Neuroprotection from acute brain injury in preterm infants

Question 1

Infants born under what gestational age are at increased risk of intracranial ischemic or hemorrhagic injury?

Answer 1

<32+6 weeks

Question 2

When are these injuries most likely to occur?

Answer 2

Within the first 72 hours after birth

Question 3

What is the pathophysiology of acute brain injury in young preterm infants?

Answer 3

• Fragile cerebral vasculature
• Immature autoregulatory system with rapid changes in perfusion causing ischemia or intraventricular hemorrhage into the brain

Question 4

What percentage of preterm infants with have abnormalities on brain imaging?

Answer 4

Approximately 21% of preterm infants born at ≤32+6 weeks gestational age (GA) show an abnormal brain image (IVH or parenchymal lesions) on cranial ultrasound

Strongly associated with neurodevelopemental impairment in the long term

Question 5

What type of brain injury is being picked up on MRI?

Answer 5

Non-cystic PVL increasingly recognized

*Cystic PVL on the decline
PVL= periventricular leukomalacia

Question 6

What percentage of brain injuries are picked up by Day 5 of life?

Answer 6

95%

Question 7

What is the relationship between rupture of membranes and brain injury?

Answer 7

Duration of rupture of membranes for longer than 72 hours is also an independent risk factor for IVH or intraparenchymal hemorrhage (odds ratio (OR) 2.33, 95% confidence interval (CI) 1.420 to 3.827)

Question 8

What is a primary risk factor for preterm delivery?

Answer 8

Chorioamnionitis

Question 9

Why are corticosteriods thought to be protective against brain injury?

Answer 9

Vasoconstriction is apparent in the fetal brain when antenatal corticosteroids are used, which may protect against injury.

Question 10

What are the SOGC guidelines for antibiotic administration for PPROM?

Answer 10

Penicillin and a macrolide (or a macrolide alone if a patient is allergic to penicillin) to any mother presenting with PPROM and expected to deliver at ≤32+6 weeks GA

Question 11

What is the optimal the timing of corticosteriod to prevent brain injury?

Answer 11

> 48 hours prior to delivery

Question 12

What are the SOGC recommendation for the administration of corticosteriods?

Answer 12

Routinely administering antenatal corticosteroids within 7 days to all mothers expected to deliver a premature infant ≤34+6 weeks GA (and between 35+0 and 36+6 weeks GA in select clinical situations) is recommended, with the optimal interval being greater than 48 hours between the last dose administered and birth

Question 13

How is magnesium sulphate thought to help with neuroprotection for preterm infants?

Answer 13

Magnesium has several intracellular actions, including anti-inflammatory effects and inhibiting the influx of calcium into cells
- Effectively decreases the risk for CP

Question 14

What are the SOGC recommendations for the administration of magnesium sulphate?

Answer 14

The current recommendation is to consider magnesium sulphate for all women experiencing imminent preterm delivery (≤ 33+6 weeks GA)

Question 15

Is there a preferred method of delivery to help protect against brain injury in preterm infants?

Answer 15

No!

There is no evidence that routine caesarean section confers protective benefit over vaginal delivery for preterm infants at risk for mortality or IVH, including intraparenchymal lesions except when they are in breech position

Question 16

What is the relationship between cord clamping and brain injury in preterm infants?

Answer 16

Delayed cord clamping or cord milking, when compared with immediate cord clamping, reduces overall risk for acute brain injury

Question 17

What are the recommendations for cord clamping vs cord milking for preterm infants?

Answer 17

All infants who do not need immediate resuscitation should receive delayed cord clamping of 30 to 120 seconds (level of evidence: 1a)
Delayed cord clamping is preferred over umbilical cord milking because the studies assessing impacts of cord milking are few, techniques vary, and there have been no follow-up studies
Cord milking may be considered when delayed cord clamping cannot occur

Question 18

What is the association between hypothermia and the risk of brain injury?

