Preterm Labor Prevention and Treatment Kerry Watrin MD August 2 nd 2007
Objectives: <ul><li>Define preterm labor and its impact </li></ul><ul><li>Describe Risk Factors for preterm birth </li></...
Definitions/ Epidemiology <ul><li>Definitions </li></ul><ul><ul><li>Preterm Labor : regular contractions with cervical cha...
Race/Ethnicity and Prematurity 2000to 2002 1.5% 10.7% White 1.4% 10.2% Asian 1.7% 11.4% Hispanic 2.0% 12.9% Native America...
Preterm Birth Causes Multifactorial <ul><li>Spontaneous Preterm Labor (31-50%) </li></ul><ul><ul><li>Intact membranes </li...
Case #1 <ul><li>24 year old NA G2P1 presents at 16 weeks </li></ul><ul><ul><li>history of spontaneous preterm birth at 26...
Case #1 Preterm Labor Precautions <ul><li>Lifestyle </li></ul><ul><ul><li>BMI 18, wt 100 lbs, </li></ul></ul><ul><ul><li>...
Prematurity Risk Factors <ul><li>High Risk/Low incidence </li></ul><ul><li>PTL after tocolysis 70% </li></ul><ul><li>Bleed...
Cervical Incompetence Risks <ul><li>Past OB History </li></ul><ul><li>Prior Midtrimester loss </li></ul><ul><li>Prior Pre...
Prematurity Interventions: Lifestyle <ul><li>Some Effect : </li></ul><ul><ul><li>Nutrition, zinc, folate and caloric suppl...
Expected pregnancy weight gain 15+ lbs > 29 Obese 15-25 lbs 26-29 High 25-35 lbs 19.8-26 Normal 28-40 lbs <19.8 Low Recomm...
Prematurity Interventions: Medical <ul><li>Effective : </li></ul><ul><ul><li>Rx Asymptomatic Bacteriuria (1970s tetracycl...
Asymptomatic Bacteriuria <ul><li>Defined as > 100K/ml single uropathogen </li></ul><ul><ul><li>Urine culture is gold stan...
Bacterial Vaginosis: Clue cell
Bacterial Vaginosis <ul><li>Common occurs in 20%, asymptomatic in 50% </li></ul><ul><li>Diagnosis by </li></ul><ul><ul><l...
Bacterial Vaginosis <ul><li>1995 small (n=426) high risk (prior PTB) </li></ul><ul><ul><li>RTC showed a 30% decrease in...
Bacterial Vaginitis Metronidazole potential harm <ul><li>Metronidazole </li></ul><ul><ul><li>2006 PREMET study, </li></ul...
Bacterial Vaginitis Clindamycin <ul><li>Clindamycin </li></ul><ul><ul><li>2003 RTC, Clindamycin low Risk, n= 494, Showed l...
Prevention with Progesterone <ul><li>High Risk Population of 463 women with prior preterm delivery (NIH study) </li></ul><...
Preterm outcomes and Progesterone NNT Relative Risk Placebo N=153 Progest N=306 7 0.66 (.51-.87) 62 41.1% 82 27.2% LBW < 2...
Progesterone Outcomes <ul><li>With Progesterone less NEC, need for O2, </li></ul><ul><li>Trend but not significant less R...
Progesterone Meta-analysis <ul><li>Cochrane: Jan 2006, 6 RTCs, 988 patients </li></ul><ul><ul><li>PTB <37 weeks, RR 0.65 (...
ACOG and Progesterone <ul><li>“ The hormone progesterone may be used as treatment to help prevent preterm birth but should...
Preterm Birth Risk Stratification <ul><li>Contractions: </li></ul><ul><ul><li>50% of those with threatened preterm labor ...
Markers for Prematurity <ul><li>Preterm Prediction Study: Case control </li></ul><ul><li>28 biologic markers studied in 2,...
Most Potent Predictive Markers For Preterm Birth < 32 weeks <ul><li> 2 positive below OR 56.5 </li></ul><ul><ul><li>59...
Other Markers of Preterm Birth < 32 weeks <ul><li>> 90 th % Ferritin OR 8.0 </li></ul><ul><li>Past Hx PTB OR 4.5* </li></...
Fetal Fibronectin <ul><li>Occurs in the choriodecidual junction </li></ul><ul><li>Decreases 16-20 wks, absent 24-34 wks </...
Fetal Fibronectin <ul><li>Asymptomatic </li></ul><ul><li>Positive (n=1,530) </li></ul><ul><ul><li>18.4% delivery <34 week...
Fetal Fibronectin <ul><li>If positive </li></ul><ul><ul><li>One in 5 symptomatic deliver in 7-10 days </li></ul></ul><ul>...
Case #2 Low Risk no prior PTB at 25 weeks <ul><li>Size < Dates, 21cm fundal height at 25 weeks </li></ul><ul><li>Transabdo...
Transvaginal Cervical Length <ul><li>1996 NEJM study of 2,915 women with US at 24 weeks, repeat on 2,531 at 28 weeks </li...
Rate of Preterm Birth <35 weeks by Cervical Length at 24 weeks 34 % < 13 mm 20 % <20 mm 8 %  25 mm Rate Delivery Length
Ultrasound Cervical Length Prediction of PTB < 35 weeks 17.2% 96.6% 94.5% 25.4% Funneling At 24 wk 17.8% 97% 92.2% 37.3% 2...
Cervical Length Caveats <ul><li>Distinguish Average Risk versus High Risk Population studies </li></ul><ul><li>Cervixes ch...
Cerclage and Short Cervix <ul><li>47,123 screened at 22-25 weeks </li></ul><ul><li>430 with cervical length < 15mm </li></...
Role of US and Cerclage High risk with 3 prior midterm losses <ul><li>Serial Cervical Length Ultrasound: </li></ul><ul...
Short Cervix and Vaginal Progesterone <ul><li>2003-2006, 24,620 screened by US at 20-25 weeks for short cervix during pren...
Contractions and Bishops Score And birth before 35 weeks <ul><li>306 high risk women, singleton pregnancy with prior PTB o...
Threatened Preterm Labor <ul><li>Preterm Labor due to what? </li></ul><ul><ul><li>Treat reversible causes, such as UTI, <...
Idiopathic Preterm Contractions in Triage <ul><li>179 randomized, </li></ul><ul><ul><li>singletons, 20-34 weeks, no ROM, ...
Contractions what to do? 4 (7%) 4 (6%) 5 (9%) PTB < 34 wks $687 $966 $717 Mean cost < 24 hours 5 (8%) 8 (13%) 7 (13%) admi...
Case #2 now with contractions <ul><li>Presents 28 weeks with contractions every 5 minutes, </li></ul><ul><li>Repeat exams ...
Case #2, Threatened PTL in High Risk (contracts, +FFN, short cervix) <ul><li>GBS prophylaxis: Penicillin </li></ul><ul><li...
The Recommendations MMWR, Vol 51 (RR-11)
CDC GBS algorithm for Threatened Preterm Delivery <ul><li>Suggested algorithm for management of threatened preterm delive...
Agents for intrapartum prophylaxis <ul><li>Recommended agents for women with documented penicillin allergy: </li></ul><ul>...
Antenatal Steroids <ul><li>Intact Membranes and PTL 24-34 weeks </li></ul><ul><ul><li>Cochrane shows benefit 26 to 34 & 6...
Antenatal Steroids <ul><li>Cochrane 2006, 21 studies, n = 3,885 women, 4,629 newborns, showing less </li></ul><ul><li>Neon...
Repeat courses of Antenatal Steroids <ul><li>Cochrane 2006 subgroup weekly repeats, n = 5-900 </li></ul><ul><ul><li>Less p...
Tocolytics: Ca Channel Blockers: dihydropryridines <ul><li>Cochrance 12 trials of 1,029 versus any tocolytic, 9 versus bet...
Tocolytics: Magnesium Sulfate <ul><li>Cochrane with 9 of 23 trials of 2000 women </li></ul><ul><li>No difference in birth ...
Tocolytics:  - mimetics <ul><li>2004 Cochrane Review: 17 trials, 11 trials with 1,320 women are placebo controlled </li>...
Tocolytics:  - mimetics <ul><li>Did reduce delivery within 48 hours </li></ul><ul><ul><li>118/541  mimetic, 158/460 C...
COX Inhibitors <ul><li>2005 Cochrane review: 13 trials of 713 women, 10 trials of indomethacin </li></ul><ul><li>Trials ar...
Tocolytics: ACOG 5/2003 <ul><li>“ All have demonstrated limited benefit”, “may prolong pregnancy 2-7 days- Level A </li></...
Tocolytics Uncontrolled thyroid or Diabetes Cardiac arrhythmia 0.25mg SQ q 20min-3hr Hold if P>120 <ul><li>Mimetic </li></...
Case #3, PPROM <ul><li>30 year old G4P3 at 30 weeks feels a “pop and gush” and has leakage of clear fluid from the vagina ...
Incidence and Natural Hx <ul><li>PROM @ term 10 % </li></ul><ul><li>PPROM 2 % </li></ul><ul><li>Prolonged > 24 hours 10...
PROM Risks <ul><li>Malnutrition, esp vit C and zinc </li></ul><ul><li>Smoking and substance abuse </li></ul><ul><li>Infec...
