for neonatal practitioners, policy makers

1. Problems of Late Preterms
L S Deshmukh
DM ( Neonatology )
Professor ( Pediatrics )
GMC, Aurangabad

2.  Term – 370/7 to 416/7 weeks gestation
 “Near Term” – terms such as near term, early term,
moderate preterm, mild preterm, borderline preterm,
etc. have been used in the past to describe infants
born anywhere between 32-37 weeks
 Late Preterm – NICHD Workshop 2005 recommended
the use of “Late Preterm” to describe infants born
between 340/7 to 366/7 weeks, or 239—259 days
counting from the first day of the LMP.
 recommended discontinuing the use of the term “Near
Term”.
Late Preterm Birth: Some Definitions

3. Gestational Age Terminology
Engle WA et al, Clin Perinatol 2008;35:325;

4.  “Near-Term” conveys that these infants are
almost term and therefore almost mature.
 This may lead to false sense of security:
- less rigorous assessment in first hours of life,
- early discharge when infant is still at risk,
- inadequate follow-up plans.
 “Late Preterm” conveys the sense that they still
premature and still vulnerable .
“All definitions are arbitrary, since maturation is
a continuum”
Raju TNK et al, Pediatrics ,2006;118 1207-14
Why “Late Preterm” - not “Near Term”?

5.  Of all preterm births, Late Preterm Births, 34 to 36 weeks, are
both the largest and fastest growing subgroup
 Since 1990, the rate of Very Preterm Birth (<32 weeks) has
remained stable at 2% of live births
 But between 1990 and 2003, Late Preterm Birth increased
more than 20%, from 7.3% to 8.8% of live births, accounting
for the majority of the increase in preterm birth rates over
the last two decades.
 As of 2005, Late Preterm Births represent 9.1% of live births
 Based on 2005 Data from the CDC on singleton births, Late
Preterm Births made up about 72% of all preterm births
2008 NCHS Data Brief: Recent Trends in Infant Mortality
in the US
Late Preterm Birth Rates

6. Increase Most Striking in
Late-Preterm Group
25% increase in Late
Preterm Group
Slide courtesy of Dr. Tonse Raju, 2007 presentation

7. 7%
5%
14%
13%
22%
40%
<32 weeks
32 weeks
33 weeks
34 weeks
35 weeks
36 weeks
Source: NCHS, final natality data
Prepared by March of Dimes Perinatal Data Center, April 2006.
75% of singleton
preterm births
36 wks
35 wks
34 wks
Slide courtesy of Dr. Tonse Raju, 2007 presentation
Preterm Singleton Live Births

8. What are the Causes of Increasing Preterm and
Late Preterm Births?
• Traditional Causes
– Maternal and fetal disorders
– Twins, triplets, and higher-order
multi-fetal pregnancy
– Errors in gestational age assessment

9. What are the Causes of Increasing Preterm and
Late Preterm Births?
•New causes
– Increasing Maternal Age
– Increasing maternal overweight/obesity
– Increasing rates of multi-fetal pregnancies
– Medical Interventions: earlier evaluation,
diagnosis and deliveries ? efforts to reduce
stillbirth rates

10. Non-Traditional Reasons/Causes?
• Some “indications” for preterm births in medical
records :
– “Prevention of post-maturity”
– “Impending labor”
• “Softer” indications :
– “borderline” non-reassuring fetal heart tracings
• Mutual Convenience :
– Maternal request
• “We have a great NICU”—no worries :
– “A little bit of huffing and puffing, can be treated
with a little bit of oxygen
Tonse N. K. Raju , 2012 AAP Workshop on
Perinatal Practice Strategies

11. Transitional
 Respiratory Distress (RDS)
 Temperature Instability
 Hypoglycemia
 Feeding difficulties
1 Late Preterm Birth: Every Week Matters, March of Dimes. March 2006.
2NICHD Workshop: Optimizing Care and Long-term Outcome of Near-term
Pregnancy and Near-term Newborn Infant. July 18-19. Bethesda, MD, 2005.
Medical Issues in Late-Preterm Infants

