Obstetrics & Gynecology Hospital of Fudan University Xu Huan Preterm Labor Obstetrics & Gynecology Hospital of Fudan University Xu Huan

Introdution Labor and delivery between 28 – 36+6 weeks 5%-10% be the leading cause of perinatal morbidity and mortality Survival rates have increased and morbidity has decreased because of technologic advances

Definition (WHO) Incidence (6%-10%) Preterm labor is the presence of contractions of sufficient strength and frequency to effect progressive effacement and dilatation of the cervix between 20 and 37 weeks’ gestation Definition (WHO) Spontaneous : 40-50% PROM : 25-40% Obstetrically indicated : 20-25% Incidence (6%-10%) 5

Survival by gestational age among live-born resuscitated infants In: Creasy, Resnik . Maternal – Fetal Medicine, 2009 6

Pathophysiology 7

Ascending intrauterine infections stage I changing flora vagina/cervix, II Microorganism alocated between the amnion and chorion, III intra amniotic infection, IV fetal invation The preterm parturition syndrome. Multiple pathologic processes can lead to activation of the common pathway of parturition. In: Creasy, Resnik . Maternal – Fetal Medicine, 2009 8

Infections associated with preterm delivery Genital * Bacterial vaginosis (BV) * Group B streptococcus * Chlamydia * Mycoplasmas Intra-uterine * Ascending (from genital tract) * Transplacental (blood-borne) * Transfallopian (intraperitoneal) * Iatrogenic (invasive procedures) Extra-uterine * Pyelonephritis * Malaria * Typhoid fever * Pneumonia * Listeria * Asymptomatic bacteriuria In:Jane Norman.Preterm labor 2005 9

Stretch Inflammation Abruption Stress Thrombin ↑ CRH ↑ Estrogen Integrins ↑IL-1β ↑TNF-α ↑COX2 ↓ PGDH ↓ PR-B ↑ MMPs ↑ IL-6 and 8 PTL or PPROM Principal biomechanical mechanisms responsible for chain pathways of preterm parturition COX2=cyclooxygenase2, PGDH=prostaglandin dehydrogenase PR-B=Progesteron receptorB.CRH=corticotropin releasing hormon MMPs=matrix metallo proteinase In: Creasy, Resnik . Maternal – Fetal Medicine, 2009 10

Risk Factors(1) Previous preterm delivery Low socioeconomic status Maternal age <18 years or >40 years Preterm premature rupture of the membranes Multiple gestation Maternal history of one or more spontaneous second-trimester abortions Maternal complications (medical or obstetric) Lack of prenatal care

Risk Factors(2) Uterine causes Abnormal placentation Myomata (particularly submucosal or subplacental) Uterine septum Bicornuate uterus Cervical incompetence Abnormal placentation

Risk Factors(3) Infectious causes Fetal causes Chorioamnionitis Bacterial vaginosis Asymptomatic bacteriuria Acute pyelonephritis Cervical/vaginal colonization Fetal causes Intrauterine fetal death Intrauterine growth retardation Congenital anomalies

Diagnosis Documented uterine contractions(4 per 20 minutes or 8 per 60 minutes) Documented cervical change (cervical effacement of 80% or cervical dilatation of 2cm or more)

Forecast uterine activity monitoring. Ultrasound Examination of Cervical length Fetal Fibronectin

Major Risks of Preterm Delivery PRETERM LABOR  Most mortality and morbidity is experienced by babies born before 34 weeks Major Risks of Preterm Delivery Death Respiratory distress syndrome Necrotising enterocolitis Jaundice Hypothermia Hypoglycaemia Infection Retinopathy of prematurity Goldenberg, Obstetrics & Gynaecology 11-2002 16

Treatment(1) An initial assessment: ascertain cervical length and dilatation and the station and nature of the presenting part Bed Rest : be placed in the lateral decubitus position

Although bed rest is often prescribed for women at high risk for preterm labor and delivery, there are no conclusive studies documenting its benefit. A recent meta-analysis found no benefit to bed rest in the prevention of preterm labor or delivery.

Treatment(2) Tocolytic therapy Magnesium sulfate (Intracellular calcium antagonism) has become the drug of choice for initiating tocolytic therapy. Terbutaline (Bricanyl) Beta2-adrenergic receptor agonist sympathomimetic; decreases free intracellular calcium ions Nifedipine(Procardia) Calcium channel blocker

Tocolytic Therapy Prostaglandin synthetase inhibitors: indomethacin, administered both orally and rectally Ritodrine (Yutopar) Same as terbutaline Nifedipine Indomethacin (Indocin) Prostaglandin inhibitor

Tocolytic therapy may offer some short-term benefit in the management of preterm labor. A delay in delivery can be used to administer corticosteroids to enhance pulmonary maturity and reduce the severity of fetal respiratory distress syndrome,

also be used to facilitate transfer of the patient to a tertiary care center No study has convincingly demonstrated an improvement in survival, long-term perinatal morbidity or mortality, or neonatal outcome with the use of tocolytic therapy alone.

