Guidelines for the diagnosis and management of premature rupture of membranes
Preterm premature rupture of membrane (PROM) refers to the spontaneous rupture of fetal membranes before delivery, which is classified into full-term PROM and preterm premature rupture of membrane (PPROM) according to the gestational week of occurrence. The incidence of full-term singleton PROM is 8%; the incidence of singleton pregnancy PPROM is 2%-4%, and the incidence of twin pregnancy PPROM is 7%-20%, and PPROM is one of the main causes of preterm delivery. Currently, there is no consensus on the principles of management of PPROM at different gestational weeks in China; there are still controversies on whether to induce labor and the method of induction of labor for those who have not delivered within a short period of time in full-term PROM; there are no unified guidelines or norms on the management of PPROM expectant treatment, the duration of fetal preservation, how to prevent infection, and the way to terminate pregnancy. Ma Xiaoping, Department of Obstetrics and Gynecology, Jiangsu Provincial Hospital of Integrative Medicine
Therefore, it is necessary to develop guidelines for the diagnosis and management of full-term PROM and PPROM. This guideline was developed with reference to the relevant guidelines on PROM from the American College of Obstetricians and Gynecologists (ACOG, 2013) and the Royal College of Obstetricians and Gynecologists (RCOG, 2010), as well as the latest evidence-based medicine, and combined with the current situation of perinatal labor in China, aiming to standardize and guide the diagnosis and management of PROM.
I. General Introduction
(I) Etiology and high-risk factors of PROM
Full-term PROM is associated with weak fetal membranes due to physiological contractions in late pregnancy, while preterm PROM is more often due to subclinical chorioamnionitis. Those with the following high-risk factors are more likely to have PROM (grade II/B)
1, maternal factors: repeated vaginal bleeding, vaginitis, long-term application of glucocorticoids, abdominal trauma, sudden increase in intra-abdominal pressure (violent cough, difficulty in defecation), smoking, drug abuse, malnutrition, history of preterm PROM in previous pregnancy, frequent sexual intercourse in late pregnancy, etc.
2, uterine and placental factors: uterine malformation, placental abruption, cervical insufficiency, post-cervical cerclage, post-cervical conization, cervical shortening, preterm labor, uterine hyperinflation (excessive amniotic fluid, multiple pregnancy), cephalopelvic disproportion, abnormal fetal position (breech, transverse), chorioamnionitis, subclinical intrauterine infection, etc.
(II) Diagnosis of PROM
1, clinical symptoms and signs: pregnant women complaining of sudden vaginal fluid or uncontrolled “leakage”, a few pregnant women only feel the vulva wetter than usual, and the amniotic fluid mixed with fetal fat flowing out from the cervix on examination of the speculum, the diagnosis can be made. It is worth noting that a sterilized speculum should be used for examination and finger-examination should be avoided to prevent episodic infection.
2. Auxiliary examination: (1) Vaginal pH measurement: normal vaginal fluid pH is 4.5~6.0 and amniotic fluid pH is 7.0~7.5. After rupture of fetal membranes, the pH of vaginal fluid increases (pH≥6.5). pH is usually measured by nitrozine or litmus paper, if there is a pool of fluid in the posterior vault and the paper turns blue, the diagnosis is clear. However, cervicitis, vaginitis, blood, soap, urine, semen, or antiseptics may cause false positives in pH paper determinations. pH has a sensitivity of 90% for diagnosing PROM and a false positive rate of 17% (grade II/B).
(2) Vaginal fluid smear: vaginal fluid is taken and applied to a slide, dried and observed under a microscope. The presence of amniotic crystals suggests amniotic fluid. Semen and cervical mucus can cause false positives. Its sensitivity in diagnosing PROM is 51% to 98%, with a false positive rate of 6%. Usually, it is used when PROM cannot be determined by the above tests (grade II/B).
(3) Biochemical index test: For pregnant women with suspected PROM that is still difficult to determine by the above examination methods, biochemical index test can be used. The most clinically used tests are insulin like growth factor binding protein-1 (IGFBP-1), placenta? placental alphamicroglobulin-1 (PAMG-1). However, there is a false positive rate of 19-30% in those with regular contractions and intact fetal membranes, so it is mainly used in pregnant women with suspected PROM who are difficult to diagnose and have no regular contractions (grade II/B).