12. First Week
 Neonatal jaundice
 Apnea
 Infection rate
Later Neonatal Period
 Poor feeding and dehydration
 Readmission to hospital
1 Late Preterm Birth: Every Week Matters, March of Dimes. March 2006.
2NICHD Workshop: Optimizing Care and Long-term Outcome of Near-term
Pregnancy and Near-term Newborn Infant. July 18-19. Bethesda, MD, 2005.
Medical Issues in Late-Preterm Infants

13. Medical Issues in Late-Preterm Infants
Early Infancy
 SIDS risk
Later Outcomes
 Learning difficulties & School failures
 Behavior problems
1 Late Preterm Birth: Every Week Matters, March of Dimes. March 2006.
2NICHD Workshop: Optimizing Care and Long-term Outcome of Near-term
Pregnancy and Near-term Newborn Infant. July 18-19. Bethesda, MD, 2005.

14. Risk factors for morbidity
• Multiple gestation
• ? Lack of antenatal corticosteroid
administration
• cesarean delivery
• Complicated vaginal delivery
• Maternal diabetes
• ? insurance

15. Neonatal Morbidity
7 times greater in LPTI
– 22% vs. 3%
10-14 times greater with
other risk factors
Shapiro-Mendoza, Pediatrics
2008

16. Neonatal morbidity Vs GA
Shapiro-Mendoza CK et al.Pediatrics 2008;121:e227
Gestational age was
significantly correlated with
morbidity risk

17. Neonatal Morbidity
Temperature instability
– 10% (0%)
Hypoglycemia
– 15% (6%)
RDS
– 29% (4%)
Apnea
– 6% (<0.1%)
Jaundice
– 54% (38%)
Feeding difficulties
– 32% (7%)
Shapiro-Mendoza, Pediatrics 2008
Engle W Clinics in Perinatology 2008

18. Rate of neonatal morbidity Vs GA
Obstet Gynecol 2009;114:258

19. clinical outcomes in near-term
Wang ML, Dorer DJ, Fleming MP, et al. Pediatrics 2004

20. Composite adverse neonatal outcome
Am J Obstet Gynecol 2008;199:367,e6.

21. Early Neonatal Outcome in Late Preterms
Indian data Femitha P et al ,
Indian J Pediatr (August 2012) 79(8):1019–1024
Significantly higher odds of developing morbidity
• Respiratory distress (12.4% vs. 5.6%, OR 2.21, 95%CI
1.21,4.11)
• need for non invasive (17.3% vs. 5.7%, OR 3.05 95% CI
• 1.69, 5.47)
• invasive ventilation (14.6% vs. 1.7%, OR 8.62, 95% CI
3.09, 24.04),
• Sepsis (20.8% vs. 5.2%, OR 5.20, 95% CI 2.71, 9.99),
• Seizures (22.8% vs. 4.8%, OR 4.75 95%CI 2.61, 8.63),
• Shock (17.6% vs. 4.4%, OR 4.00 95% CI 2.12,7.56),
• Jaundice (26% vs. 6%, OR 4.3395%CI 2.54, 7.39).

23. Mortality 0-28 days (forest plot)
Teune. Am J Obstet Gynecol 2011

24. Mortality 0-365 days (forest plot)
Teune. Am J Obstet Gynecol 2011

25. Respiratory Problems

26. Epithelial sodium (Na) absorption in the fetal
lung near birth
Perinatol 2008;25(2):75–8

27. Respiratory morbidity according to gestational age
Hibbard JU, Wilkins I, Sun L, et al. JAMA 2010;304:423

28. Respiratory Morbidity In Late Preterms
JAMA, July 28, 2010—Vol 304,

30. feeding issues
• Vulnerabilities
1. Respiratory Instability
2. Immature state regulation
3. Hypotonia and Immature Feeding Skills
4. Insufficient milk (delayed lactogenesis)

