I. Definition of preterm birth
Preterm labor is defined as delivery between 28 weeks and less than 37 weeks of gestation. There are two types of preterm labor: spontaneous preterm labor and therapeutic preterm labor; spontaneous preterm labor includes unterm delivery and premature rupture of membranes; therapeutic preterm labor is pregnancy complications or comorbidities that require interruption of pregnancy.
Diagnosis and prediction of preterm labor
1.Diagnosis of preterm labor.
(1). Preterm labor: delivery before 37 weeks of gestation is called preterm labor;
(2). Preterm labor: regular contractions (4 every 20 minutes or 8 every 60 minutes) in late pregnancy (<37 weeks), accompanied by progressive changes in the cervix (cervical tolerance ≥80%, with dilatation of the uterine orifice above 2.0 cm).
2, the prediction of preterm labor: when less than 37 weeks of gestation, pregnant women with contractions can apply the following two methods for the prediction of preterm labor prodromal delivery.
(1). Ultrasound detection of cervical length and whether the inner cervical opening is open or not: transvaginal measurement should be preferred for predicting preterm labor using cervical length, but in case of suspected placenta praevia and premature rupture of membranes and reproductive tract infection, transperineal measurement or transabdominal measurement should be chosen. The normal values of cervical length during pregnancy are: 3.2-5.3 cm for transabdominal measurement; 3.2-4.8 cm for transvaginal measurement; 2.9-3.5 cm for perineal measurement.
The prediction of preterm labor in pregnant women with preterm labor or with high risk factors for preterm labor is considered: cervical length >3.0 cm is a more reliable indicator to exclude the occurrence of preterm labor. The length of the cervix should be monitored dynamically in those with symptoms of preterm labor. The funnel-shaped endocervical opening may be temporary and is only clinically predictive when accompanied by a shortening of the cervical length.
(2). Determination of fetal fibronectin (fFN) in posterior vaginal vault secretions: fFN is a glycoprotein, synthesized and secreted by amnion, meconium and chorionic villus, which plays an adhesive role to fetal membranes. It can be positive in the posterior vaginal vault secretions before 20 weeks of normal pregnancy, but should be negative in the posterior vaginal vault secretions between 22 and 35 weeks of pregnancy, and can be positive after 36 weeks of pregnancy. The sensitivity of fFN for predicting preterm labor is about 50% and the specificity is 80%-90% for those with symptoms of preterm labor between 24 and 35 weeks of gestation. 71% sensitivity and 89% specificity for delivery within 1 week.
With symptoms of preterm labor at 24-35 weeks of gestation, but negative fFN, the negative predictive value for not delivering within 1 week is 98% and 95% for not delivering within 2 weeks. Its importance lies in its negative predictive value and the significance of the near-term prediction.
(3). Application of combined fFN test for cervical length: those with symptoms of preterm labor, premature rupture of membranes, and cervical length <3.0 cm are suspected for further testing of fFN, and if fFN is positive, the risk of preterm labor is increased. (4). Caution: vaginal examination and vaginal ultrasound test should not be performed before fFN test, and sexual intercourse is prohibited within 24 hours.
Risk factors for preterm birth
The high-risk factors for preterm birth include
1. history of preterm delivery;
2. History of late miscarriage;
3. Age <18 years or >40 years;
4, physical illness and pregnancy complications;
5, underweight (body mass index ≤ 18Kg/m2);
6, no prenatal care, poor economic status;
7, drug or alcohol abusers;
8, prolonged standing during pregnancy, especially standing for more than 40 hours per week;
9, a high risk history of reproductive tract infections or sexually transmitted infections, or combined with sexually transmitted diseases such as syphilis;
10, multiple pregnancy;
11, pregnancy after assisted conception techniques;
12, developmental malformations of the reproductive system.
IV. Treatment of preterm labor and delivery
The treatment of preterm labor includes bed rest, glucocorticoids, contraction inhibitors, broad-spectrum antibiotics and maternal-fetal monitoring.
