Eric Reynolds, MD MPH

1

The 36 Week Preemie:

Consequences of Late

Preterm Delivery

Eric Reynolds, MD MPH

Associate Professor of Pediatrics

Division of Neonatology

Kentucky Children’s Hospital

About the handout

This handout includes only the most

important slides from the lecture.

It is not intended to follow the lecture

slide-by-slide

Objectives

Scope of the Problem

National

State-Level

UK

Economic and Medical Consequences of

Late Preterm Delivery

Prematurity Facts

Prematurity is the leading cause of infant mortality in industrialized nations (March of Dimes)

Preterm delivery is increasing

Up 30% since 1981 (US)

11.7% in 199615.1% in 2006 (KY)

2

Scope of ProblemHP

KY US 2010

2004 14.4 12.5 7.6

2005 15.2 12.7

2006 15.1 12.8

2007 15.2 12.7MOD Peristats

In an average week in KY…

174 babies are born preterm

26 are very preterm (<32 weeks)…103 are Late Preterm (34-36)

Rising Rate of Prematurity in US:

1997-2007

• National Center for Health Statistics, final natality data.

• Retrieved Feb 24, 2011 from www.marchofdimes.com/peristats.

Percent of Live Births that were Preterm;

(<37 wks) Kentucky, 1997-2007



Prematurity by Gestational Age; Kentucky, 2005*

19.760.5

3.92.4

4.9

8.7

<=26

27-28

29-30

31-32

33-34

35-36

*2005 data

**Preterm birth is defined as any live birth occurring <37 completed weeks gestation

Data Source: Kentucky Vital Statistics Files, Live Birth Certificate files, 2005

3

Percent of Live Births that were

Very Preterm (<32 wks) in KY, 1996-2006



Late-Preterm: KY & Nation



Late Preterm % By State (2007)

11

9.29.39.19.9

8.6

9.2

10.5

10.111.4

10

13

11.7

10.1

9

10.7

9.8

9.8

6.5

9.8

Late Prematurity Facts

Late-Preterm infants are:

a majority of NICU admissions

The greatest percentage of NICU patients to receive

respiratory support

the majority of NICU economic costs

often the sickest babies in a NICU

more likely than a full term baby to be rehospitalized in the

first year of life

twice as likely to die in the first year of life as a full term

baby

at risk for long term health issues

4

Definitions

Language used to describe 34-37 week infants

Near Term

Marginally Preterm

Moderately Preterm

Minimally Preterm

Accepted label is now LATE PRETERM

Reflects the fact that these infants have morbidity and

mortality risks more similar to preterm infants than term

infants

Definitions

Gestational ages assigned to Late-Preterm 35-37 34-36 35-36 6/7

Lower limit not defined Nearly all 33 week infants require NICU admission

44-84% of 34 week infants require NICU care

ACOG uses 34 weeks as a critical point for medical decision making for the pregnant woman who is threatening PTL.

Unfortunately, as late as 2006, the IOM still identified terminology as a major hurdle to understanding the problems of prematurity.

Financial Costs

In 2005, the cost of

prematurity in the US

was $26.2 billion. (IOM 2007)

Medical, Educational and Lost

Productivity

In 2004, costs for initial

hospitalization of preterm

infants was $15 billion. Does not include cost of

rehospitalization or long term

problems.

Almost ½ of this goes

to Medicaid.

Medicaid

47.8%

Employer/ Other

Private

46.3%

Other*

3.6%

Uninsured/

Self Pay

2.3%

Financial Costs (KY)

Total NICU charges related to preterm birth was

$204,504,246 for calendar year 2005 with average

charges ranging from $10,919-$88,270 (KY Hospital Discharge Database, 2005)

Total amount paid by KY Medicaid for prematurity

related initial hospitalization stays for calendar year

2005: $7,421,829.49 (KY Medicaid Claims Database, 2005)

Medicaid paid more for the care of babies 35-36 weeks

then it did for babies <26 weeks.