Answer 18

Associated with increased risk of brain injury

Cold stress can accelerate oxygen consumption and impair resuscitation efforts

Question 19

What is the definition of hypotension in preterm infants?

Answer 19

No standardized definition or standardized approach to managing hypotension

• Generally accepted definition:
• MAP < GA or <30 mmHg for two consecutive measurements

Question 20

What is the association between ionotrope use and brain injury?

Answer 20

Considered to be a significant risk factor for the development of brain injury

Studies have demonstrated no clinically significant improvement in cerebral perfusion with the use of ionotropes among extremely low birth weight infants

Question 21

What are indications to start inotropic support in a preterm infant?

Answer 21

Low blood pressure, a combination of prolonged capillary refill, decreased urine output, elevated lactate or echocardiography findings
*demonstration of poor end organ perfusion

Question 22

What other causes of hypotension should be considered prior to the administration of ionotropes?

Answer 22

• Iatrogenic causes:
• Hyperinflation- chest xray to rule this out
• Dehydration- NS bolus

Question 23

What is the association between PDA and brain injury in premature infants?

Answer 23

Preterm infants with hemodynamically significant PDAs are at greater risk of brain injury** however studies have shown that use of indomethacin OR ibuprofen did not actually change long term neurodevelopmental outcomes at 18 months

Question 24

What are considerations when determining if prophylaxis for PDA closure should be given?

Answer 24

Because many PDAs often close spontaneously and the potential for side effects from cyclo- oxygenase inhibitors are significant, the prophylactic use of indomethacin or ibuprofen should be targeted based on combined risk factors including GA, exposure to antenatal steroids, and birth site [58] (level of evidence: 1a).

Question 25

How is hypercapnea defined? What is the effect of hypercapnia on cerebral blood flow?

Answer 25

PCO2 levels >60 mmHg

• Thought to impair cerebral autoregulation and cause vasodilation
• Considered to be a risk factor for brain injury in ELBW infants

Think about ICP management strategies**
- HYPERventilation causes HYPOcapnia = decreased cerebral perfusion and decreases ICP

Question 26

In what range should PCO2 be targeted within for preterm infants?

Answer 26

Both HYPER and HYPOcapnia are associated with causing brain injury in preterm infants
- Avoid <35 mmHg and >60 mmHg
Target range:
- Between 45-55 mgHg- permissive hypercapnia
- Thought to be protective from a lung perspective and minimize risk of BPD development

Question 27

What mode of ventilation is preferred in preterm infants? Why?

Answer 27

Volume targeted ventilation* VG

Try to avoid pressure targeted or hyper frequency oscillation as has been associated with higher rates of IVH

Question 28

What is the optimal positioning of a preterm infant to reduce risk of brain injury?

Answer 28

Because fluctuations in intracranial pressure may increase risk for acute brain injury–> goal to keep the infant’s head midline or neutral with the torso and the head of the bed elevated at 30 degrees

Question 29

How is transport of preterm infants thought to impact risk of brain injury?

Answer 29

Transporting a preterm infant (≤32+6 weeks GA) between facilities is believed to be an independent risk factor for acute brain injury
- Including noise, vibration and acceleration

However evidence is mixed* some thought that infants born outside of tertiary care facilities are less likely to receive corticosteroids and resuscitation from teams who are less experienced

Question 30

List 3 environmental factors that may influence the neurodevelopmental outcome of a preterm infant

Answer 30

Protective factors

• Skin to skin contact
• Maternal voice exposure
• Light cycling
• Low noise level

Others:

• Mitigate painful procedures
• Decrease opioid use
• Early parenteral nutrition for good brain growth

Question 31

Numbers to remember

Answer 31

• Less than 32 weeks- need to stay warm! Put your baby in a bag!
• Less than 33 weeks- infectious risk should receive prophylactic antibiotics
• Less than 34 weeks- should receive magnesium sulphate
• Less than 35 feels and risk of delivery within 1 WEEK should receive steroids
• Target PCo2 between- 45 to 55 mmHg with MAX of 60!