C-Section Deliveries Influencing Late Preterm Births & The Sequelae of Late Preterm Deliveries Heather Brumberg, MD, MPH, FAAP Medical Director, LHVPN Assistant Professor of Pediatrics and Clinical Public Health, NYMC Director of Regional Neonatal Public Health Programs, Maria Fareri Children’s Hospital, Valhalla, NY January 22, 2008

Shift in gestational distribution: May be in part due to change in practice to deliver earlier to avoid post-term births 1992 2003 Davidoff, MJ et al. Semin Perinatol 30(1):8-15, 2006

Over 70% of All Preterm Births Are Late Preterm (34-36 weeks gestation) Prematurity is on the rise in the United States. In 2003, 12.1% of all live births were preterm births. In 2005, this number increased to 12.5%. Late preterm infants, those babies 34-36 weeks gestation account for more than 70% of all preterm births. http://www.marchofdimes.com/files/MP_Late_Preterm_Birth-Every_Week_Matters_3-24-06.pdf

Late Preterms Increasing Over Time

Late Preterms Increasing by Race/Ethnicity Over Time

Late Preterm Birth Rates and Economic Burden 1 out of 11 births is a late preterm infant In 2005, prematurity cost the United States $26.2 billion dollars In California,1996- preventing non-medically indicated births between 34-37 weeks could have saved 49.9 million dollars However, the results in California are not generalizable because state and national data are lacking to estimate the proportion of nonindicated (and possibly preventable) preterm births. Raju, T. Clin Perinatol 33: 751-763, 2006

Why are Late Preterm Births on the Rise? C-section rate is increasing in the late preterm population Extremes in maternal age (<16, >35) linked to premature birth Assisted reproduction Obesity/fetal macrosomia Other maternal medical issues (i.e. preeclampsia) Reduction in late preterm stillbirths (Hankins and Longo, 2006; Raju, 2006)

C-Sections Increase Over Time by Gestational Age

Elective Delivery ACOG recommends elective delivery should not be preformed prior to 39 wks However, inaccuracies in dating can occur Early u/s standard, last menstrual period less accurate May not always utilized depending on timing of prenatal care Has also been implicated in increased preterm birth Fetal lung maturity is suggested if dating is unclear However, not always done due to perception of risks due to amniocentesis Little data, directly link c/s at maternal request (4-18% of all c-sections) to late preterm birth, although both rates have risen concurrently (Raju, 2006; Jain and Dudell, 2006; Fuchs and Wapner 2006)

Complications of Pregnancy as Potential Causes Preterm labor on the rise in late preterms Premature rupture of membranes also on the rise Expeditious delivery after 34 wks recommended Standard OB management of these: tocolysis and glucocorticoids up to 34 wks Similarly expert opinion recommends intervention for mild preeclampsia at 37 wks and severe as early as 34 weeks Beyond 34 wks, aggressive efforts to prevent delivery are not attempted (Dobak and Gardner, 2006; Fuchs and Wapner, 2006)

Diabetes and Pregnancy Weight Gain (Risks for C-Sections and Preeclampsia) Increased Over Time

Maternal Age (Risk for Preeclampsia) Increased Over Time

Multiple Gestation Rates Stable, BUT High Proportion are Increasingly Late Preterms (6x More Likely to be Premature) May be due to medical intervention for maternal (preeclampsia) or fetal reasons

Preeclampsia Preeclampsia on the rise (6-10% of all pregnancies), likely due to change in demographic of pregnant women Increased nulliparity, maternal age, obesity, and multiple gestations However, better management has led to reduced maternal and perinatal complications Studies did not delineate if delivery of mothers with preeclampsia was for fetal indication, preterm labor or rupture of membranes, or preeclampsia Interestingly, despite ACOG guidelines, 15% of mild preeclampsia are delivered at 34-36 wks (Sibai, 2006)

Objective To identify maternal risk factors associated with delivery of late preterm infants (34 - 36 weeks gestation) Jessica L. Kalia, DO, Paul Visintainer, PhD, Jordan Kase, MD, Heather L. Brumberg, MD, MPH E-PAS2007:61:8075.6

Methods Birth certificate data from NY State Department of Health Vital Statistics Study subjects Term (37-42 weeks gestation) infants Late preterm (34-36 weeks gestation) infants Born in Westchester County, New York 2004-2005 Data analysis Compared late preterm to term infants for delivery characteristics, receipt of prenatal care, and maternal demographics Statistical Analysis Chi square was used to compare frequencies Poisson regression was used for analysis of relative risks Statistical significance set at p < 0.05

Results: Westchester County Live Births by Weeks Gestation Late Preterms (8%) Late Preterms (8%) 2004 (n=12,306) 2005 (n=12,860)

Increased C-sections in Late Preterm Infants * * % Live Births Total: 25,166 live births * p< 0.05 *

More C-Sections in Late Preterm Infants for Maternal Conditions Related to Pregnancy * % Live Births Total: 25,166 live births * p< 0.05

