Late preterm infant: Is Late preterm infant: Is it a trend or a it a trend or a catastrophe?catastrophe?

Michael E. Speer, MDMichael E. Speer, MDProfessor of Pediatrics & Medical EthicsProfessor of Pediatrics & Medical Ethics

Baylor College of MedicineBaylor College of Medicine

Survival of extremely low-birth-Survival of extremely low-birth-weight infants (birth weight < 1000 weight infants (birth weight < 1000 g) increased 35% between the g) increased 35% between the 1980s and the 1990s1980s and the 1990s– 85% of infants with very low birth 85% of infants with very low birth

weight (between 500 and 1500 grams) weight (between 500 and 1500 grams) survivesurvive

Stoelhorst GMSJ, et. al.Stoelhorst GMSJ, et. al. Pediatrics. 2005 Pediatrics. 2005 Feb;115(2):396-405.Feb;115(2):396-405.

Improved SurvivalImproved Survival

Improved SurvivalImproved Survival

Mortality: 1980s Mortality: 1980s 1990s 1990s – 32 weeks’ gestation: 30% to 11%32 weeks’ gestation: 30% to 11%– <27 weeks’ gestation: 76% to <27 weeks’ gestation: 76% to

33%33%

Stoelhorst GMSJ, et. al.Stoelhorst GMSJ, et. al. Pediatrics. 2005 Feb;115(2):396-405. Pediatrics. 2005 Feb;115(2):396-405.

Increased MorbidityIncreased Morbidity Disabilities have also increased between 1980s & Disabilities have also increased between 1980s &

1990s1990s– Primarily chronic lung disease and neuro-developmental Primarily chronic lung disease and neuro-developmental

impairmentimpairment Sepsis: Sepsis: 37% to 51% 37% to 51% Periventricular leukomalacia: Periventricular leukomalacia: 2% to 7% 2% to 7% CLD: (OCLD: (O22 at 36 wks PMA): at 36 wks PMA): 32% to 43%32% to 43% Cerebral palsy: Cerebral palsy: 16% to 25% 16% to 25% Deafness Deafness 3% to 7%3% to 7% Neurodevelopment impairment* Neurodevelopment impairment* 26% to 36% 26% to 36%

(*major neurosensory abnormality and/or Bayley Mental Developmental Index (*major neurosensory abnormality and/or Bayley Mental Developmental Index score of <70)score of <70)

Stoelhorst 2005. Stoelhorst 2005. Pediatrics. 2005 Feb;115(2):396-405.Pediatrics. 2005 Feb;115(2):396-405.

Rising Rate of Rising Rate of PrematurityPrematurity

The preterm birth rate has The preterm birth rate has increased by 36% since the increased by 36% since the 1980s1980s**– > 540,000 each year at present> 540,000 each year at present– 21% increase since 1990 (10.6% to 21% increase since 1990 (10.6% to

12.8%) 12.8%) Primarily 34 to 36 weeks Primarily 34 to 36 weeks

gestation gestation – Increase of 25% since 1990 Increase of 25% since 1990

*NCHS 2006 final natality data;*NCHS 2006 final natality data; March of March of Dimes, 2009Dimes, 2009

Trends in Late Preterm Birth, Stillbirth, and Infant Mortality: US 1990-2004

Ananth CV, et al. Am J Obste Gynecol. 2008;199:329-31

  Preterm Birth in the Preterm Birth in the United States: 1996 - United States: 1996 -

20062006

12.812.712.512.312.111.911.611.811.611.411.0

0

2

4

6

8

10

12

14

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

<32 weeks 32-33 weeks 34-36 weeks

Source: National Center for Health Statistics Prepared by March of Dimes, Periantal Data Center, 2009

Percent of live births

>70% Late Preterm

Courtesy of Karla Damus

RISE IN LATE PRETERM BIRTHS RISE IN LATE PRETERM BIRTHS (34-36 wks)(34-36 wks)

Percentage of Births by Percentage of Births by Cesarean: 32% (2007)Cesarean: 32% (2007)