(4) Ultrasound examination: For pregnant women with suspected PROM, ultrasound detection of amniotic fluid may be helpful. If ultrasound indicates a significant decrease in amniotic fluid and the pregnant woman has a history of vaginal drainage, PROM should be highly suspected if other causes of low amniotic fluid are excluded, and PROM can be diagnosed by combining the above biochemical index tests.
(iii) Complications of premature rupture of membranes
1. Common complications of full-term PROM: full-term PROM is often a precursor of impending labor. 50% of pregnant women deliver on their own within 12 h after rupture of membranes, 20% deliver within 12-24 h, 25% deliver within 24-72 h, and 5% still cannot deliver within 72 h. The main complication of full-term PROM is intrauterine infection. The longer the time to rupture of membranes, the greater the risk of clinical chorioamnionitis, which in turn leads to maternal puerperal infection, neonatal infection, and sepsis.
2. Common complications of PPROM: 15%-25% of PPROMs are combined with clinically symptomatic chorioamnionitis. The most important complication of PPROM is prematurity and various complications due to immaturity and intrauterine infections, including respiratorydistress syndrome (RDS), intraventricular hemorrhage (IHD), and intraventricular hemorrhage (IHD). intraventricularhemorrhage (IVH) and necrotisingentercolitis (NEC), sepsis, etc. Despite aggressive treatment such as fetal preservation, about 50% of preterm fetal membranes are delivered within 1 week after rupture of membranes, which is the main cause of preterm delivery. Other common complications are fetal distress and placental abruption. Premature rupture of membranes leads to low amniotic fluid, umbilical cord compression or even cord prolapse, resulting in fetal distress or even intrauterine death. changes in uterine cavity pressure after PROM occurs about 2% to 5% of people with PPROM experience placental abruption.
(D) Prevention and monitoring of chorioamnionitis
1. Diagnosis and differential diagnosis of chorioamnionitis: chorioamnionitis is a common complication of PROM and is mutually beneficial. Chorioamnionitis can lead to adverse maternal and fetal outcomes and should be identified and prevented. The longer the time to rupture of membranes, the greater the risk of chorioamnionitis. The main manifestations of acute clinical chorioamnionitis are increased maternal temperature (≥37.8 °C), increased pulse rate (≥100 beats/min), increased fetal heart rate (≥160 beats/min), pressure pain at the fundus, odorous vaginal discharge, and increased peripheral blood leukocyte count (≥15×109/L or leftward nuclear shift). The presence of 2 or more of these symptoms or signs along with an elevated maternal temperature can be diagnosed as clinical chorioamnionitis [8-9], but any single clinical manifestation or index abnormality mentioned above is not diagnostic. Abnormalities in one index alone should be diagnosed with the appropriate differential diagnosis and closely observed and monitored. For example, the application of glucocorticoids can lead to an increase in white blood cell count; certain drugs or other conditions can cause an increased pulse rate or an increased fetal heart rate in pregnant women, such as dainty fluorescence prolongation of the amount of chorioamnionitis.
2, chorioamnionitis monitoring: it is recommended to monitor the pregnant woman’s body temperature and pulse every 4-8 hours, routine and individual blood tests and fetal heart rate monitoring and electronic monitoring of the fetus, while closely observing the amniotic fluid properties, uterine pressure pain and other signs of chorioamnionitis, early detection and treatment of chorioamnionitis. Vaginal examination can cause upstream infection of bacteria in the vagina, which can increase the risk of chorioamnionitis and postpartum endometritis, fetal infection and neonatal infection. Unnecessary vaginal examination should be minimized in anticipation of fetal preservation, induction of labor or during labor (level II/B).
3. Management of chorioamnionitis: When chorioamnionitis or suspected chorioamnionitis is clinically diagnosed, antibiotics should be applied promptly, the pregnancy should be terminated as soon as possible when chorioamnionitis is diagnosed, and cesarean section should be chosen to terminate the pregnancy if vaginal delivery cannot be performed within a short time. If available, neonatal ear swabs and uterine secretion cultures and placenta-fetal membranes should be sent for pathological examination after delivery of the fetus, but the presence of typical clinical signs of infection without pathological support does not negate the diagnosis of intrauterine infection. The newborn is treated as a high-risk infant. (Grade II/B).
