Curtis R.Cook,M.D.Phoenix Perinatal Associates

Disclosures I have no relevant financial relationships to disclose or conflicts

of interest to resolve.

I will not discuss any unapproved or off label, experimental or investigational use of a product, drug, or device.

Definition: PROM Rupture of membranes before onset of labor

Term (37+ wks) 8% incidence

Preterm (<37 0/7 wks) pPROM 3% incidence 1/3 of all preterm births

Diagnosis: PROM History

Leaking throughout the day not related to voiding Physical

Sterile speculum exam unless delivery imminent Assess dilatation, prolapse, infection and culture

Digital exam associated with increased infection Alexander et al, AJOG 2000; 183: 1003-7

Pooling or free fluid from cervix with maternal effort Arborization (ferning) pH change (vag secretions 4.5-6; amniotic fluid 7.1-7.3)

Arborization (ferning)

Testing Limitations: PROM False positives

Blood Semen BV

False negatives Scant fluid from prolonged ROM Obscuring blood on slide

Other Tests: PROM Ultrasound mostly helpful if oligo (50-70%) Fetal fibronectin sensitive, but not nonspecific

Negative strongly suggestive of intact membranes Eriksen et al. Obstet Gynecol 1992; 80:451-4

New tests for specific amniotic proteins High sensitivity (>95%) with high false positives as well

Lee et al. J Mat Fet Neonat Med 2012; 25:1690-8 Senanayake. Sri Lanka J OBG 2013 Liang et al. J Obstet Gynecol Res 2014; 40: 1555

Adjunct tests for clinically unclear cases only

Term PROM Most are followed by spontaneous labor

If expectantly managed in a large clinical trial 50% delivered within 5 hrs 95% delivered within 28 hrs

Hannah el al. NEJM 1996; 1005-10

Increased risk for infection with longer delay

Management at Term Large meta-analysis (12 RCTs and >6K patients)

Induction reduced time to delivery and NICU admits Also reduced chorioamnionitis and endometritis No increase in CS or operative vaginal deliveries

Dare et al. Cochrane Reviews 2006, Issue 1

Largest trial also showed increased pt satisfaction Hannah et al. NEJM 1996;334:1005-10

Management at Term No benefit from antibiotics except for GBS Pitocin is preferred induction agent

PG associated with increased risk for chorio Hannah et al. NEJM 1996;334:1005-10

Expectant mgmt an option if clinically stable Patient should be counseled about risks

Induction should include at least 12-18 hrs of adequate labor before declaring failed and proceeding with CS Rouse et al. Obstet Gynecol 2011; 117:267-72

Dystocia!

Preterm PROM (pPROM) Risk factors include:

Prior history of pPROM (3x) Intraamniotic infection (earlier gestations) Bleeding in 2nd/3rd trimesters (3-7x) Short cervix Smoking (2-4x)

>50% will deliver within 1 week Mercer et al. Obstet Gynecol 2003;101:178-93

Latency inversely correlated with gest age of ROM Melamed et al. J Mat Fet Neonat Med 2009; 22:1051-6

Risks of pPROM Preterm labor

>50% deliver within 1 week Clinically evident infection 15-25%; higher early GA

Kenyon et al. Cochrane Reviews 2010, Issue 8 Abruption 2-5%

Ananth et al, Obstet Gynecol 2004; 104:71-7 Fetal death 1-2% (cord accident, infection, abruption)

Mercer et al. Lancet 1995; 346: 1271-9 Increased risk for developmental delay

Spinillo et al. BJOG 1995; 102:882-7

Management of pPROM Initial evaluation

Accurate gestational age Assessment of labor (toco) Assessment of fetal well-being (continuous FHR) Documentation of fetal position

EFW, fluid and placental location

Evaluation for infection or abruption Culture for GBS Decide delivery vs expectant management

Expectant Management Antenatal steroids Latency antibiotics Magnesium for neuroprotection (<32 wks) +/- tocolysis Daily fetal monitoring Daily maternal assessment

Serial WBC and inflammatory markers are nonspecific Neonatal consultation

Antenatal Steroids

Not a concern for maternal or neonatal infection Decreases neonatal mortality, RDS, IVH and NEC Recommended 24w0d-33w6d

Roberts et al. Cochrane Reviews 2006, Issue 3 May be considered as early as 23w0d

ACOG Obstet Gynecol 2015; 126:e82-94 May be given as late as 36w6d; don’t delay delivery