Diagnosis <ul><li>Typical History , “pop and gush” 90.3% specific </li></ul><ul><li>Nitrazine , ( false positive for bloo...
Diagnosis <ul><li>AFI , to be used as an adjunct if suspicious, </li></ul><ul><li>Amniocentesis with instillation of indig...
Sterile Speculum <ul><li>The time clock starts with the first digital exam </li></ul><ul><ul><li>Studies have shown that i...
Assessment of Fetal Lung Maturity <ul><li>L/S Ratio  2.0/1 (Lecithin/Sphingomyelin) </li></ul><ul><ul><li>Predictive va...
Expectant vs Intervene <ul><li>Fetal risks </li></ul><ul><li>prematurity with RDS, IVH, NEC etc </li></ul><ul><li>asphyxia...
Antibiotics for Preterm PROM <ul><li>2003 Cochrane 22 trials, >6,000 women, </li></ul><ul><ul><li>Maternal Benefits </li>...
4/07 ACOG PPROM <ul><li>34-36 weeks, “near term ”: same as term, proceed to delivery, GBS chemoprophylaxis </li></ul><ul><...
PPROM Interventions <ul><li>Antenatal steroids </li></ul><ul><li>Recommend use in PPROM @  30-32 weeks </li></ul><ul><...
PPROM interventions <ul><li>Antibiotics goals </li></ul><ul><ul><li>GBS prophylaxis </li></ul></ul><ul><ul><li>Prolong la...
Oracle 1 trial <ul><li>4826 women <37 weeks randomized to </li></ul><ul><ul><li>erythromycin, 250mg QID </li></ul></ul><u...
Oracle 1 trial <ul><li>No significant differences in treat vs placebo for </li></ul><ul><ul><li>Low birth weight rate </li...
Cerebral Palsy <ul><li>Retrospective Case control study mentioned in discussion in Oracle 1 trial </li></ul><ul><li>59 bor...
Conclusions <ul><li>Preterm birth has multi-factorial causes </li></ul><ul><li>For prevention of Preterm Birth </li></ul><...
Conclusions <ul><li>Prevent PPROM with good nutrition, smoking and drug cessation, rx infections </li></ul><ul><li>secure ...
References <ul><li>Epidemiology/Reviews </li></ul><ul><li>Hollier, Lisa, Preventing Preterm Birth, What works, what doesn’...
References: <ul><li>Cochrane Reviews: </li></ul><ul><li>Anotayanonth, S et al, Betamimetics for inhibiting preterm labour...
References <ul><li>Preterm Labor </li></ul><ul><ul><li>Iams, J Prediction and Early Detection of Preterm Labor, OB/Gyn 200...
References <ul><li>Fetal Fibronectin </li></ul><ul><ul><li>Goldenberg, R et al, The Preterm Prediction Study: Toward a mul...
References <ul><li>Infections: BV </li></ul><ul><ul><li>Hauth, J Reduced Incidence of Preterm Delivery with Metronidazole ...
References <ul><li>Infections BV </li></ul><ul><li>USPSTF, Screening for Bacterial Vaginosis in Pregnancy, Recommendations...
References <ul><li>Preterm Contractions and Digital Cervix </li></ul><ul><ul><li>Iams, J et al, Requency of uterine contra...
References: <ul><li>Progesterone </li></ul><ul><li>Meis, P et al, Prevention of Recurrent Preterm Delivery by 17 Alpha-Hy...
References <ul><li>PPROM </li></ul><ul><li>Hartling, l et al, A systematic review of intentional delivery in women with p...
References <ul><li>Progesterone: </li></ul><ul><li>Fonseca, E et al, Progesterone and the Risk of Preterm Birth among wo...
PROM @ 34-37, “Near-term” <ul><li>Naef, AmJOB/Gyn, Jan 1998, p126 </li></ul><ul><li>prospective randomized 120 patients </...
PPROM 30-36 weeks: Metanalysis <ul><li>4 studies, 389 women, 391 babies </li></ul><ul><li>1987-98, no steroids, no tocolys...
Risk of Preterm Birth < 35 weeks compared to cervical length of the 75% 1.0 1.0 75% 40 mm 9.5 6.7 10% 26 mm 13.9 9.5 5% 22...
Lifestyle: Drug Screening <ul><li>Self Report </li></ul><ul><ul><li>3,142 Washington women, 40% participation </li></ul><...
Vaginal Progesterone <ul><li>RTC of 142 High Risk singletons with prior preterm delivery in Brazil </li></ul><ul><li>Vagin...
Tocolytics:  - mimetics 2004 Systematic Review OR 0.79 CI (0.61-1.01) 5 RTC 55%, 332/601  mimetic 65%, 332/525 placeb...
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Preterm Labor Prevention Watrin

Published on: Mar 4, 2016
Published in: Health & Medicine      
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Transcripts - Preterm Labor Prevention Watrin

  • 1. Preterm Labor Prevention and Treatment Kerry Watrin MD August 2 nd 2007
  • 2. Objectives: <ul><li>Define preterm labor and its impact </li></ul><ul><li>Describe Risk Factors for preterm birth </li></ul><ul><li>Name several ways to prevent preterm birth </li></ul><ul><li>Identify and diagnose preterm labor </li></ul><ul><li>Outline an appropriate evaluation and management algorithm for patients who present with preterm labor and PPROM </li></ul><ul><li>Understand risks and limitations of management strategies for treating patients with preterm labor and PROM </li></ul>
  • 3. Definitions/ Epidemiology <ul><li>Definitions </li></ul><ul><ul><li>Preterm Labor : regular contractions with cervical change at <37 weeks gestation </li></ul></ul><ul><ul><li>Preterm Birth : < 37 & 0/7 days </li></ul></ul><ul><ul><li>Near term or Late term : 34 & 0/7 to 36 & 6/7 weeks </li></ul></ul><ul><ul><li>Very preterm : < 32 & 0/7 weeks </li></ul></ul><ul><ul><li>Extremely Preterm : < 28 & 0/7 weeks </li></ul></ul><ul><li>Rising Rates of Preterm Birth 1981-2003 </li></ul><ul><ul><li>PTB < 37 weeks: increase from 9.4 to 12.3% </li></ul></ul><ul><ul><li>PTB “near term”, : increased from 6.3-8.8% </li></ul></ul>
  • 4. Race/Ethnicity and Prematurity 2000to 2002 1.5% 10.7% White 1.4% 10.2% Asian 1.7% 11.4% Hispanic 2.0% 12.9% Native American 4.1% 17.6% Black 1.9% 11.9% All US < 32wk US < 37wk Race/Ethnicity
  • 5. Preterm Birth Causes Multifactorial <ul><li>Spontaneous Preterm Labor (31-50%) </li></ul><ul><ul><li>Intact membranes </li></ul></ul><ul><li>PPROM (6-40%) </li></ul><ul><li>Maternal Illness/Trauma (20-30%) </li></ul><ul><ul><li>Hypertensive disorders of pregnancy (12%) </li></ul></ul><ul><ul><li>IUGR (2-4%) </li></ul></ul><ul><ul><li>Abruption and Previa (6-9%) </li></ul></ul><ul><li>Structural (20-30%) </li></ul><ul><ul><li>Multifetal pregnancy (12-28%), </li></ul></ul><ul><ul><li>Cervical Incompetence </li></ul></ul><ul><ul><li>Uterine Malformations </li></ul></ul>
  • 6. Case #1 <ul><li>24 year old NA G2P1 presents at 16 weeks </li></ul><ul><ul><li>history of spontaneous preterm birth at 26 weeks, (no bleed, PPROM, or maternal illness) </li></ul></ul><ul><li>Is this patient high risk or average risk for Preterm Birth? </li></ul><ul><li>What can I do different this pregnancy to prevent preterm birth? </li></ul>
  • 7. Case #1 Preterm Labor Precautions <ul><li>Lifestyle </li></ul><ul><ul><li>BMI 18, wt 100 lbs, </li></ul></ul><ul><ul><li>¼ PPD tobacco, some marijuana </li></ul></ul><ul><ul><li>New significant other last 1 month, not father of the baby </li></ul></ul><ul><li>Screening Labs: </li></ul><ul><ul><li>Wet Mount/Gram Stain: Bacterial Vaginosis </li></ul></ul><ul><ul><li>Informed Consent Utox: negative </li></ul></ul><ul><ul><li>Urine culture: no growth in 2 days </li></ul></ul><ul><ul><li>Ligase Chain Reaction GC/Chlamydia: negative </li></ul></ul>
