate was 64% in early PPROM before 28 weeks’ gestation and 11% in late PPROM at 28 weeks’ gestation or later. Nulliparous women had an increased risk of major complications (adjusted hazards ratio: 3.07 (95% confidence interval: 1.28–7.37)). The complication rates were highest in early PPROM and during the first three days after PPROM. Multiparous women with late PPROM, who do not deliver within the first three days, have the lowest risk of major complications and are suitable for home care. Keywords: Chorioamnionitis, cord prolapse, general obstetrics, PPROM, placental abruption, place of care
Although clinicians may find it easier to monitor the mother and her foetus in a hospital, a recent Cochrane review suggests that pregnant women might have different preferences and views (Abou El Senoun et al. 2010). The counselling of women with PPROM is based on clinical experience and considers flexibility according to patient wishes (Abou El Senoun et al. 2010; Sciscione 2010). The challenge is to advise hospitalisation for women at high risk for complications that require immediate attention and outpatient care for women at low risk of complications. However, little is known about the potential risk factors for major complications, such as infection, umbilical cord prolapse and placental abruption that necessitate immediate interventions including unplanned delivery. The objective of this study is to describe the course of pregnancies with PPROM between 22 and 33 weeks’ gestation that were managed expectantly in a hospital and to identify the clinical risk factors for major complications before planned delivery to assess whether these major complications are predictable.
Materials and methods Introduction
Study population
Pre-term pre-labour rupture of membranes (PPROM) before 37 weeks’ gestation complicates between 1 and 3% of all pregnancies and accounts for approximately 30% of all pre-term deliveries (Goldenberg et al. 2008; Buchanan et al. 2010). PPROM before 34 weeks’ gestation is associated with serious complications, such as chorioamnionitis, umbilical cord complications and placental abruption, and is an important cause of peri-natal morbidity and mortality (Mercer 2003; Goldenberg et al. 2008; Beck et al. 2010). Even when serious pregnancy complications are not present, PPROM has been demonstrated to be associated with a higher rate of adverse neonatal outcomes than spontaneous low-risk preterm deliveries (Melamed et al. 2011). In the management of women with PPROM, the objective is to maximise the benefits of foetal maturation while avoiding the potential harms of remaining in utero (Buchanan et al. 2010). Women with PPROM before 34 weeks’ gestation are typically managed expectantly in hospitals (Fox et al. 2009; Maloni 2011; Bendix et al. 2014). The optimal settings are unknown, whether hospital or outpatient, for detecting the early signs and symptoms of complications during PPROM (Abou El Senoun et al. 2010).
We conducted a retrospective cohort study with data from the medical records of women with PPROM between 22 and 33 weeks’ gestation (Figure 1) who were admitted to the Obstetric Clinic, a tertiary referral unit at Rigshospitalet, University of Copenhagen, from January 2006 to December 2010. All women with PPROM from the catchment area and women with PPROM before 28 weeks’ gestation from other hospitals in Eastern Denmark, Greenland and the Faroe Islands were admitted. PPROM was diagnosed by the presence of amniotic fluid at speculum examination and ultrasonographic signs of oligohydramnios. Gestational age was calculated from an early ultrasonographic estimation of crown–rump length.
Standard procedure for PPROM All included patients with PPROM received standard antibiotic treatment; three intravenous treatments with a combination of ampicillin and metronidazole within the first 24 h and subsequent oral treatment three times a day for six days.
Correspondence: Dr Jane Marie Bendix, RM, MHS, Department of Gynecology and Obstetrics, Nordsjaellands Hospital, University of Copenhagen, Dyrehavevej 29, Hillerod 3400, Denmark. E-mail: [email protected]
2 J. M. Bendix et al.
Audit of cases with major complications We conducted a structured qualitative audit of the major complications before planned delivery to assess whether prediction of these complications was possible. The time intervals between the displays of signs or symptoms to the diagnoses of any major complications were recorded. Furthermore, we recorded whether the maternal subjective symptoms predicted the major complication. Pregnancy-related physical complaints or discomfort that resulted in specific notes in the medical records for which treatment was not initiated were registered as women’s needs for assessment. Less serious complications that were treated medically but did not necessitate unplanned delivery were registered as supplemental medical treatments.