(v) Prevention of group B hemolytic streptococcal upstream infections
PROM is a high-risk factor for group B hemolytic streptococcus (GBS) upstream infection, and is an important pathogen causing maternal and puerperal infections, fetal infections and neonatal infections, and attention should be paid to the prevention and treatment of GBS infection. This related issue has also received increasing attention from the perinatal medicine community in China. Antibiotic treatment should be initiated immediately after rupture of membranes if there has been previous screening and GBS positive, or if no GBS culture has been performed and the time to rupture of membranes in full-term PROM is ≥18 h or the maternal temperature is ≥38 ℃. GBS culture of the lower 1/3 of the vagina and perianal secretions is recommended for pregnant women with PPROM if available, and those with positive GBS culture should be reintroduced to antibiotic therapy once labor is imminent, even if broad-spectrum antibiotics have been applied previously. Penicillin is the drug of choice, or cephalosporin antibiotics or erythromycin if allergic to penicillin. Antibiotic usage to prevent GBS infection: (1) Penicillin G at an initial dose of 4.8 million units intravenously, followed by 2.4 million units/4 h until delivery; or ampicillin at a loading dose of 2 g intravenously, followed by 1 g every 4 hours until delivery. (2) For those who are allergic to penicillin, cefazolin is used, with 2 g as the starting dose intravenously and then 1 g every 8 hours until delivery. (3) For those allergic to cephalosporins, erythromycin 500 mg intravenously every 6 hours or clindamycin 900 mg intravenously every 8 hours.
II. Treatment of full-term PROM
(a) Pregnant women with full-term PROM should be induced at the right time
After the diagnosis of full-term PROM is clear, the condition of mother and fetus should be evaluated to exclude fetal distress, chorioamnionitis, placenta abruptio, abnormal fetal position and maternal complications. The risk of intrauterine infection increases significantly as the time to rupture of membranes increases. Aggressive induction of labor within 2-12 h after rupture of membranes in those without indication for cesarean delivery significantly shortened the time between rupture and delivery and significantly reduced the risk of chorioamnionitis and maternal puerperal infection without increasing the rates of cesarean delivery and vaginal assisted delivery and other adverse pregnancy outcomes; maternal acceptance was also higher than that of control pregnant women given expectant treatment, but there was no significant difference in the rate of neonatal infection between those who were actively induced and those who were expectant. Forty-one percent of their study population was menstruating mothers and 59% were primiparous. The results of a retrospective study based mainly on primigravida showed that delaying labor until 24 h after rupture of membranes without induction of labor significantly increased the rate of neonatal infection and cesarean delivery. In full-term PROM pregnant women who do not deliver within a short period of time are more likely to have good maternal and child outcomes after active induction of labor. In the absence of a clear indication for cesarean delivery, active induction of labor within 2 to 12 h after rupture of membranes is recommended. Good regular contractions should be induced for at least 12-18 h. If the induction of labor is still in the latent phase, cesarean delivery should be considered as a diagnostic failure. Those who refuse induction of labor should be fully informed that expectant treatment may increase the risk of maternal and fetal infection (class II/B).
(ii) Method of induction of labor
For full-term PROM pregnant women with a mature cervix, intravenous administration of contractions is the preferred method of labor induction. The norms for induction of labor should be followed during induction of labor; for those with immature cervical conditions and no contraindications to cervical maturation or vaginal delivery, prostaglandin preparations can be applied to promote cervical maturation, but care should be taken to prevent infection. The use of prostaglandin-based drugs to improve cervical conditions should pay attention to the relevant obstetric norms, closely monitor contractions and fetal conditions, and promptly remove the drugs if excessive contractions or signs of fetal distress occur, and apply contraction inhibitors (class II/B) if necessary.
