Management of Mid-Trimester Premature Rupture of
Membranes: Intention to Treat.
By
Dr. Alexander E. Omu MBBS, FMCOG, FWAS, FICS, FRCOG
Professor. Department of Obstetrics and Gynaecology,
Faculty of Medicine
Kuwait University, Senior Consultant
Maternity Hospital. Kuwait
Prepared for
Objectives of the presentation
1.
2.
3.
4.
5.
6.
Definitions
Introduction
Etiology of PROM
Diagnosis
Clinical course of PPROM
Management of PPROM
Use of corticosteroids
Antibiotic therapy
Tocolysis
Amnioinfusion
Cervical plugging
7. Adjuncts to Management
8. Special circumstances affecting the
Management.
Multiple Pregnancy
Cervical Cerclage
9. Areas of future research
10. Conclusion
Introduction
☺ Dilemma of Management of Midtrimester preterm
premature rupture of membranes (PPROM)
Lack of consensus on the management.
An increased risk of
Early Preterm Birth and Extreme prematurity
Fetal infectious morbidity,
Pulmonary hypoplasia,
Skeletal deformities and
Potter's facies.
☺ Maternal infections and the sequelae
Intubated preterm baby in an
☺ Significant contribution to perinatal mortality.
incubator
☺. The aim of expectant management is to extend
latency and to maximize gestational age at delivery.
☺. Advances in obstetric and neonatal care continue
to improve outcomes for extremely premature infants
with use of surfactant agents, maternal steroids, and
advancements in neonatal technologies.
RCOG(2006): Preterm Prelabour Rupture of Membranes. Guidelines No. 44
A C OG (2007). Premature rupture of membranes. ACOG Practice Bulletin No. 80.
Obstetrics and Gynecology, 109: 1007–19.
A C OG (2008). Use of progesterone to reduce preterm birth. ACOG Committee Opinion
No. 419. Obstetrics and Gynecology, 112: 963–965.
Definition
☺ Premature rupture of membranes prior to onset of labour regardless of the gestation
☺Preterm premature rupture of membranes (PPROM) rupture of the fetal
membranes before the onset of labor at less than 37 weeks gestation.
☺ The accepted limit of viability is 24 weeks of gestation, with scattered reports
of survivors at 21-23 weeks
☺ Midtrimester (Previable) PPROM at 14-<24 weeks
☺ Incidence of PPROM is approximately 1-4 % of all pregnancies and about
30-40 % of all preterm deliveries.
☺ Midtrimester PPROM is 10-18 % of PPROM
Maxwell GL. Obstet Gynecol Surv 1993;48: 576-83
Carrol et al. CurrOpin Obstet Gynecol1996;11:441-8
Aetiology of PPROM
Bryant-Greenwood and Millar .. Biol Reprod 2000; 63:1576-1579.
Kumar et al. Placenta 2009; 30: 560-563.
Strohl et al.. Placenta 2010; 31: 18-24
Challis et al. Reproductive Sciences.2009; 16: 206215
Mechanisms ‘Physiology of PROM
☺ Rupture of the fetal membranes, term or preterm
Collagen remodeling, with activation of matrix metalloproteinases (MMPs), Relaxin
apoptosis and proinflammatory cytokines: TNF-, IL-1a and IL-8
Moore et al Placenta 2006; 27: 1037:1037-51
☺. Vaginally delivered AROM FM contain a weak zone overlying the cervix.
El Khwad et al.. J. Soc Gynecol Invest 2006; 13 :191-5
☺ Separation of the amnion from choriodecidua at delivery is almost universal.
Hypothesis that FM layer separation is part of the FM weakening process during normal
parturition.
Strohl et al. Placenta 2010;31:18-24
The sequence of FM rupture
Separation of amnion from choriodecidua occurs as part of
normal term FM rupture. FMs become significantly weaker as a
result of this separation.
☺ FM components stretch together under load;
☺ Amnion separates from choriodecidua;
☺ Choriodecidua ruptures;
☺ Amnion distends further, nonelastically; and
☺ Amnion ruptures.
Arikat et al.. Am J. Obstet Gynecol 2006; 194: 211-7
Effects of Stage of lung development
DIAGNOSIS OF PPROM
1. History of
Drainage of liquor
2. Sterile speculum
examination- visual
observation of direct
flow from cervix and
pooling in posterior
fornix.