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Statistical analyses
Figure 1. Flowchart of included women with PPROM GA 22-33.
A single course of corticosteroids was administered intramuscularly twice at a 24-h interval from gestational age of 24 0 weeks (Crowley 1996). The women with PPROM were managed expectantly as inpatients with strict activity restriction (Sciscione 2010). They received a DVD with specific instructions for physical exercise during bed rest. Daily cardiotocography (CTG) was performed and rectal temperature was monitored twice daily. The recommendations of strict activity restriction and daily CTG were based on traditionbased best clinical practice. Tocolysis with atosiban or indomethacin was administered only to gain effect from corticosteroid treatment or in cases of pre-term labour at very early gestational ages. Planned delivery was recommended at 34 weeks’ gestation.
Data collection From the medical records, we retrieved information about the date and time of PPROM, admission, onset of major complications, labour and delivery. We had specific information about tocolysis following PPROM, the mode of delivery, the gestational age at delivery, the birth weight, the Apgar score, stillbirth and neonatal death. We retrieved information about potential risk factors for major complications: gestational age at PPROM, maternal age, parity, plurality, infertility treatment, transferral, vaginal bleeding before PPROM, the ‘women’s calls for immediate medical assessment’, supplemental medical treatment, smoking, partner status and body mass index kg/m2.
Major complications before planned delivery Major complications were defined as conditions that necessitated unplanned delivery. Major complications included acute placental abruption, chorioamnionitis, umbilical cord prolapse, pathological foetal heart rate, prolapse of foetal extremities in the vagina, severe vaginal bleeding without a specific origin, abnormal umbilical flow, foetal death, incomplete twin delivery, maternal lung oedema and maternal appendicitis.
The rates of the maternal, obstetrical and neonatal characteristics were calculated as percentages or medians or mean values with standard deviations and stratified by gestational age at PPROM (22–23, 24–27, 28–31, 32–33 weeks’ gestation). The Pearson’s chi-squared test was used to examine independence within the contingency tables. The hazard ratios (HRs) for major complications before labour were estimated according to the potential risk factors using a Cox regression model. The potential risk factors were all considered in a multivariable Cox regression analysis. The unadjusted and the mutually adjusted associations between the potential risk factors are presented as HRs with 95% confidence intervals (CIs). Statistical significance was defined as a two-sided P value less than 0.05. All analyses were performed using SPSS statistical software version 20.0 (IBM SPSS Statistics). The Danish Data Protection Agency (J.nr. 2011-41-7010) and the Danish Health and Medicines Authority (J.nr. 3–3013-8/1/ EHE) approved the study. We notified a regional committee on biomedical research ethics about this study, and approval is not required for studies based on registries and medical records in Denmark (P.nr. H-2-2011-130).
Results Overall, 234 women with PPROM between 22 and 33 weeks’ gestation were included. The mean gestational age at PPROM was 27.6 weeks’ gestation (SD 4.4). The maternal and obstetric characteristics by gestational age at PPROM are summarised in Table I.
Obstetrical and peri-natal outcomes One hundred and six women (45%) gave birth within three days of PPROM. Forty-two women (18%) reached 34 weeks’ gestation and were induced or delivered by elective caesarean section. Overall, 102 (44%) women had emergency caesarean sections and 35 (15%) had emergency caesarean sections before the onset of labour. The maternal and neonatal outcomes are shown in Table II.
Major complications Overall, 84 women (36%) encountered one or more major complications. Among the 111 women with PPROM before 28 weeks’ gestation, there were 71 major complications (64%), and among the 123 women with PPROM at 28 weeks’ gestation or later, there were 13 major complications (11%). Of the major complications, 38 (45%) occurred within 3 days after PPROM, whereas 21 (25%) occurred 12 days or more after PPROM. The types of complications by gestational age at PPROM are illustrated in Table III.