  • 8. Prematurity Risk Factors <ul><li>High Risk/Low incidence </li></ul><ul><li>PTL after tocolysis 70% </li></ul><ul><li>Bleeding > 20 wk OR 5.3 </li></ul><ul><li>Twins 40% </li></ul><ul><li>Unicornate uterus 30% </li></ul><ul><li>Gravida 9+ 32% </li></ul><ul><li>Incompetent cervix 25% </li></ul><ul><li>Prior preterm birth 25%, with 25-70% </li></ul><ul><li>Prior PPROM 29% </li></ul><ul><li>Preterm contracts 25% </li></ul><ul><li>High Incidence/mild risk </li></ul><ul><li>Threaten Ab (30%) OR 4.1 </li></ul><ul><li>Smoking (25%) OR 1.3 </li></ul><ul><li>Black Race (9%) OR 1.5 </li></ul><ul><li>Drug use (8%) OR 2.0 </li></ul><ul><li>UTI/Bacteruria (5%) 2.0 </li></ul><ul><li>Anemia (5%) OR 2.2 </li></ul><ul><li>Chronic HTN (5%) OR 1.8 </li></ul><ul><li>Mild PIH (5%) OR 1.7 </li></ul><ul><li>3+ Abortions OR 2.9 </li></ul><ul><li>Late to Care OR 2.0 </li></ul><ul><li>Scoring systems have low predictive value </li></ul>
  • 9. Cervical Incompetence Risks <ul><li>Past OB History </li></ul><ul><li>Prior Midtrimester loss </li></ul><ul><li>Prior Preterm delivery @ 24-30 weeks </li></ul><ul><li>Previous cerclage </li></ul><ul><li>History of multiple 1st Trimester TOP (  2) </li></ul><ul><li>History of one 2 nd trimester TOP </li></ul><ul><li>Structural Uterine </li></ul><ul><li>DES exposure </li></ul><ul><li>Uterine malformation </li></ul><ul><li>Hx of Cone Biopsy </li></ul><ul><li>Current Pregnancy </li></ul><ul><li>multiple pregnancy </li></ul>
  • 10. Prematurity Interventions: Lifestyle <ul><li>Some Effect : </li></ul><ul><ul><li>Nutrition, zinc, folate and caloric supplementation, </li></ul></ul><ul><ul><li>Smoking cessation </li></ul></ul><ul><ul><li>Drug abstinence </li></ul></ul><ul><ul><li>Income support, France and Germany </li></ul></ul><ul><li>Unknown/Maybe : </li></ul><ul><ul><li>Domestic Violence screen </li></ul></ul><ul><ul><li>Light duty for fatigue work </li></ul></ul><ul><li>Ineffective: </li></ul><ul><ul><li>Nutrition counseling, vitamins and minerals </li></ul></ul><ul><ul><li>Hydration </li></ul></ul><ul><ul><li>Patient Education to detect contractions </li></ul></ul><ul><ul><li>Psychological support </li></ul></ul><ul><li>Harmful </li></ul><ul><ul><li>Nutrition, Protein supplementation </li></ul></ul><ul><ul><li>Bedrest </li></ul></ul>
  • 11. Expected pregnancy weight gain 15+ lbs > 29 Obese 15-25 lbs 26-29 High 25-35 lbs 19.8-26 Normal 28-40 lbs <19.8 Low Recommended wt gain BMI Kg/m2 Wt/ht category
  • 12. Prematurity Interventions: Medical <ul><li>Effective : </li></ul><ul><ul><li>Rx Asymptomatic Bacteriuria (1970s tetracycline) </li></ul></ul><ul><ul><li>Progesterone Supplementation </li></ul></ul><ul><ul><li>Cerclage if prior incompetent cervix </li></ul></ul><ul><li>Unknown/Maybe : </li></ul><ul><ul><li>STD treatment </li></ul></ul><ul><ul><li>BV Rx in high risk </li></ul></ul><ul><ul><li>Anticoagulant in Thrombophilias </li></ul></ul><ul><ul><li>Nurse phone calls to home </li></ul></ul><ul><li>Ineffective : </li></ul><ul><ul><li>More or enhanced prenatal care </li></ul></ul><ul><ul><li>Risk Scoring systems </li></ul></ul><ul><ul><li>Home Uterine Monitoring </li></ul></ul><ul><ul><li>Treatment of BV in low risk women </li></ul></ul><ul><ul><li>Cerclage in only short cervix </li></ul></ul><ul><ul><li>Peridontal Disease treatment </li></ul></ul><ul><li>Harmful : </li></ul><ul><ul><li>Antibiotics with intact membranes </li></ul></ul><ul><ul><li>Tocolysis > 48 hours </li></ul></ul>
  • 13. Asymptomatic Bacteriuria <ul><li>Defined as > 100K/ml single uropathogen </li></ul><ul><ul><li>Urine culture is gold standard </li></ul></ul><ul><ul><li>Dipstick 86% sensitive, 86% specific, 54% PPV, 97% NPV </li></ul></ul><ul><li>5-10% of all pregnancies </li></ul><ul><li>Outcomes if treated (Cochrane database) </li></ul><ul><ul><li>Pyelonephritis OR 0.24 (0.19-0.32) </li></ul></ul><ul><ul><li>Pre-term birth OR 0.60 (0.45-0.80) </li></ul></ul>
  • 14. Bacterial Vaginosis: Clue cell
  • 15. Bacterial Vaginosis <ul><li>Common occurs in 20%, asymptomatic in 50% </li></ul><ul><li>Diagnosis by </li></ul><ul><ul><li>wet mount (3 of 4 criteria: clue cells, pH > 4.5, positive whiff test with KOH for amine odor, thin homogenous discharge) </li></ul></ul><ul><ul><li>gram stain, criteria on type and amount of bacteria </li></ul></ul><ul><li>Increased risk of OB complications, RR or 2.3 for preterm delivery, 2.4 for PROM, 3.2 for chorioamnionitis </li></ul>
  • 16. Bacterial Vaginosis <ul><li>1995 small (n=426) high risk (prior PTB) </li></ul><ul><ul><li>RTC showed a 30% decrease in preterm birth with Rx using Erythromycin (14d) and Metronidazole (7d) </li></ul></ul><ul><li>2000 Large trial (n= 1953) low risk for PTB </li></ul><ul><ul><li>diagnosis by gram stain and treatment with metronidazole 2gm stat alone, with no effect </li></ul></ul><ul><li>AHRQ 2001 Review </li></ul><ul><ul><li>I rating for “high risk women” </li></ul></ul><ul><ul><li>D rating for “low risk asymptomatic women” </li></ul></ul>
  • 17. Bacterial Vaginitis Metronidazole potential harm <ul><li>Metronidazole </li></ul><ul><ul><li>2006 PREMET study, </li></ul></ul><ul><ul><ul><li>900 screened 24 and 27 weeks for fetal fibronectin, 116 positive, 100 randomized, 400mg TID Metonidazole, 11/53 treated delivered < 37 weeks vs. 18/46 control, RR 1.6 (CI 1.05-2.4) </li></ul></ul></ul><ul><ul><li>2001 Trichomonas study, </li></ul></ul><ul><ul><ul><li>16-23 weeks, asymptomatic, treated with 2 grams for 2 doses, PTB 60/320 treated, 31/297 placebo, RR 1.8 (CI 1.2-2.7) </li></ul></ul></ul><ul><ul><li>2004 Meta-analysis of 4 studies, </li></ul></ul><ul><ul><ul><li>182/1,375 treated vs. 180/1,373 control, RR 0.92 (CI 0.52-1.62) for preterm birth, no difference </li></ul></ul></ul>
  • 18. Bacterial Vaginitis Clindamycin <ul><li>Clindamycin </li></ul><ul><ul><li>2003 RTC, Clindamycin low Risk, n= 494, Showed less Preterm Birth 11/244 vs. 28/241, NNT is 17, and less late miscarriage 13-24 weeks, 2 vs. 10, NNT of 10 </li></ul></ul>
  • 19. Prevention with Progesterone <ul><li>High Risk Population of 463 women with prior preterm delivery (NIH study) </li></ul><ul><ul><li>>50% Black, Average prior birth at 30-31 weeks, one third with more than one prior preterm delivery </li></ul></ul><ul><ul><li>Exclusions: multifetal pregnancy, planned cerclage, use of heparin or progesterone, chronic HTN on meds, seizure disorder </li></ul></ul><ul><ul><li>Randomized 2/1 (310/153) double blind placebo weekly IM injections of 250mg 17  hydroxyprogesterone caproate starting 16-20 weeks </li></ul></ul><ul><ul><li>Groups equal except average of 1.4 vs 1.6 prior preterm births in progesterone vs placebo </li></ul></ul>
  • 20. Preterm outcomes and Progesterone NNT Relative Risk Placebo N=153 Progest N=306 7 0.66 (.51-.87) 62 41.1% 82 27.2% LBW < 2500 gm 12 0.58 (.37-.91) 30 19.6% 35 11.4% Delivery < 32 wk 10 0.67 (.48-.93) 47 30.7% 63 20.6% Delivery < 35 wk 5 0.66 (.54-.81) 84 54.9% 111 36.3% Delivery < 37 wk
  • 21. Progesterone Outcomes <ul><li>With Progesterone less NEC, need for O2, </li></ul><ul><li>Trend but not significant less RDS, and ventilatory support, birth wt < 1,500 gms </li></ul><ul><li>No difference in fetal or neonatal death, IVH grade 3 and 4, sepsis, anomalies </li></ul><ul><li>One infant in progesterone group with torsion of testicles and subsequent infarction </li></ul>
