Pharmacologic Management of Preterm Labor and Prevention of Preterm Birth

giane paula p. ruiz

OVERVIEW
Women's health is a major concern in the Nation today, particularly in the areas of maternal health and pregnancy. Of specific concern are effective strategies for identifying and treating women with symptoms of preterm labor so as to prevent preterm births and subsequent infant morbidity and mortality

INTRODUCTION
Preterm delivery is the major cause of perinatal mortality in the developed world and occurs in approximately 7% of all deliveries. Severe morbidity, especially respiratory distress syndrome, intraventricular haemorrhage, bronchopulmonary dysplasia and necrotising enterocolitis, are far more common in preterm infants than in term infants. Long-term impairments such as cerebral palsy, visual impairment and hearing loss are also more common in preterm infants.

OBJECTIVES
Define preterm labor and its impact Describe risk factors for preterm birth Name several ways to prevent preterm birth Identify and diagnose preterm birth Outline an evaluation and effective management once preterm labor is and preterm birth To aid pharmacists in making decisions in providing pharmacologic care to women during pregnancy

DEFINITION OF TERMS
Preterm birth, or the birth of an infant of less than 37 weeks gestation, is a leading cause of neonatal mortality in the United States Preterm labor is regular contractions that occur prior to 37 weeks gestation and are associated with cervical changes.

RISK FACTORS FOR PRETERM LABOR AND BIRTH

Medical Condition such as:
Bacterial vaginosis Intrauterine infection Nongenital tract infection Maternal abdominal surgery Maternal endocrine disorders Multiple gestation -- Periodontal disease -- Cervical length shorter than 3 cm -- Tobacco use -- Oternine abnormalities -- Placenta previa -- Placental abruption

RISK FACTORS FOR PRETERM LABOR AND BIRTH

Nonwhite race Short interpregnancy interval Maternal physical or emotional stress Maternal thinness Previous preterm birth Preterm premature rupture of membranes (PPROM)

ASSESSMENT OF PRETERM LABOR

2.1 Review history Medical Surgical Obstetric

2.2 Assess for signs and symptoms of preterm labour

Lower abdominal cramping Pelvic pressure Lower back pain Vaginal spotting or show Regular uterine activity Cervical effacement / dilatation

2.3 Physical examination and initial Investigations

Vital signs Mid-stream urinalysis and consider microscopy/culture/sensitivity Maternal abdominal examination Fetal heart rate +/- cardiotocograph (CTG) Sterile speculum examination Exclude premature rupture of membranes (PROM) Obtain fFN test if not contraindicated [refer section 2.4] High vaginal swab with M/C/S Low vaginal/ anorectal swab for Group

 Cervical length - Before the onset of labour, the cervix shortens and softens. Various methods have been tried to detect these changes, such as manual vaginal examination, transabdominal ultrasound, and transvaginal ultrasound. Of these modalities, transvaginal scanning appears to have the highest sensitivity, whereas transabdominal scanning was not predictive.

2.4 Diagnostic tests

 Transvaginal ultrasonography of a cervix demonstrating funneling of the amniotic membrane protruding into the internal os (long arrow) and shortened cervical length of 1.5 cm (short arrow).

2.4 Diagnostic tests

Fetal Fibronectin testing - Fetal fibronectin is an extracellular matrix glycoprotein produced by the chorionic cells. It is normally present in vaginal secretions until 22 weeks, and then disappears from the cervicovaginal secretions, only to reappear before the onset of labour at term. If the adhesive fibronectin interface between the chorion and the decidua is damaged by mechanical factors or infection, fibronectin may reappear in the vaginal secretions earlier, and its detection has therefore been proposed as a predictor of preterm labour.

MANAGEMENT OF PRETERM LABOR

NONPHARMACOLOGICAL TREATMENT
The effectiveness of these interventions is uncertain. It includes 1. BED REST 2. ABSTENTION FROM INTERCOURSE AND ORGASM 3. HYDRATION (ORAL OR IV)

PHARMACOLOGICAL TREATMENT
The decision to intiate pharmacologic therapy for preterm labor involves several factors: 1. The probability of progressive labor 2. Gestational stage 3. The maternal and fetal or neonatal risks associated with treatment

CORTICOSTEROIDS

ANTIBIOTICS

Bethamethasone Dexamethasone Hydrocortisone Clindamycin Metronidazole Penicillin G

TOCOLYTICS

Magnesium Sulfate Beta Adrenergic Agonists

Ritodrine Tertbutaline Nylidrin Isoxuprine Nifedipine

Calcium Channel Blockers

NSAIDS
Ketorolac Sulindac Indomethacin

Progesterone

CORTICOSTEROIDS
It is indicated between 26 and 34 weeks gestation who are at risk for preterm birth owing to preterm labor, PPROM, or severe preeclampsia or other medical conditions that necessitate preterm delivery. The effect of treatment is optimal if the baby is delivered more than 24 hours and less than 7 days after the start of treatment. These also aid in fetal lung maturity.

CORTICOSTEROIDS
Caution in patients with severe preeclampsia/hypertension. Impaired glucose tolerance may occur if repeated doses of corticosteroids are given, especially in conjunction with beta agonist therapy. The extremely rare complication of adrenal insufficiency should be considered if there is an unexplained collapse of either the mother or baby who are exposed to repeated courses of neonatal corticosteroids.