PPROM and major complications before planned delivery 3 Table I. Maternal and obstetrical characteristics by gestational age at PPROM. Gestational age in weeks at PPROM
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Overall Maternal age (years) 24 25–29 30–34 35 Nulliparious Singleton pregnancy Infertility treatment*
Vaginal bleeding prior to PPROM* Transferrals Body Mass Index kg/m2,* 25 25–29.9 30 Smoking during pregnancy* Cohabitant with partner*
Total
22 23 n (%)
24 27 n (%)
28 31 n (%)
32 33 n (%)
22 33 n (%)
37 (16)
74 (32)
50 (21)
73 (31)
234 (100)
1 (3) 5 (14) 15 (41) 16 (43) 13 (36) 31 (84) 5 (14) 14 (38) 27 (73)
10 (13) 13 (18) 26 (35) 25 (34) 38 (51) 58 (78) 10 (14) 21 (28) 51 (69)
4 (8) 17 (34) 13 (26) 16 (32) 37 (74) 33 (66) 15 (31) 6 (12) 16 (32)
4 (6) 19 (26) 28 (38) 22 (30) 48 (67) 51 (71) 14 (19) 3 (4) 25 (34)
19 (8) 54 (23) 82 (35) 79 (34) 136 (59) 173 (74) 44 (19) 44 (19) 119 (51)
18 (49) 12 (35) 4 (12) 4 (12) 26 (87)
47 (64) 18 (25) 6 (9) 18 (26) 55 (89)
35 (70) 8 (17) 5 (10) 6 (13) 35 (85)
53 (73) 15 (21) 3 (4) 8 (11) 59 (91)
153 (65) 53 (24) 18 (8) 36 (16) 175 (88)
*Totals may vary as data were missing for some categories.
Overall, there were 38 cases (16%) of chorioamnionitis, 29 cases (12%) of foetal distress, 9 cases (4%) of placental abruption and 6 cases (3%) of cord prolapse (Table III). Some women encountered more than one specific major complication. One
woman declined induction of labour at 34 weeks’ gestation and sustained severe chorioamnionitis at 35 weeks’ gestation. There were no cases of deep vein thrombosis or maternal deaths before delivery. However, a woman with serious drug abuse died from
Table II. Maternal and neonatal outcomes by gestational age of PPROM. Gestational age in weeks at PPROM
Overall Tocolysis after PPROM Supplemental medical treatment Latency time from PPROM to delivery 24 h 1–2 days 3–5 days 6–8 days 9–11 days 12 days Onset of labour Spontaneous Induction Emergency caesarean before labour Mode of delivery* Vaginal Caesarean section Emergency Elective Deliveries at 34 weeks Deliveries with adverse neonate outcome€ GA at delivery (weeks) mean SD Neonatal outcome Newborns Birth weight (g) mean SD Neonates with adverse outcome € Apgar score, 7 at 5 min# UApH 7.15§ Antenatal deaths Peri- and neonatal deaths
Total
22 23 n (%)
24 – 27 n (%)
28 – 31 n (%)
32 – 33 n (%)
22 – 33 n (%)
37 (16) 14 (38) 12 (32)
74 (32) 39 (53) 13 (18)
50 (21) 21 (42) 4 (8)
73 (31) 33 (45) 1 (1)
234 (100) 107 (46) 30 (13)
2 (5) 5 (14) 4 (11) 3 (8) 3 (8) 20 (54)
13 (17) 10 (14) 11 (15) 9 (12) 10 (14) 21 (28)
14 (28) 10 (20) 4 (8) 5 (10) 2 (4) 15 (30)
37 (51) 15 (20) 11 (15) 6 (8) 2 (3) 2 (3)
66 (28) 40 (17) 30 (13) 23 (10) 17 (7) 58 (25)
29 (78) 4 (11) 5 (14)
50 (68) 3 (4) 18 (24)
40 (80) 3 (6) 4 (8)
46 (63) 14 (19) 8(11)
165 (71) 24 (10) 35 (15)
20 (54)
32 (43)
31 (62)
44 (60)
127 (54)
17 (46) 0 0 18 (49) 25.3 2.3