All less than 26 = $1,375,179.58

35-36 weeks = $1,748,349.17

5

Semin Perinatol

Feb 2006;30(1)

April 2006;30(2)

Risk of Chronic Disease

Barker Hypothesis

LBW and increased risk for:

Coronary artery disease

Insulin resistance

Length of Stay

More Late Preterm infants had delayed discharge

term infants.

Not statistically significant, not powered for this outcome

Reasons: Jaundice 8 vs 1

Resp Dist 8 vs 2

Poor Feeding 22 vs 2

Other 12 vs 2

Total 50 vs 7

Wang Pediatrics 2004;114:372-376

Rehospitalization

Late Preterm infants are more likely than a full term baby to be rehospitalized in the first year. 2.4%: >40weeks

3.4%: 38-40weeks

6.3%: 35-37weeks

Reasons Jaundice, Feeding difficulty, Dehydration, others

Male > Female

Mixed results from studies of early discharge

Escobar Semin Perinatol 2006;30(1):28-33 Escobar Pediatrics 1999;104:1-9

Escobar Arch Dis Child 2005;90:125-131 Oddie Arch Dis Child 2005;90:119-124

6

Temp Instability

The Late Preterm infant is more likely than term infants to have temperature instability 10% vs 0% in term (OR infinite)

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

Due to Immature epidermis

Higher ratio of surface area to birthweight

More frequent delivery room interventions

If untreated, infant can loose 2-3 C in the first 30 minutes

Hypoglycemia

What’s Normal?

20, 30, 36, 40, 45, 47, 60, 55-100 (mg/dL)

No data on long-term effects of moderate

hypoglycemia (47) on Late Preterm infants

Risk to earlier preterm infants (30.5 + 2.7 weeks) has

been established

Late Preterm more likely to have hypoglycemia

15.6% vs 5.3% (OR 3.3, CI 1.1-12.2)

10-15% in other studies

Lucas Br Med J 1988;297:1304-1308


Laptook, Jackson Semin Perinatol 2006;30(1):24-27

Poor Feeding

The Late Preterm infant is more likely to

require intravenous infusion

26.7% vs 5.3% (OR 6.48, CI 2.27-22.91)

Reasons:

Hypoglycemia, poor feeding, dehydration


7

Poor Feeding

The rhythms of suck, swallow and breath are

being integrated into coordinated feeding

from 32-37 weeks.

Most babies have mastered feeding coordination

by 35 weeks,

But some have not

76% of Late Preterm with “poor feeding” had

delayed discharge vs 28.6% of term infants. >48 hours post-vaginal delivery / 96 post c-section


Post-Discharge Nutrition

Breast is best

Term vs Premie Follow-up formula

Factors affecting nutritional needs

BW <1000 gm*

Discharge Wt <1850 gm*

Serum Prealbumin <10mg/dL*

Growth <2SD or 5th percentile*

Big babies get term formula, Small ones get premie

follow-up formula

BPD*

Osteopenia*

Chronic disease

Limited or decreased intake

*Nutritional Care of High-Risk Newborns, 3rd edition,

Groh-Wargo et al eds. Precept Press, Chicago, 2000

Hyperbilirubinemia

Late Preterm more likely to have jaundice

54.4% vs 37.9% (OR 1.95,

CI 1.04-3.67)

Delayed discharge (1 term vs

8 Late Preterm)Wang Pediatrics 2004;114:372-376

Infants discharged from normal

newborn nursery at <38weeks

have an OR >7 of being

re-admitted for hyperbilirubinemiaMaisels Pediatrics 1998;101:995-998

Hyperbilirubinemia

Subcommittee on Hyperbilirubinemia Pediatrics 2004;114;297-316

8

Sepsis/Sepsis Work-ups

Late Preterm infants more likely to undergo

sepsis evaluation

36.7% vs 12.6% (OR 3.97, CI 1.82-9.21)

More likely to be treated with 7 day course

of antibiotics

No difference in actual culture proven sepsis


Length of Stay (Days)

64

71

32

49

12

37

8

24 21

54

0

10

20

30

40

50

60

70

80

<28

weeks

28-32 33-36 >36 Total

Not Infected

Infected

Abdu A, et al. (Abstract) J Invest Med. 2009;57(1):387.

