Management of Mid-Trimester Premature Rupture of Membranes: Intention to Treat.

ByDr. Alexander E. Omu MBBS, FMCOG, FWAS, FICS,

FRCOGProfessor. Department of Obstetrics and

Gynaecology,Faculty of Medicine

Kuwait University, Senior ConsultantMaternity Hospital. Kuwait

Prepared for

Objectives of the presentation

1. Definitions2. Introduction3. Etiology of PROM4. Diagnosis5. Clinical course of PPROM6. Management of PPROM Use of corticosteroids Antibiotic therapy Tocolysis Amnioinfusion Cervical plugging7. Adjuncts to Management8. Special circumstances affecting the

Management. Multiple Pregnancy Cervical Cerclage9. Areas of future research10. 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 ☺ Significant contribution to perinatal mortality. ☺. 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. 44A 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.

Intubated preterm baby in an incubator

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: 576-83Carrol 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: 206-215

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

1. History of Drainage of liquor2. Sterile speculum examination- visual observation of direct flow from cervix and pooling in posterior fornix.3. Ferning test4. Nitrazine test5. Amnisure6. Fetal fibronectionBiomaker of impeding labour

Prolactin -fetal protein

UltrasoundWeekly HVSWeekly CBCNSTBPP or Modified BPPVital signs***Routine AmniocentesisNot recommended

Digital examination be avoided

DIAGNOSIS OF PPROM

RCOG (2006);Guideline No. 4493.1% positive

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; 184:368-736. 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 asuggestion 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.

 

Spontaneous labor 29 (50.9)

Chorioamnionitis 18 (31.6)

Nonreassuring fetal testing 5 (8.8)

Intrauterine fetal demise 5 (8.8)

Indications for Delivery among Patients with PPROM from 14 to 23 Completed Weeks' Gestation*

Falk et al. J. Perinatol 2004; 24: 611–616.

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.

14-16 weeks 17-19 weeks 20-23 weeks 24+ week delivery only

0

5

10

15

20

25

30

35

8.3

13

29.7

00 0

5.7

28.6

Survival at gestation of PROM

Survival at gestation at Delivery

Surv

ival

Per

cent

age

(%)

Fig 2 Perinatal outcome according to gestation at Midtrimester PROM and Delivery

Outcome of Expectant Managemennt of Midtrimester PPROMA plea for limits1 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.

A. Mitrimester PPROM in TWINS/Higher order ***Counseling1. Termination of pregnancy if symptomatic2. 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.

Special considerationsOthers1. Infertility Male factor Many failures2. Cervical Cerclage

removal3 Older women4 Patient’s wish5 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

Conclusions1.Early Diagnosis and surveillance2.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.

Albert Einstein Wiston Churchill Charles Darwin Isaac

Newton4. Don’t Abort Destiny.

4. What is common among these men?

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