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

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.