Intraventricular Herrohage

Intraventricular Hemorrhage And Hemorrhagic Disease of the Newborn

James A Singer 2009

• All photographs, MRI and CT Scan images are from the public domain.

Patient Presentation: A 15-year-old female presented to the ED with lower abdominal pain and bleeding. She states that she has felt some contractions. A 23 week infant was born by cesarean section for preterm labor and vaginal bleeding. The past medical history shows that the pregnancy was complicated by teenage motherhood, little or no prenatal care. At delivery, the infant was found to have the umbilical cord wrapped around the neck. The pertinent physical exam shows him to be 760 grams, appropriate for gestation age.

He was limp and blue. There were no spontanious breaths or movements. HR was 60 per minute. The RT began bag/mask at 100% with the nurse providing chest compressions. After 2 minutes of compressions, the heart rate was 80 per minute with the infant gasping and started to pink up. Bagging continued at a rate of 40 bpm. At the 5 minute mark the Apgar was 6. S N/A O Acrocyanosis. CXR underaerated bilaterally and clouded. ABGs: pH 7.18, PaCO2 47, HCO3 14, PaO2 60. A Atelectasis Metabolic acidosis RDS P CMV per protocol with O2 therapy and hyperinflation protocols

Complications of Prematurity Acute – – – – – – – –

RDS Pulmonary Interstitial Emphysema (PIE) Pneumothorax Patent Ductus Arteriosus Necrotizing Enterocolitis (NEC) Intra-ventricular hemorrhage (IVH) Multiple transfusions Bacterial and fungal infections

Complications of Prematurity

Chronic Bronchopulmonary dysplasia (BPD) Retinopathy of prematurity (ROP) Periventricular leukomalacia (PVL) Learning disabilities Failure to thrive Renal stones Hearing loss

Injury to the germinal matrix has substantial mortality and morbidity rates.

IVH

Most common form of intracranial hemorrhage (subdural and subarachnoid hemorrhage are less common) 20% in infants <1500 g or <32 weeks Incidence varies inversely with gestational age >50% IVH occur in first 24 hours of life, 90% by 10 days

Pathogenesis Germinal matrix is a highly vascular weakly supported structure that is prone to rupture and hypoxic-ischemic injury

IVH Risk factors Extreme prematurity Birth asphyxia Need for vigorous resuscitation Pneumothorax Sudden elevations or fluctuations in BP Other: labor, seizures, dyssynchronous ventilation, hypothermia, hypercarbia, acidosis, rapid bicarbonate infusion, rapid volume infusion, PDA/PDA ligation

Clinical Presentation includes: On Physical Examination: Alteration in mentation - seizures, posturing, coma or decreased consciousness Apnea Respiratory distress including tachypnea and retractions Irregular breathing Fontannel - full or bulging Hypotension or blood pressure lability Hypnotic Pallor Poor perfusion Laboratory Values: Acidosis Bloody cerebrospinal fluid Hematocrit drop Hypoglycemia

The term Intraventricular Hemorrhage refers to all 4 grades. The term Periventricular Hemorrhage refers to a grade IV IVH. Grade I: hemorrhage limited to the subependymal germinal matrix Grade II: hemorrhage in the subependymal germinal matrix with extension into the ventricular system but without lateral ventricular dilation Grade III: hemorrhage in the subependymal germinal matrix with extension into the ventricular system with lateral ventricular dilatation Grade IV: hemorrhage in the subependymal germinal matrix with extension into the brain tissue (i.e. intraparenchymal hemorrhage)

Diagnosis Using Sonography

Sonography is the Gold Standard for bedside diagnosis.

Determination of ventricular dilation can be difficult on sonography, but is important clinically.

Grade I: hemorrhage limited to the subependymal germinal matrix

Grade II: Hemorrhage in the subependymal germinal matrix with extension into the ventricular system but without lateral ventricular dilation

Grade III: Hemorrhage in the subependymal germinal matrix with extension into the ventricular system with lateral ventricular dilatation

Grade IV: Hemorrhage in the subependymal germinal matrix with extension into the brain tissue (i.e. intraparenchymal hemorrhage)

Grade IV: Hemorrhage in the subependymal germinal matrix with extension into the brain tissue (i.e. intraparenchymal hemorrhage) -MRI Scan

This image shows a intraventricular hemorrhage where the clot forms a cast of the ventricle

Most follow-up studies have found that the neurological outcome is associated with the grading of the IVH. Grades I and II do not increase the chance of neurologic morbidity measurably. Grades III and IV have a high rate of morbidity including cerebral palsy, seizures, and mental retardation. Periventricular white matter ischemia often evolve into cystic lesions called Periventricular leukomalacia or PVL. The presence of PVL carries a high risk of neurologic morbidity.

