The etiology of perinatal arterial ischemic strokes may be maternal, fetal or both. Venous thrombo-embolism is almost always catheter associated in new-borns. Preliminary guidelines for management of perinatal arterial ischemic strokes exist but are mostly based on adult studies. We report a unique case of perinatal arterial ischemic stroke, lower extremity arterial and inferior vena-caval thrombosis. Our patient was treated with unfractionated heparin for 10 days then switched to low molecular heparin to complete 6 months of therapy. The patient responded well to therapy and shows minimal signs of permanent neurologic deficits after 6 months.
Thrombosis is a rare but important clinical entity in children. Perinatal arterial ischemic stroke is defined as arterial thrombosis or embolization leading to focal disruption of cerebral blood flow, after 20 weeks of gestation through 28 days after birth [1,2]. Among the pediatric population, neonates have the highest incidence of arterial ischemic strokes, reported to be as high as 18 per 100,000 full term, live births [
We present a case of a full term newborn with multiple arterial and venous emboli possibly secondary to placental vascular thrombosis. She responded well to heparin therapy without thrombolytic interventions and had minimal neurologic deficit at six month follow up
An African American female was born to a 19 year old primi-para mother at 41 weeks of gestation. Mother had no significant personal or family history of medical illness or coagulation disorders. She received good prenatal care with a negative screening for sexually transmitted disease. She was found to be colonized with group B streptococcus and received two doses of vancomycin prior to delivery. Prenatal ultrasound studies were within normal limits and did not suggest any congenital anomalies. The baby was born via uncomplicated vaginal delivery with normal APGARs and vital signs. Anthropometric measurements were appropriate for gestational age. Upon physical examination, immediately after delivery, the baby was noted to have pallor of the right lower extremity with absent femoral and dorsalis pedis artery pulses on the same side. A Doppler ultrasound evaluation performed within the first hour of birth showed a thrombus in the right external iliac artery extending distally to the popliteal artery occluding the vessels. She was also found to have a thrombus in the inferior vena-cava. She was transferred to the neonatal intensive care unit (NICU) for further management. In the NICU, the baby was clinically stable with no neurologic deficits. A screening head ultrasound, performed at hour 6 of birth, suggested a small germinal matrix hemorrhage. This was followed by a magnetic resonance imaging (MRI), magnetic resonance arteriography (MRA) and venography (MRV) of the whole body around hour 10 of delivery. There was again a low T2 signal structure seen at the expected position in the inferior vena cava (IVC) at the level of right hepatic lobe with non-visualization of IVC caudal to this position (
gram did not show any abnormalities.
Thromboembolic evaluation, including factor II, factor VIII, antithrombin III, protein S and protein C activity were all within normal limit for age. Genetic testing of both baby and the mother is negative for mutations for factor V Leiden, prothombin variant or methylene tetrahydrofolate reductase. Mother had a borderline low protein C activity at 64% (normal range: 70% - 128%). Since this was done at immediate post-partum period, she was advised to follow up with adult hematologist. The placental histopathology revealed fetal thrombotic vasculopathy, suggesting possible intrauterine thrombotic events. The baby was immediately started on low dose heparin infusion at 15 Units/Kg/hr and was switched to enoxaparin after 10 days of therapy. The dose of enoxaparin was adjusted to bring the activated factor IX levels within the therapeutic range. No thrombolytic intervention was recommended due to a small germinal matrix hemorrhage seen on head ultrasound. She responded well to the therapy, with no evidence of clot propagation, worsening of intracerebral hemorrhage and with significant improvement of perfusion of left lower extremity within the first day of life hence did not require surgical intervention. Serial imaging studies showed gradual return of blood flow through the IVC and stable cerebral vasculature. She was discharged home on enoxaparin for 6 months with close outpatient follow-up. Repeat MRI, MRA and MRV imaging at 5 months age showed resolution of inferior vena-cava clot and brain changes consistent with her chronic infarcts. She is receiving physical therapy and has a minimal residual right sided weakness. She continues to thrive and has achieved age appropriate developmental milestones. She continues to follow-up with her neurologist and is expected to do well if affected cerebral hemisphere is non-dominant.
This is a unique case of perinatal arterial ischemic stroke along with lower extremity arterial and IVC thrombosis in a term baby. The etiology of perinatal arterial ischemic stroke is multifactorial and is not identified in most cases [7,8]. Maternal and fetal factors may interplay in the pathogenesis. Normal physiology of pregnancy put mothers in a hypercoagulable state, hence a slightly lower protein C level in our patient’s mother. Other factors in maternal history which have been associated with perinatal arterial ischemic strokes include history of infertility, chorioamnionitis, premature rupture of membrane, placental vasculopathy and preeclampsia. Congenital heart diseases, coagulopathy, infections, trauma, drugs, perinatal asphyxia and intravascular catheters constitute some of the fetal risk factors [7,9].
Our patient was symptomatic at birth and we postulate that she probably had an in-utero triggering event. Histopathology of the placenta revealed thrombotic vasculopathy which could be the initial triggering event leading to thrombosis in the IVC in-utero. This ultimately resulted in obliteration and fibrosis of a segment of the IVC with establishment of extensive collateral circulation which help venous return from lower extremities. We also postulate subsequently that, a dislodged thrombus from IVC-thrombus passed through the patent foramen ovale to the left heart and hence to systemic circulation (middle cerebral and external iliac arteries), resulting in the stroke and the right lower extremity ischemia. Whilst chorioamnionitis has been identified as an important risk factor of placental vasculopathy, the exact etiology in our patient is not completely clear.
There is no consensus on the treatment of perinatal ischemic strokes. The American College of Chest Physicians (ACCP) recommends administration of heparin (unfractionated or low-molecular weight) as first line therapy for symptomatic patients [
Some studies suggest, about a third of neonates with arterial ischemic strokes develops permanent neurologic deficits or cerebral palsies [
In conclusion, most of the time, no risk factors are identified in perinatal arterial ischemic strokes; therefore, Physicians do not tend to treat them. However, if the patient’s condition warrants an immediate intervention, unfractionated heparin should be considered as a first line therapy. Also, the evaluation for thromboembolism in the perinatal period must include histopathology review of the placenta.