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Prevention of Intraventricular Hemorrhage
in preterm infants
Andrew Whitelaw MD FRCPCH
Emeritus Professor of Neonatal Medicine
University of Bristol
Bristol, UK
Rio de Janeiro, 29th August 2014
Highly vascular germinal matrix Unstable cerebral blood flow
0
5
10
15
20
25
30
35
<750 751-1000 1001-
1250
1251-
1500
1551-
2250
Birth weight (g)
Pe
rce
nt w
ith
IV
H
Incidence of Intraventricular haemorrhage (IVH)
in premature newborn infants
Sheth RD. Trends in incidence and severity of intraventricular hemorrhage.
J Child Neurol. 1998 Jun;13(6):261-4.
Vermont-Oxford Network
Infants 500-1500g
Grade 3 or 4 IVH 6.2% in 2000-1
Grade 3 or 4 IVH 6.2% in 2008-9
Corresponds to 4,000 to 5,000 annually in US
Risk factors for IVH
Very short gestation
Male gender
Labour and vaginal delivery v elective Caesarean
Respiratory distress syndrome
Pneumothorax
Early hypothermia (marker of prolonged resuscitation)
Fluctuating blood pressure/cerebral blood flow
Early hypotension and rapid correction
Coagulopathy and thrombocytopenia
IVH in term infants is different from IVH in prematures Wu YW, et al . Intraventricular hemorrhage in term neonates
caused by sinovenous thrombosis. Ann Neurol. 2003 ;54:123-6.
29 term infants with IVH in 5 yr UCSF
Perinatal asphyxia
Congenital heart disease
ECMO
9 cerebral sinovenous thrombosis:
Presented with seizures, apnoea or temperature
3 Thrombophilia
Voutsinas L, et al.. Clin Imaging. 1991;15:273-5.
Protein C deficiency.
Kita H, et al. No To Shinkei. 1990;42:297-302.
Homocystinuria
Interventions shown to prevent IVH in randomised clinical trials
Antenatal corticosteroids Postnatal Muscle relaxation Ethamsylate Vitamin E Indomethacin Delayed cord clamping Volume targeted ventilation
Antenatal steroid and IVH
Antenatal steroid and neurodevelopmental delay
Antenatal dexamethazone is associated with more PVL than is
betamethazone
Corticosteroids target
Very short gestation
Male gender
Labour and vaginal delivery v elective Caesarean
Respiratory distress syndrome
Pneumothorax
Early hypothermia (marker of prolonged resuscitation)
Fluctuating blood pressure/cerebral blood flow
Early hypotension and rapid correction
Coagulopathy and thrombocytopenia
Indomethacin and IVH
Indomethacin and severe IVH
Indomethacin and death/disability at 1+yr
Indomethacin and specific impairments
Indomethacin reduces IVH
No reduction in disability or death
Not recommended as routine
Ethamsylate and IVH
Ethamsylate and severe IVH
Ethamsylate and disability
No reduction in disability or death.
Not recommended as routine
Vitamin E and IVH in preterm infants
Reduced IVH
IV vit E increased Sepsis
IV vit E increased parenchymal infarction
No effect on mortality
Not recommended routinely
Brion LP et al. Cochrane Library 2003.
Perlman J. Reduction in intraventricular hemorrhage by
Elimination of fluctuating blood flow velocity in preterm infants
with respiratory distress syndrome. NEJM 1985; 312: 1353-7
IVH
Panc 5/14
No Panc 10/10
Severe IVH
Panc 0/14
No Panc 7/10
Neuromuscular paralysis and IVH
Neuromuscular paralysis and IVH
• Reduction in IVH in one small trial
• Modern ventilators can synchronize with the infant’s breathing
• Uncertainty over effects of long periods of neuro-muscular paralysis
• Not recommended as routine
Delayed cord clamping (30-45 seconds): and IVH
Delayed cord clamping (30-45 sec)and severe IVH
Mercer JS et al. Seven month developmental outcomes
of very low birth weight infants enrolled in a randomized
trial of delayed versus immediate cord clamping. J
Perinitalogy 2010; 30: 11-16
Infants 24-31 weeks
Higher motor scores in male infants at 7 months
The umbilical cord should NOT be clamped EARLY
but resuscitation has to be possible while cord intact.