No Difference in Commencement of Prenatal Care Percent Live Births Total: 25,166 live births

Extremes of Maternal Age Have Higher Rates of Late Preterm Infants % Live Births * % Live Births * Total: 25,166 live births * p < 0.05

No Difference in Medicaid Use

Summary of Relative Risks for Late Preterm Infants

Conclusions Late preterm delivery more likely at extremes of maternal age Maternal conditions related to pregnancy more likely to result in c-section delivery of late preterm infant C-section delivery more likely in late preterms Elective c-section rates are not significantly different between term and late preterms No difference in commencement of prenatal care between term and late preterms No socioeconomic difference in late preterm and term mothers as measured by primary medicaid use

Morbidity & Mortality Morbidities Total Mortality Singleton Live Births RR (95% CI) United States 2.9 (2.8-3.0) Canada 4.5 (4.0-5.0) Wang M et al Pediatrics 114: 372-376, 2004 Neu J, Semin Perinatol. 30: 77-80, 2006 Raju, T et al. Pediatrics 118: 1207-21, 2006 Kramer, MS et al, JAMA 284: 843-849, 2000

Infant Mortality Late preterms 3 times more likely to die than term infants in their first year of life Late preterms 6 times as likely to die than term babies in their first week of life (early neonatal period) Late preterms 3 times as likely to die than term babies after their first week to 27 days (late neonatal period) Leading cause is congential anomalies (Tomashek et al. 2007)

Other Outcomes Increased risk of rehospitalization, most commonly due to jaundice (63%) and infection (13%; Shapiro-Mendoza et al. 2006) Increased risk of SIDS 1.37 per 1,000 live births (33-36 wks) vs. 0.69 per 1,000 live births (term) as well as increased risk of apnea and apparent life threatening events (Clapp 2006) Suck-swallow immaturity and slow motility/gastric emptying also leads to prolonged hospitalization and readmission (Neu 2006)

At 34 weeks, the overall brain weight is 65% of term weight At 34 weeks, the overall brain weight is 65% of term weight. It is possible that ex utero brain growth is different from in utero brain growth. Studies need to be done in this area. Kinney HC. Seminars in Perinatology 30: 81-88, 2006.

Neurodevelopmental Outcomes More likely to have developmental delay by 3 y/o RR (95%CI)= 1.46 (1.42-1.50) More likely to be referred for special needs, special education, and have problems with school readiness than term counterparts Small studies also suggest higher risk of cerebral palsy, speech disorders, behavioral abnormalities Increased risk of hyberbilirubinemia (jaundice) and kernicterus Abnormal movements, hearing impairment, spasticity, abnormal movement of eyes (Engle, 2007; Adams-Chapman, 2006)

Objective Compare the enrollment in EI and the utilization of therapeutic services between moderately preterm (32-36 weeks gestation) and very preterm (<32 weeks gestation) infants at 12 months ± 2 months corrected age The goal of our study was to compare at 12 mo ± 2mo corrected age, the enrollment in EI and the utilization of therapeutic services between moderately preterm and very preterm infants. We targeted enrollment in EI because in order for a child to qualify for this service, there must be at least a 33% developmental delay. This is an objective measurement that can be translated across examiners and developmental testing methods. It is important to understand that we looked at enrollment in EI not just babies who were referred for evaluation. Jessica L. Kalia DO, Paul Visintainer PhD, Heather L. Brumberg MD, MPH, Maria Pici MD, Jordan Kase MD E-PAS2007:61:6280.25

Why Early Intervention? Used as a surrogate to assess neurodevelopment Objective measurement 33% delay in at least 1 area of development Must be receiving services, not just referred for EI evaluation

Methods Preterm infants followed at the Regional Neonatal Follow-up Clinic in White Plains, NY from Jan 2005 through Oct 2006 Included all patients <37 weeks gestation who had an evaluation at 12 months ± 2 months corrected age (CA) Stratified into moderately preterm (32-36 weeks gestation) and very preterm (<32 weeks gestation) groups Antenatal, maternal, and neonatal variables obtained by NICU discharge summaries and parental report Logistic regression, Chi square, and Fisher’s exact tests used for analysis In this retrospective study, our cohort of infants were preterm infants followed at the regional neonatal follow up clinic in White Plains, NY from Jan 2005 to Oct 2006. All preterms who had an evaluation at the follow up clinic at 12 mo ± 2mo corrected age were included and then stratified into moderately preterm and very preterm groups. We analyzed antenatal, maternal, and neonatal variables obtained by parental report and NICU discharge summaries.

Results Our dataset contained 497 preterm infants, of which 169 met our inclusion criteria. Of those, 77 were very preterm and 92 were moderately preterm. 208 babies were not yet 12 mo +/- 2 mo corrected age at the time of the study. 20% of the preterm babies were lost to follow up. 19 did not have an examination at the clinic during the time window we were studying. Over 65% of the patients we studied were born at Westchester Medical Center. The remainder were born in hospitals throughout the lower Hudson Valley region.

