Preterm Premature Rupture of Membranes
Premature rupture of membranes (PROM) is defined as spontaneous rupture of the membranes prior to labor. When PROM occurs at less than 37 weeks gestational age, it is defined as preterm premature rupture of membranes (PPROM). Suspicion for PPROM is a commonly encountered clinical scenario in obstetric triage. PPROM occurs in 3% of pregnancies, causes one-third of preterm births, and is associated with brief latency from rupture of membranes to delivery (Mercer, 2003). Risk factors associated with PPROM include subclinical intrauterine infection, placental abruption, and uterine overdistention (Simhan & Canavan, 2005). However, most women who develop PPROM have no identifiable risk factors (Waters & Mercer, 2011). Timely diagnosis and treatment are necessary to optimize care. Even with conservative management, 50% to 60% of pregnant women will deliver within 1 week of rupture (Mercer, 2003). While several interventions have been shown to improve neonatal and maternal outcomes after PPROM, early preterm infants delivered after PPROM commonly face significant complications such as respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and sepsis (Mercer, 2003).
The most common presenting symptom for PPROM is a gush of vaginal fluid. However, women may complain of increased discharge, urinary incontinence, perineal moisture, or leakage of small amounts of fluid (Simhan & Canavan, 2005). The differential diagnoses for leakage of fluid or increased perineal dampness include PPROM, urinary incontinence (which increases during pregnancy), increased vaginal discharge (physiologic secondary to pregnancy), and expression of cervical mucus.
HISTORY AND PHYSICAL EXAMINATION
A standard obstetric history in the setting of suspected PPROM includes a past medical, surgical, social, obstetric, gynecologic, and social history. Medications 160and allergies are included in the history. Careful review of the prenatal chart is important. Clinical risk factors for spontaneous preterm birth such as prior preterm delivery, prior cervical surgery, or shortened cervix on transvaginal ultrasound are included in the history. Frequently, the gestational age is critical in decision making so medical records must be carefully reviewed to determine exact pregnancy dating. The history includes duration and amount of leakage of fluid, and whether fetal movement, contractions, and vaginal bleeding are present. Reports of the color of the fluid and odor need to be noted by the provider.
A physical exam in a pregnant woman with suspicion for PPROM is performed to confirm the diagnosis and assess maternal and fetal status. The physical examination includes all the components of a basic physical exam including vital signs, general appearance, and a cardiac and lung assessment. The abdominal exam, noting whether or not fundal tenderness is present, is critical because this finding may signify a diagnosis of chorioamnionitis.
Diagnosis of PPROM is made by sterile speculum exam. On speculum exam, the dilatation and effacement of the cervix are only visually inspected. Prolapsed umbilical cord needs to be ruled out. Fluid seen coming directly from the cervical os confirms the diagnosis. The finding of pooling of vaginal fluid in the posterior fornix increases the likelihood of PPROM having occurred. If present, cervical fluid is analyzed to confirm the diagnosis. However, small amounts of vaginal pooling can occur with urinary incontinence or severe vaginal infections such as herpes simplex virus (HSV). A second clue may be vaginal pH. The vaginal pH is usually acidic with a pH of 4.5 to 6.0, and amniotic fluid is slightly alkaline with a pH of 7.1 to 7.2. Amniotic fluid in the vagina will usually change the color of nitrazine paper from yellow to blue–green as the pH increases beyond 6.4 to 6.8. Blood, semen, bacterial vaginosis, and alkaline urine may all decrease the pH of the vagina and result in a false positive nitrazine test (Simhan & Canavan, 2005).
A final test of vaginal fluid is assessment for “ferning” or “arborization.” Amniotic fluid obtained with a sterile swab from the posterior fornix of the vagina and placed on a clean slide and allowed to dry will produce fern-like crystals (secondary to salt content) when viewed with microscope magnification. The slide is allowed to dry for 10 minutes, and the false negative rate increases the less time left to dry. Cervical mucus may also cause ferning, although these crystals tend to be thicker and darker. Because of this risk for false positive results, care should be taken to avoid swabbing cervical mucus (Simhan & Canavan, 2005).