Assessment and management of PPROM
According to the size of gestational weeks, PPROM can be divided into lifeless PPROM (<24 gestational weeks), pprom far from full term (24~31 weeks +6), and near full term pprom (32~36 weeks +6). The pprom far from full term (24~31 weeks of gestation +6) can be divided into 24~27 weeks of gestation +6 and 28~31 weeks of gestation +6 according to our situation, and the pprom near full term is further divided into 32~33 weeks of gestation +6 and 34~36 weeks of gestation +6.< p="">
(I) General rules of PPROM treatment
(1) Comprehensive assessment of maternal and fetal status: (1) Accurate verification of gestational weeks: based on menstrual cycle, time of conception, and ultrasound measurement data during early and mid-term pregnancy.
(2) Assessment of the presence of infection.
(3) Assessment of fetal status: fetal size, fetal orientation, amniotic fluid index, presence of fetal distress; presence of fetal malformations.
(4) Evaluate whether the mother has other comorbidities or complications, such as placental abruption, etc.
(2) Determine the management plan: make decision based on 4 aspects: gestational week, maternal and fetal status, local medical level and the wishes of the pregnant woman and her family: give up the fetus and terminate the pregnancy; expect fetal preservation treatment; if the benefit of termination of pregnancy is greater than the expectation of prolonging the gestational week, then actively induce labor or deliver by cesarean section if indicated.
(1) Immediate termination of pregnancy to give up the fetus: ① gestational weeks <24 weeks: the stage of a non-viable child, due to the need to expect several weeks to obtain the possibility of survival, the high incidence of adverse outcomes in preterm infants, and the high risk of maternal and child infection, most do not advocate the continuation of pregnancy, to induce labor is appropriate. In addition, the number of women who are in the perinatal stage of pregnancy is still limited to 28 weeks of gestation, and those who are not in the perinatal stage of pregnancy can be terminated according to the wishes of the mother and her family. < p="">
(2) Expectant fetal preservation: (1) Those who are eligible for fetal preservation at 24~27 weeks+6 weeks of gestation and those who are requested by the pregnant woman and her family; however, the process of fetal preservation is long and risky, and they should be fully informed of the risks in the process of expectant fetal preservation. However, if the amniotic fluid is already too small and the maximum depth of amniotic fluid is <20 mm, termination of pregnancy should be considered. (2) If there is no contraindication to continue the pregnancy at 28-33 weeks +6 weeks of gestation, the pregnancy should be preserved and extended to 34 weeks of gestation, and glucocorticoids and antibiotics should be given during the process of fetal preservation, and the condition of mother and fetus should be closely monitored.
(3) It is not advisable to continue fetal preservation by induction of labor or cesarean section: (1) If the fetus is 34~36 weeks+6 weeks of gestation and is close to full term, more than 90% of the fetal lungs are mature, the probability of RDS in newborns is significantly reduced, and the survival rate of preterm infants is close to that of full term infants, it is not advisable to preserve the fetus; although there is no sufficient evidence that active induction of labor can significantly reduce the incidence of serious neonatal infections in terms of the outcome of neonatal infections. Although there is insufficient evidence that active induction of labor significantly reduces the incidence of serious neonatal infections, active induction of labor can reduce adverse neonatal outcomes due to chorioamnionitis, amniotic fluid deficiency, and fetal distress (grade II/B).
For 34 to 34 weeks +6 weeks of gestation, since RDS occurs in more than 5% of newborns, there is no unanimous opinion in domestic and international academic circles on whether to extend the gestational week to 35 weeks, and it is recommended to decide whether to expect to keep the fetus according to the condition and wishes of the pregnant woman and the local medical level, but to warn that extending the gestational week increases the risk of chorioamnionitis.
(2) Regardless of the gestational week, those with clearly diagnosed intrauterine infection, clearly diagnosed fetal distress, fetal abruption, etc., should not continue the pregnancy.
(II) Expectation of treatment in the process of fetal preservation
1.Promoting fetal lung maturation: prenatal application of glucocorticoids to promote fetal lung maturation can reduce the occurrence of neonatal RDS, IVH, NEC, and does not increase the risk of maternal and fetal infection (grade I/A).
