1. Complications of Delivery Before 39 Weeks: OB Perspective Roger B. Newman MD Maas Endowed Chair For Reproductive Sciences Professor and Vice-Chairman Department of Ob-Gyn Medical University of South Carolina

2. Complications of Delivery <39 Wks Learning Objectives Rates of late-preterm birth in US Rates of late-preterm birth in US Reasons for the increase Reasons for the increase Indications/contraindications for IOL Indications/contraindications for IOL Advantages/disadvantages of IOL Advantages/disadvantages of IOL Recommendations Recommendations

3. Preterm Birth in US Has increased 20% in past 15 years: 10.6% in 1990 to 12.7% in 2005 Has increased 20% in past 15 years: 10.6% in 1990 to 12.7% in 2005 “Late-Preterm” (34-36 weeks) increasing at a greater rate than other PTB subgroups “Late-Preterm” (34-36 weeks) increasing at a greater rate than other PTB subgroups “Late-Preterm” birth rate was 7.3% in 1990 vs 9.1% in 2005; 25% increase “Late-Preterm” birth rate was 7.3% in 1990 vs 9.1% in 2005; 25% increase

4. Delivery Indications: Late- Preterm Births 292,627 late-preterm births in 2001: US Birth Cohort Linked Birth / Death Files (singletons) 292,627 late-preterm births in 2001: US Birth Cohort Linked Birth / Death Files (singletons) 76.8% had maternal/fetal indication or spontaneous labor; 23.2% (67.909) no recorded indication 76.8% had maternal/fetal indication or spontaneous labor; 23.2% (67.909) no recorded indication No recorded indication associated with: older age, non-Hispanic white, ≥ 13 yrs of education, multiparity, southern, midwest, or western region, or prior child ≥ 4000 g birth weight No recorded indication associated with: older age, non-Hispanic white, ≥ 13 yrs of education, multiparity, southern, midwest, or western region, or prior child ≥ 4000 g birth weight Reddy et al, Pediatrics 2009

5. Induction of Labor United States Doubled from ’90 to ’06: 9.5% to 22.5% Some for medical/Ob indications Most: marginal or elective Doubled from ’90 to ’06: 9.5% to 22.5% Some for medical/Ob indications Most: marginal or elective Why? Better cervical ripening agents Patient/MD convenience Relaxed attitudes re: marginal indications Concerns re: fetal death with expect Rx Why? Better cervical ripening agents Patient/MD convenience Relaxed attitudes re: marginal indications Concerns re: fetal death with expect Rx CDC 2009; Rayburn, AJOG 2002; Moore, Clin Ob-Gyn 2006

6. Accuracy of Vital Statistic Data Birth Certificates Ohio Perinatal Quality Collaborative 2008 Ohio Perinatal Quality Collaborative 2008 20 Ohio hospitals To decrease nonmedically-indicated scheduled deliveries To decrease nonmedically-indicated scheduled deliveries All scheduled deliveries: 36-38 6/7 wks All scheduled deliveries: 36-38 6/7 wks Comparison of chart abstraction vs birth certificates Comparison of chart abstraction vs birth certificates 11% in BC vs 1% in chart 11% in BC vs 1% in chart

7. Birth Certificate Data vs Chart Abstracted Data Bailit; Induction rates derived from birth certificate data. Am J Obstet Gynecol 2010

8. Conceptual Diagram

9. Timing of Indicated Late- Preterm and Early-Term Birth Workshop Feb. 2011, sponsored by Eunice Kennedy Shriver NICHD and SMFM Workshop Feb. 2011, sponsored by Eunice Kennedy Shriver NICHD and SMFM Synthesize available evidence regarding conditions resulting in medically-indicated late-preterm or early-term births Synthesize available evidence regarding conditions resulting in medically-indicated late-preterm or early-term births Based on available data and expert opinion, optimal timing for delivery was determined by consensus Based on available data and expert opinion, optimal timing for delivery was determined by consensus Spong, Mercer, D’Alton et al OBGYN, 2011 Spong, Mercer, D’Alton et al OBGYN, 2011