43(58) 2 (3) 4 (5) 17 (23) 26.9 2.5
17(34) 3 (6) 6 (12) 2 (4) 31.1 1.6
26 (36) 4 (6) 32 (44) 7 (10) 32.9 0.7
102 (44) 9 (4) 42 (18) 44 (19) 29.4 3.5
43 (100) 675 220 21 (49) 18 (42) . 4 (9) 9 (21)
91 (100) 963 298 18 (20) 11 (12) 5 (6) 3 (3) 5 (5)
68 (100) 1717 349 2 (3) 0 2 (3) 0 0
95 (100) 1854 322 8 (8) 0 7 (7) 0 1 (1)
297 (100) 1411 573 49 (17) 29 (10) 15 (5) 7 (2) 15 (5)
* Five women delivered first twin vaginally and the second twin by caesarean. #Apgar score were missing for 30 neonates. §Umbilical cord arterial pH were missing for 73 neonates. €Adverse neonatal outcome; low apgar score ( 7 at 5 min.), low umbilical cord arterial pH ( 7.15), ante-, peri- or neonatal death.
4 J. M. Bendix et al. Table III. Major complications by gestational age at PPROM.
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Gestational age in weeks at PPROM
Women with major complications Placental abruption Chorioamnionit Cord prolapse Foetal distress Vaginal bleeding (abruption not suspected) Prolapse of extremities Other complications* Diagnosis of major complication initiated by Symptoms, subjective Signs, objective Unknown Latency time from PPROM to major complication 24 h 1–2 days 3–5 days 6–8 days 9–11 days 12 days Time interval from symptoms to diagnosis Immediate ( 1 h) Hours ( 1 h) Days Time from diagnosis to delivery 1 h 1 – 2 h 2 h
Total
22 – 23 n (%)
24 – 27 n (%)
28 – 31 n (%)
32 – 33 n (%)
22 – 33 n (%)
28 (33) 3 (11) 16 (57) 0 9 (32) 2 (7) 1 (4) 3 (11)
43 (51) 5 (12) 18 (42) 5 (12) 10 (23) 5 (12) 4 (9) 6 (14)
7 (8) 1 (14) 4 (57) 0 6 (86) 0 0 0
6 (7) 0 0 1 (17) 4 (67) 0 0 1 (17)
84 (100) 9 (11) 38 (45) 6 (7) 29 (35) 7 (8) 5 (6) 10 (12)
21 (78) 6 (21) 1 (4)
35 (81) 8 (19) 0
4 (57) 2 (29) 1 (14)
2 (33) 4 (67) 0
62 (74) 20 (24) 2 (2)
5 (18) 1 (3) 4 (14) 3 (11) 1 (4) 14 (50)
15 (35) 8 (18) 3 (7) 6 (14) 6 (14) 5 (12)
1 (13) 2 (29) 0 2 (29) 0 2 (29)
3 (50) 3 (50) 0 0 0 0
24 (29) 14 (17) 7 (8) 11 (13) 7 (8) 21 (25)
16 (59) 6 (22) 5 (19)
24 (60) 5 (12) 11 (28)
4 (67) 2 (33) 0
5 (83) 1 (17) 0
49 (62) 14 (18) 16 (20)
4 (14) 5 (18) 19 (68)
5 (12) 9 (21) 29 (67)
0 2 (29) 5 (71)
2 (33) 1 (17) 3 (50)
11 (13) 17 (20) 56 (67)
omen may encounter more than one complication, hence the sum of the different complications may exceed the number of women W with major complications. *Other complications, abnormal umbilical flow, foetal death, maternal lung oedema and appendicitis.
multiple organ failure on the first day after delivery following severe chorioamnionitis and intrauterine foetal death. The interval between the occurrence of symptoms and the diagnosis of major complications was less than 1 h for 49 patients (62%), and 11 patients (13%) delivered within 1 h of the occurrence of symptoms (Table III). Sixty-two of these complications (74%) were detected as subjective symptoms. Fifty-six women (67%) had latencies of more than 2 h from the diagnosis of a major complication to delivery (Table III).