  • 22. Progesterone Meta-analysis <ul><li>Cochrane: Jan 2006, 6 RTCs, 988 patients </li></ul><ul><ul><li>PTB <37 weeks, RR 0.65 (CI 0.54-0.79), PTB < 34 weeks (one study) RR 0.15 (CI .04-.64), </li></ul></ul><ul><ul><li>Less LBW RR 0.63 (.49-.81), IVH RR 0.25 (.08-.82) </li></ul></ul><ul><ul><li>“ Not enough evidence”, desired further information on harms and other maternal and neonatal outcomes </li></ul></ul><ul><li>European: May 2006, 9 studies, n > 5,800, </li></ul><ul><ul><li>“ women at high risk of preterm birth should be recommended progestational agent therapy” </li></ul></ul><ul><ul><li>PTB < 37 weeks, RR 0.42 (CI 0.31-0.57) NNT 9, PTB < 34 weeks, RR 0.51 (CI 0.34-0.77) NNT 42, </li></ul></ul><ul><ul><li>RDS RR 0.55 (CI 0.31-0.96) </li></ul></ul><ul><ul><li>Harms not significant </li></ul></ul>
  • 23. ACOG and Progesterone <ul><li>“ 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” </li></ul>
  • 24. Preterm Birth Risk Stratification <ul><li>Contractions: </li></ul><ul><ul><li>50% of those with threatened preterm labor deliver term pregnancies, can we further define risk </li></ul></ul><ul><li>Biochemical Markers </li></ul><ul><ul><li>Fetal Fibronectin </li></ul></ul><ul><li>Biophysical Markers </li></ul><ul><ul><li>Cervical Length </li></ul></ul>
  • 25. Markers for Prematurity <ul><li>Preterm Prediction Study: Case control </li></ul><ul><li>28 biologic markers studied in 2,929 women at 23 weeks </li></ul><ul><li>50 (1.7%) delivered < 32 weeks </li></ul><ul><li>127 (4.3%) delivered < 35 weeks </li></ul>
  • 26. Most Potent Predictive Markers For Preterm Birth < 32 weeks <ul><li> 2 positive below OR 56.5 </li></ul><ul><ul><li>59% of cases and 2.4% of controls </li></ul></ul><ul><li>Fetal Fibronectin OR 32.7 </li></ul><ul><li>> 90 th % AFP OR 8.3 </li></ul><ul><li>> 90 th % Alk Phos OR 6.8 </li></ul><ul><li>< 10% Cvx (25 mm) OR 5.8 </li></ul><ul><li>> 75% GCSF OR 5.5 </li></ul><ul><li>Any three tests positive </li></ul><ul><ul><li>20% of cases and none of controls </li></ul></ul>
  • 27. Other Markers of Preterm Birth < 32 weeks <ul><li>> 90 th % Ferritin OR 8.0 </li></ul><ul><li>Past Hx PTB OR 4.5* </li></ul><ul><li>Vaginal pH  5.0 OR 3.3* </li></ul><ul><li>Chlamydia Positive OR 2.6 </li></ul><ul><li>Low Wt, BMI <19.8 OR 2.4 </li></ul><ul><li>History of bleeding OR 1.8 </li></ul><ul><li>* P <.05 </li></ul>
  • 28. Fetal Fibronectin <ul><li>Occurs in the choriodecidual junction </li></ul><ul><li>Decreases 16-20 wks, absent 24-34 wks </li></ul><ul><li>Taken from the vaginal fornix for 10 seconds, not in cervix </li></ul><ul><li>No prior coitus or vaginal exam for 24 hrs </li></ul><ul><li>ROM or bleeding make inaccurate </li></ul>
  • 29. Fetal Fibronectin <ul><li>Asymptomatic </li></ul><ul><li>Positive (n=1,530) </li></ul><ul><ul><li>18.4% delivery <34 weeks </li></ul></ul><ul><ul><li>LR 4.01 (2.93 to 5.49) </li></ul></ul><ul><li>Negative (n=23,150) </li></ul><ul><ul><li>96.8% deliver >34 weeks </li></ul></ul><ul><ul><li>LR 0.78 (0.72-0.84) </li></ul></ul><ul><li>Symptomatic </li></ul><ul><li>Birth in 7-10 days </li></ul><ul><ul><li>Positive (n=1,270) </li></ul></ul><ul><ul><ul><li>21% deliver in 7-10d </li></ul></ul></ul><ul><ul><ul><li>LR 5.42 (4.36-6.74) </li></ul></ul></ul><ul><ul><li>Negative (n= 5865) </li></ul></ul><ul><ul><ul><li>1% deliver in 7-10d </li></ul></ul></ul><ul><ul><ul><li>LR 0.25 (0.2-0.31) </li></ul></ul></ul><ul><li>Delivery < 34weeks </li></ul><ul><ul><li>Positive (n=189) </li></ul></ul><ul><ul><ul><li>46.6%, LR 3.64 </li></ul></ul></ul><ul><ul><li>Negative (n= 498) </li></ul></ul><ul><ul><ul><li>93.4%, LR 0.32 </li></ul></ul></ul>
  • 30. Fetal Fibronectin <ul><li>If positive </li></ul><ul><ul><li>One in 5 symptomatic deliver in 7-10 days </li></ul></ul><ul><ul><li>One in 5 asymptomatic will deliver by 34 wks </li></ul></ul><ul><ul><li>Nearly half symptomatic deliver by 34 weeks </li></ul></ul><ul><li>If negative </li></ul><ul><ul><li>One in 100 symptomatic deliver in 7-10 days </li></ul></ul><ul><ul><li>Three in 100 asymptomatic deliver < 34 weeks </li></ul></ul><ul><ul><li>6-7 in 100 symptomatic deliver < 34 weeks </li></ul></ul>
  • 31. Case #2 Low Risk no prior PTB at 25 weeks <ul><li>Size < Dates, 21cm fundal height at 25 weeks </li></ul><ul><li>Transabdominal Ultrasound shows </li></ul><ul><ul><li>normal growth </li></ul></ul><ul><ul><li>cervix is with 1.2 cm length and 1.2 cm wide fluid filled beaking in upper canal </li></ul></ul><ul><li>Transvaginal Ultrasound repeat shows </li></ul><ul><ul><li>2.3 cm long cervix, with again beaking down 1.3-1.5 cm of the length, 1.0 cm from beak tip to external os </li></ul></ul><ul><li>One hour of tocodynometer shows no contractions </li></ul><ul><li>Vaginal exam is 2-3 cm long, closed, firm </li></ul><ul><li>Outpatient vaginal Fetal Fibronectin is negative </li></ul><ul><li>What precautions for this incidental US finding? </li></ul>
  • 32. Transvaginal Cervical Length <ul><li>1996 NEJM study of 2,915 women with US at 24 weeks, repeat on 2,531 at 28 weeks </li></ul><ul><li>126 with preterm birth < 35 weeks, 4.3% </li></ul><ul><li>Was a general population, 42% were nulliparous </li></ul><ul><li>16% had history of prior preterm birth </li></ul><ul><li>There was only 2mm difference between parous and nulliparous women, not clinically important </li></ul><ul><li>Mean length was 35.2mm at 24 weeks and 33.7 mm at 28 weeks </li></ul>
  • 33. Rate of Preterm Birth <35 weeks by Cervical Length at 24 weeks 34 % < 13 mm 20 % <20 mm 8 %  25 mm Rate Delivery Length
  • 34. Ultrasound Cervical Length Prediction of PTB < 35 weeks 17.2% 96.6% 94.5% 25.4% Funneling At 24 wk 17.8% 97% 92.2% 37.3% 25mm 24 weeks 16.7% 97.6% 94.7% 31.3% 20 mm 28 weeks 25.7% 96.7% 97% 23% 20mm 24 weeks PPV NPV Specificity Sensitivity Finding
  • 35. Cervical Length Caveats <ul><li>Distinguish Average Risk versus High Risk Population studies </li></ul><ul><li>Cervixes change from the inside out, but digital vaginal exam of Bishops ≥ 4 is significant </li></ul><ul><li>Ultrasound Higher risk of Preterm Birth with </li></ul><ul><ul><li>Funneling > 25% </li></ul></ul><ul><ul><li>Earlier shortening 16 versus 24 weeks </li></ul></ul><ul><ul><li>More rapid rate, <3mm/week reassuring,  5mm per week concerning at 20-24 weeks </li></ul></ul>
  • 36. Cerclage and Short Cervix <ul><li>47,123 screened at 22-25 weeks </li></ul><ul><li>430 with cervical length < 15mm </li></ul><ul><li>253 in RTC </li></ul><ul><li>No difference in delivery before 33 weeks with placement of Shirodkar suture </li></ul><ul><ul><li>22% (28 /127 cerclage), 26% (33/126 control) </li></ul></ul><ul><ul><li>RR 0.84 (CI 0.54-1.31) </li></ul></ul><ul><li>No difference in perinatal or maternal morbidity and mortality </li></ul>
  • 37. Role of US and Cerclage High risk with 3 prior midterm losses <ul><li>Serial Cervical Length Ultrasound: </li></ul><ul><ul><li>May have a role in management </li></ul></ul><ul><ul><li>Assessments should begin no earlier than 16-20 weeks </li></ul></ul><ul><ul><li>No role for history of 1 st trimester losses </li></ul></ul><ul><li>Cerclage </li></ul><ul><ul><li>Only benefit in subgroup 3 prior midtrimester losses or preterm deliveries, 33% watched, 15% cerclage with delivery before 33 weeks, n=107, total groups n=1,292 </li></ul></ul><ul><ul><li>No benefit in subgroups of one prior MTL/PTD, two prior MTL/PTD, history cone biopsy or cervical amputation, twins, prior TOP/uterine anomalie </li></ul></ul>ACOG Practice Bulletin #48, Nov 2003