Patient Characteristics Moderately Preterm Very Preterm p value Gestational age (weeks) # 34 ± 1 28 ± 2 <0.001 Birth wt (grams) # 2124 ± 493 1114 ± 374 Length of stay (weeks) # 2.3 ± 2.0 8.9 ± 5.4 5 min Apgar ^ 9 (6,9) 7 (1,9) Sex, n (%) NS Male 55 (60) 37 (48) Female 37 (40) 40 (52) Delivery type, n (%) NSVD 27 (32) 20 (26) C/S 40 (48) 39 (51) Stat C/S 17 (20) 18 (23) We looked at various antenatal and neonatal characteristics of the babies included in our study. The very preterm and moderately preterm babies were significantly different from each other in obvious ways such as mean GA , birthweight, length of stay, and 5 minute Apgar score. # mean ± SD , ^median (min,max), NS = not significant

Patient Demographics Moderately Preterm Very Preterm p value Multiple gestation, n (%) 0.02 Singleton 62 (67) 60 (78) Twins 21 (22) 17 (22) Triplets 9 (10) 0 (0) Medicaid, n (%) 80 (87) 71(92) NS Maternal age (years) # 31 ± 7 29 ± 7 Maternal race, n (%) 0.01 Caucasian 34 (38) 14 (18) African American 20 (22) 21 (28) Hispanic 30 (33) 26 (34) Other 6 (7) 15 (20) Maternal substance abuse, n (%) 8 (9) 7 (9) Multiple gestation differs between the moderately preterm and very preterm groups due to the 9 triplets in the moderately preterm group. There are also racial differences between the two groups. # mean ± SD , NS = not significant

Rate of Therapy Use * * * * * p= <0.05 * From this data, we can see that 36% of MP used EI, 28% used PT, 17% OT, 16% ST and 8% special education. This is a substantial number of services needed by babies considered to be “near” term. We also may be underestimating their use of speech therapy and special education as these services are usually started after 12 months of age. * p= <0.05

Very Preterm vs. Moderately Preterm Odds Ratios EI PT OT Speech * Special Ed When we looked at the unadjusted odds ratios comparing the use of therapies in very preterms to moderately preterms, not surprisingly we found that very preterm infants were more likely to utilize EI, PT, OT, speech therapy and special education. 1 10

Very Preterm vs. Moderately Preterm Adjusted Odds Ratios EI Adjusted for: 5 minute Apgar score Caffeine BPD RDS Length of stay PT OT Speech However, when we adjusted for the neonatal characteristics that were significantly different between the moderately preterm and very preterm infants- the 5 minute Apgar score, caffeine for apnea of prematurity, BPD, RDS, and length of stay there was no significant difference between the likelihood of very preterms and moderately preterms to use EI, PT, OT, speech tx and special education. Perhaps extrauterine brain growth is different than intrauterine, and any degree of prematurity, even moderate prematurity may put babies are at risk for developmental delays. Special Ed 1 10

Summary Over 1/3 of moderately preterm infants were enrolled in EI and 28% received physical therapy When adjusting the odds ratios for neonatal factors, there was no difference in the odds of utilizing therapies between the two gestational age groups We conclude that in our cohort of infants, over 1/3 of the moderately preterm infants were enrolled in EI and 28% received PT. When we adjusted for factors such as the 5 minute Apgar score, caffeine for apnea of prematurity, BPD, RDS and length of stay, there was no difference in the odds of utilizing therapies between moderately preterm and very preterm infants.

Conclusion Moderately preterm babies are at risk and must be screened and referred for interventional therapies They should not be considered “small” full term infants Therefore we conclude that moderately preterm babies are at risk for developmental delay and must be screened and referred for interventional therapies. We should not treat them as small full term infants.

Implications If our results could be extrapolated to the general population, there would be 150,000 moderately preterm and 75,000 very preterm infants enrolled in EI per year We speculate that if our results could be extrapolated to the general population, being that there are almost 4.2 million births per year and a 12.5% prematurity rate, there would be 150,000 moderate preterms and 75,000 very preterm infants enrolled in early intervention each year. Quite a few moderately preterm infants! Future studies need to be done on this rapidly growing group of moderately preterm infants. Prospective and longitudinal studies could be done to show developmental, behavioral, cognitive, psychomotor and medical outcomes of these at risk infants. Thank you.

Acknowlegements Westchester Medical Center Jordan Kase MD Jessica Kalia, DO Sergio Golombek MD, MPH Dept of Epidemiology, NY Medical College Paul Visintainer PhD Children’s Rehabilitation Center Maria Pici MD NY State Department of Vital Statistics -Larry Schoen, Director of the Statistical Analysis and Program Support Unit in the Bureau of Biometrics and Health Statistics -Daljit Singh, Biostatistician

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