(a) Bed rest
(ii) Glucocorticoids
The role of glucocorticoids is to promote fetal lung maturation, and also to promote other fetal tissue development. The application of glucocorticoids to pregnant women before therapeutic preterm delivery and at risk of preterm delivery is suspected to reduce the risk of neonatal respiratory distress syndrome, ventricular hemorrhage and neonatal necrotizing small intestinal colitis, reduce neonatal mortality and do not increase the rate of infection.
1. Indications for the application of glucocorticosteroids.
(1) Those who have not reached 34 weeks of gestation and have the possibility of preterm delivery within 7 days;
(2) Gestational week > 34 weeks but there is clinical evidence that the fetal lung is not mature;
(3) Gestational diabetes mellitus with unsatisfactory glycemic control.
2, glucocorticoid application method: dexamethasone 5mg, intramuscular injection, once every 12 hours for 2 days, or betamethasone 12mg, intramuscular injection, once a day for 2 days, or intra-amniotic injection of dexamethasone 10mg once, intra-amniotic injection of dexamethasone is suitable for patients with gestational diabetes mellitus. For multiple pregnancies, dexamethasone 5mg intramuscularly once every 8 hours for 2 days or betamethasone 12mg intramuscularly once every 18 hours for 3 times.
3.Side effects of glucocorticoids.
(1) Increase in blood sugar of pregnant women;
(2) Reduced immunity of mother and child. Multi-course application may have certain effects on fetal neurological development, therefore, repeated prenatal and multi-course application is not recommended.
4. Contraindications to glucocorticoids: those with confirmed evidence of intrauterine infection.
(iii) Uterine contraction inhibitors
Uterine contraction inhibitors prolong the gestational cycle by 2-7 days, but do not reduce the rate of preterm delivery. It helps to transfer the fetus to a medical center with neonatal intensive care unit facilities in a timely manner while still in utero and ensures prenatal glucocorticoid application. All contraction inhibitors have varying degrees of side effects and are not recommended for long-term use. Commonly used contraction inhibitors include: magnesium sulfate, β-adrenergic agonist, indomethacin, nifedipine and contraction antagonist, etc.
1, magnesium sulfate: calcium antagonist, inhibition of neuromuscular impulses, relaxation of smooth muscle. Pregnancy medication belongs to class B.
(1) usage: the first dose of magnesium sulfate is 5g, half an hour intravenous drip, thereafter to intravenous drip 2g/h, after contraction inhibition continue to maintain 4 to 6h after changing to 1g/h, after contraction disappears continue to drip 12h, while monitoring breathing, heart rate, urine output, knee reflex. If possible, monitor the blood magnesium concentration. Blood magnesium concentration 1.5 ~ 2.5 mmol / l can inhibit contractions, but the blood magnesium concentration is too high can inhibit breathing, serious cases can make the heart stop.
(2) contraindications: severe muscle weakness, renal insufficiency, recent history of myocardial infarction and history of heart disease.
(3)Side effects: Pregnant women: fever, flushing, headache, nausea, vomiting, muscle weakness, hypotension, reduced motor reflex, respiratory depression in severe cases, pulmonary edema, cardiac arrest; fetus: no stress test NST non-responsive type increase; neonate: respiratory depression, low Apgar score, reduced intestinal motility, abdominal distension;
(4) monitoring indicators: maternal urine volume, respiration, heart rate, knee reflex, Mg2+ concentration; application of magnesium sulfate need to prepare 10% calcium gluconate 10ml for detoxification backup.
2, β adrenergic receptor agonist: ritodrine stimulates uterine adrenergic β receptors, reduces intracellular calcium ion concentration, thus inhibiting uterine smooth muscle contraction. Pregnancy medication belongs to category B.
(1)Usage: Dissolve 100mg of ritodrine in 500ml of glucose liquid and administer intravenously at a rate of 0.05mg/min at the beginning, then increase 0.05mg every 10-15min until 0.35mg/min until contractions stop. Thereafter, continue to maintain for 12h, gradually reduce the dose and then switch to oral administration. If the heart rate is ≥140 beats, the drug should be stopped.
(2) Absolute contraindications: maternal heart disease, abnormal liver function, preeclampsia, prenatal hemorrhage, uncontrolled diabetes mellitus, tachycardia, hypotension, pulmonary hypertension, hyperthyroidism, chorioamnionitis.
