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Antenatal steroids

Candidates for Use of Antenatal Corticosteroids [2,9, 10]

  • All fetuses between 24 +0  and 34 +6 weeks' gestation at risk of preterm delivery within 7 days 
  • In preterm premature rupture of membranes at less than 32 weeks' gestation in the absence of clinical chorioamnionitis, antenatal corticosteroid use is recommended. Treatment at 32 to 33 weeks may also be beneficial
  • Fetuses greater than 34 weeks gestation at risk of preterm delivery within 7 days in the presence of an immature lung profile[2]
  • Patients eligible for therapy with tocolytics should also be eligible for treatment with antenatal corticosteroids.
  • Antenatal corticosteroids are most effective in reducing RDS in pregnancies that deliver 24 hours after
    and up to 7 days after administration of the second dose of antenatal corticosteroids. Because treatment with corticosteroids for less than 24 hours is still associated with significant reductions in neonatal mortality, RDS, and IVH, antenatal corticosteroids should be given unless immediate delivery is anticipated.
  • A single rescue course of antenatal corticosteroids may given if more than two weeks have elapsed since the last course of antenatal steroids , the fetus is less than 32 6/7 weeks, and the fetus is likely to deliver within the next week [9].


    Royal College of Obstetricians and Gynaecologists advises:"
     

    • Antenatal corticosteroids can be considered for women between 23+0 and 23+6 weeks of gestation who
      are at risk of preterm birth. The decision to administer corticosteroids at gestations less than 24+0 weeks should be made at a senior level taking all clinical aspects into consideration.
    • Antenatal corticosteroids should be given to all women at risk of iatrogenic or spontaneous preterm
      birth up to 34+6 weeks of gestation.
    • Antenatal corticosteroids should be given to all women for whom an elective caesarean section is planned prior to 38+6 weeks of gestation."



    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.

                         6 mg given intramuscularly every 12 hours for 4 doses

    (0.5 , 0.75 , 4 mg tablets, 4 mg/mL solution )


     

    REFERENCE(S)
    1. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes.JAMA.1995 1;273(5):413-8. PMID:7823388
    2.The effect of antenatal steroids for fetal maturation on perinatal outcomes-interim draft statement. NIH Consens Statement Online 1994 Feb 28-Mar 2 [cited 10/7/06];12(2):1 24.http://consensus.nih.gov/1994/1994AntenatalSteroidPerinatal095html.htm
    3. Jobe AH and Soll RF. Choice and dose of corticosteroid for antenatal treatments.Am J Obstet Gynecol.2004;190(4):878-81.PMID: 15118606
    4. Ballard PL, Ballard R. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet Gynecol.1995 Jul;173(1):254-62.PMID:7631700
    5. Crowther Ca, et al. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial.Lancet.2006 367(9526):1913-9.PMID:16765760
    6. Wapner R.J. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am J Obstet Gynecol.2006 ;195(3):633-42. Epub 2006 Jul 17. PMID:16846587
    7. Morrison JC, Whybrew WD, Bucovaz ET, Schneider JM. Injection of corticosteroids into mother to prevent neonatal respiratory distress syndrome. Am J Obstet Gynecol 131:358,1978. PMID:352152
    8. Morrison JC, Schneider JM, Whybrew WD, Bucovaz ET. Effect of corticosteroids and Fetomaternal disorders on the L:S ratio. Obstet Gynecol 56:583, 1980 PMID:6893624
    9.Antenatal corticosteroid therapy for fetal maturation. Committee Opinion No. 475. American College of Obstetricians and Gynecologists. Obstet Gynecol 2011;117:422–4. PMID:21252775
    10. Royal College of Obstetricians and Gynaecologists. Green–top Guideline No.7: Antenatal corticosteroids to reduce neonatal morbidity and mortality. London: RCOG; 2010


    Prevention of Recurrent Preterm Labor

    17 alpha-hydroxyprogesterone caproate (Delalutin® , Makena®)
    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

