Betamethasone (Celestone® )
Corticosteroid. Anti-inflammatory.

• Indicated for the reduction of neonatal mortality, (respiratory distress syndrome) RDS, and (intraventricular hemorrhage) IVH in women at risk for preterm delivery at less than 34 weeks.

                      12 mg intramuscularly every 24 hours for 2 doses
            
 

Dexamethasone (Decadron® )
Corticosteroid. Anti-inflammatory.

• Indicated for the reduction of neonatal mortality, (respiratory distress syndrome) RDS, and (intraventricular hemorrhage) IVH in women at for preterm delivery at less than 34 weeks.

Hydrocortisone (Cortef, Solu-Cortef ®)
Corticosteroid. Anti-inflammatory.

Prevention of Recurrent Preterm Labor

17 alpha-hydroxyprogesterone caproate (Delalutin® )
Synthetic Progestin 

• Documented history of previous spontaneous singleton birth before 37 weeks gestation.

           250 mg IM every week from 16 to 36 weeks' gestation          
 

Progesterone
Progestin

• Documented history of previous spontaneous singleton birth before 37 weeks gestation, a prior cervical cerclage, or a uterine anomaly.

          100 mg progesterone vaginal suppository in polyethylene glycol base nightly from 24 to 34 weeks' gestation.

See micronized progesterone Prometrium ®

Prophylaxis for perinatal (Group B Streptococcal )GBS disease*
Intrapartum prophylaxis is indicated if:

• Previous infant with invasive GBS disease.
• GBS bacteriuria during any trimester of the  current pregnancy
  
• Positive GBS screening culture during current pregnancy (unless a planned cesarean delivery, in the absence of labor or amniotic membrane rupture, is performed)
• Unknown GBS status (culture not done, incomplete, or results unknown) and any of the following:
  • Delivery at < 37 weeks gestation
  • Amniotic membrane rupture >18 hours
  • Intrapartum temperature > 100.4 ^o F (> 38.0 ^o C)
    If amnionitis is suspected, broad-spectrum antibiotic therapy that includes an agent known
    to be active against GBS should replace GBS prophylaxis.

• Intrapartum NAAT**  or vaginal and rectal GBS culture is positive for GBS.
   

Recommended (Drug of Choice)	Penicillin G, 5 million units IV initial dose, then 2.5 to 3 million units IV every 4 hours until delivery
Alternative	Ampicillin, 2 g IV initial dose, then 1 g IV every 4 hours until delivery
If penicillin-allergic
Patient does not have a history of anaphylaxis, angioedema, respiratory distress or urticaria following administration of a penicillin or a cephalosporin	Cefazolin 2 g IV initial dose, then 1 g every 8 hours until delivery
Patients at high risk for anaphylaxis GBS susceptible to clindamycin and erythromycin.	Clindamycin, 900 mg IV every 8 hrs until delivery
Patients at high risk for anaphylaxis GBS resistant to clindamycin or erythromycin or susceptibility unknown	Vancomycin 1 g IV every 12 hours until delivery

Abbreviation: NAAT = Nucleic acid amplification tests

**If intrapartum NAAT is negative for GBS but any other intrapartum risk factor (delivery at <37 weeks' gestation, amniotic membrane rupture at ≥18 hours, or temperature ≥100.4°F [≥38.0°C]) is present, then intrapartum antibiotic prophylaxis is indicated.

Penicillin-allergic patients at high risk for anaphylaxis are those who have experienced immediate hypersensitivity to penicillin (e.g., angioedema or urticaria) including a history of penicillin-related anaphylaxis; other high-risk patients are those with asthma or other diseases that would make anaphylaxis more dangerous or difficult to treat, such as persons being treated with beta-adrenergic-blocking agents.

Penicillin should be continued for a total of at least 48 hours, unless delivery occurs sooner. At the physician's discretion, antibiotic prophylaxis may be continued beyond 48 hours in a GBS culture-positive woman if delivery has not yet occurred. For women who are GBS culture positive, antibiotic prophylaxis should be reinitiated when labor likely to proceed to delivery occurs or recurs.

REFERENCE
Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B sreptococcal disease--revised guidelines from CDC, 2010.MMWR Recomm Rep. 2010 Nov 19;59(RR-10):1-36. PMID:  21088663
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htm

TOCOLYTICS
"There is no clear first-line tocolytic drug. If tocolytic drugs are used, the choice of drug should be individualized and based on maternal condition, potential drug side effects, and gestational age. Prolonged use of any tocolytic drug may potentially increase the maternal-fetal risk without offering a clear benefit." [1G]

Tocolysis is generally not indicated for

• Gestation > 34 weeks
• Fetal death-in-utero
• Fetal malformation where palliative care only is planned
• Suspected fetal compromise as determined by ultrasound or antenatal testing warranting delivery
• Placental Abruption (Unless minor and remote from term)
• Chorioamnionitis 
• Pre-eclampsia
• Negative fetal fibronectin (Unless cervical change occurs)

Indomethacin (Indocin® )
Nonsteroidal antiinflammatory (Prostglandin synthetase inhibitor/Cyclo-oxygenase (COX) inhibitor)
 

• Acute Treatment of Preterm Labor at less than 32 weeks
       Initial dose 50 to 100 mg PO. May repeat in one hour if no decrease in contraction frequency , then 25 to 50 mg every 6 hours.
   