Potential risks of major complications Table IV shows crude and mutually adjusted HRs for major complications. Nulliparous women (adjusted HR: 2.76; 95% CI: 1.15–6.64) had a significantly increased risk of major complications. The incidence rates (IR) of major complications by gestational age at PPROM were high in the first three days after PPROM and decreased with latency from PPROM. Overall, the IR was 5%, and this rate was higher when PPROM occurred before 28 weeks (Table V). Therefore, we compared the incidences of major complications between the women with PPROM before 28 weeks’ gestation and those with PPROM at 28 weeks’ gestation or later (Table VI). The rate of precipitated deliveries (less than 2 h from diagnosis of a major complication or the onset of labour) was higher among the women with PPROM before 28 weeks’ gestation (Table VI). The crude risk factors for major complications among the 116 women who did not deliver within 3 days following PPROM are shown in Table VII. Only PPROM before 28 weeks’ gestation
(OR: 9.7, 95% CI: 1.7–54.1) remained a significant risk factor for major complications after mutual adjustment for all risk factors (Table VII). For all women with major complications the risk of their neonates having an adverse outcome was significantly raised (OR: 5.4; 95% CI: 2.7–10.9); when we stratified the gestational age at PPROM earlier or later than 28 weeks’ gestation the risk remained significantly raised for the early PPROM with (OR: 3.9, range: 1.5–10.5), but not for the late PPROM (data not shown).
Discussion Our study describes the courses of pregnancies with PPROM between 22 and 33 weeks’ gestation that were managed expectantly in a tertiary hospital setting until 34 weeks’ gestation. We identified clinical risk factors for major complications before planned delivery. The present study offers new insights into major maternal and foetal complications in the latency following PPROM, which are the main reason for hospitalisation of women with PPROM. The majority of other related studies have focused on the effect of PPROM duration on neonatal outcomes (Manuck et al. 2009; Melamed et al. 2011; Nayot et al. 2012; Frenette et al. 2013; van der Heyden et al. 2013). Our study population was treated according to standard guidelines, which were unchanged during the study period. One limitation is that this observational study was based on a consecutive sample of cases from a tertiary hospital that included
PPROM and major complications before planned delivery 5 Table IV. Risk factors of major complications in pregnancies with PPROM.
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No major complication n (%) Total PPROM (Gestational age in weeks) 22–23 24–27 28–31 32–33 Maternal age (years) 24 25–29 30–34 35 Parity* Nulliparous Multiparous Pregnancy* Singleton Multiple Infertility treatment* No Yes Transferral No Yes Vaginal bleeding prior to PPROM No Yes Women’s need of assessment* None 1–2 3–4 5 Supplemental medical treatment* None 1–3 Smoking status* Non-smokers Smokers Partner status* Cohabitant Single status Body Mass Index kg/m2* 25 25–29.9 30
Major complication n (%)
Crude hazard ratio (95%CI)
Ajusted hazard ratio (95%CI)
150 (64)
84 (36)
9 (24) 31 (42) 43 (86) 67 (92)
28 (76) 43 (58) 7 (14) 6 (8)
2.43 (0.90–6.53) 2.88 (1.11–7.46) 0.85 (0.26–2.71) 1
1.73 (0.47–6.35) 2.22 (0.68–7.27) 0.75 (0.18–3.10) 1
12 (63) 38 (70) 58 (71) 42 (53)
7 (37) 16 (30) 24 (29) 37 (47)
0.95 (0.38–2.35) 1 0.95 (0.48–1.85) 1.12 (0.60–2.09)
0.38 (0.09–1.8) 1 0.48 (0.18–1.31) 1.45 (0.56–3.76)
100 (74) 49 (51)
36 (26) 47 (49)
1.05 (0.66–1.58) 1