(3) Relative contraindications: diabetes mellitus, migraine, occasional tachycardia.
(4) Side effects: Pregnant women: tachycardia, tremor, palpitations, myocardial ischemia, anxiety, shortness of breath, headache, nausea, vomiting, hypokalemia, hyperglycemia, pulmonary edema; fetus: tachycardia, arrhythmia, myocardial ischemia, hyperinsulinemia; neonate: tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intracranial hemorrhage.
(5) Monitoring indicators: electrocardiogram, blood sugar, blood potassium, heart rate, blood pressure, lung condition, dynamic monitoring of angina symptoms and urine volume before and after medication, and total fluid restriction to 2400 ml/24h.
3, nifedipine: calcium channel blocker, so that the intracellular calcium ion concentration decreases and inhibits contractions. Pregnancy medication belongs to category C.
(1)Usage: First loading dose of 30mg orally or 10mg sublingually, 1 time for 20min for 4 times in a row. after 90min change to 10-20mg/4-6h orally or 10mg/4-6h sublingually, apply for no more than 3d.
(2)Side effects: Decreased blood pressure, palpitations, decreased placental blood flow, and slowed fetal heart rate.
(3) Contraindications: heart disease, hypotension and kidney disease.
4, indomethacin: non-steroidal anti-inflammatory drugs, prostaglandin (PG) synthase inhibitor, has the effect of making PG levels fall, reduce the role of contractions, pregnancy medication belongs to the B / D category.
(1) Usage: 150-300mg/d, first loading dose of 100-200mg, rectal administration, fast absorption; or 50-100mg orally, later 25-50mg/4-6h, limited to short-term application before 32 weeks of pregnancy.
(2) Side effects: Pregnant women: mainly gastrointestinal symptoms, nausea, vomiting and epigastric discomfort, etc., prolonged vaginal bleeding, increased bleeding during delivery; fetus: if used after 34 weeks of gestation, decreased PG levels cause arterial catheter constriction and narrowing, fetal heart failure and limb edema, decreased renal blood flow, and low amniotic fluid;
(3) Contraindications: peptic ulcer, indomethacin allergy, coagulation dysfunction and liver and kidney disease.
5.Atosiban (contractin receptor antagonist): Atosiban is a contractin derivative, which competes with contractin for contractin receptors and plays a role in inhibiting contractions. Compared with other 3 different β sympathomimetic drugs, atosiban has a lower incidence of side effects and has been used clinically as a uterine contraction inhibitor in Europe, but its wider application needs to be further evaluated.
(iv) Antibiotics
Although the main cause of preterm labor is due to infection, studies have shown that antibiotics do not prolong the gestational weeks and reduce the rate of preterm labor.1. Antibiotics should be applied individually to pregnant women with a history of preterm labor or other high-risk pregnancies for preterm labor, taking into account their medical conditions.2. Routine antibiotics are recommended for the prevention of infection in pregnant women with preterm labor who have premature rupture of membranes (see Management of premature rupture of membranes in preterm labor).
(E) Fetal monitoring
The main monitoring of fetal status includes amniotic fluid volume and umbilical artery blood flow monitoring and fetal biophysical score, timely detection of fetal distress, and evaluation of fetal growth and development and estimation of fetal weight by ultrasound measurement.
(vi) Maternal monitoring
This includes monitoring of vital signs, especially temperature and pulse, which often allows early detection of signs of infection. Regular rechecking of blood and urine routine and C-reactive protein, etc.
(vii) Timing of delivery
The choice of delivery timing includes.
1. For unavoidable preterm labor, all contraction inhibitors should be discontinued.
2, When the risk of prolonged pregnancy is greater than the risk of fetal immaturity, prompt termination of pregnancy should be chosen.
3. the decision to terminate the pregnancy at <34 weeks of gestation is made on an individual basis. If there is a definite intrauterine infection then the pregnancy should be terminated as soon as possible. For patients with ≥34 weeks of gestation, they can go with the flow of nature.