If a pregnant woman provides a clinical history highly suspicious for PPROM, but the diagnosis is not confirmed by initial speculum exam, the woman can be placed in a semi-upright position and reexamined after 1 hour to allow for vaginal pooling. As a last resort, if results are still equivocal, amniocentesis with injection of indigo carmine dye may be performed. A tampon is placed; if any dye leaked from the cervix, a blue staining would be noted on the tampon, confirming the diagnosis of PPROM.
The physical exam includes assessment of fetal well-being with continuous fetal heart rate monitoring. Contractions are assessed by palpation and/or tocometry. Since women with PPROM are at risk for chorioamnionitis, presence or absence of pertinent physical exam findings consistent with infection are noted. Exhibit 15.1 lists the clinical criteria for chorioamnionitis (Gibbs, Blanco, St. Clair, & Castaneda, 1982; Tita & Andrews, 2010).
Clinical Criteria for Chorioamnionitis
Maternal temperature 100°F or higher with no other explanation for fever and any two of the following:
Maternal heart rate over 120 beats per minute
Fetal heart rate over 160 beats per minute
Foul smelling amniotic fluid
Maternal WBC count greater than 14K or bandemia (>9%)
WBC, white blood cell.
Sources: Adapted from Gibbs et al. (1982) and Tita and Andrews (2010).
LABORATORY AND IMAGING STUDIES
Multiple laboratory tests are currently marketed to assess findings in the diagnosis of PPROM. The AmniSure test for rupture of membranes is an immunoassay for placental alpha microglobulin (PAMG-1). There are low levels of PAMG-1 in vaginal secretions and blood, but very high levels in amniotic fluid. AmniSure has been shown to be 94% to 99% sensitive and 88% to 100% specific in detecting rupture of membranes across a range of studies (Birkenmaier et al., 2011; Cousins, Smok, Lovett, & Poeltler, 2005; Lee et al., 2007; Ng et al., 2013). Other tests include Actim PROM and ROM Plus, which assess for placental protein 12 and a combination of placenta protein 12 and alpha-fetoprotein, respectively. Test characteristics appear to be similar to AmniSure (Erdemoglu & Mungan, 2004; Thomasino, Levi, Draper, & Neubert, 2013). Because of the costs of these tests, they are primarily used either for women with unclear rupture of membrane status or if providers with appropriate clinical training are unavailable to assess for pooling, ferning, and nitrazine changes.
If a pregnant woman has unknown Group B Streptococcus (GBS) status, vaginal and rectal cultures will be collected during the pelvic exam. If sexually transmitted infections are suspected, appropriate cultures are also collected and sent. A digital cervical exam is contraindicated if the woman is less than 34 weeks gestation, unless active labor or imminent delivery is suspected. Research demonstrates that latency (time from rupture to delivery) is decreased when serial examinations are performed (Alexander et al., 2000).
If the woman is between 32 and 34 weeks gestational age and has significant vaginal pooling, amniotic fluid may be obtained for lung maturity testing. Fluid can be collected using a 5- or 10-mL syringe attached to an intravenous catheter (with the needle removed). As much fluid as possible is obtained from the vaginal pool to maximize the probability that the sample is adequate for laboratory analysis for any lung maturity studies.
Ultrasound examination is a critical part of the evaluation for PPROM. Oligohydramnios offers supporting evidence for PPROM having occurred but is not the gold standard for the diagnosis. Normal or increased fluid volume does not preclude the diagnosis. Fetal presentation and placentation are additionally noted. An estimated fetal weight determined by biometry is obtained. In terms of laboratory work, a complete blood count is performed, as well as a GBS culture if the woman’s status is unknown.