Structural Neurologic

Complications

86/1011 (9%) had a report of a neurological complication: IVH, grades I-II 29

HIE/prolonged seizures 30

Other 7

Coma 6

IVH, grades III-IV 6

Brain atrophy 4

Intracranial infarct 2

Brain death 2

Clark RH J Perinatol 2005;25:251-257

9

Two-Year Follow-up

Late Preterm Infants Have Worse 24-Month

Neurodevelopmental Outcomes Than Term Infants

Studied 7500 (6300 term and 1200 late preterm)

Bayley exams at 24 months

Late preterm infants:

had lower MDI (85 vs. 89) and PDI (88 vs. 92) (p<0.0001).

were more likely to have severe or mild mental or

psychomotor delay.

were more likely to have MDI <70 (but not PDI)

Lower MDI was associated with modifiable social

factors. GA was largest contributor to lower PDI.Woythaler et al, Pediatrics 2011;127:e622-e629

Respiratory Failure

Late Preterm more likely to have

respiratory distress

28.9% vs 4.2%

(OR 9.14, CI 2.9-37.8)


Primary Diagnosis

437, 43.3%

33, 3.3%

32, 3.2%

31, 3.1%

24, 2.4%

98, 9.7%84, 8.3%

72, 7.1%

41, 4.1%

63, 6.2%

40, 4.0%

24, 2.4%14, 1.4% 11, 1.1%

6, 0.6%

RDS

MAS

Pneumonia / sepsis

Surgical support

Major GI anomaly

Primary Dx unknown

TTN

Heart disease

PPHN

HIE

CDH left-sided

Aspiration syndrome

Lung hypoplasia - not CDH

Major neuro anomaly

CDH right-sided

Clark RH 2006

10

TTN

Delayed Transition

Usually benign respiratory condition that does not usually require mechanical ventilation

About 4% of pulmonary diagnoses in Clark’s study

“Malignant” TTN syndrome(Keszler‘92)

Predilection for PPHN following elective c-section

Clark J Perinatol 2005 Apr;25(4):251-7

Respiratory Distress Syndrome

Incidence is inversely related to GA

Surfactant deficiency or dysfunction, epithelial injury, and vascular protein leak

Primary problem is loss of FRC and deflation stability

Most common pulmonary diagnosis in patients >34 weeks

Safe lung recruitment is essential to the prevention of acute lung injury


Pneumonia

Associated chorioamnionitis

Most common is GBS

Difficult to distinguish from RDS

Can be associated with shock

Acute lung injury and inflammation inhibit surfactant function

Clark RH 2006

PPHN

Suprasystemic

pulmonary vascular

resistance causes right

to left shunting

at the FO and/or PDA

CXR - clear

Very wide swings in

PaO2

1-4% of live births

Actual incidence is

difficult to ascertain

Clark RH 2006

11

Air Leaks

Includes:

Pneumothorax

Pneumopericardium

Pneumomediastinum

PIE

Assymptomatic PTX in

1% of routine x-rays

Association with MAS

Decreased incidence in

surfactant treated

patients

Meconium Aspiration Syndrome

10–15% of deliveries have MSAF

Only 1/20 develop MAS

9.7% of pulmonary diagnosis in Clark’s study

Historically, the most common indication for ECMO

Pathophysiology: “check valve” obstruction, air trapping, PPHN, andsurfactant inactivation

Clark RH 2006


Congenital Diaphgragmatic Hernia

Incidence 1:4000 births

Left side most common

Severe PPHN is common

Mortality approximately 40–50% even with ECMO support

Not specific to Late Preterm infants, but carries higher mortality in this group

Chronic Lung Disease

10% develop chronic lung disease

16% on ventilators at 30 days or discharge

77 / 945 (8%) of survivors discharged on O2

Most common pulmonary diagnosis leading to

CLD is RDS

Clark RH J Perinatol 2005;25:251-257

12

Late Preterm and RSV

Preterm infants are at increased risk for severe

RSV disease.