3. Ferning test
4. Nitrazine test
5. Amnisure
6. Fetal fibronection
Biomaker of
impeding labour
Ultrasound
Weekly HVS
Weekly CBC
NST
BPP or
Modified BPP
Vital signs
***Routine
Amniocentesis
Not
recommended
Prolactin
-fetal protein
93.1% positive
Digital examination be avoided
RCOG (2006);Guideline No. 44
Management of Midtrimester PPROM: KEY POINTS
☺ Midtrimester PPROM is associated with the same risk factors as PPROM later in
gestation
☺ Approximately 75% of these women will deliver within 1 week of presentation.
☺ The frequency of chorioamnionitis is higher early in the latency period and at lower
residual amniotic fluid volumes
☺ Abruptio placentae and cord prolapse are more common in pregnancies complicated
by PPROM
☺ Neonatal survival is primarily related to gestational age at delivery, and is
comparable to that in preterm deliveries matched for gestational age without
PPROM.
☺. The neonatal risk of both pulmonary hypoplasia and musculoskeletal deformation
decrease with advancing gestational age, shorter latency, and greater residual
amniotic fluid volume.
☺. Maternal risks from midtrimester PPROM are lower than fetal/neonatal risks and
include infection, need for cesarean delivery, and need for classical hysterotomy.
☺. Absence of amniotic fluid leakage associated with resealing of membranes and
reaccumulation of amniotic fluid confers a prognosis comparable to that of
pregnancies without PPROM.
MANAGEMENT
☺ Prophylactic antibiotics. Erythromycin 250 mg 6 hourly for 10 days
Any pennicilin, Clindamycin and gentamycin; Increased latency period.
Usefulness proven by 22 RCTs in 6000 women- RCOG Guigeline No 36;
Kenyon et al ORACLE 1. Lancet 2001;979:357-60
☺. Antenatal corticosteroids from 24 weeks of gestation
Meta-analysis of 15 RCTs in 1400: Reduced risks of RDS, IVH and NEC
☺. Prophylactic tocolysis: In women with uterine activity and require transfer or
antenatal corticosteroids. No effect on latency period or reduce neonatal morbidity.
☺.Amnioinfusion. Not supported by Cochrane Review and many other studies. but a
recent study of 71 women with PPROM before 26 weeks showed intrauterine survival
was higher in treated group than in control group (64.8% vs 32.3 %, P<0.001)
De Santis et al. Fetal Diagn Ther 2003;18:412-17
☺. Fibrin glue to improve AFI and reduce Pulmonary hypoplasia. Some success stories.
Still needs more research.
Sciscione et al.. Am J. Obstet Gynecol 2001; 184:368-73
6. Outpatient monitoring- Rigorous selection process-
For children whose mothers had pPROM, the prescription of antibiotics seemed to
have little effect on the health and educational attainment of children at 7 years
which was surprising since antibiotics might have been expected to improve clinical
outcomes in this group as positive amniotic fluid cultures are found in 32% of
women at presentation, and in as many as 75% during subsequent labour. The
reasons for this are not clear but might be linked to the length of antibiotic
exposure which in this group of women was fairly short, since about 60% gave
birth within a week.
There is also evidence that antibiotics neither eradicate nor prevent intra–amniotic
infection.
For children whose mothers had spontaneous preterm labour the prescription of
erythromycin (with or without co-amoxiclav) was associated with an increase in the
proportions of children with any level of functional impairment from 38% to 42% (OR
1.18, 95% CI 1.02–1.37). Similarly proportions of children with cerebral palsy increased
from 1.7% to 3.3% (OR 1.93, 95% CI 1.21–3.09) associated with erythromycin and
from 1.9% to 3.2% (OR 1.69, 95% CI 1.07–2.67) with co–amoxiclav. There was a
suggestion that more children who developed cerebral palsy had been born to mothers
who had received both antibiotics.40 It is not clear why receipt of antibiotics increased
the risk of functional impairment and cerebral palsy. Rates of subclinical infection in this
group are found to be relatively low at 13–22%, and an absence of benefit is therefore
not unexpected, but evidence of harm is surprising.
Indications for Delivery among Patients with PPROM from 14 to 23 Completed
Weeks' Gestation*
Spontaneous labor
29 (50.9)
Chorioamnionitis
18 (31.6)
Nonreassuring fetal
testing
5 (8.8)
Intrauterine fetal
demise
5 (8.8)
The most common complications of neonates include respiratory distress syndrome
(RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and sepsis.
The maternal risks include the uterine infection and its sequelae.
Falk et al. J. Perinatol 2004; 24: 611–616.