Check amniotic fluid at start of therapy and in 48 hours after start of therapy. Discontinue after 48 hours, or if delivery seems likely within  24 hours.

Contraindicated in patients with history of peptic ulcer, hemolytic dysfunction, kidney or liver disease, pregnancy at or after 32 weeks gestation, IUGR, chorioamnionitis, oligohydramnios, ductal dependent cardiac defects, and twin transfusion syndrome. Use with caution in asthma patients.

Maternal side effects: gastrointestinal irritation, heartburn, nausea and vomiting. Possible hypertension when used with beta blockers.
Fetal side effects: may cause premature closure of the ductus arteriosus, decreased renal function with oligohydramnios

( 25 and 50 mg  capsules, 25 mg / 5 mL oral suspension; 50 mg rectal suppositories. )
 

REFERENCES
Gordon MC, Samuels P. Indomethacin. Clin Obstet Gynecol.1995 ;38(4):697-705.PMID:8616967
King J et al. Cyclo-oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database Syst Rev.2005  18;(2):CD001992.  PMID:15846626
Macones GA, et al. The controversy surrounding indomethacin for tocolysis. Am J Obstet Gynecol.2001;184:264-72.PMID:11228471
Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 7th edition,Baltimore, MD: Williams & Wilkins,2005 p 823-831.
Friedman S , et. al., Indomethacin tocolysis and white matter injury in preterm infants. 2005 ;18(2):87-91.PMID:16203592
Loe SM, et al., Assessing the neonatal safety of indomethacin tocolysis: a systematic review with meta-analysis.Obstet Gynecol. 2005;106(1):173-9. PMID:15994634
Panter KR, et. al., The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial.Br J Obstet Gynaecol. 1999;106(5):467-73PMID:10430197
Norton ME. Teratogen update: fetal effects of indomethacin administration during pregnancy.Teratology.1997 ;56(4):282-92. PMID:9408979
Haas DM et al., Tocolytic Therapy: A Meta-Analysis and Decision Analysis Obstetrics & Gynecology .2009 Mar 113(3):585-594
Hearne AE, Nagey DA.Therapeutic agents in preterm labor: tocolytic agents. Clin Obstet Gynecol. 2000 Dec;43(4):787-801. PMID: 11100296
Indomethacin capsules TEVA Pharmaceuticals USA Inc 07/2010. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6422d983-a063-41ae-aa96-7ae2284cb123
Accessed 11/19/11

 Nifedipine( Adalat®,  Procardia® )
Calcium channel blocker

• Acute Treatment of Preterm Labor

  Nifedipine 20 mg PO . May repeat in  30 minutes if contractions persist.
  After contractions have been controlled give nifedipine 20 mg every 3 to 8 hours

  OR

  10 mg orally every 20 minutes for three doses total, followed by 20 mg orally every 4 to 6 hours..  

  Maximum dose 160 mg/day

  Discontinue after 48 hours, pulse > 120 BPM, or blood pressure less than 90 / 60 mm Hg
   

REFERENCES
Carlan SJ, et al.Randomized comparative trial of indomethacin and sulindac for the treatment of refractory preterm labor.Obstet Gynecol. 1992 Feb;79(2):223-8.PMID: 1731289
Sawdy RJ, et al. A double-blind randomized study of fetal side effects during and after the short-term maternal administration of indomethacin, sulindac, and nimesulide for the treatment of preterm labor. Am J Obstet Gynecol. 2003 Apr;188(4):1046-51. PMID: 12712108
Peek MJ, et al. Medical amnioreduction with sulindac to reduce cord complications in monoamniotic twins. Am J Obstet Gynecol. 1997 Feb;176(2):334-6.PMID: 9065177
Hearne AE, Nagey DA.Therapeutic agents in preterm labor: tocolytic agents.Clin Obstet Gynecol. 2000 Dec;43(4):787-801. PMID: 11100296
CLINORIL (sulindac) MERCK SHARP & DOHME Pty., Ltd. July 2010
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6f0e1d2c-83ba-4cb5-75b9-58638c13f9a8" target="_blank">http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6f0e1d2c-83ba-4cb5-75b9-58638c13f9a8