    • In women with a singleton pregnancy , no history for preterm birth , and cervical length is 20 mm or less before or at 24 weeks

              200 mg progesterone vaginal suppository nightly until 36 weeks weeks' gestation OR

              Vaginal progesterone 8% gel (90 mg daily)

    See micronized progesterone Prometrium ®

    REFERENCES
    1. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.N Engl J Med. 2003 Jun 12;348(24):2379-85. Erratum in: N Engl J Med. 2003 ;349(13):1299. PMID:12802023
    2. Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 7th edition,Baltimore, MD: Williams & Wilkins,2005 p 789,790.
    3. Hartikainen-Sorri AL, et. al. Inefficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy.Obstet Gynecol.1980;56(6):692-5. PMID:7443111
    4.Resequie LJ et al. Congenital malformations among offspring exposed in utero to progestins, Olmsted County, Minnesota, 1936-1974.Fertil Steril. 1985 ;43(4):514-9.PMID:3987922
    4. Kester PA .Effects of prenatally administered 17 alpha-hydroxyprogesterone caproate on adolescent males. Arch Sex Behav.1984 ;13(5):441-55.PMID:6517685
    5. Jafee b , et. al., Aggression, physical activity levels and sex role identity in teenagers exposed in utero to MPA.Contraception. 1989 ;40(3):351-63.PMID:2527728
    6. Da Fonseca EB, et al Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study.Am J Obstet Gynecol.2003 ;188(2):419-24.PMID:12592250
    7.Dodd JM, et al., Prenatal administration of progesterone for preventing preterm birth. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004947. Review. PMID:16437505
    8. ACOG Committee Opinion. Use of progesterone to reduce preterm birth. Obstet Gynecol.2003 ;102(5 Pt 1):1115-6. PMID:14672496
    9.  Progesterone and preterm birth prevention: translating clinical trials data into clinical practice.
    Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Am J Obstet Gynecol. 2012 May;206(5):376-86. PMID: 22542113
    10.  Micronized progesterone gel capsules<(200 mg vaginally daily) package insert http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=849e9f62-7414-3c22-9cb1-934f953400fc
    12.. Prochieve® (progesterone gel) package insert  http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9f8dc923-65d7-42ff-b718-97e7a7e87822


     


    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


    Ketorolac (Toradol®)
    Nonsteroidal antiinflammatory (Prostglandin synthetase inhibitor/Cyclo-oxygenase (COX) inhibitor)

    • Acute Treatment of Preterm Labor at less than 32 weeks

         Loading dose 60 mg Loading IM then 30 mg intramuscularly every 6 hour X 48 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

    ( 15 mg/mL or  30 mg/mL 2 mL vials )

    REFERENCES
    Schorr SJ,et al. A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor. South Med J. 1998 Nov;91(11):1028-32.PMID: 9824184
    Hearne AE, Nagey DA.Therapeutic agents in preterm labor: tocolytic agents.Clin Obstet Gynecol. 2000 Dec;43(4):787-801. PMID: 11100296
    Ketorolac Tromethamine Injection, USP Baxter Healthcare Corporation 06/2010 http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=19520

     


    Magnesium Sulfate Injection, USP
    Competitive inhibitor of calcium.

    • Acute Treatment of Preterm Labor

      Administer a loading dose of 4-6 grams IV over 20  minutes,  then 2 grams/hour via an infusion pump, preferably a smart pump with operational dose range alerts.
      Increase magnesium sulfate by 1 gram per hour until patient has one or less contractions per 10 minutes or a maximum dose of 4 grams per hour is reached. 

      Once tocolysis is achieved continue at lowest possible dose for 12-24 hours. Discontinue and obtain magnesium level if there are signs of toxicity.

    Continuous monitoring of fetal oxygen saturation by pulse oximetry. Assess patient for signs of toxicity (e.g.,  somnolence,  muscle paralysis, loss of patellar reflexes) or pulmonary edema at intervals of 15 minutes for the first hour, 30 minutes for the second hour, and then hourly.

