The Late Preterm Infant Data by Reese H

The “Late Preterm” Infant Data by: Reese H. Clark, M. D. Presented by: Bryan L. Ohning, M. D. , Ph. D.

The “Late Preterm” Infant What is the Problem ?

From the March of Dimes Web Site: http: //www. marchofdimes. com/peristats In 2005, 1 in 8 babies (12. 7% of live births) were born preterm in the United States. Between 1995 and 2005, the rate of infants born preterm in the United States increased more than 15%. The preterm birth rate in the United States is highest for black infants (18. 1%), followed by Native Americans (13. 8%), Hispanics (12. 0%), whites (11. 5%) and Asians (10. 5%). In 2005, compared with singleton births (one baby), multiple births in the United States were about 6 times as likely to be preterm. Between 1996 and 2004 there was an increase of nearly 60, 000 singleton preterm births. 92 percent of those infants were delivered by a cesarean section.

From the March of Dimes Web Site: http: //www. marchofdimes. com/peristats Following three decades of increases in our nation, in 2008 we saw the first two-year decline in the preterm birth rate, a 4 percent drop from 2006. The 2008 preliminary preterm birth rate dropped to 12. 3 percent, from the 2006 final rate of 12. 8 percent. The March of Dimes says 79 percent of the decline was among babies born just a few weeks too soon. Overall, the United States received a "D" on the report card, when national preterm birth rates are measured against the Healthy People 2010 goals. The United States has a high rate of preterm birth compared to most industrialized countries.

From the March of Dimes Web Site: http: //www. marchofdimes. com/peristats In 2005, the annual societal economic cost (medical, educational, and lost productivity) associated with preterm birth in the United States totaled to be at least…… 26. 2 billion dollars!

http: //www. marchofdimes. com/peristats

Definitions

Optimizing Care and Outcome for Late-Preterm (Near-Term) Infants. Raju et al. Pediatrics 2006; 118; 1207 -1214 The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists define a “preterm” infant as one who is born before the end of the 37 th week (259 th day) of pregnancy, counting from the first day of the last menstrual period. Various subsets of preterm infants between 33 weeks and term have been described as “marginally preterm, ” “moderately preterm, ” “minimally preterm, ” and “mildly preterm”.

Optimizing Care and Outcome for Late-Preterm (Near-Term) Infants. Raju et al. Pediatrics 2006; 118; 1207 -1214 The panel suggested designating infants born between the gestational ages of 34 0/7 weeks through 36 6/7 weeks as “Late Preterm” and discontinue the use of the phrase “near term. ” The panel was of the opinion that “near term” can be misleading, conveying an impression that these infants are “almost term, ” resulting in underestimation of risk and lessdiligent evaluation, monitoring, and follow-up. The panel confirmed that gestational age should be rounded off to the nearest completed week, not to the following week. Thus, an infant born on the 5 th day of the 36 th week (35 weeks and 5/7 days) is at a gestational age of 35 weeks, not 36 weeks.

Cesarean Section Rate Changes

http: //www. cdc. gov/nchs/Vital. Stats. htm

http: //www. marchofdimes. com/peristats

A Shift in Gestational Age

CDC web site -- http: //205. 207. 175. 93/Vital. Stats/Report. Folders/report. Folders. aspx

Gestational Age of NICU Patients

Raju et al. Pediatrics 2006; 118; 1207 -1214 Factors that potentially are contributing to increasing preterm births in the United States Increasing proportion of pregnant women >35 years of age Multiple births Medically indicated deliveries secondary to better surveillance of the mother and the fetus Attempts to reduce stillbirths

Mortality Differences By Gestational Age

Mortality of Late-Preterm (Near-Term) Newborns in Utah Young P et al. Pediatrics 2007; 119; 659 -665 NICU Admissions:

Mortality of Late-Preterm (Near-Term) Newborns in Utah Young P et al. Pediatrics 2007; 119; 659 -665

Infant Mortality Rate is the number of Infant deaths per 1000 live births http: //205. 207. 175. 93/Vital. Stats/Table. Viewer/table. View. aspx? Report. Id=3274

Mortality Risk By Mode of Delivery Are C/Sections safer than Vaginal Delivery ?

http: //wonder. cdc. gov/lbd. html

Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term. Liu S et al. CMAJ. 2007; 176: 455 -460. Canadian Institute for Health Information's Discharge Abstract Database Retrospective population-based cohort study of all women in Canada (excluding Quebec and Manitoba) who delivered from April 1991 through March 2005. Healthy women who underwent a primary cesarean delivery for breech presentation constituted a surrogate "planned cesarean group" considered to have undergone low-risk elective cesarean delivery, for comparison with an otherwise similar group of women who had planned to deliver vaginally, the “planned vaginal delivery group”.

Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term. Liu S et al. CMAJ. 2007; 176: 455 -460. Caesareans group had an overall rate of morbidity of 27. 3 per 1000 deliveries compared to 9. 0 per 1000 planned vaginal deliveries. Cesarean group had increased postpartum risks of: cardiac arrest (OR 5. 1, 95% CI 4. 1– 6. 3) wound hematoma (OR 5. 1, 95% CI 4. 6– 5. 5), hysterectomy (OR 3. 2, 95% CI 2. 2– 4. 8) major puerperal infection (OR 3. 0, 95% CI 2. 7– 3. 4) anesthetic complications (OR 2. 3, 95% CI 2. 0– 2. 6) venous thromboembolism (OR 2. 2, 95% CI 1. 5– 3. 2) hemorrhage requiring hysterectomy (OR 2. 1, 95% CI 1. 2– 3. 8) and stayed in hospital longer (adjusted mean difference 1. 47 d, 95% CI 1. 46– 1. 49 d) A limitation of this study: women with severe health conditions are more likely to pre-schedule births by caesarean.

Original Article Timing of Elective Repeat Cesarean Delivery at Term and Neonatal Outcomes Alan T. N. Tita, M. D. , Ph. D. , Mark B. Landon, M. D. , Catherine Y. Spong, M. D. , Yinglei Lai, Ph. D. , Kenneth J. Leveno, M. D. , Michael W. Varner, M. D. , Atef H. Moawad, M. D. , Steve N. Caritis, M. D. , Paul J. Meis, M. D. , Ronald J. Wapner, M. D. , Yoram Sorokin, M. D. , Menachem Miodovnik, M. D. , Marshall Carpenter, M. D. , Alan M. Peaceman, M. D. , Mary J. O'Sullivan, M. D. , Baha M. Sibai, M. D. , Oded Langer, M. D. , John M. Thorp, M. D. , Susan M. Ramin, M. D. , Brian M. Mercer, M. D. , for the Eunice Kennedy Shriver NICHD Maternal–Fetal Medicine Units Network N Engl J Med Volume 360(2): 111 -120 January 8, 2009

Study Overview • Among a large cohort of women with singleton pregnancies who underwent elective repeat cesarean sections, more than a third of deliveries were performed before 39 weeks of gestation • Compared with deliveries at or after 39 weeks, deliveries before 39 weeks of gestation (even those during the last 3 days before week 39) were associated with an increased risk of a composite primary outcome that included neonatal death, respiratory complications, need for mechanical ventilation, treated hypoglycemia, newborn sepsis, and admission to the neonatal intensive care unit.

Respiratory Issues by Gestational Age

Proportion of Patients At Each EGA (Data Based on 434, 665 NICU infants where Respiratory Support Type Was Reported, 1997 -2008)

The Epidemiology of Respiratory Failure in Neonates Born at an Estimated Gestational Age of 34 Weeks or More Reese H. Clark, MD The Near-Term Respiratory Failure Research Group Journal of Perinatology 2005; 25: 251– 257

Study Population Inclusion criteria ≥ 34 weeks’ EGA Intubated 72 hours and expected to need ventilation for ≥ 6 hours Parental consent Delivery service available Ability to refer for extracorporeal membrane oxygenation (ECMO) Exclusion criteria Not on ventilator No delivery service

Endpoints Death Oxygen support at discharge or 30 days, whichever comes first Brain injury Intracranial hemorrhage Seizures requiring treatment until discharge Brain atrophy or stroke

Demographics (1011 patients enrolled) EGA (weeks) Birth weight (kg) Maternal age (years) Median Apgars @ 1/5 Male gender Antenatal steroids 37 ± 2 3 ± 0. 6 28 ± 6 7/8 622 (62%) 91 (9%)

Demographics Race Black Hispanic White Delivery Vaginal delivery Elective Cesarean section Emergent Cesarean section Forceps extraction Vacuum extraction 116 (12%) 147 (15%) 687 (69%) 408 (41%) 229 (23%) 324 (32%) 20 (2%) 30 (3%)

Outcomes Of the 1011 patients enrolled: 51 (5%) died Deceleration of care Other cause of death Progressive respiratory failure Renal failure Major congenital anomaly 8 5 11 4 23 73 (7. 2%) patients met ECMO criteria and 36 (3. 6%, 49%) were treated with ECMO 73 (7. 2%) died or were treated with ECMO

Causes of Death

Occurrence of Chronic Lung Disease 109/1011 (10%) had a diagnosis of chronic lung disease and 17 (16%) of these 106 were on a ventilator at 30 days or discharge 77/945 (8%) of survivors went home on oxygen

Outcomes Median ventilator days in survivors was 3 (1 -5 quartiles) and in non-survivors was 5 (3 -15 quartiles) Median age at discharge for survivors (LOS) was 13 days (9 -21 quartiles) Median age at death was 7 days (2 -27 quartiles) 86/1011 (9%) had a report of a neurological complication