  • 38. Short Cervix and Vaginal Progesterone <ul><li>2003-2006, 24,620 screened by US at 20-25 weeks for short cervix during prenatal care, 413 with cervix ≤ 15mm, 250 accepted randomization, groups equal, </li></ul><ul><li>200mg micronized progesterone vaginally each night, 24 to 33 and 6/7 weeks, avoid intercourse </li></ul><ul><li>PT Birth < 34 weeks, 26/125 progesterone vs. 43/125 placebo RR 0.60 (CI 0.38-0.86), NNT = 7 </li></ul><ul><li>Not large enough to see neonatal outcomes </li></ul>
  • 39. Contractions and Bishops Score And birth before 35 weeks <ul><li>306 high risk women, singleton pregnancy with prior PTB or 2 nd trimester bleeding </li></ul><ul><li>Contractions  4 per hour </li></ul><ul><ul><li>RR was with 3.0 but not significant, </li></ul></ul><ul><ul><ul><li>At 24 weeks CI (0.6-14.6) </li></ul></ul></ul><ul><ul><ul><li>At 28 weeks CI (1.0- 8.7) </li></ul></ul></ul><ul><ul><li>Sens 6.7%, Specificity 92.3%, PPV 25%, NPV 84.7% </li></ul></ul><ul><ul><li>75% deliver at term </li></ul></ul><ul><li>Bishops Score  4 </li></ul><ul><ul><li>Significant only at 22-24 weeks OR 2.4 (CI 1.7-10.6) </li></ul></ul><ul><ul><li>Sens 32 %, Specificity 91.4%, PPV 42.1%, NPV 87.4% </li></ul></ul>
  • 40. Threatened Preterm Labor <ul><li>Preterm Labor due to what? </li></ul><ul><ul><li>Treat reversible causes, such as UTI, </li></ul></ul><ul><ul><li>Consider occult trauma of domestic violence, contractions of substance abuse </li></ul></ul><ul><ul><li>Watch for PPROM, about 1/3 of preterm birth </li></ul></ul><ul><li>For Idiopathic Preterm Labor Four Categories </li></ul><ul><ul><li>Inflammation/ Infection </li></ul></ul><ul><ul><li>Uterine Over-distension/ Structural </li></ul></ul><ul><ul><li>Decidual Hemorrhage/ Bleeding </li></ul></ul><ul><ul><li>Premature activation of normal initiators of labor </li></ul></ul>
  • 41. Idiopathic Preterm Contractions in Triage <ul><li>179 randomized, </li></ul><ul><ul><li>singletons, 20-34 weeks, no ROM, no maternal of fetal complication, reassuring FHT </li></ul></ul><ul><ul><li>3 contractions/30 min,  1cm dilated,  80% effaced </li></ul></ul><ul><ul><li>Eligible for discharge when contractions < 2 in 30 minutes, no digital cervical change, one hour apart, </li></ul></ul><ul><ul><li>Preterm labor if cervical change of dilation of 1 cm or effacement of 25% </li></ul></ul><ul><li>Terbutaline with 1-2 hour less triage stay </li></ul><ul><li>No significant outcome differences between </li></ul><ul><ul><li>Observation, </li></ul></ul><ul><ul><li>Hydration of 500cc crystalloid then 200 cc/hour, </li></ul></ul><ul><ul><li>Terbutaline one Subcutaneous dose of 0.25mg </li></ul></ul>
  • 42. Contractions what to do? 4 (7%) 4 (6%) 5 (9%) PTB < 34 wks $687 $966 $717 Mean cost < 24 hours 5 (8%) 8 (13%) 7 (13%) admitted 8 (13%) 8 (13%) 10 (18%) More tocolysis 79% 57% 64% Triage < 4hrs 4.1  5.1 hrs 6.0  5.7 hrs 5.2  5.1 hrs Mean time to discharge Terbutaline x1, n=61 Hydration N=62 Observation N=56
  • 43. Case #2 now with contractions <ul><li>Presents 28 weeks with contractions every 5 minutes, </li></ul><ul><li>Repeat exams and labs </li></ul><ul><ul><li>Digital cervix some change 1 cm long, medium consistency, posterior, -3 station, closed </li></ul></ul><ul><ul><li>Fetal Fibronectin now positive </li></ul></ul><ul><ul><li>US length repeated slightly progressed, 1.2 cm length, 0.7 cm from tip of funnel to external os, </li></ul></ul><ul><ul><li>GBS culture done, (at 24 hours is positive) </li></ul></ul><ul><ul><li>Hematocrit 29.5 </li></ul></ul><ul><li>What approach now with short US cervix, positive fetal fibronectin, and slight clinical shortening? </li></ul>
  • 44. Case #2, Threatened PTL in High Risk (contracts, +FFN, short cervix) <ul><li>GBS prophylaxis: Penicillin </li></ul><ul><li>Given Terbutaline 0.25mg SQ/dose tocolysis to allow 48 hours steroids </li></ul><ul><li>Given Betamethasone 12mg IM q 24 hours times 2 doses </li></ul><ul><li>? FeSO4 325mg TID </li></ul><ul><li>Observe in hospital with level 3 NICU </li></ul>
  • 45. The Recommendations MMWR, Vol 51 (RR-11)
  • 46. CDC GBS algorithm for Threatened Preterm Delivery <ul><li>Suggested algorithm for management of threatened preterm delivery (labor or rupture of membranes at <37 weeks’ gestation) which does not proceed rapidly to delivery: </li></ul><ul><ul><li>Culture and start IV antibiotics </li></ul></ul><ul><ul><li>Culture negative at 48 hrs: stop antibiotics </li></ul></ul><ul><ul><li>Culture positive: no data on duration of antibiotics before active labor, when active labor begins give IAP </li></ul></ul><ul><ul><li>Culture negative and undelivered within 4 wks: re-screen </li></ul></ul>
  • 47. Agents for intrapartum prophylaxis <ul><li>Recommended agents for women with documented penicillin allergy: </li></ul><ul><ul><li>Not at high risk for anaphylaxis: cefazolin </li></ul></ul><ul><ul><li>At high risk for anaphylaxis: </li></ul></ul><ul><ul><ul><li>Clindamycin or erythromycin if susceptibility testing feasible </li></ul></ul></ul><ul><ul><ul><li>Vancomycin if erythromycin or clindamycin not options </li></ul></ul></ul>
  • 48. Antenatal Steroids <ul><li>Intact Membranes and PTL 24-34 weeks </li></ul><ul><ul><li>Cochrane shows benefit 26 to 34 & 6/7 weeks </li></ul></ul><ul><li>PPROM and no chorioamnionitis, 24-32 wk </li></ul><ul><li>Single course recommended </li></ul><ul><ul><li>Cochrane 2006 </li></ul></ul><ul><li>Doses </li></ul><ul><ul><li>2 doses Betamethasone 12mg q 24 hours </li></ul></ul><ul><ul><li>4 doses Dexamethasone 6mg q 12 hours </li></ul></ul>
  • 49. Antenatal Steroids <ul><li>Cochrane 2006, 21 studies, n = 3,885 women, 4,629 newborns, showing less </li></ul><ul><li>Neonatal Death: RR 0.69 (CI .58-.81) </li></ul><ul><li>RDS: RR 0.66 (CI .59-.73) </li></ul><ul><li>IVH: RR 0.54 (CI .43-.69) </li></ul><ul><li>NEC: RR 0.46 (CI .29-.74) </li></ul><ul><li>NICU Ventilator RR 0.80 (CI .65-.99) </li></ul><ul><li>Neonatal Sepsis RR 0.56 (CI .38-.85) </li></ul><ul><li>Develop Delay RR 0.49 (CI .24-1.00) </li></ul>
  • 50. Repeat courses of Antenatal Steroids <ul><li>Cochrane 2006 subgroup weekly repeats, n = 5-900 </li></ul><ul><ul><li>Less perinatal death RR 0.63 (.48-.92) NNT 7 </li></ul></ul><ul><ul><li>Less RDS RR 0.55 (.43-.72) NNT 9 </li></ul></ul><ul><ul><li>Less Chronic Lung RR 0.72 (.54-.96) NNT 15 </li></ul></ul><ul><li>Lancet 2006, RTC single repeat dose, n = 982 </li></ul><ul><ul><li>Less RDS RR 0.82 (.71-.95) NNT = 12 </li></ul></ul><ul><ul><li>Severe lung disease RR 0.60 (.42-.79) NNT = 12 </li></ul></ul><ul><li>Pediatrics Feb 2007, single repeat dose, n = 249 </li></ul><ul><ul><li>No difference in neonatal death, RDS or IVH </li></ul></ul><ul><ul><li>Increased RDS if delivers in first 24 hours after second dose of steroids </li></ul></ul>
  • 51. Tocolytics: Ca Channel Blockers: dihydropryridines <ul><li>Cochrance 12 trials of 1,029 versus any tocolytic, 9 versus betamemetics, Outcomes </li></ul><ul><li>Less birth in 48 hrs (vs  agonist) RR 0.72 </li></ul><ul><li>Less birth in 7 days RR 0.76 (0.60-0.97) </li></ul><ul><li>Less birth < 34 weeks RR 0.83 (0.69-99) </li></ul><ul><li>Less RDS RR 0.63 (0.46-.88) NNT 14 </li></ul><ul><li>Less NEC RR 0.21 (0.05-0.96) </li></ul><ul><li>Less IVH RR 0.59 (0.36-.98) NNT 13 </li></ul><ul><li>Less Adverse Effects NNT of 3 </li></ul><ul><li>Conclusion: “calcium channel blockers should be preferred to betamimetics” </li></ul>