10. Induction of Labor Contraindications Prior classical CS Prior classical CS Prior transmural uterine incision Prior transmural uterine incision Placenta or vasa previa Placenta or vasa previa Umbilical cord prolapse Umbilical cord prolapse Transverse lie Transverse lie

11. Induction of Labor Disadvantages Increased Cesarean rate Increased Cesarean rate Iatrogenic prematurity Iatrogenic prematurity Cost Cost

12. Induction of Labor 37-38 wks vs ≥39 wks Prospective observational study 18,000 deliveries in 27 HCA hospitals 3 month epoch in 2007 Prospective observational study 18,000 deliveries in 27 HCA hospitals 3 month epoch in 2007 Planned elective IOL: 31% of all deliveries Planned elective IOL: 31% of all deliveries Population 790 at 37-38 wks (28.3%) 2004 at ≥39 wks (71.7%) Population 790 at 37-38 wks (28.3%) 2004 at ≥39 wks (71.7%) Clark, AJOG, 2009

13. Induction of Labor 37-38 wks vs ≥39 wks Results: higher NICU adm (7.7 vs 3.0%) Results: higher NICU adm (7.7 vs 3.0%) Cesarean rates correlated with cx dilatation in both nullips and multips Cesarean rates correlated with cx dilatation in both nullips and multips Term should no longer be 37 wks Term should no longer be 37 wks Clark, AJOG, 2009

14. Induction of Labor Nulliparity Matched cohort of nullips, singleton, ceph Matched cohort of nullips, singleton, ceph Population: Belgium 7683: elective IOL 7683: spontaneous labor Population: Belgium 7683: elective IOL 7683: spontaneous labor 38-41 weeks 38-41 weeks BW 3000-4000gms BW 3000-4000gms Cervical status and ripening not known Cervical status and ripening not known Cammu, AJOG 2002

15. Induction of Labor Nulliparity Higher Cesarean: 10 vs 7% (1 st stage problems) Higher Cesarean: 10 vs 7% (1 st stage problems) Higher instrumental delivery: 32 vs 29% Higher instrumental delivery: 32 vs 29% More epidurals: 80 vs 58% More epidurals: 80 vs 58% More NICU: 11 vs 9% More NICU: 11 vs 9% Nullips should be informed before elective IOL Nullips should be informed before elective IOL Cammu, AJOG 2002

16. Induction of Labor Nulliparity Retrospective cohort: Tacoma, Wash Retrospective cohort: Tacoma, Wash Elective IOL (n=263) Low risk at 38-41 wks Compared to spon labor Elective IOL (n=263) Low risk at 38-41 wks Compared to spon labor Primary outcome: Cesarean OR 2.4, CI 1.2,4.9 Primary outcome: Cesarean OR 2.4, CI 1.2,4.9 Longer labor (4 hrs) and more cost ($273) Longer labor (4 hrs) and more cost ($273)

17. Induction of Labor Nulliparity Multiple cohort studies: Cesarean rate doubled for elective and medical inductions Multiple cohort studies: Cesarean rate doubled for elective and medical inductions Primarily due to unfav cervix: Bishop ≤5 Primarily due to unfav cervix: Bishop ≤5 RPT showed no diff in Cesarean with favorable cx (Bishop ≥ 5) RPT showed no diff in Cesarean with favorable cx (Bishop ≥ 5) Nielsen, J Mat Fet Neo Med 2005