Follow-Up Data

Short-term outcomes of infants born at 35 and 36 weeks gestation: We need to ask more questions. Escobar GJ, et al. Semin Perinatol. 2006; 30: 28 -33. Newborns born at 35 and 36 weeks gestation experienced considerable mortality and morbidity. Approximately 8% required supplemental oxygen support for at least 1 hour, almost 3 times the rate found in infants born at > or =37 weeks. Following discharge from the birth hospitalization, 35 to 36 week infants were much more likely to be re-hospitalized than term infants, and this increase was evident both within 14 days as well as within 15 to 182 days after discharge. Had more problems with hyperbilirubinemia

School outcomes of late preterm infants: special needs and challenges for infants born at 32 to 36 weeks gestation. Chyi LJ et al. J Pediatr 2008; 153: 25 -31. Examined school outcomes from kindergarten to grade 5 of infants born at 32 weeks to 36 weeks’ gestation. When compared with a large group (n = 13, 671) of term infants followed in the Early Childhood Longitudinal Study. Kindergarten Cohort (ECLS-K), late preterm infants (n = 767) had lower reading and math scores than their term counterparts in 1 st grade. Late preterm infants also had higher participation in special education during early grades and higher odds for belowaverage reading skills in all grades, although there was resolution of test score differences by the 3 rd and 5 th grade.

Late preterm infants have worse 24 -month neurodevelopmental outcomes than term infants. Woythaler MA, Mc. Cormick MC, Smith VC. Pediatrics 2011; 127: e 622 -e 629. BACKGROUND: Late preterm infants (34 -37 weeks' gestation) are often perceived at similar risks for morbidity and mortality as term infants. OBJECTIVE: To compare the neurodevelopmental outcomes of late preterm to term infants. METHODS: Study sample of 6300 term and 1200 late preterm infants came from the Early Childhood Longitudinal Study. Birth Cohort. General estimating equations were used to get weighted odds of having developmental delay, mental index scores (MDI) or psychomotor index scores (PDI) < 70, at 24 months of age.

Late preterm infants have worse 24 -month neurodevelopmental outcomes than term infants. Woythaler MA, Mc. Cormick MC, Smith VC. Pediatrics 2011; 127: e 622 -e 629. Late preterm infants compared with term infants had lower MDI (85 vs 89) and PDI (88 vs 92), both P <. 0001, respectively. A higher proportion of late preterm infants compared with term infants had an MDI <70 (21% vs 16%; P <. 0001). After controlling for statistically significant and clinically relevant descriptive characteristics, late preterm infants still had higher odds of mental developmental delay (odds ratio: 1. 52 [95% confidence interval: 1. 26 -1. 82] or physical developmental delay (odds ratio: 1. 56 [95% confidence interval: 1. 30 -1. 89]).

Late-preterm birth and its association with cognitive and socioemotional outcomes at 6 years of age. Talge NM, Holzman C, Wang J, Lucia V, Gardiner J, Breslau N. Pediatrics. 2010; 126: 1124 -1131. Data came from a study of low- and normal-weight births sampled from urban and suburban settings between 1983 and 1985 (low birth weight, n = 473; normal birth weight; n = 350). Random sampling was used to pair singletons born latepreterm with a term counterpart whose birth weight z score was within 0. 1 SD of his or her match (n = 168 pairs). With random-effects models, we evaluated whether pairs differed in their IQ scores and teacher-reported behavioral problems at the age of 6 years.

Late-preterm birth and its association with cognitive and socioemotional outcomes at 6 years of age. Talge NM, Holzman C, Wang J, Lucia V, Gardiner J, Breslau N. Pediatrics. 2010; 126: 1124 -1131 In adjusted models, late-preterm birth was associated with an increased risk of full-scale (adjusted odds ratio [a. OR]: 2. 35 [95% confidence interval (CI): 1. 20 -4. 61]) and performance (a. OR: 2. 04 [95% CI: 1. 09 -3. 82]) IQ scores below 85. Late-preterm birth was associated with higher levels of internalizing and attention problems, findings that were replicated in models that used thresholds marking borderline or clinically significant problems (a. OR: 2. 35 [95% CI: 1. 28 -4. 32] and 1. 76 [95% CI: 1. 04 -3. 0], respectively). CONCLUSIONS: Late-preterm birth is associated with behavioral problems and lower IQ at the age of 6, independent of maternal IQ, residential setting, and sociodemographics.

Dr Jain’s Comments What is most striking about these observations is that the late preterm infants included in the study were presumably healthy, had no reported “neonatal compromise, ” and would have been completely missed even if neurologic follow-up and early intervention programs were in place for high-risk infants

The “Late Preterm” Infant To Summarize: Frequently require NICU admission More medical interventions needed Longer Length of Stay Much higher costs Higher mortality Worse Neurodevelopmental Outcomes