Interrupted lung development

34 week infant at 52% of the lung volume of a term infant.

Decreased maternally-transmitted antibody levels

32-35 week infants have mean serum IgG levels 43%

lower than that of term infants.

Welsman LE. Pediatr Infect Dis J. 2003;22(2 suppl):S33-S39

Colin A. Pediatrics 2010;126:115-128

Lanston C. Am Rev Respir 1984;129:607-613

Yeung CY. Lancet. 1968;1(7553):1167-1170

Rare Complications

Apnea and Bradycardia Not found in term babies, only rarely in late preterm

Necrotizing Enterocolitis (NEC) Associated with other markers of compromised perfusion

Cerebral Palsy Associated with chorioamnionitis (11% attributable risk)

Increased risk for SIDS

Neonatal Death


Solutions are not easy!

Some babies are going to be preterm

PTL with advanced dilation

34 week mom with proteinuria, hypertension, headache and

abdominal pain.

Balancing the risk of prolonging a high-risk pregnancy to

32-36 weeks versus neonatal cost and complications

For some babies mortality/morbidity may or may not be

less if the pregnancy is continued to term

Culture of litigation and practice of defensive medicine

C-section on Demand

Power of Education and

Commitment

Labor Induction Process Improvement: A patient

Quality-of-Care InitiativeJM Fisch et al. Obstetrics & Gynecology 2009;113(4):797-803

Over a 4 year period:

Decreased overall inductions from 24.9% to 16.6%

Decreased elective inductions from 9.1% to 6.4%

Decreased elective inductions before 39 weeks from

11.8% to 4.3%

Decreased frequency of C-section among

nulliparous women from 34.5% to 13.8%

Pitt

13

Power of Education and

Commitment

Decreasing Elective Deliveries Before 39

Weeks of Gestation in an Integrated Health

Care SystemBT Oshiro et al. Obstetrics & Gynecology 2009;113(4):804-811

Elective delivery before 39 weeks decreased from

28% to 10% in 6 months.

Intermountain Health

Conclusions

Late Preterm infants represent a large portion of what

we do in the NICU.

Late Preterm infants have morbidity and mortality

statistics more similar to preterm infants than term

babies.

“Even with appropriate size and favorable Apgar scores [Late-

Preterm] infants have significantly more documented medical

problems when compared to term babies”.

Despite recent modest improvements, late preterm

infants are a major public health problem in Kentucky

and the US.

Good News

Preterm Birth Rate Drops Three Percent

Fewer Babies Face Health Risks of an Early Birth

WHITE PLAINS, N.Y., APRIL 6, 2010- The nation's preterm birth

rate dropped for the second consecutive year.

The preterm birth rate dropped to 12.3 percent, according to the

report, "Births: Preliminary Data for 2008," which was released

today by the National Center for Heath Statistics. That's down from

the 2007 preliminary rate of 12.7 percent. The declines follow a

more than 20 percent increase in the preterm birth rate between

1990 and 2006.

The March of Dimes says 79 percent of the decline in the preterm

birth rate occurred among late preterm babies.

http://www.marchofdimes.com/peristats/whatsnew.aspx?id=39&dv=wn

Acknowledgments

Susan DeGraff

MOD

Peristats

http://www.marchofdimes.com/peristats

Healthy Babies are Worth the Wait

http://www.prematurityprevention.org

Documents

Eric Reynolds, MD MPH