(H) Choice of delivery method
The choice of delivery mode should be fully communicated with the pregnant woman and her family that
1.Cesarean section is feasible for those who have indications for cesarean delivery, but it should be performed on the basis of estimating the possibility of survival of preterm infants.
2. Close monitoring of fetal heartbeat and careful use of sedatives that may inhibit fetal breathing should be performed for vaginal delivery. Perineal laterotomy should be performed routinely during the second stage of labor.
(ix) Others
Postpartum hemorrhage should be prevented if contraction inhibitors are used. Refer the preterm infant to neonatal ICN or ask an experienced physician for neonatal consultation and treatment.
V. Premature rupture of fetal membranes in preterm labor
1. Definition of premature rupture of fetal membranes: It refers to the rupture of fetal membranes that occurs before 37 weeks of gestation without delivery, mainly caused by infection.
2.Diagnosis of premature rupture of membranes in preterm labor: through clinical manifestations, medical history and simple experiments.
(1) Medical history is very important for the diagnosis of premature rupture of membranes in preterm labor, thus should not be ignored and should be understood in detail.
(2) Sodium dinitrophenylazo naphthol disulfonate test paper test of vaginal secretions to detect PH ≥ 7.
(3) The fluid in the vaginal vault pool is taken and placed in a glass slide, dried and observed under the microscope for amniotic fluid crystals. All the above tests were positive, and its accuracy rate of diagnosing premature rupture of membranes in preterm labor was 93.1%.
3, the diagnosis of intrauterine infection: determine the presence of chorioamnionitis is mainly based on clinical diagnosis. Placenta after delivery. Fetal membranes and umbilical cord pathological examination, cesarean section of the uterine cavity and newborn ear swabs for bacterial culture suspicious to help confirm the diagnosis, and can be used as a reference when choosing antibiotics. Clinical diagnostic indicators of intrauterine infection are as follows (diagnosis can be made with 3 or more of the following).
(1) elevated body temperature ≥ 38°C.
(2) pulse rate ≥ 110 beats.
(3) fetal heart rate >160 beats or <120 beats.
(4) elevated blood leukocytes up to 15?span>109/L or with leftward nuclear shift.
(5) elevated C-reactive protein level.
(6) offensive odor of amniotic fluid.
(7) pressure pain in the uterus.
4. Treatment of premature rupture of membranes: vaginal bacterial culture is needed before drug treatment.
(1) antibiotics: its role is sure, can reduce the rate of neonatal disease and death, as well as the incidence of puerperal infection. Penicillins are preferred, and those with penicillin allergy are switched to insured bacteriocin antibiotics.
(2) Glucocorticoid: clinically no obvious signs of intrauterine infection, can be applied, the method and dose of the same as preterm delivery.
(3) contraction inhibitors: if there is no contraction, it is not necessary to use them, if there is contraction and the pregnancy is <34 weeks, no clinical signs of infection can be applied for a short time.
(4) Termination: if the pregnancy is <34 weeks, the umbilical cord should be used if there is no intrauterine infection, glucocorticoids and antibiotics should be used, and the condition of mother and child should be closely monitored, if infection is found, the pregnancy should be terminated immediately. For hospitals without NICU, patients should be transferred to hospitals with NICU as soon as possible if there is no possibility of delivery in the short term. At >34 weeks of gestation, there is no need to routinely perform fetal preservation and let nature take its course.
VI. Prevention of preterm labor
The prevention of preterm labor includes.
1.Improvement of personal factors and socio-economic factors.
2. Standardized prenatal care. Those with high risk factors for preterm labor should pay attention to measuring cervical length and detecting fFN in vaginal or cervical secretions during routine ultrasound examination at 20 to 24 weeks of gestation.
3.Treatment of maternal diseases, such as hypertensive disorders in pregnancy, systemic lupus erythematosus, nephropathy, systemic infections (such as pyelonephritis, pneumonia, appendicitis, etc.), syphilis, lower genital tract infections, etc.
4. Prophylactic endocervical ring ligation is only applicable to those with loose endocervical opening.
5. Pay attention to health education and contraction monitoring of pregnant women.