18. Bishop’s Score ScoreDilatation EffacementStationPositionConsistency 0closed 0 – 30%-3posteriorfirm 11-2 cm40 -50%-2mid-positionmoderately firm 23-4 cm60 -70%-1,0anterior Soft 35+ cm80+%+1,+2 0closed 0 – 30%-3posteriorfirm 11-2 cm40 -50%-2mid-positionmoderately firm 23-4 cm60 -70%-1,0anterior Soft 35+ cm80+%+1,+2 A point is added: Preeclampsia/Each prior vaginal delivery A point is added: Preeclampsia/Each prior vaginal delivery A point is subtracted: Postdates/Nulliparity/pPROM A point is subtracted: Postdates/Nulliparity/pPROM Cesarean RatesFirst Time MothersWomen with Past Vaginal Deliveries BS 0 - 345% 7.7% BS 4 – 610% 3.9% BS 7 - 101.4% 0.9%

19. Bishop’s Score

20. Induction of Labor Nulliparity Retrospective cohort: Northwestern Retrospective cohort: Northwestern Elective IOL (n=294) Nullip Bishop ≥ 5 39-40 5/7 wks Compared to expectantly managed Elective IOL (n=294) Nullip Bishop ≥ 5 39-40 5/7 wks Compared to expectantly managed Primary Outcome: Cesarean ( 21 vs 20%) Primary Outcome: Cesarean ( 21 vs 20%) IOL: longer labor (13 vs 9 hrs) IOL: longer labor (13 vs 9 hrs) Osmundson, ObstetGynecol, 2010

21. Induction of Labor Multiparas No increased Cesarean rate No increased Cesarean rate Most data retrospective, but one small PRT Most data retrospective, but one small PRT Large population-based cohort 1775 low risk multips at term IOL vs 5785 similar pts with spon labor Cervical ripening agents if unripe Cesarean similar: 3.8 vs 3.6% (RR 1.07) Large population-based cohort 1775 low risk multips at term IOL vs 5785 similar pts with spon labor Cervical ripening agents if unripe Cesarean similar: 3.8 vs 3.6% (RR 1.07) Nielsen, J Mat Fet Neo Med 2005; Dublin, AJOG 2000

22. Induction of Labor Respiratory Morbidity 33,289 deliveries ≥ 37 wks 33,289 deliveries ≥ 37 wks RDS or TTN requiring adm to NICU RDS or TTN requiring adm to NICU Comparison with overall baseline term rates Comparison with overall baseline term rates Elective induction at term with vag deliv 37-37 6/7: 12.6/1000, OR 2.5, CI 1.5-4.22 38-38 6/7: 7.0/1000, OR 1.4, CI 0.8-2.2 39-39 6/7: 3.2/1000, OR 0.6, CI 0.4-1.0 Elective induction at term with vag deliv 37-37 6/7: 12.6/1000, OR 2.5, CI 1.5-4.22 38-38 6/7: 7.0/1000, OR 1.4, CI 0.8-2.2 39-39 6/7: 3.2/1000, OR 0.6, CI 0.4-1.0 Morrison, BJOG, 1995

23. Induction of Labor Respiratory Morbidity Same comparison in failed IOL/Cesarean 37-37 6/7: 57.7/1000, OR 11.2, CI 5.4-13.1 38-38 6/7: 9.4/1000, OR 1.8, CI 0.6-5.9 39-39 6/7: 16.2/1000, OR 3.2, CI 1.4-7.4 Same comparison in failed IOL/Cesarean 37-37 6/7: 57.7/1000, OR 11.2, CI 5.4-13.1 38-38 6/7: 9.4/1000, OR 1.8, CI 0.6-5.9 39-39 6/7: 16.2/1000, OR 3.2, CI 1.4-7.4 Elective delivery by Cesarean without labor: Increased freq at all gestational ages Elective delivery by Cesarean without labor: Increased freq at all gestational ages Morrison, BJOG 1995

24. Timing of Elective Repeat Cesarean MFMU Network: secondary analysis of Cesarean registry MFMU Network: secondary analysis of Cesarean registry 19 academic centers 1999-2002 19 academic centers 1999-2002 N=13,258 for elective term repeat Cesarean 37 wks: 6.3% 38 wks: 29.5% 39 wks: 49.1% N=13,258 for elective term repeat Cesarean 37 wks: 6.3% 38 wks: 29.5% 39 wks: 49.1% Tita, NEJM, 2009