Fresh frozen plasma 10 ml/kg after delivery and at 24 h
without coagulopathy screening
Beverley (1985)
IVH
Plasma 7/38
No plasma 14/42
Fresh frozen plasma 10 ml/kg after abnormal coagulation
INR > 1.4 or APTT >50 sec on screening at 2 h
(infants 23-26 w).
Dani (2009)
IVH
Early screen 34.5%
No early screen 61.1%
Factor XIII infusion at 6 hr reduced IVH
from 75% to 15%
in preterm infants at high risk if IVH
Shirata A. Thrombosis Research 1990;57: 755-63
Tranexamic acid did not reduce IVH in
a randomised trial.
Hensey O. Arch Dis Child 1984; 59: 719-21.
Recombinant Factor VII did not
Prevent IVH. Veldman A.
Ped Crit Care Med 2006; 7: 34-9
Recommendations to reduce IVH based
on epidemiology and pathophysiology but not
supported by randomised trials
Carteaux P et al.
Evaluation and development of potentially
better practices for prevention of brain
hemorrhage and ischemic brain injury in very
low birth weight infants.
Pediatrics 2003; 111: e489-496.
Practices which may prevent IVH
1. Delivery in tertiary center with NICU
Direct clinical management and delivery by maternal
fetal medicine specialists
Antibiotics for preterm rupture of membranes
2. Delivery room resuscitation by neonatologists and
an experienced team
Maintain baby’s temperature at 36.0 or above
Maintain cardiorespiratory stability during surfactant
administration
Practices which may prevent IVH
1. Delivery in tertiary center with NICU
Direct clinical management and delivery by maternal
fetal medicine specialists
Antibiotics for preterm rupture of membranes
2. Delivery room resuscitation by neonatologists and
an experienced team
Maintain baby’s temperature at 36.0 or above
Maintain cardiorespiratory stability during surfactant
administration
3. Minimise pain and stress responses
Reduce environmental noise
Minimize handling
Minimize lighting
Judicious use of narcotic sedation
4. Neutral head position and elevate head
(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).
5. Avoid rapid correction of hypotension
6. Optimize respiratory management
Avoid hypocapnia/severe hypercapnia
Avoid routine chest physiotherapy
Avoid routine suctioning
7. Limit sodium bicarbonate
3. Minimise pain and stress responses
Reduce environmental noise
Minimize handling
Minimize lighting
Judicious use of narcotic sedation
4. Neutral head position and elevate head
(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).
5. Avoid rapid correction of hypotension
6. Optimize respiratory management
Avoid hypocapnia/severe hypercapnia
Avoid routine chest physiotherapy
Avoid routine suctioning
7. Limit sodium bicarbonate
3. Minimise pain and stress responses
Reduce environmental noise
Minimize handling
Minimize lighting
Judicious use of narcotic sedation
4. Neutral head position and elevate head
(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).
5. Avoid rapid correction of hypotension
6. Optimize respiratory management
Avoid hypocapnia/severe hypercapnia
Avoid routine chest physiotherapy
Avoid routine suctioning
7. Limit sodium bicarbonate
3. Minimise pain and stress responses
Reduce environmental noise
Minimize handling
Minimize lighting
Judicious use of narcotic sedation
4. Neutral head position and elevate head
(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).
5. Avoid rapid correction of hypotension
6. Optimize respiratory management
Avoid hypocapnia/severe hypercapnia
Avoid routine chest physiotherapy
Avoid routine suctioning
7. Limit sodium bicarbonate
3. Minimise pain and stress responses
Reduce environmental noise
Minimize handling
Minimize lighting
Judicious use of narcotic sedation
4. Neutral head position and elevate head
(Cowan F & Thoresen M. Pediatrics 1985; 75: 1038-47).
5. Avoid rapid correction of hypotension
6. Optimize respiratory management
Avoid hypocapnia/severe hypercapnia
Avoid routine chest physiotherapy
Avoid routine suctioning
7. Limit sodium bicarbonate
Take home message: Prevention of IVH
• Antenatal betamethazone 24 mg 24 hr before delivery
• Antibiotics for preterm rupture of membranes
• Delayed cord clamping
• Maintain temperature >36.0.
• Minimize pain and stress/handling/noise/light
• Judicious opiate sedation, rarely pancuronium.
• Neutral head position with head up tilt.
• Avoid rapid swings in blood pressure and CO2
• Minimize chest physio and tube suction
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