Births by caesarean section by country (2000)# 1   Italy: 333 live births per 1,000  (33.3%)# 2   Australia: 217 live births per 1,000  (21.7%)# 3   USA: 211 live births per 1,000  (21.1%)# 4   Germany: 209 live births per 1,000 (20.9%)# 5   Canada: 205 live births per 1,000  (20.5%)# 6   Ireland: 204 live births per 1,000 (20.4%)# 7   New Zealand: 202 live births per 1,000 (20.2%)# 8   Austria: 172 live births per 1,000  (17.2%)# 9   France: 171 live births per 1,000  (17.1%)# 10 United Kingdom: 170 live births per 1,000  (17.0%)# 11 Belgium: 159 live births per 1,000 (15.9%)# 12 Finland: 157 live births per 1,000  (15.7%)# 13 Denmark: 145 live births per 1,000  (14.5%)# 14 Sweden: 144 live births per 1,000  (14.4%)# 15 Norway: 137 live births per 1,000 (13.7%)# 16 Netherlands: 129 live births per 1,000 (12.9%)

Weighted average: 185.3 live births per 1,000 (18.5%)

Cesarean Section Rates – Latin America (2005)

Median rate 33% (quartile range 24–43)

Elective 49%

Intrapartum 46%

Emerg. s Labour5%

Lancet. 2006;367:1819-29

World Wide Cesarean Section Rates - WHO Asia – 27.3% (2007 – 2008)*

– China 46.2%– Sri Lanka 30.6% – Viet Nam 35.6%– Thailand 34.1%

Latin America – 35% (2005)– Brazil 36% (2009)

Private clinic rate: >90%

– Ecuador 40% (2005)– Paraguay 42% (2005)

*Lancet. 2010;375:Pages 490-499

Rates are not necessarily current http://blog.fortiusone.com/2009/04/22/birth-in-the-usa/

Risk of Placenta Accreta and Risk of Placenta Accreta and Hysterectomy by Number of Cesarean Hysterectomy by Number of Cesarean Deliveries Compared with the First Deliveries Compared with the First Cesarean DeliveryCesarean DeliveryCesarean Cesarean SectionSection

Accreta Accreta [n(%)][n(%)]

Odds RatioOdds Ratio Hysterectomy Hysterectomy [n(%]) [n(%])

Odds RatioOdds Ratio

FirstFirst 15 (0.2)15 (0.2) 40 (0.7)40 (0.7)

SecondSecond 49 (0.3)49 (0.3) 1.3 (.7–2.3)1.3 (.7–2.3) 67 (0.4)67 (0.4) 0.7 (0.4–0.97)0.7 (0.4–0.97)

ThirdThird 36 (0.6)36 (0.6) 2.4 (1.3–4.3)2.4 (1.3–4.3) 57 (0.9)57 (0.9) 1.4 (0.9–1.2)1.4 (0.9–1.2)

FourthFourth 31 (2.1)31 (2.1) 9.0 (4.8–16.7)9.0 (4.8–16.7) 35 (2.4)35 (2.4) 3.8 (2.4–6.0)3.8 (2.4–6.0)

FifthFifth 6 (2.3)6 (2.3) 9.8 (3.8–25.5)9.8 (3.8–25.5) 9 (3.5)9 (3.5) 5.6 (2.7–11.6)5.6 (2.7–11.6)

Six or Six or MoreMore

6 (6.7)6 (6.7) 29.8 (11.3–78.7)29.8 (11.3–78.7) 8 (9.0)8 (9.0) 15.2 (6.9–33.5)15.2 (6.9–33.5)

Obstet Gynecol 2006;107:1226–32.

Indications for Late Preterm Birth

05

101520253035404550

Medical Obstetric Anomaly Labor None Indication

%

23.2

Reddy U, et al. Pediatrics. 2009;124:234-9

14.4 15.9

1.3

48.9

Clinical IssuesClinical Issues

Risks of Elective Delivery– 13,258 Elective Cesarean Sections

Rates of adverse respiratory outcomes, mechanical ventilation, sepsis, hypoglycemia, NICU admission, and hospitalization for 5 days or more.

Increased by a factor of 1.8 to 4.2 for births at 37 weeks

Increased by a factor of 1.3 to 2.1 for births at 38 weeks.

