Prelabor rupture of membranes

Fetal membranes likely break because they become weak and fragile. This weakening is a normal process that typically happens at term as the body prepares for labor and delivery. However, this can be a problem when it occurs before 37 weeks (preterm). The natural weakening of fetal membranes is thought to be due to one or a combination of the following. In PROM, these processes are activated too early:[12]

• Cell death: when cells undergo programmed cell death, they release biochemical markers that are detected in higher concentrations in cases of PPROM.
• Poor assembly of collagen: collagen is a molecule that gives fetal membranes, as well as other parts of the human body such as the skin, their strength. In cases of PPROM, proteins that bind and cross-link collagen to increase its tensile strength are altered.
• Breakdown of collagen: collagen is broken down by enzymes called matrix metalloproteinases (MMPs), which are found at higher levels in PPROM amniotic fluid. This breakdown results in prostaglandin production which stimulates uterine contractions and cervical ripening. MMPs are inhibited by tissue inhibitors of matrix metalloproteinases (TIMPs) which are found at lower levels in PPROM amniotic fluid.[10]

Infection and inflammation likely explains why membranes break earlier than they are supposed to. In studies, bacteria have been found in the amniotic fluid from about one-third of cases of PROM. Often, testing of the amniotic fluid is normal, but a subclinical infection (too small to detect) or infection of maternal tissues adjacent to the amniotic fluid, may still be a contributing factor. In response to infection, the resultant infection and release of chemicals (cytokines) subsequently weakens the fetal membranes and put them at risk for rupture.[10] PROM is also a risk factor in the development of neonatal infections.[13]

Many genes play a role in inflammation and collagen production, therefore inherited genes may play a role in predisposing a person to PROM.[10]

• Prelabor rupture of membranes (PROM): when the fetal membranes rupture early, at least one hour before labor has started.[8]
• Prolonged PROM: a case of prelabor rupture of membranes in which more than 18 hours has passed between the rupture and the onset of labor.[15]
• Preterm prelabor rupture of membranes (PPROM): prelabor rupture of membranes that occurs before 37 weeks gestation.
• Midtrimester PPROM or pre-viable PPROM: prelabor rupture of membranes that occurs before 24 weeks' gestation. Before this age, the fetus cannot survive outside of the mother's womb.[14]

The following tests should only be used if the diagnosis is still unclear after the standard tests above.

• Ultrasound: Ultrasound can measure the amount of fluid still in the uterus surrounding the fetus. If the fluid levels are low, PROM is more likely.[8] This is helpful in cases when the diagnosis is not certain, but is not, by itself, definitive.[11]
• Immune-chromatological tests are helpful, if negative, to rule out PROM, but are not that helpful if positive since the false-positive rate is relatively high (19–30%).[11]
• Indigo carmine dye test: a needle is used to inject indigo carmine dye (blue) into the amniotic fluid that remains in the uterus through the abdominal wall. In the case of PROM, blue dye can be seen on a stained tampon or pad after about 15–30 minutes.[9] This method can be used to definitively make a diagnosis, but is rarely done because it is invasive and increases risk of infection. But, can be helpful if the diagnosis is still unclear after the above evaluations have been done.[9]

It is unclear if different methods of assessing the fetus in a woman with PPROM affects outcomes.[16]

Like amniotic fluid, blood, semen, vaginal secretions in the presence of infection,[9] soap,[10] urine, and cervical mucus[8] also have an alkaline pH and can also turn nitrazine paper blue.[9] Cervical mucus can also make a pattern similar to ferning on a microscope slide, but it is usually patchy[9] and with less branching.[8]

Other conditions that may present similarly to premature rupture of membranes are the following:[8]

• Urinary incontinence: leakage of small amounts of urine is common in the last part of pregnancy
• Normal vaginal secretions of pregnancy
• Increased sweat or moisture around the perineum
• Increased cervical discharge: this can happen when there is a genital tract infection
• Semen
• Douching
• Vesicovaginal fistula: an abnormal connection between the bladder and the vagina
• Loss of the mucus plug

Both expectant management (watchful waiting) and an induction of labor (artificially stimulating labor) are considered in this case. 90% of women start labor on their own within 24 hours, and therefore it is reasonable to wait for 12–24 hours as long as there is no risk of infection.[14] However, if labor does not begin soon after the PROM, an induction of labor is recommended because it reduces rates of infections, decreases the chances that the baby will require a stay in the neonatal intensive care unit (NICU), and does not increase the rate of caesarean sections.[11] If a woman strongly does not want to be induced, watchful waiting is an acceptable option as long as there is no sign of infection, the fetus is not in distress, and she is aware and accepts the risks of PPROM.[11] There is not enough data to show that the use of prophylactic antibiotics (to prevent infection) is beneficial for mothers or babies at or near term because of the potential side effects and development of antibiotic resistance.[19]