2.76 (1.15–6.64) 1
105 (61) 44 (73)
68 (39) 16 (27)
1 1.50 (0.81–2.78)
1 2.50 (0.87–7.16)
117 (63) 32 (73)
69 (37) 12 (27)
1 0.85 (0.45–1.61)
1 0.49 (0.19–1.24)
90 (78) 60 (50)
25 (22) 59 (50)
1 1.80 (1.08–3.02)
1 1.88 (0.84–4.20)
134 (71) 16 (36)
56 (29) 28 (64)
1 1.21 (0.75–1.95)
1 1.84 (0.84–4.20)
93 (71) 32 (64) 11 (39) 7 (47)
38 (29) 18 (36) 17 (61) 8 (53)
1 0.58 (0.32–1.05) 0.85 (0.47–1.55) 0.43 (0.19–1.00)
1 0.61 (0.25–1.45) 1.55 (0.57–4.08) 0.59 (0.19–1.83)
131 (68) 12 (40)
63 (32) 18 (60)
1 0.66 (0.38–1.17)
1 0.50 (0.21–1.20)
128 (68) 19 (53)
59 (32) 17 (47)
1 1.86 (1.05–3.31)
1 1.35 (0.48–3.78)
116 (66) 13 (57)
59 (34) 10 (43)
1 1.38 (0.68–2.80)
1 1.79 (0.53–6.03)
112 (71) 23(47) 10 (56)
45 (29) 26 (53) 8 (44)
1 1.42 (0.86–2.35) 1.45 (0.65–3.24)
1 1.37 (0.63–2.96) 0.58 (0.15–2.67)
*Totals may vary as data were missing for some categories. Ajusted HR, mutually ajusted.
women from the local catchment area and transferrals from other hospitals. We identified PPROM before 28 weeks’ gestation as the adjusted risk factor for major complications. The accumulation of major complications before 28 weeks’ gestation, mainly chorioamnionitis, may indicate that choriodecidual infection or inflammation play more important roles (Mercer 2003) in women with early PPROM than those with late PPROM and that the prescribed standard treatment with antibiotics is insufficient in early PPROM. The risk factors may be useful for individual management and for choosing the optimal place of care during latency. Hospitalisation during the expectant management of PPROM is recommended by the American College of Obstetricians and Gynecologists (ACOG 2013), whereas The Royal College of Obstetricians and Gynaecologists guidelines are equivocal regarding a recommendation for the place of care, however without providing specific criteria (RCOG 2010).
Twenty-one years ago, Carlan et al. (1993) randomised women with PPROM before 37 weeks’ gestation to outpatient (n 28) versus hospital (n 27) management and found no difference in latencies or neonatal outcomes. Similarly, a non-randomised retrospective cohort study of selected women with PPROM before 34 weeks’ gestation who had not delivered after 72 h revealed no differences in major adverse maternal or peri-natal outcomes between those who were cared for in hospital (n 91) and those in an outpatient setting (n 53) (Beckmann and Gardener 2013). We performed an audit to examine whether the major complications that occur during hypothetical home care are predictable. To assess the risk of home care, we estimated the reduction in complications rates using several cut-offs that are based on gestational age at PPROM and latency (Table VI). We found that major complications occurred more often in the first days after PPROM and that the rate was higher in early than in late PPROM. If home care were introduced to women with PPROM before 28 weeks’ gestation with
5 (84/1866.8) 99 (24/24.2) 25 (14/56.6) 8 (7/92.8) 7 (11/166.5) 6 (7/116.1) 1 (21/1410.6) 2 (1/59.7) 0 (0/7.8) 11 (1/9.1) 0 (0/20.6) 0 (0/22.2) 0 (0/0) 0 (0/0) 6 (5/87.4) 41 (3/7.4) 33 (2/6.0) 0 (0/16.2) 0 (0/14.1) 0 (0/17.6) 0 (0/26.1)
Table VI. Major complications according to latency from PPROM to onset of major complications or labour. Major Precipitated Total GA at Days after Overall complications deliveries* latency Incidence 2 h n (%) (days) PPROM PPROM (n) n (%) rate 22–27
28–33
1 (2/150.5) 0 (0/1.2) 11 (1/9.1) 0 (0/8.3) 6 (1/17.9) 0 (0/8.1) 0 (0/105.9)
Total 33
All 1 3 6 9 12 All 1 3 6 9 12
111 85 71 60 45 37 123 64 45 32 21 17
71 (64) 51 (60) 42 (59) 35 (58) 26 (58) 19 (51) 13 (11) 9 (14) 4 (9) 4 (13) 2 (10) 2 (12)