Tita A, et al. NEJM. 2009;360:111-120

Clinical IssuesClinical Issues

http://www.femalepatient.com/html/arc/sig/PatS/articles/http://www.femalepatient.com/html/arc/sig/PatS/articles/034_09_041.asp034_09_041.asp

Khashu, M. et al. Pediatrics 2009;123:109-113

Mortality Higher in Preterm (33-36 wk) versus Term (37-40 wk)

Mortality: Late Mortality: Late Preterm vs Term Preterm vs Term Infant: 1995-2002Infant: 1995-2002

Mortality/1000 live births

Late PT Term Ratio

Overall (0 – 364 days)

7.9 2.4 3x

Early neonatal (0 – 6 days)

2.8 0.5 6x

Late neonatal (7 – 27 days)

1.4 0.4 3x

Post neonatal (28-364 days)

3.7 1.6 2x

Tomashak KM. J Pediatr 2007; 151;450

Khashu, M. et al. Pediatrics 2009;123:109-113

RR of morbidity, preterm versus term

Shapiro-Mendoza, C. K. et al. Pediatrics 2008;121:e223-e232

Proportion with newborn morbidity during birth hospitalization according

to gestational age

Clinical outcomes in near-term and full-term infants

(% of patients studied)

Wang, M. L. et al. Pediatrics 2004;114:372-376

Early Respiratory Morbidity Early Respiratory Morbidity in Late Preterm Infantsin Late Preterm Infants

34 35 36 37 39

TTN (%) 2.4 1.6 1.1 0.7 0.4

Ventilator (%)

3.3 1.7 0.8 0.5 0.3

Weeks of Gestation

McIntire & Leveno. Obstet. Gynecol. 2008;111:35-41

Early Respiratory MorbidityEarly Respiratory Morbidity

GA (wk) Oxygen > 1 hour

Assisted Ventilation

38-40 Reference Reference

37 2.04 (1.61-2.59) 2.35 (1.84-3.02)

36 4.95 (3.95-6.21) 5.24 (4.11-6.68)

35 8.76 (6.77-11.4) 0.04 (6.88-11.9)

34 18.67 (14-24.9) 19.8 (14.7-26.6)

Odds Odds RatiosRatios

Escobar GJ. Semin Perinatal. 2006;30:28-33

Early & Late Nutritional Early & Late Nutritional MorbidityMorbidity

Inadequate caloric intake:Inadequate caloric intake: – Poor suck/swallow coordinationPoor suck/swallow coordination– FatigueFatigue

Feeding intoleranceFeeding intolerance– Delayed stoolingDelayed stooling– Feeding residualsFeeding residuals

Exaggerated physiologic jaundiceExaggerated physiologic jaundice DehydrationDehydration HypernatremiaHypernatremia Increased need for parenteral nutritionIncreased need for parenteral nutrition Failure to thriveFailure to thrive

Breastfeeding IssuesBreastfeeding Issues

Decreased milk Decreased milk productionproduction

Poor latchPoor latch Poor sucking Poor sucking

efforteffort Poor coordinationPoor coordination Potential Potential

alteration in alteration in bondingbonding

Wang, M. L. et al. Pediatrics 2004;114:372-376

Neonatal gestational age versus length of hospital stay

Primary Reason Documented for Discharge Delay of Near-Term and Full-Term Neonates

Primary Reason for Delay of Discharge

Near Term

Full Term Comment

Jaundice 8/49 (16.3%)

1/36 (0.03%)

P = .072; 95% CI: 0.083–311.1; OR: 6.71

Respiratory distress 8/26 (30.8%)

2/4 (50%)

P = .58; 95% CI: 0.03–7.36; OR: 0.46

Poor feeding 22/29 (75.9%)

2/7 (28.6%)