When the fetus is 34 to 37 weeks gestation, the risk of being born prematurely must be weighed against the risk of PROM. Previously it was recommended that delivery be carried out as if the baby was term.[11][8] A 2017 Cochrane review however found waiting resulted in better outcomes when pregnancy is before 37 weeks.[5]

Before 34 weeks, the fetus is at a much higher risk of the complications of prematurity. Therefore, as long as the fetus is doing well, and there are no signs of infection or placental abruption, watchful waiting (expectant management) is recommended.[11] The younger the fetus, the longer it takes for labor to start on its own,[9] but most women will deliver within a week.[10] Waiting usually requires a woman to stay in the hospital so that health care providers can watch her carefully for infection, placental abruption, umbilical cord compression, or any other fetal emergency that would require quick delivery by induction of labor.[11]

In 2017, a review of watchful waiting vs the early birth strategy was conducted to ascertain which was associated with a lower overall risk. Focusing on the 24–37-week range, the review analysed twelve randomised controlled trials from the "Cochrane Pregnancy and Childbirth's Trials Register", concluding that "In women with PPROM before 37 weeks' gestation with no contraindications to continuing the pregnancy, a policy of expectant management with careful monitoring was associated with better outcomes for the mother and baby."[5]

There is believed to be a correlation between volume of amniotic fluid retained and neonatal outcomes before 26 weeks' gestation.[10] Amniotic fluid levels are an important consideration when debating expectant management vs clinical intervention, as low levels, or oligohydramnios, can result in lung and limb abnormalities.[10] Additionally, labor and infection are less likely to occur when there are sufficient levels of amniotic fluid remaining in the uterus.[8] Serial amnioinfusion in pregnancies with PPROM-related oligohydramnios at less than 26 weeks gestation, successfully alleviates oligohydramnios, with perinatal outcomes that are significantly better than the outcome in those with the persistent condition and is comparable with gestations with PPROM in which oligohydramnios never develops.[20]

• Monitoring for infection: signs of infection include a fever in the mother, fetal tachycardia (fast heart rate of the fetus, more than160 beats per minute), or tachycardia in the mother (more than 100 beats per minute). White blood cell (WBC) counts are not helpful in this case because WBC's are normally high in late pregnancy.[11]
• Steroids before birth: corticosteroids (betamethasone) given to the mother of a baby at risk of being born prematurely can speed up fetal lung development and reduce the risk of death of the infant, respiratory distress syndrome, brain bleeds, and bowel necrosis.[11] It is recommended that mothers receive one course of corticosteroids between 24 and 34 weeks when there is a risk of preterm delivery. In cases of PPROM these medications do not increase the risk of infection even though steroids are known to suppress the immune system. More than two courses is not recommended because three or more can lead to small birth weight and small head circumference.[11] In pregnancies between 32 and 34 weeks (right around the time that fetal lungs mature) vaginal fluid can be tested to determine fetal lung maturity using chemical markers which can help to decide if corticosteroids should be given.[9]
• Magnesium sulfate: Intravenous magnesium sulfate is given to the mother in cases when there is a risk of preterm birth before 32 weeks. This has been shown to protect the fetal brain and reduce the risk of cerebral palsy.[11]
• Latency antibiotics: The time from PROM to labor is termed the latency period, and there is an inverse relationship between gestational age and the length of latency, meaning that the earlier the rupture, the longer it will take for labor to begin naturally.[8] As expected, antibiotics given to mothers that experience PPROM serve to protect against infections during this lengthened latency period. Additionally, antibiotics increase the time that babies stay in the womb. Antibiotics don't seem to prevent death or make a difference in the long-term (years after the baby is born). But, because of the short-term benefits, routine use of antibiotics in PPROM is still recommended.[21] The American Congress of Obstetricians and Gynecologists (ACOG) recommends a seven-day course of intravenous ampicillin and erythromycin followed by oral amoxicillin and erythromycin if watchful waiting is attempted before 34 weeks.[11] Amoxicillin/clavulanic acid increases the risk of fetal bowel death (necrotizing enterocolitis) and should be avoided in pregnancy.[11]
• Prophylactic antibiotics: If a woman is colonized with GBS, than the typical use of antibiotics during labor is recommended to prevent transmission of this bacteria to the fetus, regardless of earlier treatments.[11]