23 (21) 16 (19) 15 (21) 13 (22) 9 (20) 7 (19) 11 (10) 4 (6) 2 (4) 2 (6) 2 (10) 1 (6)
1306.3 1308.4 1283.3 1239.1 1139.8 1059.1 542.3 524.6 492.9 444.4 377.0 341.5
5% 4% 3% 3% 2% 2% 2% 2% 1% 1% 1% 1%
3 (7/202.1) 400 (2/0.5) 24 (1/4.2) 0 (0/3.8) 4 (2/26.5) 9 (1/10.8) 1 (1/156.3)
1 (1/110.9) 0 (0/0.4) 0 (0/3.0) 0 (0/0) 0 (0/6.0) 0 (0/0) 1 (1/101.5)
2 (3/105.8) 0 (0/1.1) 34 (1/2.9) 0 (0/0) 14 (1/7.2) 0 (0/0) 1 (1/94.6)
3 (1/39.0) 133 (1/0.8) 0 (0/1.5) 0 (0/3.6) 0 (0/0) 0 (0/9.7) 0 (0/23.4)
* Precipitated deliveries less than 2 h from onset of major complication or labour.
acency time from PPROM to onset of major complication or labour. L Incidence rate (IR) (number of major complications/accumulated latency time in days).
10 (10/102.1) 222 (2/0.9) 80 (2/2.5) 8 (1/11.9) 9 (1/11.0) 10 (2/19.5) 4 (2/56.3) 7 (13/180.0) 563 (9/1.6) 33 (1/3.0) 0 (0/0) 9 (2/22.1) 9 (1/11.0) 0 (0/142.3) 5 (18/341.5) 6 (13/208.7) 800 (4/0.5) 200 (2/1.0) 0 (0/1.0) 34 (4/11.8) 25 (4/15.9) 16 (2/12.5) 11 (3/26.9) 20 (1/5.0) 12 (1/8.5) 6 (2/30.9) 2 (6/288.7) 1 (2/147.5) 4 (10/279.1) 100 (1/1.0) 40 (1/2.5) 0 (0/0) 0 (0/7.6) 0 (0/0) 3 (8/268.0) Overall IR % Latency time 24 h, IR 1–2 days, IR 3–5 days, IR 6–8 days, IR 9–11 days, IR 12 days, IR
30 29 28 27 22
23
24
25
26
Gestational age at PPROM
Table V. Incidence rate of major complications according to gestational age at PPROM.
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31
32
6 J. M. Bendix et al.
latency of nine days or more and to women with PPROM between 28 and 33 weeks’ gestation with latency of 3 days or more, a total of 1633 days would be spent at home. This home care would also result in 30 major complications at home (1 per 54 days). However, even with the low incidence of 2% in the PPROM before 28 weeks’ gestation with latencies of 9 days or more, there would still be 26 (58%) major complications (1 per 44 days) at home and 9 (20%) precipitated deliveries below 2 h. In contrast, among the cases of PPROM at 28 weeks’ gestation or later, only 4 (9%) major complications (1 per 123 days) and 2 (4%) precipitated deliveries would have occurred at home. The questions arise of how many major complications at home are acceptable and the extent to which the results and prognoses of these cases would have been better had the mothers been cared for in a hospital. To minimise the number of major complications in PPROM cases before 28 weeks’ gestation, inpatient care should last for 8 days or more, and the risk factors for major complications should be considered. Alternatively, women with PPROM before 28 weeks’ gestation should remain hospitalised until delivery. For women with PPROM at 28 weeks’ gestation or later, home care seems to be quite safe after 3 days of inpatient care regardless of the risk factors. Several studies have shown that women who are hospitalised during labour are exposed to a greater number of interventions than women who experience labour and delivery at home (Janssen et al. 2009; Blix et al. 2012). The interventions due to complications in our study might have been needed and appropriate, but we cannot be certain that they were all necessary or would have been performed if the women had been cared for at home. An additional concern regarding outpatient management is that treatments for major complications might be delayed if the patient is at home (Ellestad et al. 2008; Abou El Senoun et al. 2010). However, Carlan and colleagues argue that emergency conditions occur at a reasonable level in carefully selected patients (Carlan et al. 1993; Bartfield and Carlan 1998).