25. Timing of Elective Repeat Cesarean Composite outcome: respiratory, sepsis, hypoglycemia, NICU admit, death 37wks: 15.3%, OR 2.1, CI 1.7-2.5 38 wks: 11.0%, OR 1.5, CI 1.3-1.7 39 wks: 8.0% Composite outcome: respiratory, sepsis, hypoglycemia, NICU admit, death 37wks: 15.3%, OR 2.1, CI 1.7-2.5 38 wks: 11.0%, OR 1.5, CI 1.3-1.7 39 wks: 8.0% Individual outcomes also signif different Individual outcomes also signif different No diff between 39 and 40 wks No diff between 39 and 40 wks Increased morbidity at 41 wks Increased morbidity at 41 wks Tita, NEJM 2009 Tita, NEJM 2009

26. Elective Repeat Cesarean Delivery & Incidence of Primary Outcome

27. Timing of Elective Repeat Cesarean 2-3 stillbirths avoided with delivery < 39 wks 2-3 stillbirths avoided with delivery < 39 wks 176 extra cases of primary outcome 176 extra cases of primary outcome 145 extra admissions to NICU 145 extra admissions to NICU 63 extra cases of RDS 63 extra cases of RDS Also increased morbidity 38 4/7-38 6/7 Also increased morbidity 38 4/7-38 6/7 Tita, NEJM 2009 Tita, NEJM 2009

28. Neonatal Morbidity Elective Cesarean Elective Cesarean at term: breech, social, CPD, repeat, fundal scar Elective Cesarean at term: breech, social, CPD, repeat, fundal scar Amsterdam ’94-’98: n=324 Amsterdam ’94-’98: n=324 Decreased respiratory morbidity with advancing gest age (p<0.05) 37-37 6/7 wks:8.4% 38-38 6/7wks:4.4% 39+ wks:1.8% Decreased respiratory morbidity with advancing gest age (p<0.05) 37-37 6/7 wks:8.4% 38-38 6/7wks:4.4% 39+ wks:1.8% van den Berg, EJOG, 2001

29. Economic Consequences Decision Analysis Cohort of 100,000 patients Induction at 39, 40, 41 wks vs expectant Rx All patients delivered by 42 wks Cohort of 100,000 patients Induction at 39, 40, 41 wks vs expectant Rx All patients delivered by 42 wks IOL at 39 weeks 12,000 excess Cesareans Additional cost: $100 million 133 fetal deaths avoided Regardless of cx ripeness or parity IOL at 39 weeks 12,000 excess Cesareans Additional cost: $100 million 133 fetal deaths avoided Regardless of cx ripeness or parity Kaufman, AJOG, 2002

30. Decision Analysis Kaufman, AJOG, 2002 IOL less expensive IOL less expensive Later gestational ages Multips Favorable cervix Most costly Most costly Nullips with unfavorable cervix Cost halved with favorable cervix (Bishop > 5) Still overall added expense

31. Induction of Labor Bottom Line No evidence for elective IOL No evidence for elective IOL Need large randomized studies Maternal and neonatal safety Reduced unexplained fetal death Cost-effectiveness Need large randomized studies Maternal and neonatal safety Reduced unexplained fetal death Cost-effectiveness

32. Complications of Delivery <39 Wks Final Thoughts IOL only if continuing preg has greater maternal/fetal risks than the intervention IOL only if continuing preg has greater maternal/fetal risks than the intervention No elective IOL at term without indications Increased Cesarean rate Iatrogenic prematurity Increased cost No proven benefits No elective IOL at term without indications Increased Cesarean rate Iatrogenic prematurity Increased cost No proven benefits Bishop score best at predicting success Bishop score best at predicting success Elective primary or repeat Cesarean < 39 weeks inappropriate without indication Elective primary or repeat Cesarean < 39 weeks inappropriate without indication Term should now be considered 39 weeks Term should now be considered 39 weeks