  • 52. Tocolytics: Magnesium Sulfate <ul><li>Cochrane with 9 of 23 trials of 2000 women </li></ul><ul><li>No difference in birth < 48 hrs RR 0.85 CI 0.58-1.25), 11 trials of 881 women </li></ul><ul><li>No difference in birth < 37 or <34 weeks </li></ul><ul><li>Increase risk of fetal and pediatric mortality RR 7.82 (1.20-6.62), 7 trials 727 infants </li></ul><ul><li>No difference in neonatal morbidity </li></ul><ul><li>Non-significant reduction in CP in one trial of 99 infants RR 0.14, (CI 0.01-2.60) </li></ul><ul><li>Conclusion: Mg Sulfate is ineffective as tocolysis and has increased infant mortality </li></ul>
  • 53. Tocolytics:  - mimetics <ul><li>2004 Cochrane Review: 17 trials, 11 trials with 1,320 women are placebo controlled </li></ul><ul><li>No benefit for </li></ul><ul><ul><li>Perinatal death RR 0.84 (CI 0.46-1.55) </li></ul></ul><ul><ul><li>Neonatal death RR 1.00 (CI 0.48-2.09) </li></ul></ul><ul><ul><li>RDS RR 0.87 (CI 0.71-1.08) </li></ul></ul>
  • 54. Tocolytics:  - mimetics <ul><li>Did reduce delivery within 48 hours </li></ul><ul><ul><li>118/541  mimetic, 158/460 Control </li></ul></ul><ul><ul><li>OR 0.56, (CI 0.42-0.74) </li></ul></ul><ul><li>Allows time for antenatal steroids </li></ul><ul><li>Had more side-effects requiring discontinuation of treatment </li></ul><ul><ul><li>3 RTCs, 25/88 (28%)  mimetic, 0/86 control </li></ul></ul><ul><ul><li>OR 11.5 (CI 4.8-27.5) </li></ul></ul>
  • 55. COX Inhibitors <ul><li>2005 Cochrane review: 13 trials of 713 women, 10 trials of indomethacin </li></ul><ul><li>Trials are small, and there is insufficient evidence </li></ul><ul><li>Placebo controlled one trial 36 women </li></ul><ul><ul><li>Birth < 37 weeks, 3/18 indomethacin vs. 14/18 placebo, RR 0.21 (CI 0.07-.62) </li></ul></ul><ul><li>Versus another tocolytic, 3 trials 168 women </li></ul><ul><ul><li>Birth < 37 weeks, 13/85 COX vs 24/83 other, RR 0.53 (CI .31-.94) </li></ul></ul>
  • 56. Tocolytics: ACOG 5/2003 <ul><li>“ All have demonstrated limited benefit”, “may prolong pregnancy 2-7 days- Level A </li></ul><ul><ul><li>“ No clear first-line tocolytic drug” Level A </li></ul></ul><ul><ul><li>“ Neither maintenance treatment nor repeated acute tocolysis improve perinatal outcome, neither should be undertaken” Level A </li></ul></ul><ul><ul><li>“ Bedrest, pelvic rest, hydration, antibiotics should not be routinely recommended” Level B </li></ul></ul><ul><li>Goals of tocolytic therapy </li></ul><ul><ul><li>Allow administration of steroids, Level A </li></ul></ul><ul><ul><li>Allow Maternal transport to tertiary care facility, level A </li></ul></ul><ul><ul><li>Allow for imminent GBS chemoprophylaxis, Level A </li></ul></ul>
  • 57. Tocolytics Uncontrolled thyroid or Diabetes Cardiac arrhythmia 0.25mg SQ q 20min-3hr Hold if P>120 <ul><li>Mimetic </li></ul><ul><li>Terbutaline </li></ul>Myasthenia gravis Also using Calcium channel Blocker 4-6 gm IV bolus in 20 min, then 2-3gm/hr Mag Sulfate Renal failure, Active Ulcer Coagulation disorders NSAID asthma trigger 50 rectal, 50-100 mg PO, then 25-50 orally q6 x 48 hrs NSAID Indomethacin (<32 weeks) Maternal hypotension Also using Magnesium 30-40 mg load PO 10-20 q 4-6hrs CCB Nifedipine Contra- indication Dose and Route Agent
  • 58. Case #3, PPROM <ul><li>30 year old G4P3 at 30 weeks feels a “pop and gush” and has leakage of clear fluid from the vagina </li></ul><ul><li>Her risk factors include previous PPROM at 32 weeks, smoker, anorexia nervosa but no vaginal infections </li></ul><ul><li>What is the management approach? </li></ul>
  • 59. Incidence and Natural Hx <ul><li>PROM @ term 10 % </li></ul><ul><li>PPROM 2 % </li></ul><ul><li>Prolonged > 24 hours 10% of term </li></ul><ul><li>Prolonged latency > 48 hrs 62% of preterm </li></ul><ul><li>Chorioamnionitis will develop in 10% of those lasting beyond 24 hours at term, and in 25% of expectantly managed preterm </li></ul><ul><li>Increased incidence of abruption, cord accident, infection </li></ul>
  • 60. PROM Risks <ul><li>Malnutrition, esp vit C and zinc </li></ul><ul><li>Smoking and substance abuse </li></ul><ul><li>Infections esp staph aureus, GBS, Chlamydia, GC, Trichomonas, Bacteroides </li></ul><ul><li>1st and 3rd Timester Bleeding </li></ul><ul><li>Incompetent cervix </li></ul><ul><li>Genetic weak collagen </li></ul><ul><li>Overdistension or trauma </li></ul><ul><li>PPROM recurs 25% </li></ul>
  • 61. Diagnosis <ul><li>Typical History , “pop and gush” 90.3% specific </li></ul><ul><li>Nitrazine , ( false positive for blood, BV, semen, turns at pH 6.4-6.8) 98.9% sensitive, and 90.3% accurate </li></ul><ul><li>Fern, 87% accurate, onset after 20 weeks,ok with meconium or blood unless 1 to 1 ratio, cervical mucous (fine) vs amniotic (coarse), </li></ul><ul><li>Pooling </li></ul>
  • 62. Diagnosis <ul><li>AFI , to be used as an adjunct if suspicious, </li></ul><ul><li>Amniocentesis with instillation of indigo carmine dye </li></ul><ul><li>Vaginal Pool lung maturity tests, PG accurate, LS will decrease with blood, (accurate if Hct <3) and Meconium, FLM not tested on vag pool </li></ul><ul><li>Cultures, GBS, GC, Chlamydia, wet mount </li></ul>
  • 63. Sterile Speculum <ul><li>The time clock starts with the first digital exam </li></ul><ul><ul><li>Studies have shown that infection rate rises with the number of digital exams (  3 is statistically significant, and 7 exams is worse than 3) </li></ul></ul><ul><ul><li>visual estimation on sterile speculum is accurate for cervical effacement and dilation </li></ul></ul><ul><li>Keep our fingers out of there !!! </li></ul><ul><li>Accurate Dates, term (>34 weeks) vs preterm <34 weeks </li></ul><ul><li>Presentation, breech or unstable lie with polyhydramnios with risk of cord prolapse, premie breech calls for C/section route of delivery, use Leopolds or bedside Ultrasound </li></ul>
  • 64. Assessment of Fetal Lung Maturity <ul><li>L/S Ratio  2.0/1 (Lecithin/Sphingomyelin) </li></ul><ul><ul><li>Predictive value for mature 95-100%, </li></ul></ul><ul><ul><li>Predictive valule for immature 33-50% </li></ul></ul><ul><ul><li>L/S of blood in 2.0, meconium interferes, should process within one hour decreases with time </li></ul></ul><ul><li>Phosphastidylglycerol (PG), present </li></ul><ul><ul><li>Predictive value for mature 95-100% </li></ul></ul><ul><ul><li>Predictive value for immature 23-53% </li></ul></ul><ul><ul><li>Not effected by blood/meconium, ok vaginal pool </li></ul></ul><ul><li>Flourescence Polarization (FLM)  55 mg/g </li></ul><ul><ul><li>Predictive value for mature 96-100% </li></ul></ul><ul><ul><li>Predictive value for immature 47-61% </li></ul></ul><ul><ul><li>Vaginal pool accuracy not known, affected by blood and meconium </li></ul></ul>
  • 65. Expectant vs Intervene <ul><li>Fetal risks </li></ul><ul><li>prematurity with RDS, IVH, NEC etc </li></ul><ul><li>asphyxia due to cord compression, prolapse, or placental abruption </li></ul><ul><li>neonatal sepsis </li></ul><ul><li>in micropremies, aplasic lungs </li></ul><ul><li>Maternal Risks </li></ul><ul><li>infections, chorioamnionitis, sepsis </li></ul><ul><li>abruption </li></ul>