Gyamfi-Bannerman et al. NEJM 2016; 374: 1311-20

Latency Antibiotics Antibiotics

Reduces maternal and neonatal infections Increases latency period to delivery Reduces pooled neonatal morbidity

Kenyon et al. Cochrane Reviews 2010, Issue 8

MFMU trial with 2d IV Amp/Erythro and 5d po Mercer et al, JAMA 1997; 278: 989-95

No substitute for severe PCN allergy Still need GBS prophylaxis in labor if pos or unknown

Magnesium Neuroprotection Magnesium given before delivery <32 wks

Decreases moderate to severe CP (RR 0.71; CI 0.55-0.91) Doyle et al. Cochrane Reviews 2009, Issue 1

Largest trial (MFMU) 85% of patients had pPROM 6g load and then 2g/hr with assessment at 12 hrs Retreatment if needed (rebolus if off >6 hrs)

Rouse et al. NEJM 2008; 359: 895-905

Should establish a hospital protocol

Tocolysis Insufficient evidence to support/refute use in pPROM Meta-analysis showed increased latency and infection

Limited by only 2 trials using latency abx and steroids Mackeen et al. Cochrane Reviews 2011, Issue 10

Not indicated if active labor No prolongation of latency No improved neonatal outcomes

Garite et al. AJOG 1987; 157: 388-93

Delivery Timing: pPROM Expectant management <34 wks Delivery at 34 wks vs 37 wks decreases chorio

RR 0.31; CI 0.1-0.8 Underpowered to determine if reduces risk neo sepsis

RR 0.66; CI 0.3-1.5 van der Ham et al. AJOG 2012; 207: 276

Previable pPROM

Previable pPROM <1% of pregnancies Neonatal M&M decreases with increased latency

40-50% deliver < 1 wk and 70-80% <2-5 wks Muris et al. Eur J OBG Reprod Bio; 2007; 131: 163-8

Better survival if >22 wks vs <22 wks (57.7 vs 14.4%) Waters et al. AJOG 2009; 201:230-40

Pulmonary hypoplasia 10-20% High mortality, but rarely if >23 wks

Farooqi et al. Obstet Gynecol 1998;92:895-901

Previable Management Offer IOL after appropriate counseling Support decision for expectant mgmt if desired Initial period of observation for bleeding or infection Reasonable to administer latency antibiotics No indication for steroids <23 wks No tocolysis indicated Outpatient management an option until viability

ACOG. Obstet Gynecol 2015; 126: e82-94

Midtrimester Amniocentesis Up to 1% risk for pPROM; especially if bleeding

Reaccumulation more likely than spont pPPROM Small series with 72% reaccumulation w/i 1 month Perinatal survival 91%

Borgida et al. AJOG 2000; 183: 937-9

Previable pPROM

Cerclage and pPROM Retrospective studies show prolonged latency Possible increased maternal and neonatal infections Antibiotics not recommended beyond 7d Only published trial inadequately powered

Garite et al. AJOG 2014; 211: 339 Use best clinical judgment

Consider retaining <25 wks if clinically stable

Herpes Virus

Herpes and pPROM Primary infection vertical transmission 30-50% Recurrent infection transmission <3% Small case series with no vertical transmission

Antiviral therapy Expectant mgmt if recurrent active lesions <34 wks Delivery by CS if active lesions when delivery indicated

Major et al. AJOG 2003; 188: 1551-4

Similar approach with HIV especially if low viral load

Next Pregnancy Increased risk for recurrence (13.5%) RR 3.3 (2.1-5.2)

Mercer et al. AJOG 1999; 181: 1216 Stop smoking Treat vaginal infections 17P starting weeks 16-20 until 37 wks

Meiss et al. NEJM 2003; 348: 2379-85 Serial cervical length 16-24 wks w/cerclage if <2.5 cm

Berghella et al. Obstet Gynecol 2011; 117:663-71

Summary 37wks+ deliver and GBS as indicated 34 0/7-36 6/7 wks same with possible late steroids 24 0/7-33 6/7 expectant mgmt with abx and steroids

Mag neuroprotection if <32 0/7 <24 wks counseling and then delivery or expectant

Abx with possible steroids if 23 0/7 or greater No tocolysis No mag neuroprotection previable

ACOG. Obstet Gynecol 2015; 126: e82-94

Research Repeat steroids in pPROM

Current Mednax protocol (NCT#02469519) Quality measure

% of eligible pts 24-34 wks given steroids and abx