• Preventative tocolysis (medications to prevent contractions): the use of tocolytic medications to prevent labor contractions is controversial. On the one hand, this can delay delivery and allow the fetus more time to develop and benefit from antenatal corticosteroid medication, on the other hand it increases the risk of infection or chorioamnionitis. The use of tocolysis has not shown to benefit mom or baby and currently there is not enough data to recommend or discourage its use in the case of preterm PROM.[11][22]
• Therapeutic tocolysis (medications to stop contractions): Once labor has started, using tocolysis to stop labor has not been shown to help, and is not recommended.[11]
• Amnioinfusion: This treatment attempts to replace the lost amniotic fluid from the uterus by infusing normal saline fluid into the uterine cavity. This can be done through the vagina and cervix (transcervical amnioinfusion) or by passing a needle through the abdominal wall (transabdominal amnioinfusion). Current data suggests that this treatment prevents infection, lung problems, and fetal death. However, there have not been enough trials to recommend its routine use in all cases of PPROM.[23]
• Home care: Typically women with PPROM are managed in the hospital, but, occasionally they opt to go home if watchful waiting is attempted. Since labor usually starts soon after PPROM, and infection, umbilical cord compression, and other fetal emergencies can happen very suddenly, it is recommended that women stay in the hospital in cases of PPROM after 24 weeks.[11] Currently, there is not enough evidence to determine meaningful differences in safety, cost, and women's views between management at home vs. the hospital.[24]
• Sealing membranes after rupture: Infection is the major risk associated with PROM and PPROM.[25] By closing the ruptured membranes, it is hoped that there would be a decrease in infection, as well as encouraging the re-accumulation of amniotic fluid in the uterus to protect the fetus and allow for further lung development. Common techniques include placing a sponge over the ruptured membrane and the use of oral autoimmune stimulating drugs to encourage the body's immune system to repair the rupture. There is currently insufficient research to determine whether these or other resealing techniques improve maternal or neonatal outcomes when compared to the current standard of care.[26]

Before 24 weeks, a fetus is not viable meaning it cannot live outside the mother. In this case, either watchful waiting at home or an induction of labor done.[11]

Because the risk of infection is so high, the mother should check her temperature often and return to the hospital if she develops any signs or symptoms of infection, labor, or vaginal bleeding. These women are typically admitted to the hospital once their fetus reaches 24 weeks and then managed the same as women with PPROM before 34 weeks (discussed above). When possible, these deliveries should take place in a hospital that has expertise in the management of the potential maternal and neonatal complications, and has the necessary infrastructure in place to support the care of these patients (i.e. neonatal intensive care unit).[27] Antenatal corticosteroids, latency antibiotics, magnesium sulfate, and tocolytic medications are not recommended until the fetus reaches viability (24 weeks).[11] In cases of pre-viable PPROM, chance of survival of the fetus is between 15 and 50%, and the risk of chorioamnionitis is about 30%.[9]

Chorioamnionitis is a bacterial infection of the fetal membranes, which can be life-threatening to both mother and fetus. Women with PROM at any age are at high risk of infection because the membranes are open and allow bacteria to enter. Women are checked often (usually every 4 hours) for signs of infection: fever (more than 38 °C or 100.5 °F), uterine pain, maternal tachycardia, fetal tachycardia, or foul-smelling amniotic fluid.[10] Elevated white blood cells are not a good way to predict infection because they are normally high in labor.[9] If infection is suspected, artificial induction of labor is started at any gestational age and broad antibiotics are given. Caesarean section should not be automatically done in cases of infection, and should only be reserved for the usual fetal emergencies.[9]

At any gestational age, an opening in the fetal membranes provides a route for bacteria to enter the womb. This can lead to chorioamnionitis (an infection of the fetal membranes and amniotic fluid) which can be life-threatening to both the mother and fetus.[8] The risk of infection increases the longer the membranes remain open and baby undelivered.[11] Women with preterm PROM will develop an intra-amniotic infection 15–25% of the time, and the chances of infection increase at earlier gestational ages.[11]

PROM occurring before 37 weeks (PPROM) is one of the leading causes of preterm birth. Thirty to 35% of all preterm births are caused by PPROM.[10] This puts the fetus at risk for the many complications associated with prematurity such as respiratory distress, brain bleeds, infection, necrotizing enterocolitis (death of the fetal bowels), brain injury, muscle dysfunction, and death.[8] Prematurity from any cause leads to 75% of perinatal mortality and about 50% of all long-term morbidity.[28] PROM is responsible for 20% of all fetal deaths between 24 and 34 weeks' gestation.[10]

Before 24 weeks the fetus is still developing its organs, and the amniotic fluid is important for protecting the fetus against infection, physical impact, and for preventing the umbilical cord from becoming compressed. It also allows for fetal movement and breathing that is necessary for the development of the lungs, chest, and bones.[8] Low levels of amniotic fluid due to mid-trimester or previable PPROM (before 24 weeks) can result in fetal deformity (e.g. Potter-like facies), limb contractures, pulmonary hypoplasia (underdeveloped lungs),[11] infection (especially if the mother is colonized by group B streptococcus or bacterial vaginosis), prolapsed umbilical cord or compression, and placental abruption.[9]

Most cases of PROM occur spontaneously, but the risk of PROM in women undergoing a second trimester amniocentesis for prenatal diagnosis of genetic disorders is 1%. Although no studies are known to account for all cases of PROM that stem from amniocentesis. This case, the chances of the membranes healing on their own and the amniotic fluid returning to normal levels is much higher than spontaneous PROM. Compared to spontaneous PROM, about 70% of women will have normal amniotic fluid levels within one month, and about 90% of babies will survive.[11]