  • 66. Antibiotics for Preterm PROM <ul><li>2003 Cochrane 22 trials, >6,000 women, </li></ul><ul><ul><li>Maternal Benefits </li></ul></ul><ul><ul><ul><li>Less chorioamnionitis : RR 0.57 (CI 0.37-0.86) </li></ul></ul></ul><ul><ul><li>Neonatal Benefits </li></ul></ul><ul><ul><ul><li>Prolonged latency : > 48 hours RR 0.71, (CI 0.58 to 0.87), > 7 days RR 0.80, (CI 0.71 to 0.90) </li></ul></ul></ul><ul><ul><ul><li>Neonatal infection : RR 0.68, (CI 0.53 to 0.87) </li></ul></ul></ul><ul><ul><ul><li>US abnormality at discharge : RR 0.82, (CI 0.68 to 0.98) </li></ul></ul></ul><ul><ul><ul><li>Oxygen need: RR 0.88, (CI 0.81 to 0.96) </li></ul></ul></ul><ul><ul><li>Neonatal Harms </li></ul></ul><ul><ul><ul><li>NEC with Amoxicillin Clavulanate: RR 4.60, 95% CI 1.98 to 10.72 </li></ul></ul></ul>
  • 67. 4/07 ACOG PPROM <ul><li>34-36 weeks, “near term ”: same as term, proceed to delivery, GBS chemoprophylaxis </li></ul><ul><li>32-33 & 6/7 weeks : expectant management, antibiotics to prolong latency, GBS chemoprophylaxis, +/- steroids </li></ul><ul><li>< 32 weeks : expectant management, single course steroids, antibiotics to prolong latency, GBS chemoprophylaxis </li></ul><ul><li>Antibiotics: recommend 7 total days, with 1st 48 hours Ampicilln/Amoxicillin and Erythromycin IV, then 5 more days PO </li></ul>
  • 68. PPROM Interventions <ul><li>Antenatal steroids </li></ul><ul><li>Recommend use in PPROM @  30-32 weeks </li></ul><ul><li>Cochrane 2006 Subgroup Analysis </li></ul><ul><ul><li>Less neonatal death RR 0.58 (.43-.80) NNT 15 </li></ul></ul><ul><ul><li>Less RDS RR 0.67 (.55-.82) NNT 10 </li></ul></ul><ul><ul><li>Less NEC RR 0.39 (.18-.86) NNT 23 </li></ul></ul><ul><ul><li>No difference in chorioamnionitis </li></ul></ul>
  • 69. PPROM interventions <ul><li>Antibiotics goals </li></ul><ul><ul><li>GBS prophylaxis </li></ul></ul><ul><ul><li>Prolong latency </li></ul></ul><ul><ul><ul><li>>48hrs, 73%, >7d to 41% </li></ul></ul></ul><ul><li>less </li></ul><ul><ul><li>chorio 16 vs 25%, </li></ul></ul><ul><ul><li>neonatal + blood culture 2 vs 10%, </li></ul></ul><ul><ul><li>& neonate infxn 11 vs 15% </li></ul></ul><ul><li>same </li></ul><ul><ul><li>abnormal cranial US, death, RDS, NEC </li></ul></ul>
  • 70. Oracle 1 trial <ul><li>4826 women <37 weeks randomized to </li></ul><ul><ul><li>erythromycin, 250mg QID </li></ul></ul><ul><ul><li>augmentin, 250/125mg QID </li></ul></ul><ul><ul><li>both or placebo </li></ul></ul><ul><li>Gives short term benefit without short term harm </li></ul><ul><li>Delivery delay 48 hours </li></ul><ul><ul><li>98.8% treated vs 95.6% control NNT = 33 </li></ul></ul><ul><li>Delivery delay by 7 days </li></ul><ul><ul><li>63.3% treated vs 57.7% control NNT = 18 </li></ul></ul>
  • 71. Oracle 1 trial <ul><li>No significant differences in treat vs placebo for </li></ul><ul><ul><li>Low birth weight rate </li></ul></ul><ul><ul><li>RDS </li></ul></ul><ul><ul><li>Need for O2 at 36 weeks post conception </li></ul></ul><ul><ul><li>Positive neonatal blood cultures </li></ul></ul><ul><li>Short term harm </li></ul><ul><ul><li>Augmentin with more necrotizing colitis </li></ul></ul><ul><ul><li>1.8% Augmentin vs 0.7%, NNH = 91 </li></ul></ul><ul><li>Long term harm unknown </li></ul><ul><ul><li>Histologic chorioamnionitis is correlated with more US neonatal brain abnormalities, ? If we keep them in longer how will they do in kindergarten </li></ul></ul>
  • 72. Cerebral Palsy <ul><li>Retrospective Case control study mentioned in discussion in Oracle 1 trial </li></ul><ul><li>59 born < 32 weeks with Cerebral palsy </li></ul><ul><li>Risk factors </li></ul><ul><ul><li>Prolonged ROM > 24 hours OR 2.3 (1.2-4.3) </li></ul></ul><ul><ul><li>Chorioamnionitis OR 4.2 (1.4-12.0) </li></ul></ul><ul><ul><li>Maternal infection OR 2.3 (1.2-4.5) </li></ul></ul>
  • 73. Conclusions <ul><li>Preterm birth has multi-factorial causes </li></ul><ul><li>For prevention of Preterm Birth </li></ul><ul><ul><li>Optimize lifestyle and nutrition </li></ul></ul><ul><ul><li>Screen for asymptomatic Bacteriuria </li></ul></ul><ul><ul><li>Progesterone holds promise in high risk populations </li></ul></ul><ul><li>Threatened Preterm Labor is a common problem, yet 50% deliver at term </li></ul><ul><ul><li>Before using reactive tocolytics evaluate for possible causes, Preterm contractions due to what? </li></ul></ul><ul><li>Interventions that are bottom-line in threatened preterm labor are: </li></ul><ul><ul><li>Antenatal steroids </li></ul></ul><ul><ul><li>Maternal Transport and delivery at tertiary care center </li></ul></ul><ul><ul><li>GBS prophylaxis </li></ul></ul>
  • 74. Conclusions <ul><li>Prevent PPROM with good nutrition, smoking and drug cessation, rx infections </li></ul><ul><li>secure the diagnosis & keep your fingers out of there </li></ul><ul><li>secure the dates, transfer premies to appropriate level NICU/maternal unit, induce near-term PROM ≥ 34 weeks </li></ul><ul><li>Antibiotic and Steroid use </li></ul><ul><ul><li>Betamethasone  32 weeks </li></ul></ul><ul><ul><li>Erythromycin for 48 hours for latency for steroids <32 weeks </li></ul></ul><ul><ul><li>GBS prophylaxis </li></ul></ul>
  • 75. References <ul><li>Epidemiology/Reviews </li></ul><ul><li>Hollier, Lisa, Preventing Preterm Birth, What works, what doesn’t, Obstetrical and Gynecological Survey, 2005, Vol 60, #2, p124-131 </li></ul><ul><li>Siman, H & Caritis S, Review Article, Drug Therapy, Prevention of Preterm Delivery, NEJM 2007, Aug 2 nd , 357; p 477-87 </li></ul><ul><li>Tonse, R, Epidemiology of Late Preterm (Near-term) Births; Clinical Perinatology 2006, 33: p751-763 </li></ul><ul><li>ACOG Practice Bulletins : </li></ul><ul><li>October 2001, #31, Assessment of Risk Factors for Preterm Birth </li></ul><ul><li>May 2003, #43, Management of Preterm Labor </li></ul><ul><li>Nov 2003, #48, Cervical Insufficiency </li></ul><ul><li>April 2007, #80 Premature Rupture of the Membranes </li></ul>
  • 76. References: <ul><li>Cochrane Reviews: </li></ul><ul><li>Anotayanonth, S et al, Betamimetics for inhibiting preterm labour, Oct 18 th 2004 </li></ul><ul><li>Crowther, C et al, Magnesium Sulfate for preventing preterm birth in threatened preterm labor, Oct 21 st 2002 </li></ul><ul><li>King, J et al, Cyclo-oxygenase (COX) inhibitors for treating pretem labour, Feb 2 nd 2005 </li></ul><ul><li>King, J et al, Calcium Channel Blockers for inhibiting Preterm Labor, Jan 20 th , 2003 </li></ul><ul><li>Roberts D, Dalziel, S; Antenatal Steroids for accelerating fetal lung maturation in women at risk of preterm birth, May 15 th 2006 </li></ul>
  • 77. References <ul><li>Preterm Labor </li></ul><ul><ul><li>Iams, J Prediction and Early Detection of Preterm Labor, OB/Gyn 2003: 101: 402-12 </li></ul></ul><ul><ul><li>Slattery, M and Morrison J, Preterm delivery, Lancet, Vol 360, 11/9/2002, p 1489-1497 </li></ul></ul><ul><ul><li>Gerdingen, D, Premature Labor Part 1; Risk Assessment, Etiologic Factors and Diagnosis, Journal American Board of Family Practice, Sept-Oct 1992 Vo 5, #5, p 498 </li></ul></ul><ul><ul><li>Goldenberg, R and Rouse D, Prevention of Premature Birth, NEJM, July 30, 1998, Vol339, #5, P 313-320 </li></ul></ul><ul><li>Cervical Length </li></ul><ul><ul><li>Iams, J et al, The length of the cervix and the risk of spontaneous premature delivery, NEJM, Vol 334, #9, p567-96 </li></ul></ul><ul><ul><li>Meekai S To, et al, Cervical cerclage for prevention of preterm delivery in women with short cervix: randomized controlled trial, Lancet, Vol 363, June 5 th 2004, p 1849-53 </li></ul></ul>
