Management of Preterm, Small for Gestational Age

Infants: Before Birth to Adolescence

Exploring the MazeExploring the Maze

Pediatrician:

You are called to the high risk pregnancy

unit for a consultation:• Primigravida at 25 weeks• Hypertensive: BP = 160/110• 3+ proteinuria on dipstix• Headache• Peripheral oedema with 6kg weight gain in the

past 4 weeks

Investigations:

• Bloods:• Hb 140g/L• WCC 18,000• Plats 103 x 109/L• MPV: 12.9• Uric Acid 467• AST 25• Albumin 29

Investigations

• Ultrasound:• EFW: 450g (HC at 5th %ile, AC and FL <1%ile)• AFI 76• Umb arterial doppler: S/D ratio 7.2

• What else do you need to know?

• What are you going to say?

Obstetrical Determinants of Survival and Handicap

• Antenatal treatment with glucocorticoids: 50% reduction in RDS related mortality in later GA

• Willingness to perform c/section for >800g• C/section for <800g associated with more

handicap• Obstetricians routinely underestimate

neonatal prospects for survival and survival without handicap

Perinatal Outcomes at 23 -28 wks GA1983-1989

n=1024

Still birth rate

Synnes et al, 1994

0

5

10

15

20

25

30

35

23 24 25 26 27 28

GA

% S

till b

irth

Perinatal Outcomes at 23 -28 wks GA1993-1997

n=278

Still birth rate

El-Metwally et al 2000

0

10

20

30

40

50

60

70

22 23 24 25

GA

% S

tillb

irths

LDR Deaths

05

101520253035404550

23 24 25 26 27 28

GA

% L

DR

Dea

ths

Synnes et al, 1994

LDR Deaths

El-Metwally et al 2000

0

5

10

15

20

25

30

35

40

22 23 24 25

GA

LDR

dea

ths

Death < 7 days

0

5

10

15

20

25

30

35

40

23 24 25 26 27 28

GA

% D

eath

< 7

day

s

Synnes et al, 1994

Death 7 - >28 days

0

2

4

6

8

10

12

14

23 24 25 26 27 28

GA

Death

7->

28days

Synnes et al, 1994

Survival to discharge

0102030405060708090

100

23 24 25 26 27 28

GA

% S

urvi

val t

o D

/C

Synnes et al, 1994

Survival to discharge

0

10

20

30

40

50

60

70

80

22 23 24 25

GA

% S

urvi

val t

o d/

c

El-Metwally et al 2000

Management

25 wks gestational age by early u/s

13% still birth 11% LDR death 66% live to NICU

23% death < 7 days 6% death <28 days 6% death >28 days55% survival to d/c

NICU morbidity

66% BPD 18% IVH6% NEC 43% Air leaks 23% Sepsis/Meningitis 55% PDA

Synnes et al, 1994

Major Morbidity and Mortality vs Birth Weight

0102030405060708090

501-750

741-1000

1001-1250

1251-1500

Birth Weight (grams)

Per

cent Major Morbidity

Mortality

NICHHD, 2001

18 month outcomes for 25 wks GA

32% impaired

17% CP 13% Blind 2% Deaf 10% Low MDI

Synnes et al, 1994

Other Factors to Consider

• Multiple gestation

• Gender

• SGA

• Antenatal steroids

Effect of SGA on Mortality:25 wks GA

0102030405060708090

100

400 600 800 1000 1200

Birthweight (grams)

% M

orta

lity

Synnes et al, 1994

Cognition and SGA vs AGA

• Significantly greater cognitive and neurologic morbidity in SGA vs AGA

• No differences by birth weight between the groups in cognitive performance or neurologic status

• Cognitive impairment associated with neurologic abnormality in both groups

• Higher incidence of neurologic deficit

in SGA infants greater cognitive impairment in the SGA infants

McCarton et al, 1996

SGA vs AGA with Neurologic Impairment

Percentage of AGA and SGA preterms with cognitive retardation as a function of neurological status

Cognitive test scores as a function of neurological status at 3 years in AGA and SGA preterms.