P = .029; 95% CI: 0.94–93.4; OR: 7

Neonates (total) with discharge delay

5050 77

Wang, M. L. et al. Pediatrics 2004;114:372-376

GA at Presentation to ED: GA at Presentation to ED: 20032003

80.2

17.7

1.60

10

20

30

40

50

60

70

80

90

% GA

TermLate PretermEarly Preterm

Jain S. Clinics in Perinatology. 2006;33:935-945

Lung MaturationLung Maturation

PulmonaryPulmonary– Persistent airway obstruction Persistent airway obstruction

demonstrated in healthy premature demonstrated in healthy premature infants (infants (36 wk GA) compared with 36 wk GA) compared with infants born at term:infants born at term: 6–10 weeks after birth6–10 weeks after birth: : FEF in healthy FEF in healthy

30–34 wk GA infants (30–34 wk GA infants (PP<0.001)<0.001)11

At age 1At age 1: : V VmaxmaxFRC in healthy 29–36 wk FRC in healthy 29–36 wk GA infants (GA infants (PP<0.05)<0.05)22

1.1. Friedrich L, et al.Friedrich L, et al. Am J Resp Crit Care Med. 2006;173:442-447. 22.2. Hoo A-F, et al.Hoo A-F, et al. J Pediatr. J Pediatr. 2002;141:652-658.2002;141:652-658.

FEF: forced expiratory flow; VmaxFRC: maximal expiratory flow at functional residual capacity.

4.48.0

12.19.4 8.2

56.3

0

10

20

30

40

50

60

Boyce TG, et al. J Pediatr. 2000;137:865-870.

28 wks GA

Low-risk**29 to <33 wks GA

33 to <36 wks GA

RS

V-r

ela

ted

Ho

sp

ita

liza

tio

ns

pe

r 1

00

Ch

ild

ren

<6

Mo

nth

s o

f A

ge

BPD CHD

*Retrospective study of enrollees in Tennessee Medicaid, July 1989-June 1993.**Low-risk defined as all other children born at term.

Risk of Infection: RSVRisk of Infection: RSV

56.3

12.19.4 8.2 8.

04.4

Infection

Changes in brain volume and Changes in brain volume and maturation with increasing maturation with increasing gestational agegestational age

Kapelloou, O et al. PLOS Med 2006;3:e265

Brain Growth During Gestation

Hüppi PS, et al. Ann Neurol. 1998 Feb;43(2):224-35.

Neurologic Maturation: Cerebral White Matter

Hüppi PS, et al. Ann Neurol. 1998 Feb;43(2):224-35.

Neurologic Maturation

From Conel, 1939-59

NeurodevelopmentalNeurodevelopmental

Early School-Age Early School-Age OutcomeOutcome

AgAgee

%%

Late Late PreterPreter

mmN=7152N=7152

% % TermTermN=152N=152

,661,661

Unadjusted RRUnadjusted RR

[95% CI][95% CI]Adjusted RRAdjusted RR

[95% CI][95% CI]

Developmental delay/disability

0–3 4.24 2.96 1.43 (1.36–1.51) 1.36 (1.29–1.43)

Disability in prekindergarten 3 4.46 3.89 1.15 (1.09–1.20) 1.13 (1.08–1.19)

Disability in prekindergarten 4 7.40 6.60 1.12 (1.08–1.16) 1.10 (1.05–1.14)

Not ready to start school 4 5.09 4.40 1.16 (1.11–1.21) 1.04 (1.00–1.09)

Exceptional student education

5 13.30 11.9 1.13 (1.09–1.16) 1.10 (1.07–1.13)

Retention in kindergarten 5 7.96 6.17 1.29 (1.24–1.34) 1.11 (1.07–1.15)

Suspension in kindergarten 5 1.80 1.22 1.48 (1.37–1.60) 1.19 (1.10–1.29)Morse SB et al. Pediatrics. 2009;123:e622-e629

0

0.5

1

1.5

2

2.5

CP* MR+ Work^ OMD#

34-36 6/ 7 wk

=/ > 37 wk

Disabilities Related to GA at Birth (Adults)

%

*RR: 2.7(2.2 – 3.3)

+RR: 1.6(1.4 – 1.8)

^RR: 1.4(1.3 – 1.5)

#RR: 1.5(1.2 – 1.8)

* Cerebral Palsy

+ Mental Retardation

^ Disability Affecting Work

# Other Major Disability

Moster D et al. NEJM. 2008; 359:262-273