  • 78. References <ul><li>Fetal Fibronectin </li></ul><ul><ul><li>Goldenberg, R et al, The Preterm Prediction Study: Toward a multiple marker test for spontaneous preterm birth,Am J Ob Gyn Sept 2001, Vol 185, #3, p 643-651 </li></ul></ul><ul><ul><li>Honest, H, Accuracy of cervicovaginal fetal fibronectin test in predicting risk of spontaneous preterm birth: systemic review, BMJ, Vol 325, Aug 10 2002, p1-10 </li></ul></ul><ul><li>Tocolysis </li></ul><ul><ul><li>Gyetvai, Kristen, et al, Tocolytics for Preterm Labor: A Systematic Review, OB/Gyn Vol 94 (5 part 2) Nov 1999, p 869-877 </li></ul></ul>
  • 79. References <ul><li>Infections: BV </li></ul><ul><ul><li>Hauth, J Reduced Incidence of Preterm Delivery with Metronidazole and Erythromycin in women with Bacterial Vaginosis, NEJM Dec 28, 1995, p 1732-1736 </li></ul></ul><ul><ul><li>Carey, C et al, Metronidazole to prevent preterm delivery in pregnant women with asymptomatic Bacterial Vaginosis NEJM, Vol 342 (8) Feb 24 th 2000, pp 534-540 </li></ul></ul><ul><ul><li>Riggs M & Klebanoff M, Treatment of vaginal infections to prevent preterm birth: a Meta-Analysis, Clinical Obstetrics and Gynecology, 2004 Vol47, #4, p796-807 </li></ul></ul><ul><ul><li>Shennan A, et al, A Randomized controlled trial of metronidazole for prevention of preterm birth in women with positive Cevicovaginal fetal fibronectin: the PREMET study, BJOG 2006, 113:, p 65-74 </li></ul></ul>
  • 80. References <ul><li>Infections BV </li></ul><ul><li>USPSTF, Screening for Bacterial Vaginosis in Pregnancy, Recommendations and Rationale, Amer Fam Physician, March 15 th , 2002, Vol 65, #6 p 1147-1150 </li></ul><ul><li>Ugwumadu, A et al, Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial, Lancet vol 361, 3/22/2003, p 983-988 </li></ul><ul><li>Infections </li></ul><ul><li>2002 revised group B strep prevention guidelines. MMWR in Volume 51, RR-11.August 16 th 2002 </li></ul>
  • 81. References <ul><li>Preterm Contractions and Digital Cervix </li></ul><ul><ul><li>Iams, J et al, Requency of uterine contractions and the risk of spontaneous preterm birth NEJM 2002: 346: 250-5 </li></ul></ul><ul><ul><li>Guinn, D et Al Management options in women with preterm uterine contractions: a randomized controlled trial, Am J Obstet Gynecol Vol 177, #4, 1997, p 814-815 </li></ul></ul><ul><li>Other </li></ul><ul><ul><li>Crowther, C et al, Neonatal Respiratory Distress Syndrome after Repeat exposure to antenatal corticosteroids: a randomized controlled trial; Lancet 2006, 367, p1913-19 </li></ul></ul><ul><ul><li>Peltoniemi, O et al, Randomized Trial of a single repeat dose of betamethasone treatment in imminant preterm birth, Peds Feb 2007, vol 119, #2, p 290-298 </li></ul></ul>
  • 82. References: <ul><li>Progesterone </li></ul><ul><li>Meis, P et al, Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate, NEJM Vol 348 #24, June 12 th 2003, p 2379-85 </li></ul><ul><li>Da Fonseca, E 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 OB Gyn, Vol 188 (2) Feb 2003, pp 419-424 </li></ul><ul><li>Coomarssamy, A et al, Progesterone and the prevention of preterm birth, a critical review of the evidence, European J OB/Gyn, 2006, 129: p111-118 </li></ul><ul><li>Dodd, JM et al, Prenatal administration of progesterone for preventing preterm birth, Cochrane, Jan 25 th 2006 </li></ul>
  • 83. References <ul><li>PPROM </li></ul><ul><li>Hartling, l et al, A systematic review of intentional delivery in women with premature prelabor rupture of membranes, j of Mat-fetal and Neonatal Med, March 2006 19 (3), 177-187 </li></ul><ul><li>Wu, Y et al, Chorioamnionitis as a risk factor for Cerebral Palsy, a meta-analysis, JAMA, 2000, 284: p1417-24 </li></ul><ul><li>Grier, M et al, Do antibiotics improve neonatal outcomes in PPROM, J of Fam Prac, Vol 50(7), July 2001, p626 </li></ul><ul><li>Kenyon et al, Broad-Spectrum antibiotics for preterm prelabour rupture of fetal membranes: The ORACLE I randomized trial, Lancet 2001; 357: 979-88 </li></ul><ul><li>Naef, R et al, PROM at 34 to 37 weeks gestation: aggressive vs conservative management, Am J OB/Gyn 1998; 178: 126-30 </li></ul>
  • 84. References <ul><li>Progesterone: </li></ul><ul><li>Fonseca, E et al, Progesterone and the Risk of Preterm Birth among women with a Short Cervix, NEJM, 2007, Aug 2 nd , 357; p 462-9 </li></ul><ul><li>Rouse, D et al, A Trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins, NEJM, 2007, Aug 2 nd , 357; 454-61 </li></ul>
  • 85. PROM @ 34-37, “Near-term” <ul><li>Naef, AmJOB/Gyn, Jan 1998, p126 </li></ul><ul><li>prospective randomized 120 patients </li></ul><ul><li>RDS - 3 induce/ 3 expectant </li></ul><ul><li>Neonate mech vent, 2 induce/ 3 expectant </li></ul><ul><li>Chorioamnionitis 2% induce / 16% expectant significant to p=0.007 </li></ul><ul><li>neonatal sepsis 0 induce / 3 expectant NS </li></ul>
  • 86. PPROM 30-36 weeks: Metanalysis <ul><li>4 studies, 389 women, 391 babies </li></ul><ul><li>1987-98, no steroids, no tocolysis, only one study gave antibiotics as GBS prophylaxis </li></ul><ul><li>Intentional delivery with </li></ul><ul><ul><li>Less chorioamnionitis RR .16 (CI .10-.23) NNT 6 </li></ul></ul><ul><ul><li>Maternal shorter length of stay, 1.4 days shorter </li></ul></ul><ul><li>No difference (induce/wait) in </li></ul><ul><ul><li>RDS 33/191 vs 36/200, IVH 6 vs 3, NEC 1 vs 2 </li></ul></ul><ul><ul><li>Confirmed Neonatal sepsis 11/191 to 12/200 </li></ul></ul><ul><ul><li>NICU stay 11 vs 11.7 days </li></ul></ul><ul><ul><li>Perinatal mortality 0/191 to 3/200 (2 anomalies) </li></ul></ul>
  • 87. Risk of Preterm Birth < 35 weeks compared to cervical length of the 75% 1.0 1.0 75% 40 mm 9.5 6.7 10% 26 mm 13.9 9.5 5% 22 mm 24.9 14 1% 13 mm 28 weeks RR of PTB 24 weeks RR of PTB Percentile On Curve Length
  • 88. Lifestyle: Drug Screening <ul><li>Self Report </li></ul><ul><ul><li>3,142 Washington women, 40% participation </li></ul></ul><ul><li>Ever used IV Drugs 2% </li></ul><ul><li>Ever Cocaine 15% </li></ul><ul><li>Ever methamphetamine 11% </li></ul><ul><li>This Pregnancy </li></ul><ul><ul><li>Marijuana 7% </li></ul></ul><ul><ul><li>ETOH binge or daily use 2% </li></ul></ul><ul><ul><li>Tobacco 18% </li></ul></ul>
  • 89. Vaginal Progesterone <ul><li>RTC of 142 High Risk singletons with prior preterm delivery in Brazil </li></ul><ul><li>Vaginal Progesterone 100mg nightly 24-34 weeks </li></ul><ul><li>13/70 (18.6%) Placebo and 2/72 (2.8%) progesterone delivered before 34 weeks, RR of 0.11, NNT of 4 </li></ul>
  • 90. Tocolytics:  - mimetics 2004 Systematic Review OR 0.79 CI (0.61-1.01) 5 RTC 55%, 332/601  mimetic 65%, 332/525 placebo LBW < 2,500 gms OR 0.76 CI (0.57-1.01) 6 RTC 18%, 117/639  mimetic 25%, 140/565 placebo RDS OR 1.08 CI (0.72-1.62) 7 RTC 9%, 62/682  mimetic 8%, 48/604 placebo Perinatal Mortality OR Sample Finding

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