    Contraindicated in myasthenia gravis, hypocalcemia, heart block, and renal failure

    SIDE EFFECTS: Headache, nausea, vomiting, dizziness, flushing, sweating, hypotension,  Deep tendon reflexes begin to diminish when magnesium levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard.

    For magnesium toxicity administer Calcium Gluconate (10 mL of 10% solution over 10 minutes) by slow intravenous injection

    (40 grams magnesium sulfate in 1000 ml water for Injection).
     

    REFERENCES
    Gordon MC, Iams JD.Magnesium sulfate.Clin Obstet Gynecol. 1995 Dec;38(4):706-12.PMID: 8616968
    Crowther CA, Magnesium sulphate for preventing preterm birth in threatened preterm labour.Cochrane Database Syst Rev. 2002;(4):CD001060. Review.PMID: 12519550
    Lyell DJ, et al. Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: a randomized controlled trial.Obstet Gynecol. 2007 Jul;110(1):61-7. PMID: 17601897
    Doyle LW, et al., Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004661. PMID: 19160238
    Haas DM et al., .Tocolytic Therapy: A Meta-Analysis and Decision Analysis Obstetrics & Gynecology .2009 Mar 113(3):585-594 PMID:
    19300321
    Lyell DJ, et al., Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: a randomized controlled trial.
    Obstet Gynecol. 2007 Jul;110(1):61-7.PMID:  17601897


     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
       

    Contraindicated in patients with allergy to nifedipine, sick sinus syndrome , secondary or tertiary heart block, hypotension, and hepatic dysfunction.
     

    Side effects include tachycardia,  cutaneous flushing, headache, dizziness, nausea, vasodilatation, and severe hypotension in a hypovolemic patients. Drug induced maternal hepatoxicity has also been reported.

    (10, 20 mg immediate release capsules; 30, 60, 90 mg extended release capsules. )

    REFERENCES
    King JT, Flenady V, et al.. Calcium channel blockers for inhibiting preterm labour; a systematic review of the evidence and a protocol for administration of nifedipine. Aust NZJ Obstet Gynaecol. 2003;43:192-198.
    Papatsonis DN, et al. Nifedipine and ritodrine in the management of preterm labor: a randomized multicenter trial. Obstet Gynecol.1997;90(2):230-4. PMID:9241299
    Ferguson JE 2nd et al. ,A comparison of tocolysis with nifedipine or ritodrine: analysis of efficacy and maternal, fetal, and neonatal outcome. Am J Obstet Gynecol.1990;163(1 Pt 1):105-11.PMID:2197860
    Houtzager BA and Hogendoorn SM. Long-term follow up of children exposed in utero to nifedipine or ritodrine for the management of preterm labour.BJOG.2006;113(3):324-31.PMID:16487205
    King JF, et al.Calcium channel blockers for inhibiting preterm labour. Cochrane Database Syst Rev.2003;(1):CD002255. PMID:12535434
    Ray D and Dyson D. Calcium channel blockers.Clin Obstet Gynecol. 1995 ;38(4):713-21.PMID:8616969
    Zhang J and Klebanoff MA. Low blood pressure during pregnancy and poor perinatal outcomes: an obstetric paradox.Am J Epidemiol. 2001 Apr 1;153(7):642-6.PMID:11282790
    Steer PJ et al. Maternal blood pressure in pregnancy, birth weight, and perinatal mortality in first births: prospective study.BMJ.2004 4;329(7478):1312. Epub 2004 Nov 23. PMID:15561733
    Lyell DJ, et al. Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: a randomized controlled trial.Obstet Gynecol. 2007 Jul;110(1):61-7. PMID:17601897