Viability to 34 Weeks Gestational Age
At many centers, viability is defined as early as 23 weeks 0 days gestational age. However, some fetuses at 24 to 26 weeks gestational age may not be considered viable because of associated conditions (severe intrauterine growth restriction, major congenital anomalies, genetic syndromes, or other conditions predisposing to poor prognoses). Care must be individualized, and determination of viability includes the entire clinical picture, as well as input from neonatologists and the family’s goals for care. Not all centers have neonatal intensive care unit (NICU) facilities to manage extreme prematurity (neonates born at 28 or fewer weeks gestational age). Obstetrical providers should be aware of their center’s NICU capabilities and potential benefit of maternal transfer for PPROM within a system of regionalized perinatal care if both the status of the mother and the fetus are stable.
The mainstays of management for viable PPROM until 34 weeks include hospital admission, administration of betamethasone, latency antibiotics, and close evaluation of maternal and fetal status. Women who present with PPROM are at risk for chorioamnionitis and abruption, both contraindications to expectant management. The pregnant woman is assessed on a daily basis for chorioamnionitis, abruption, preterm labor, and nonreassuring fetal status (either with a nonstress test or biophysical profile).
Evidence supports the administration of betamethasone or dexamethasone in the setting of PPROM from 24 to 34 weeks gestational age. Steroids reduce the risk of RDS, NEC, and IVH. There appears to be no increased risk of maternal infectious morbidity from steroid administration (Roberts & Dalziel, 2006). Leukocytosis occurs after steroid administration and may not be representative of infection. The American College of Obstetricians and Gynecologists (ACOG, 2016c) states that steroids may be considered for pregnant women as early as 23 0/7 weeks of gestation at risk of preterm delivery within 7 days. Regarding late preterm steroid administration between 34 0/7 weeks and 36 6/7 weeks for patients with PPROM, the ACOG states: “Recent data indicate that administration of betamethasone in the late preterm period between 34 0/7 weeks and 36 6/7 weeks reduces respiratory morbidity in newborns. Although subgroup analysis was not done, approximately 20% of study patients had preterm PROM. It is assumed that patients with preterm PROM will benefit from betamethasone in the late preterm period” (2016c). Regarding rescue steroids, the ACOG states: “Whether to administer a rescue course of corticosteroids with PROM at any gestational age is controversial, and there is insufficient evidence to make a recommendation for or against” (2016a). These recommendations may change as evidence regarding risks and benefits evolves and it is recommended to consult up-to-date documents from the ACOG.
For patients presenting with PPROM prior to 32 weeks, maternal administration of magnesium sulfate may provide neuroprotective benefits for neonates. The beneficial effects of the antenatal magnesium sulfate (BEAM) trial demonstrated that pregnant women at risk for preterm delivery between 24 and 31 weeks because of PPROM or advanced preterm labor who were randomized to magnesium sulfate had a significantly lower risk of a child born with cerebral palsy (Rouse et al., 2008). While protocols and dosing regimens may vary by center, 163administration of magnesium sulfate for 24 hours, in the absence of maternal contraindications, for patients presenting with PPROM prior to 32 weeks is a reasonable clinical strategy. If a patient with PPROM is not at risk of imminent delivery 24 hours after presentation, magnesium may be discontinued.
Administration of latency antibiotics improves neonatal outcomes. Level 1 evidence demonstrates that antibiotic administration reduces RDS, NEC, neonatal sepsis, bronchopulmonary dysplasia, and pneumonia, while increasing latency (Hutzal et al., 2008; Mercer et al., 1997). Latency antibiotics along with antepartum steroids likely reduce perinatal mortality. A typical antibiotic regimen includes 48 hours of intravenous ampicillin and erythromycin, followed by 5 days of oral ampicillin and erythromycin (Mercer et al., 1997). Ampicillin and amoxicillin cover Group B Streptococcus and provide gram-negative and some anaerobic coverage. Erythromycin offers coverage of genital mycoplasma along with some coverage of gram-positive cocci. Azithromycin, which has a better side effect profile than erythromycin, may be used as an alternate macrolide. Amoxicillin-clavulanic acid should be avoided because of a possible increased risk of NEC. Exhibit 15.2 offers proposed antibiotic regimens, which may vary by medical center.