IVH And Vitamin K History Townsend in Boston (1864) described 50 cases of “hemorrhagic disease of the newborn” during first 2 weeks of life In 1929, Vitamin K isolated from alfalfa by Dam and Doisy (Nobel Prize, 1942), and conducted clinical trials showing Vitamin K protects against HDN 1961, American Academy of Pediatrics and American College of Obstetrics and Gynecology recommended routine prophylaxis with Vitamin K for all newborns

IVH and Vitamin K Often Fatal Condition Diffuse hemorrhage in healthy to premature infants During the first week of life Particularly in low birth weight babies Results of low levels of prothrombin and other vitamin K dependent clotting factors, (Factors II, VII, IX and X) caused by vitamin K deficiency An exaggerated deficiency of clotting factors normal in the first few days of life Incidence between 2.5 to 17.0 per thousand newborns not given vitamin K prophylactically

IVH And Vitamin K Common Clinical Manifestations Bleeding in the: – – – – – – – –

gastrointestinal tract urinary tract umbilical stump nose scalp intracranial hemorrhage Shock death

IVH and Vitamin K Late HDN Between 2-12 weeks of life, Especially in breast-fed babies. Immaturity of liver affects production of clotting factors Late HDN ( Hemorrhagic Disease Newborn ) primarily in breast fed infants without or inadequate vitamin K rates of 4.4-7.2/100,000 live births

Vitamin K And The Newborn Prophylactic use of Vitamin K recommended by the American Academy of Pediatrics, and by the American College of Obstetricians and Gynecologists since 1961. Up until 1987, administration of vitamin K at birth was mandatory in only five states in the US AAP recommendation renewed in 1993 and remains current

IVH And Vitamin K

Controversy regarding oral versus parenteral use of routine Vitamin K largely resolved Intramuscular administration within the first 6 hours after birth more effective in preventing both early and late onset HDN

Role of Opiates for Pain Control And IVH

Is there a relationship between chronic opiate exposure in the first week of life and incidence of IVH and PVL in VLBW infants?

Opioid analgesia has been recommended for ventilated preterm neonates because of: – Increased pain sensitivity resulting from immature pain modulatory mechanisms – Hyperalgesia of long duration after tissue injury – Acute physiological and behavioral responses to painful stimuli – Humane and ethical considerations for providing comfort.

NEOPAIN Trial

(Neurologic Outcomes and Preemptive Analgesia in Neonates )

There were higher rates of the composite outcome and severe IVH in the subgroup born at 27–29 weeks of gestation (K J S Anand) Open-label morphine during 25 to 72 hours after starting study drug infusion was associated with severe IVH (Richard W. Hall, MD*)

Ventilated VLBW infants who are chronically exposed to higher doses of opiates during the first week of life have a significant increase in the incidence of cardiovascular instability and subsequent adverse neurological outcomes.

Use of higher doses of morphine during the first 7 days in VLBW infants was associated with increased hemodynamic instability – Hypotension – Inotrope use – Steroids for hypotension Use of higher doses of morphine during the first 7 days in VLBW infants was associated with increased incidence of severe IVH and PVL (periventricular leukomalacia ). The increased risk of PVL was associated with cumulative morphine exposure and not to birth weight, gestational age, steroid administration or indices of disease severity.

Summary Most common form of intracranial hemorrhage (subdural and subarachnoid hemorrhage are less common) 20% in infants <1500 g or <32 weeks Incidence varies inversely with gestational age >50% IVH occur in first 24 hours of life, 90% by 10 days Grades I and II does not increase the chance of neurologic morbidity measurably. Grades III and IV have a high rate of morbidity including cerebral palsy, seizures, and mental retardation. Results of low levels of prothrombin and other vitamin K dependent clotting factors, (Factors II, VII, IX and X) caused by vitamin K deficiency increase the incidence of IVH. Open-label morphine during 25 to 72 hours after drug infusion was associated with severe IVH. The increased risk of PVL was associated with cumulative morphine exposure and not to birth weight, gestational age, steroid administration or indices of disease severity.