(1) Indications for application: Glucocorticoids should be given to those who are not contraindicated to expect fetal preservation treatment at <34 gestational weeks. However, the effect of glucocorticosteroids given before 26 weeks of gestation is uncertain, and it is recommended that glucocorticosteroids be given after reaching 26 weeks of gestation. ≥In view of the current state of perinatal medicine in China and the recent guidelines for preterm delivery developed by the Obstetrics and Gynecology Section of the Chinese Medical Association, it is recommended that in pregnant women with PPROM at 34 to 34 weeks + 6 weeks of gestation, the decision to give fetal lung maturation treatment should be based on their individual situation and the local medical level, but if the pregnant woman is combined with gestational diabetes mellitus, it is recommended to give fetal lung maturation treatment. (2) Specific use: Dexedrine is recommended for PPROM at 34 to 34 weeks + 6 weeks of gestation.
(2) Specific use: Dexamethasone 6 mg intramuscularly in pregnant women (commonly used dose in China is 5 mg) every 12 hours for 4 doses, or betamethasone 12 mg intramuscularly in pregnant women once a day for 2 doses. After administration of the first dose, it takes effect within 24-48 h and can continue to function for at least 7 d. It is recommended even for pregnant women who are estimated to be unable to complete 1 course of treatment and can have some effect, but it is not advisable to shorten the interval of use. If a single course of glucocorticosteroid therapy was used before 32 weeks of gestation and the pregnant woman has not yet delivered, after 2 weeks of application of 1 course of therapy, the gestational week is still less than 32 weeks + 6, and it is estimated that the pregnancy will be terminated in the short term, another course of therapy can be applied, but the total course of therapy should not exceed 2 times. There is no special treatment for pregnant women with combined diabetes or gestational diabetes, but attention should be paid to monitoring blood glucose levels and preventing ketosis caused by excessive blood glucose.
2, the application of antibiotics: the main cause of PPROM is infection, mostly subclinical infection, 30% to 50% of PPROM amniotic cavity can be found in evidence of infection. Even if there is no infection at that time, it is still prone to episodic infection due to rupture of membranes during expectant fetal preservation. The value of prophylactic antibiotic application for PPROM is positive, effectively prolonging the incubation period of PPROM, reducing the incidence of chorioamnionitis, decreasing the rate of delivery within 48 h and 7 d after rupture of membranes, and decreasing the rate of neonatal infection as well as the rate of abnormalities on neonatal cranial ultrasound (grade I/A).
The specific application method: ACOG recommended effective antibiotics with evidence-based medicine, mainly ampicillin combined with erythromycin intravenously for 48 h, followed by oral amoxicillin combined with entero-erythromycin for 5 d. The specific dosage is, ampicillin 2 g + erythromycin 250 mg every 6 hours intravenously for 48 h, amoxicillin 250 mg combined with entero-erythromycin 333 mg every 8 hours for 5 d In pregnant women with penicillin allergy, erythromycin alone can be given orally for 10 d. Ampicillin + potassium clavulanate antibiotics should be avoided because of the increased risk of necrotizing small bowel colitis in newborns. However, because antibiotic resistance is very serious in China, the choice of drugs and programs should be based on individual circumstances with reference to the antibiotic program recommended by ACOG.
3, the use of contraction inhibitors: PROM will occur after the occurrence of different degrees of contractions, PPROM caused by contractions are mostly due to subclinical infection induced prostaglandin synthesis and secretion of a large number of related, if there are regular contractions, it is recommended to apply contraction inhibitors 48 h, to complete the treatment of glucocorticoids to promote fetal lung maturation, to reduce the occurrence of neonatal RDS, or timely referral to a hospital with neonatal ICU. The risk of chorioamnionitis and placental abruption should be re-evaluated if regular contractions are still present after completion of the above treatment, and further preservation of the fetus is contraindicated if there is definite infection or if labor has already entered.
Randomized controlled studies suggest that the application of magnesium sulfate to pregnant women at risk of delivery before 32 weeks of gestation reduces the rate of cerebral palsy in surviving infants. Therefore, magnesium sulfate may be considered for fetal neurological protection in PPROM pregnant women less than 32 weeks of gestation who are at risk of delivery at any time, but there is no uniform protocol.
