Atypical timing and presentation of periventricular haemorrhagic infarction in preterm infants: the role of thrombophilia

Abstract

Aim Periventricular haemorrhagic infarction (PVHI) is a complication of preterm birth associated with cardiorespiratory instability. To date, the role of thrombophilia as a possible additional risk factor in infants with atypical timing and presentation of PVHI has not been investigated. Method This was a retrospective cohort study of preterm infants who developed PVHI with an atypical timing and presentation either of antenatal onset or late in the postnatal course in the absence of a preceding sudden deterioration of their clinical condition. In infants with atypical PVHI mutation analysis of the factor V Leiden (G1691A), prothrombin (G20210A) gene, and C677T and A1298C polymorphisms in the MTHFR gene was performed, and plasma lipoprotein(a) and homocysteine levels were measured. Results Sixty‐two preterm infants who presented with a PVHI were studied. Seventeen had an atypical presentation (seven males, 10 females; median birthweight 1170g [range 580–1990g]; median gestational age 30.6wks [range 28.7–33.7wks]). The typical PVHI group comprised 28 males and 17 females (median birthweight 1200g [range 670–2210g]; median gestational age 29.6wks [range 25.3–33.6wks]). Among the 17 infants with atypical presentation, the factor V Leiden mutation was found in seven infants (41%) as well as in the mothers of six of these seven infants; in one infant this was concomitant with a prothrombin gene mutation. A polymorphism in the MTHFR gene was also present in these infants. In two infants with an atypical presentation who were tested for this, a mutation in the COL4A1 gene was found (reported previously). All but two of the infants with an atypical presentation developed spastic unilateral cerebral palsy. Interpretation An atypical presentation of PVHI in preterm infants tends to occur more often in the presence of thrombophilia. Testing of thrombophilia, especially factor V Leiden and prothrombin gene mutation, is recommended in these infants.

Maternal Race, Demography, and Health Care Disparities Impact Risk for Intraventricular Hemorrhage in Preterm Neonates

“…In addition, we do not have either the time of onset for IVH nor measures of thrombophilia, as atypical timing of IVH may be characterized by evidence of coagulopathy. [42] We did not collect physiologic measures of the cerebral circulation. [43, 44] Injury to the white matter of the brain is an important cause of neurodevelopmental impairment; we did not evaluate magnetic resonance imaging studies to detect white matter injury.…”

The role of FV 1691G>A, FII 20210G>A mutations and MTHFR 677C>T; 1298A>C and 103G>T FXIII gene polymorphisms in pathogenesis of intraventricular hemorrhage in infants born before 32 weeks of gestation

“…That is the reason why further analysis of the FII G20210A mutation and its impact on IVH incidence in preterm infants was not performed. In contrast to previous studies published by Baier et al [27], Gopel et al [4], Hartemann et al [31], Petaja et al [28], Ryckman et al [7], and Aden et al [8], Ramenghi showed that infants with VLBW and heterozygous for FII G20210A mutation are at increased risk for developing IVH [26]. …”

Can Functional Polymorphisms in <b><i>VEGF</i></b> and <b><i>MMP</i></b> Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

“…A study performed in Germany demonstrated genetic predisposition in the protein C anticoagulant pathway in 66% of children with congenital porencephaly [29]. Harteman et al [26] discussed that another mutation in F5 led to periventricular hemorrhagic infarction while Göpel et al demonstrated that the F5 Leiden mutation leads to enhanced bleeding control in VLBW infants [30]. …”