Conclusion More than half of the women delivered more than three days after PPROM, and this proportion decreased with gestational age at PPROM. One-third of the women experienced one or more major complications before planned delivery. The complication rate was 64% in the women with PPROM before 28 weeks’ gestation compared with a rate of 11% in the women with PPROM at 28 weeks’ gestation or later. Women with late PPROM who do not deliver within the first few days had a reduced risk of major complications.
PPROM and major complications before planned delivery 7 Table VII. Risk factors of major complications in PPROM GA 22–33 and latency 2days.
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No major complication n (%) Total PPROM (Gestational age in weeks) 22–27 28–33 Maternal age (years) 24 25–29 30–34 35 Parity* Nulliparous Multiparous Pregnancy Singleton Multiple Infertility treatment* No Yes Transferral No Yes Vaginal bleeding prior to PPROM No Yes Women’s need of assessment* None 1 – 2 3 – 4 5 Supplemental medical treatment* None 1–3 Smoking status* Non-smokers Smokers Partner status* Cohabitant Single status Body Mass Index kg/m2* 25 25
Major complication n (%)
Crude OR (95%CI)
Ajusted OR (95%CI)
70 (60)
46 (40)
29 (41) 41 (91)
42 (59) 4 (9)
8 (57) 12 (63) 28 (74) 22 (49)
6 (43) 7 (37) 10 (26) 23 (51)
NS 1 NS NS
NS 1 NS NS
39 (72) 30 (50)
15 (28) 30 (50)
NS 1
NS 1
59 (59) 11 (69)
41 (41) 5 (31)
1 NS
1 NS
58 (60) 12 (71)
38 (40) 5 (29)
1 NS
1 NS
37 (76) 33 (49)
12 (24) 34 (51)
1 3.18 (1.42–7.13)
1 NS
57 (69) 13 (39)
26 (31) 20 (61)
1 3.37 (1.46–7.80)
1 NS
29 (63) 24 (71) 8 (36) 6 (55)
17 (37) 10 (29) 14 (64) 5 (45)
1 NS 0.71 (0.28–1.84) 2.99 (1.04–8.57) NS 1.42 (0.38–8.57)
1 NS NS NS
56 (64) 11 (42)
31 (36) 15 (58)
1 2.46 (1.01–6.02)
1 NS
58 (65) 9 (47)
31 (35) 10 (53)
1 NS
1 NS
51 (59) 5 (63)
36 (31) 3 (43)
1 NS
1 NS
48 (71) 20 (48)
20 (29) 22 (52)
14.85 (4.79–45.98) 1
1 2.64 (1.19–5.87)
9.69 (1.73–54.11) 1
1 NS
justed OR, mutually ajusted. A NS, not statsitically significant. *Totals may vary as data were missing for some categories.
In clinical practice these women might be offered home care. Large pragmatic controlled trials are required to evaluate whether home care is a superior alternative to hospital care for women with late PPROM who did not deliver within the first few days. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper. The study was supported by grants from the Nordsjaellands Hospital, Hillerod, University of Copenhagen, Denmark; TrygFonden; Lundbeckfonden and the Danish Association of Midwives.
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