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4. Monitoring during expectation: Conservative expectation treatment with high breech bed rest, avoiding unnecessary anal and vaginal examinations, dynamic monitoring of amniotic fluid volume, fetal condition, presence of placental abruption and regular monitoring for signs of chorioamnionitis and prodromal labor. There is no consensus on the best frequency of monitoring, but the current monitoring methods include regular ultrasound monitoring of fetal growth and amniotic fluid volume, fetal heart monitoring, and detection of infection indicators, and cervical secretion culture and mid-stage urine culture can be considered for long term fetal preservation to detect chorioamnionitis in time. During the bed rest period, attention should be paid to prevent some complications that may result from prolonged bed rest, such as thrombosis and muscle atrophy. In case of infection, fetal distress, placenta abruptio, and persistent low amniotic fluid during conservative treatment, termination of pregnancy should be considered, while those with stable disease can expect to terminate pregnancy after ≥34 weeks of gestation.
(iii) Mode of delivery
The choice of delivery method for PPROM should be based on the gestational week, survival rate of preterm infants, the presence of amniotic fluid or chorioamnionitis, whether the fetus can tolerate contractions, fetal orientation, etc. PPROM is not an indication for cesarean delivery, and the delivery method should follow the standard obstetrical routine, and vaginal trial of labor should be chosen when there is no clear indication for cesarean delivery. The indications for cesarean delivery should be relaxed if there are any abnormalities. In vaginal delivery, routine perineal incision is not necessary and prophylactic forceps are not recommended. If there are indications for cesarean delivery, cesarean delivery should be preferred; in case of breech fetus, cesarean delivery should be preferred, but it should be weighed according to the gestational week and local medical conditions; after delivery of PPROM fetus, it is recommended to perform pathological examination of placenta and fetal membranes to determine whether there is histopathological chorioamnionitis. For suspected intrauterine infection or definite intrauterine infection perform culture of amniotic cavity and neonatal ear swab.
(iv) Other issues
1. Management of hypohydramnios: Amniotic fluid index <5 cm or maximum vertical depth of amniotic fluid plane <2 cm is considered as hypohydramnios, which is a common complication of PPROM. It is recommended to use the maximum vertical depth of the amniotic horizontal plane to monitor the amniotic fluid volume of PPROM. Appropriate amniotic fluid volume is important for fetal lung development. If the amniotic fluid is too low before 26 weeks of gestation it can lead to fetal lung hypoplasia; fetal deformation such as POTTER face, limb contracture and skeletal deformation. In addition, low amniotic fluid is also a high risk factor for chorioamnionitis and fetal distress. However, amniotic cavity perfusion does not improve pregnancy outcome. Intra-amniotic perfusion in anticipation of fetal preservation does not significantly improve the incidence of pulmonary dysplasia, and amniotic perfusion during labor does not significantly reduce the incidence of fetal distress or decrease the rate of cesarean delivery. Therefore, amniocentesis is not recommended in cases of low amniotic fluid. If the amniotic fluid is too low, monitor closely for chorioamnionitis and fetal distress and terminate the pregnancy when appropriate.
2.Whether to expect fetal preservation at home: clear PROM is not suitable for fetal preservation at home because it is difficult to predict the change of condition at any time; if the membranes are broken at high level, after a period of hospitalization and observation, the amniotic fluid is no longer flowing, the ultrasound indicates normal amniotic fluid volume and there are no related complications, you can consider going home, but monitor the body temperature and regular prenatal checkup.
3. Treatment of PPROM after cervical cerclage: Cervical cerclage is a high risk factor for PPROM, about 38% of PPROM occurs. Is the stitches removed immediately? It is also a frequent clinical problem. Currently, there is a lack of prospective randomized controlled studies; retrospective studies have found that if retaining the annuloplasty line can significantly prolong the gestational week for more than 48 h, but can significantly increase the incidence of maternal chorioamnionitis, neonatal infection and neonatal sepsis; therefore, individualized management is recommended, and for pregnant women with PPROM at < 24 weeks of gestation, the line can be removed to abandon the fetus; for PPROM at 24 to 27 weeks +6 For PPROM at 24 to 27 weeks +6 weeks of gestation, the decision to expect treatment and give fetal lung maturation is based on the patient's informed consent and individual circumstances; for PPROM at 28 to 31 weeks +6 weeks of gestation, removal of the stitches or retention can be considered based on individual circumstances after completion of fetal lung maturation without contraindications; at ≥32 weeks of gestation, removal of the stitches should be considered once PROM is diagnosed (level II/B).