Current practice with respect to neonatal haemostasis is not evidence based. There is varying practice as to whether or not coagulation screening is performed, as well as when intervention is indicated. This aim of this systematic review is to evaluate whether administration of frozen plasma improves morbidity or mortality in neonates. To assess the effects of frozen plasma administration on development of intraventricular hemorrhage in preterm infants < 32 weeks gestation. Secondary aims include subgroup analyses designed to determine if the effect of fresh frozen plasma administration depends on the factors as delineated below. Fresh frozen plasma is frequently administered to treat perceived predisposition to bleeding or perceived abnormalities in clotting in neonates, including fresh frozen or solvent-detergent plasma, cryoprecipitate, fibrinogen, recombinant factor VIIa, and platelets. Frozen plasma (FP) is human-derived plasma, which contains plasma proteins including procoagulant and inhibitory components of the coagulation cascades, acute phase proteins, immunoglobulins and albumin. Transfusing very low birth weight infants with fresh frozen plasma, either as a prophylactic or therapeutic agent, is common practice for preventing or limiting, intracranial hemorrhage. Nevertheless, the benefit of this practice has not been clearly shown. Systematic reviews of plasma product administration in preterm infants and subgroup analyses are needed, as existing reviews (Kuperman et al. 2013, Venkatesh et al. 2013, Kuperman et al 2012, Yang et al 2012, Poterjoy BS et al. 2009, Brunskill et al 2009, Stanworth 2007, Robertson 2006, Stanworth 2006, Stanworth et al 2004, Evans et al 2004, Murray NA et al 2003) have assessed only some of the effects of fresh frozen plasma on mortality and morbidity in preterm infants or very low birth weight infants. The present systematic review analyzes a broader spectrum of risks and benefits of blood product administration, in preterm infants and in very low birth weight infants. All published, unpublished and ongoing, randomised and quasi-randomised controlled clinical trials in which at least one of the primary or secondary outcome variables (see below) has been analysed, are eligible for inclusion in this review. Appropriate studies of premature infants (<32 weeks’ gestation) will be eligible for inclusion in this review. Infants with known inherited coagulation defects or antenatal diagnoses of intraventricular haemorrhage will not be eligible for inclusion. The review will differentiate between infants receiving fresh frozen plasma based on abnormal coagulation result but with no evidence of bleeding versus empirical treatment early in the postnatal period. Cranial ultrasound findings of intraventricular haemorrhage will be classified according to the criteria set out by Papile et al (1978). Other episodes of bleeding will be diagnosed clinically. Co-morbidities potentially affecting coagulation such as confirmed sepsis and perinatal depression (Apgar Score <5 at 5 minutes) will be noted and subgroup analysis performed. We will include infants who have been proved to have abnormal coagulation result or those who are unscreened. We will exclude infants who have evidence of bleeding (IVH, pulmonary, gastrointestinal) before recruitment. We will exclude studies including infants after 24 hours or after detection of any IVH on ultrasound. We will exclude infants included in clinical trials involving administration of any other pharmacological agent(s) Randomised or quasi-randomised allocation of the infant to plasma product administration in the treatment group versus either placebo, or no treatment. Studies will be accepted regardless of dose and route of administration of blood product. The treatment group may have received fresh frozen plasma either prophylactically or as rescue treatment. However, studies assessing the effect of another intervention, to which the blood product is only a cointervention (e.g. studies assessing the effect of hypoventilation on IVH, in which blood product were also provided) will not be included.