32. Late Preterm Infant Risk Factors for feeding
problems
• Initially, may feed well with small volumes
• Unable to take larger volumes after discharge
- Great Pretenders
• Skin-to-skin in delivery room not done
• Separation from mother
• Delayed initiation of feeding
• Infrequent feeding
• Sleepy, non-demanding behavior, needs to be
awakened for feedings
Adapted from Tomashek et al; Sem Perinatol 2006; 30:61

33. Hypoglycemia in the Late
Preterm Infant
• The incidence of hypoglycemia inversely
proportional to GA
• Glucose levels fall 1-2 hrs after birth
• Late preterm infants:
- Immature hepatic glycogenolysis
- Decreased adipose tissue lipolysis
- Deficient hepatic gluconeogenesis and
ketogenesis

34. Hyperbilirubinemia
• Readmission due to jaundice
–7 to 13 fold increased risk
• Slower meconium passage
• Low milk intake
• Decreased activity of bili-conjugating enzyme
• Bilirubin peak levels typically occur
around 5 to 7 days of life
• Kernicterus is seen more frequently in LPT

36. Risk zones of near-term newborns according to the percentile
tracks based on the hour-specific serum bilirubin values
Pediatrics 2004

37. Hyberbilirubinemia
• Preventative goals
–Optimize milk intake
–Promote rapid meconium clearance and
increase stool volume
–Prevent excessive weight loss
• more structured approach to management
and follow-up (predischarge bilirubin , GA,
and other clinical risk factors ) Bhutani VK ,
Indian Pediatr, 2012

38. Kernicterus in Late Preterm Infants Cared for as
Term Healthy Infants.
 125 cases in US, 1979 – 2002
 “healthy at discharge”
 Sources – parents, MDs RNs, literature, med-legal
 69% male
 Nearly all breastfed [follow up scheduled for 2 weeks]
 97% discharge <72 h (58% < 48 h)
 25% Late Preterm infants
 LGA with kernicterus
 35% Late Preterm infants were LGA*
 25% Term infants were LGA*
Bhutani, Semin Perinatol 2006; 30:89-97
Kernicterus Registry Incidence & Patient Profile

39. Kernicterus in Late Preterm Infants
 Largest group on Kernicterus Registry
Late Preterm Infants due to :
Suboptimal milk intake
Bilirubin binding to albumin less than term
Delayed follow-up visits
 Signs of kernicterus may be more subtle
- Hypertonia, irritability Posturing,

40. Neurological Issues

45. Neurologic Immaturity
Decreased awake state
Low tone
Poor coordination of
suck/swallow/breathe

46. Death and/or severe neurologic disorder and
gestational age.
JB,Vintejoux A, Sagot P, et al. Int J Epidemiol 2010;39:772
The risk of death
severe neurologic disorder defined by is
chemic encephalopathy, grade 3or 4 IVH,
cystic PVL, and/or seizures

47. Developmental delay, CP, & GA
Petrini JR et al, J Pediatr 2009;154:174

48. Discharge Criteria
• not be considered before 48 hours after birth.
• Vital signs should be within normal range for
the 12 hours proceeding discharge.
• Passage of one stool spontaneously.
• Adequate urine output.
• 24 hours of successful feeding: ability to
coordinate sucking, swallowing and breathing
while feeding.
• If weight loss greater than 7% in 48 hours,
consider further assessment before discharge.
• Risk assessment plan for jaundice for infants
discharged within 72 hours of birth.
Ramachandrappa A et al, Pediatr Clin N Am 56 (2009) 565–577

49. Readmission
• LPIs are readmitted 2 to 3 times more often than
term infants
• Common reasons:
– Jaundice, infection, feeding issues, failure to
thrive
• Risk factors:
– Primigravida mother, breastfeeding, maternal
complications