    Progesterone
    Progestin

    • Maintenance tocolysis

       
      200 to 400 mg of progesterone vaginally until delivery

    REFERENCES
    1. Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2008 Feb;48(1):58-63. PMID:18275573
    2. Arikan I, et al., Effect of progesterone as a tocolytic and in maintenance therapy during preterm labor.Gynecol Obstet Invest. 2011;72(4):269-73. PMID:22086108
    3. Bomba-Opon DA, Ket. al., Vaginal progesterone after tocolytic therapy in threatened preterm labor.
    J Matern Fetal Neonatal Med. 2012 Jul;25(7):1156-9. PMID:21967664
    4. Areia A, et al., Progesterone use after successful treatment of threatened pre-term delivery.J Obstet Gynaecol. 2013 Oct;33(7):678-81. PMID:24127952
    5. Su LL, et al., Progestational agents for treating threatened or established preterm labour.
    Cochrane Database Syst Rev. 2014 Jan 31;1:CD006770. PMID:24482121



    Sulindac (
    Clinoril®)
    Nonsteroidal antiinflammatory (Prostglandin synthetase inhibitor/Cyclo-oxygenase (COX) inhibitor)

    • Acute Treatment of Preterm Labor at less than 32 weeks
        
      200 mg orally every 12 hours X 48 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

    ( 200 mg tablets)

    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


     

    Terbutaline  (Brethine®)
    Systemic
    beta2-adrenergic receptor agonist sympathomimetic (decreases free intracellular calcium ions)

    • Acute Treatment of Preterm Labor

           0.25 mg SC every 15 to 30 minutes up to a total dose of 0.5 mg in 4 hours. Then 0.25 mg every 3 hours.
      Discontinue after 48 hours or pulse greater than 120 beats per minutes.


    Contraindicated in cardiac disease, poorly controlled diabetes, antepartum hemorrhage, hypertension, hyperthyroidism, fetal distress, severe preeclampsia, severe intrauterine growth restriction (IUGR), chorioamnionitis, and abruption. 

    Side effects include chest pain, dyspnea, tachycardia, palpitation, tremor, headaches, hypokalemia, hyperglycemia, nausea/vomiting, nasal stuffiness, pulmonary edema, and fetal tachycardia.

    (1 mg / mL ampules)

    REFERENCES
    Anotayanonth S et al. Betamimetics for inhibiting preterm labour.Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004352. PMID:15495104
    Boyle JG.  Beta-adrenergic agonists.Clin Obstet Gynecol. 1995 ;38(4):688-96. PMID:8616966
    Dodd Jm. et al., Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003927.PMID:16437467
    Haas DM et al., Tocolytic Therapy: A Meta-Analysis and Decision Analysis Obstetrics & Gynecology .2009 Mar 113(3):585-594
    de Heus R, et al., Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study. BMJ. 2009 Mar 5;338:b744. doi: 10.1136/bmj.b744. PMID: 19264820
     
    Hearne AE, Nagey DA.Therapeutic agents in preterm labor: tocolytic agents.Clin Obstet Gynecol. 2000 Dec;43(4):787-801. PMID:11100296


    GENERAL REFERENCES


    1G.ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologist. Number 43, May 2003. Management of preterm labor.Obstet Gynecol. 2003 May;101(5 Pt 1):1039-47. PMID:12738177
    2G.Tocolytic Drugs for Women in Preterm Labour (1B) - Oct 2002. Clinical Green Top Guidelines 2006 Royal College of Obstetricians and Gynaecologists http://www.rcog.org.uk/index.asp?PageID=536
     Accessed 10/7/06
    3G. Sosa C. et al. ,Bed rest in singleton pregnancies for preventing preterm birth.Cochrane Database Syst Rev.2004;(1):CD003581. PMID:14974024
    4G. Stan C. et al., Hydration for treatment of preterm labour. Cochrane Database Syst Rev. 2002;(2):CD003096. PMID:12076470
    5G. Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev 2002;CD001060. PMID:12519550
    6G.Hill WC, Risks and complications of tocolysis.Clin Obstet Gynecol.1995 ;38(4):725-45. PMID:8616971
    7G.Haas DM et al., .Tocolytic Therapy: A Meta-Analysis and Decision Analysis Obstetrics & Gynecology .2009 Mar 113(3):585-594
    8G
     Prediction and prevention of preterm birth. Practice Bulletin No. 130. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:964–73. PMID:22996126 
     

     

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