McCarton et al, 1996

Patient DR• Resuscitated by resident with bag and mask positive pressure

ventilation with 100% FiO2

• Pediatrician arrived at 1-2 minutes age

• Infant was pink and crying without intubation

• Neonatologist arrived at 10 minutes of age and full treatment was decided to be undertaken

• Infant intubated in DR and transported to NICU

• Apgars 6/7/8

Postpartum History

• Vitals: temp 34.8 HR 144 RR 52

• Weight 480 g (<5%)

• Length 28.5 cm (<5%)

• HC 22 cm (5%)

• Bruises over scalp buttocks

• Hct 39%

NICU Course

• Respiratory – HMD ventilated 25 days with 105 days O2– BPD noted on day 27– Apnea x 54 days treated with aminophylline

• CNS: normal cranial u/s

• OPHTHO: ROP grade 2 on day 64

• GU: bilateral inguinal hernia repair

NICU Course

• FEN/MET– Hyperglycemia day 9 with insulin drip– Umbilical artery catherization, TPN– Osteopenia of prematurity day 38– Low T4 associated prematurity

• HEME:– Anemia of prematurity and iatrogenic loss– Multiple blood transfusions

• GI: jaundice peak 7.8mg/dl onset day 2• ID: suspected sepsis x 2

Impact of NICU Practices on the Developing Brain

• Excess free radicals—O2, iron• High frequency ventilation with low lung volume?• Hypocarbia/hypercariba or rapidly changing PaCO2 levels?• Caffeine?• Postnatal steroids• Indomethacin ok?• Dopamine?• Sulfite preservatives?• High osmalality drugs?• Anesthetics and pain meds: fentanyl vs. morphine, versed?• Stimulation: visual, auditory, pain• Hyperthermia

Gressens et al, 2002

Discharge

• 42 ½ weeks gestational age• 113 days chronological age• 2440g • HC 35 cm• Length 43 cm• Meds: vits

4 months follow-up

• Growth– 3400g (<3%) – length 51.9cm (<3%) – HC 40cm (10%)

• Scars: right nasal notching, heel scars

• Neurodevelopmental exam: – some decrease truncal tone – poor head control

8 months corrected age

• Growth <5%– 5780g– Length 61.6cm– HC 42.7cm

• Neurodevelopmental exam: – Slight decreased tone and strength– Poor balance– Immature uncoordinated grasp– Minimal vocalizations– Crab-crawls – Not pulling to stand

• Eye exam normal

18 months corrected age

• Growth (<5%)– 7590g– Length 72.5cm– 45.8cm

• Neurodevelopmental exam: Bayley = 17month – Strongly right-handed– Babbling, using a few words– Abnormal movement: scooting on bottom using left arm– High activity, low persistence and short attention

3 years • Growth

– 10.74 kg (-2.74 SD)– 88.4cm (-2.66 SD)– 47.5cm (-2.65 SD)

• Neurodevelopment– Soft, hoarse voice referred to

ENT for evaluation– Better expressive than receptive

language– Difficulty following longer directions– Peabody motor scales 31 months:

balance problems, right hand dominant, immature fine pincer

– Stanford-Binet low average

4 ½ years• Growth

– 11.8kg (-2.98 SD)– 96.2cm (-2.32 SD)– HC 47.8cm (-2.64 SD)– Bone age 4 years at 4 years 10 months

• PET tubes• Neurodevelopment: “bounced around the

room”– High pain tolerance– Slight incoordination– Right side preference– Cognition: 77% verbal; performance 8%– Nonverbal: 16%– Visual-motor: 9%– Visual-Motor Integration: 14%

8 years• Growth:

– 23 kg (-1.19 SD)– Height 121cm (-1.69 SD)– HC 49.7cm (-1.64 SD)

• Neurodevelopment: recommend learning assistance– Right-side dominant– Tight hamstrings– Brisk reflexes– Poor balance– Average cognitive, poor non cognitive– Poor recall of visual patterns/spelling– Poor arithmetic– Poor pencil use

14 years

• Growth– 48.3kg (-2.38 SD)– 153.1cm (-1.39 SD)– 51.5cm (-2.43 SD)

• Neurodevelopment– Psyched eval: complex learning problem especially

with math– Poor output and distractible– Difficulty keeping on task– Verbal within normal range, better comprehension

than expression– Performance 10%

Outcomes in Young Adulthood: Educational disadvantage associated with VLBW

persists to early adulthood

• 20 year outcomes for 242 survivors mean 29.7 wks, 1179g vs. 233 controls with normal birth weight

• 51% normal IQs• Fewer high school grads: 74% v 84% (p<0.04)• Less postsecondary study: 30% v 53% (p<0.04)• Subnormal height: 10% v 5% (p<0.04)• Neurosensory impairments: 10% v 1% (p<0.001)

Hack et al NEJM 2002