50. Readmission after NICU Discharge
Group (LOS) n Rehospit. %
≥ 37 wk (< 96 h) 2593 2.2
≥37 wk (≥ 96 h) 1133 2.8
33-36 wk (< 96 h) 545 5.7
33-36 wk (≥ 96 h) 1196 2.2
< 32 wk (all LOS) 587 3.4
Escobar et al., Pediatrics 1999

51. Readmission Diagnoses
• Dehydration, Weight Loss
• Hypernatremia
• Severe Hyperbilirubinemia

55. Comparison of frequency of different methods
of therapy
Archives of Perinatal Medicine 16(2), 83-85, 2010

56. Early School Age Outcomes
Morse SJ et. al: Pediatrics, 2009

57. Linnet KM et al., Arch Dis Child 2006

61. Is There an Expanded Role for
Antenatal Steroids at > 34 weeks?
• Late preterm infants have been excluded
from most randomized studies; or the
number randomized is too few to study
accurately.
• In the majority of studies utilizing a single
course of Betamethasone, the benefit seems
to outweigh the risk.

62. Antenatal Steroids for Term Cesarean Section
ASTECS study group
• 1995 –2002
• 10 centers in the UK; N= 998 women
• Randomized to receive Betamethasone
• 48 hours prior to elective c/s > 37 wks
• # Adm to SCU with respiratory distress
Stutchfield et al BMJ 2005

63. Antenatal Steroids for Term Cesarean Section
ASTECS study group
• Combined respiratory morbidity
5.1% vs. 2.4% ( 0.46, CI 0.23-0.93)**
• Respiratory distress syndrome
1.1% vs 0.2% ( 0.21, CI 0.03 –1.32 )
• Transient tachypnea of the newborn
4.0% vs. 2.1% ( 0.54, CI 0.26 – 1.12 )
Stutchfield et al BMJ 2005

64. Antenatal Steroids ?
• Cochrane Database , 2009
- results from the single trial promising
- larger samples are needed
• Effectiveness of antenatal corticosteroids in
reducing respiratory disorders in late preterm
infants: randomised clinical trial Porto AMF et al,
BMJ. 2011; 342: d1696.
• - No effect on RDS
• - decreased need for PT for jaundice

65. Late preterm infants: the known and the
unknown
What’s known
a. Mortality rises with each week lost in gestation
below 39 weeks.
b. Excess morbidity, mostly transient, is related to
global immaturity.
c. Birth at earlier gestations has an impact on health
and mortality beyond the neonatal period.
d. Long-term neurologic outcomes are a cause of
concern.
Mohan SS et al , Clin Perinatol 38 (2011) 547–555

66. Late preterm infants: the known and
the unknown
What’s unknown
a. Are adverse outcomes due to early delivery or due to
the events preceding late preterm birth?
b. Are outcomes after preterm labor, preterm rupture of
membranes, or medically indicated late preterm birth
different?
c. Can late preterm births and iatrogenic prematurity be
safely reduced?
d. Can interventions, such as antenatal steroids, improve
outcomes?
Mohan SS et al , Clin Perinatol 38 (2011) 547–555

67. Conclusions
• All preterm deliveries need to be indicated
(medical or obstetric indications only)
• Understand and watch for specific medical
complications
 Respiratory Distress
 Hypoglycemia
 Temperature instability/hypothermia
 Feeding difficulties
 Jaundice/ hyperbilirubinemia
 Keep a low threshold for NICU transfer

68. Conclusions
 Early discharge should not occur in these infants and
diligent follow up is important, both in the post
neonatal period and for continued long-term care.
 Long- term Problems :
- Learning difficulties, school failures;
– Medical, psychological, and behavioral problems
into adult lives
They need to be treated as preterm infants

69. Knowledge is Power
Educate yourselves
Educate your colleagues
Educate your patients
Together we can make a big impact on the
number of late preterm infants born with just a little knowledge
and prevention…
Conclusion

71. Questions?