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Increased risk of intraventricular hemorrhage in preterm infants with thrombophilia
J Petäjä1, L Hiltunen, V Fellman
1Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, FIN-00290 Helsinki, Finland. jari.petaja@dlc.fi
Insights
Congenital resistance to activated protein C (Gln506-FV) is a significant risk factor for intraventricular hemorrhage (IVH) in newborn infants, especially premature ones. This genetic factor increases the risk of IVH considerably.
Area of Science:
- Neonatal Medicine
- Genetics
- Hematology
Background:
- Cerebral intraventricular hemorrhage (IVH) in newborns has a complex cause, potentially involving blood clotting issues.
- Adult venous thrombosis research suggests coagulation abnormalities might be a risk factor for neonatal IVH.
Purpose of the Study:
- To investigate if specific coagulation abnormalities, known risk factors for adult venous thrombosis, are also risk factors for IVH in newborn infants.
- To assess the prevalence of factor V Gln506-FV and prothrombin G20210A-FII mutations in neonates with and without IVH.
Main Methods:
- Compared frequencies of Gln506-FV and G20210A-FII mutations in 22 neonates with IVH (grades II-IV) against 29 neonates without IVH.
- Evaluated mutation frequencies against those in 302 healthy adults for Gln506-FV and 526 for G20210A-FII.
- Calculated odds ratios and absolute risks associated with Gln506-FV, particularly for premature infants.
Main Results:
- Four (18%) neonates with IVH were heterozygous for Gln506-FV; one (5%) was heterozygous for G20210A-FII.
- Only one (3%) neonate without IVH was a Gln506-FV carrier.
- The odds ratio for Gln506-FV in IVH infants was 5.9 (p=0.013) compared to the general population.
- The absolute risk of IVH for premature infants (<30 weeks) with heterozygous Gln506-FV was estimated at 80%, versus 14% for all premature infants.
Conclusions:
- The Gln506-FV mutation is significantly more prevalent in newborns with IVH than in the general population, suggesting it is a risk factor.
- Gln506-FV may be a considerable risk factor for IVH in premature infants.
- Thrombophilic coagulation abnormalities warrant further investigation as potential contributors to neonatal IVH.
Abstract:
The multifactorial etiology of cerebral intraventricular hemorrhage (IVH) may involve coagulation disturbances and venous infarction. We tested whether coagulation abnormalities associated with adult venous thrombosis would constitute a risk factor for IVH in newborn infants. In 22 infants (gestational age 24.3--39.9 wk, median 28.0 wk) with neonatal IVH grade II to IV, the frequencies of congenital resistance to activated protein C due to a point mutation in the factor V gene (Gln506-FV) and a polymorphism in the prothrombin gene (G20210A-FII) were assessed and compared with those observed in 29 premature newborn infants without IVH and in 302 (Gln506-FV) or 526 (G20210A-FII) healthy adults. In infants with IVH, four (18%) heterozygous carriers of Gln506-FV and one (5%) heterozygous carrier of G20210A-FII were found. One infant without IVH was heterozygous for Gln506-FV (3%). When compared with the frequency of Gln506-FV in the general population, the odds ratio for being a carrier of Gln506-FV for patients with IVH was 5.9 (95% confidence interval 1.7--20.3, p = 0.013) and for patients without IVH 0.9 (95% confidence interval 0.1--7.6, p > 0.99). The absolute risk of IVH in a newborn infant with heterozygous Gln506-FV and born before 30 wk of gestation was estimated at 80%, whereas the corresponding risk for all infants born before 30 wk was 14%. Gln506-FV was more common in newborn infants with IVH than in the general population, whereas there was no difference in the frequencies of Gln506-FV in infants without IVH and in the general population. Thus, Gln506-FV may be a risk factor of IVH. The risk of IVH in a premature infant with Gln506-FV or other established thrombophilic coagulation abnormality may be considerable.