Potential Complications Associated With the Use of Tocolytic Agents : Magnesium sulfate • Pulmonary edema • Profound hypotension* • Profound muscular paralysis* • Maternal tetany* • Cardiac arrest* • Respiratory depression*

Beta-adrenergic agents • Hypokalemia • Hyperglycemia • Hypotension • Pulmonary edema • Arrhythmias • Cardiac insufficiency • Myocardial ischemia • Maternal death

Indomethacin (Indocin) • Renal failure • Hepatitis • Gastrointestinal bleeding Nifedipine (Procardia) • Transient hypotension

Treatment(3) Corticosteroid Therapy Dexamethasone and betamethasone for fetal maturation reduces mortality, respiratory distress syndrome and intraventricular hemorrhage in infants between 28 and 34 weeks of gestation. benefits start at 24 hours and last up to seven days after treatment The potential benefits or risks of repeated administration of corticosteroids after seven days are unknown.

Treatment(4) Antibiotic Therapy women who received antibiotics sustained pregnancy twice as long as those who did not receive antibiotics had a lower incidence of clinical amnionitis. poor fetal outcome (death, respiratory distress, sepsis, intraventricular hemorrhage or necrotizing colitis) occurred less frequently in women receiving antibiotics

Treatment(5) Labor and deliverey With modern neonatal care, the lower limit of potential viability is 24 weeks or 500g, although these limits vary with the expertise of the neonatal intensive care unit. Continuous fetal heart monitoring and prompt attention to abnormal fetal heart rate patterna are extremely important. With a vertex presentation, vaginal delivery is preferred. Use of outlet forceps and an episiotomy to shorten the second stage are advocated. Cesarean section for delivery of the very low birth weight baby For the breech fetus estimated at less than 1500g, neonatal outcome is improved by cesarean section

Premature of membrane

Definition Premature rupture of the membranes (PROM) is defined as amniorrhexis (spontaneous rupture of membranes) prior to the onset of labor at any stage of gestation

Incidence PROM occurs in about 10-15% of all delivery PROM is associated with 10% of term pregnancy

Cause of PROM(1) The cause of PROM is not clearly understood, perhaps associated with the follow factors: Trauma Sexual intercourse (particularly in the late gestational weeks) lax of internal os of uterine

Cause of PROM(2) Vaginal infection due to bacteria, virus, TOXO, CMV, HPV, HSV, et al STDs sexually transmitted diseases play an important role in the cause of PROM, because such infections are more commonly found in women with PROM than in those without PROM Increased of intra-uterine pressure (such as multiple pregnancy and hydraminios) Abnormalities in presentation and position

Cause of PROM(3) Smoking the risk of PROM is at lease doubled in women who smoke during pregnancy Other factors for PROM include the follow Prior PROM A short cervical length Prior preterm delivery Bleeding in early pregnancy

Manifestation and Diagnosis Fluid passing through the vagina suddenly, and then small amounts of fluid flow through the vagina intermitently, particularly when the increased of abdorminal pressure (cough, sneeze, et al) Intermittent urinary leakage is common during pregnancy, especially near term Increased vaginal secretions in pregnancy Perineal moisture Increased cervical discharge Urinary incontinence Vesicovaginal fistula May be mistaken for the fluid

Experimental Test(1) The Nitrazine test uses pH to distinguish amniotic fluid from urine and vaginal secretions, the paper turns dark blue in response to the amniotic fluid Amniotic fluid is quite alkaline having a pH above 7.0, but vaginal secretions in pregnancy usually have pH values of less 6.0

Experimental Test(2) The “fern” test : placing a sample on a microscopic slide, air drying, and examining for ferning The amniotic fluid does fern The other fluid does not fern

Risk of PROM Preterm labor: 75% Intrauterine infection(chorioamnionitis, 30-50% of case) Puerperal infection

Fetal and neonatal complications Fetal and neonatal pneumonia, sepsis Neonatal respiratory distress syndrone Neurologic dysfunction Intracranial hemorrhage Prolapse of umbilical cord Abruptio placenta

Evaluation The gestational age( LMP, ultrasound and uterus fundal height measurement) The presence of uterine contractions (abdominal examination) The amount of amniotic fluid (ultrasound) Fetal heart rate (FHR monitor) Fetal maturity (L/S or PG) The likelihood of chorioamnionitis (white blood cell count) The likelihood of prolapse of umbilical cord

Management(1) Conservative expectant management Management of chorioamnionitis Tocolytic therapy Use of corticosteroids Labor and delivery Surfactant therapy

Management(2) If PROM occurs at term(37 weeks’ gestational age or more), awaiting the onset of spontaneous labor for 12-24h should be considered, because spontaneous labor will ensue in 90% of patients within 24 hours If the time from PROM to the inset of labor exceeds 24h, induction of labor should be considered by oxytocin If the evaluation suggests intrauterine infection or chorioamnionitis, antibiotic and delivery are indicated and the antibiotic prescribed should have a broad spectrum of coverage If the infant is a preterm breech, and the onset of PROM occurs after 30 weeks’ of gestational, possibly by ceasarean delivery

Management(3) If the gestational age is less 30 weeks’, vaginal deliverly should be chosen If the fetus is significantlypreterm and the absence of infection, expectant management is generally chosen

Management(4) Patients must be assessed carefully Uterine tenderness daily Electronic fetal monitoring used frequently Fetal movement monitoring by the mother Frequent ultrasound assessment helps to determine amniotic fluid Frequently WBC counts, usually daily for several days Antibiotic should be used and antibiotic therapy may prolong the latency period after preterm PROM and improve the perinatal outcome

Management(5) To enhance fetal pulmonary matrurity in patients with preterm PROM Corticosteroid therapy (such as betamethasone and dexamethasone) is generally recommended in patients whose gestational age is 34 weeks’ or less

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