CORTICOSTEROIDS
Betamethasone (Celestone ) 12 mg intramuscularly every 24 hours for 2 doses Dexamethasone (Decadron ) 6 mg given intramuscularly every 12 hours for 4 doses (0.5 , 0.75 , 4 mg tablets, 4 mg/mL solution ) Hydrocortisone (Cortef, Solu-Cortef )
500 mg given IV every 12 h x 4 doses.

ANTIBIOTICS
Amoxicillin-clavulanate should be avoided in women who are at risk for preterm birth because of the increased chance of neonatal necrotizing enterocolitis. Bacterial vaginosis, an overgrowth of anaerobic bacteria, is associated with an increased risk of preterm birth; treatment of the vaginosis reduces the risk clindamycin 300 mg twice daily for 7 days metronidazole 500 mg twice daily for 7 days metronidazole 250 mg three times daily for 7 days

ANTIBIOTICS
Antibiotics don't prolong pregnancy, but there is clear data showing that it is helpful to treat women who carry a bacteria called group B streptococcus (GBS). IV administration of one dose of ampicillin 2 g followed by ampicillin 1 g every 6 hours for 48 hours

TOCOLYTICS
Objectives 1. Delay delivery so that steroids may be given 2. Allow safe transport of the mother if possible 3. Prolong pregnancy when there is self limiting causes of labor e.g sepsis

TOCOLYTICS
Inhibit uterine contractions. The choice of tocolytic should be based on maternal condition, potential adverse effects, gestational age, and cost. Most tocolytic drugs prolong gestation for 2 to 7 days

Magnesium Sulfate
one of the most common obstetric drugs in the U.S., is used primarily for seizure prophylaxis in preeclampsia. Despite its lack of proven efficacy, magnesium sulfate is also the most commonly used tocolytic agent in the U.S

TOCOLYTICS

Beta adrenergic agonist

Terbutaline -a beta-adrenergic agonist, is a potent cardiovascular (CV) stimulant that is associated with an increased risk of pulmonary edema and maternal and fetal CV abnormalities. A bronchodilator, it is approved to prevent and treat bronchospasms associated with asthma, bronchitis, and emphysema. Ritodrine Salbutamol Isoxuprine Nylidrin

TOCOLYTICS

Calcium channel blockers Calcium Channel Blocker

Nifedipine ( Tocolytic of choice) It reduces the risk of preterm delivery within 7 days of treatment prior to 34 weeks gestation. Compared with beta-agonists, nifedipine also lowers the risk of RDS, necrotizing enterocolitis, intraventricular hemorrhage, neonatal jaundice, and NICU admission. A calcium channel blocker that relaxes smooth muscle. It is an effective tocolytic with fewer side effects than other tocolytics available

TOCOLYTICS

NSAIDS (Prostaglandin inhibitors)

NSAIDs act as tocolytic agents by blocking the inflammatory process that triggers labor. Indomethacin Ketorolac Sulindac

TOCOLYTICS

TOCOLYTICS
Contraindications Gestation > 34 weeks Labour is too advanced In utero fetal death Lethal fetal anomalies Suspected fetal compromise Placental abruption Suspected intra-uterine infection Maternal hypotension: BP < 90 mmHg

PROGESTERONE PROGESTERONE
The hormone progesterone may be used as treatment to help prevent preterm birth but should be restricted to pregnant women with a documented history of preterm birth before 37 weeks gestation. Most trials use 250 mg 17-alphahydroxyprogesterone caproate (17OHPC) intramuscular injection

PROGESTERONE PROGESTERONE
Reduction of PTL of 15-70% Natural progesterone vaginal suppositories reduce the risk of preterm birth by up to 45% and decrease the incidence of respiratory distress and neonatal morbidity and mortality in pregnant women with a shortened cervix Vaginal gel 90 mg or 200 mg suppository

EMERGING TREATMENTS

 ATOSIBAN, a synthetic peptide, is a

competitive antagonist of oxytocin at uterine oxytocin receptors and has been developed as a new tocolytic therapy in the treatment of preterm labour. Atosiban may be marginally less effective in the management of preterm labour than the beta2-agonists (ritodrine, terbutaline, and salbutamol) currently used as tocolytics.

 BARUSIBAN has a higher selectivity and

potency at the oxytocin receptor level which potentially could lead to a faster onset of action and longer duration of action following parenteral administration than the previous generation of peptide oxytocin antagonist. Barusiban is currently undergoing clinical phase II trials to evaluate its effect in uterine contractility.

Role of the Pharmacist

Providing pharmacologic care to women during pregnancy can be rewarding, but it is often challenging. The health of the pregnant woman, as well as the health of the fetus, must be taken into account when drug therapy is being considered.

Role of the Pharmacist

Pharmacists must remain up-to-date on current clinical guidelines and the use of drugs during pregnancy in order to ensure healthy outcomes for mother and child. A collaborative approach between the obstetrician, neonatologist, pharmacist, and other health care providers is essential to reduce the burdens of preterm labor and birth