Fig 2 Perinatal outcome according to gestation at Midtrimester PROM and Delivery
35
29.7
28.6
Survival Percentage (%)
30
Survival at gestation of PROM
Survival at gestation at Delivery
25
20
13
15
10
8.3
5.7
5
0
0
0
0
14-16 weeks
17-19 weeks
20-23 weeks
24+ week delivery
only
Outcome of Expectant Managemennt of Midtrimester PPROM
A plea for limits
1 Mean Maternal antenatal Hospital stay 21 days (2-35)
2. Cesarean section rate 33.7%
3. Postpartum infection morbidity 32.4%
And Neonatal complications
Pulmonary Hypoplasia
Respiratory Distress Syndrome
Potter”s facies
“in very early midtrimeste PPROM, the maternal complication rate outweighs the poor
neonatal outcome and expectant management should be reconsidered
Grisaru-Granosky et al. J. Perinatol 2003; 23:235-239.
OUTCOME OF MIDTRIMESTER PPROM
1. In three small studies of PROM managed expectantly,
(a) Perinatal survival ranged from 25% to 63%,
(b) Normal neurologic and physical development occurred in 55% to 68% of
survivors.
(c) Chorioamnionitis occurred in 41% to 77% of the patients in these studies.
Taylor and Garite . 1984; 64:615-20.
Major and Kitzmiller . Am J Obstet Gynecol 1990; 163:838-44.
2.
In 1993, Morales and Talley summarized six studies of expectant management
of midtrimester PROM that demonstrated neonatal survival ranging from 22% to
63%, with approximately 60% of survivors having normal development at I year.
Morales and Talley Am J Obstet Gynecol 1993; 168: 503-7.
3.
Mercer's analysis of four midtrimester PROM studies using age-specific survival
rates revealed a 23% rate of survival for PROM at 22 weeks EGA or earlier,
compared with 53.9% at 23 weeks or more.
Mercer BM. Obstet Gynecol Clin North Am 1992; 19:339-51.
Special considerations
A. Mitrimester PPROM in TWINS/Higher order
***Counseling
1. Termination of pregnancy if symptomatic
2. Conservative management:
Counselling
Consent .
Surveillance for chorioamnionitis
* Glucocorticoids at and beyond 24 week.
* Antibiotic:
Ampicillin
Amoxacillin
Erythromycin
Azithromycin .
Metronidazole
No Tocolysis
* Termination at 34 weeks unless indicated earlier.
3 Rescue of Twin 2 after spontaneous expulsion of twin 1.
antibiotics, corticosteroids and tocolysis (MgSO4
* Serial ultrasounds until 34 weeks to assess cervical length?
 Biophysical profiles (BPP) should begin at 28 weeks.
 Delivery plan should be at 34-35 weeks of gestation
1 de Jong et al. Eur J Obstet Gynecol Reprod Biol. 1995;63:91-4.
2 Jazayeri et al. J Reprod Med. 2002;47:167-9.
3. Mercer et al. Am J Obstet Gynecol. 1993;168:1467-73.
4. Preis et al. Ginekol Pol. 2004:966-70.
Others
1. Infertility
Male factor
Many failures
2. Cervical Cerclage removal
3 Older women
4 Patient’s wish
5 Ethics
Other factors affecting neonatal survival rates
☺ Socio-economic status
☺ Neonatal technology
☺ Use of surfactant
☺ Staff Expertise and training
☺ Time and Place:
EPICURE, EPIPAGE and EPILLI
☺ (a) Only 16% of those born at 22 weeks admitted to NICU, only 1% survived until
discharge. Of those born in the 23rd week, 54% were admitted to the neonatal
intensive care unit and only 11% survived.
(b) Neurological and developmental disability after extremely preterm birth (22–25
weeks) was observed in 49% of babies evaluated after 30 months.
Bodeau-Livinoc et al. Paediatrics: 2008; 122:1014-1021
☺. Other authors have concluded that expectant management of PPROM offers
better perinatal and long-term survival than previously believed. Of ten infants born
following successfully managed PPROM occurring 14-19 weeks, four were alive 5
years later, 3/4 had survived without any major impairment neurological impairment.
H Helmer. BJOG 2006; 113: 11-112
☺. In Germany, intervention is mandatory if there is even a small chance of survival.
Future Research
☺Role and Genetics of Relaxin, Fibulin and Matrix
metalloproteinases Family of Proteins
☺ Possible Drug Development to be used for prophylaxis
☺Research into resuscitation of extreme low birthweight babies.
☺Give every baby delivered alive a chance to live
Conclusions
1.Early Diagnosis and surveillance
2. Counselling and involvement of couple in decisions.
3. While PPROM at very early gestation is a serious complication
and a major management dilemma often associated with poor
outcome, the prognosis is not without hope.
4. What is common among these men?
Wiston Churchill
4.
Albert Einstein
Don’t Abort Destiny.
Charles Darwin
Isaac Newton
THANK YOU