Postnatal Human Cytomegalovirus Infection in Preterm Infants Has Long Term Neuropsychological Sequelae Katharina F. Brecht, MSc 1 , Rangmar Goelz, MD 2 , Andrea Bevot, MD 1 , Ingeborg Kr € ageloh-Mann, MD, PhD 1 , Marko Wilke, MD, PhD 1 , and Karen Lidzba, PhD 1 Objective To evaluate whether an early postnatal infection poses a long-term risk for neuropsychological impair- ment to neonates born very prematurely. Study design Adolescents born very preterm (n = 42, 11.6-16.2 years, mean = 13.9; 15 girls; 19 with and 23 without an early postnatal human cytomegalovirus [CMV] infection) and typically developing, term born controls (n = 24, 11.3-16.6 years, mean = 13.6; 12 girls) were neuropsychologically assessed with the German version of the Wechsler Intelligence Scale and the Developmental Test for Visual Perception. Results As expected, the full cohort of adolescents born preterm had significantly lower scores than term born controls on IQ (preterm: mean [SD] = 98.43 [14.83], control: 110.00 [8.10], P = .015) and on visuoperceptive abilities (95.64 [12.87] vs 106.24 [9.95], P = .016). Furthermore, adolescents born preterm with early postnatal CMV infection scored significantly lower than those without this infection regarding overall cognitive abilities (92.67 [14.71] vs 102.75 [13.67], P = .030), but not visuoperceptive abilities (91.22 [10.88] vs 98.96 [13.45], P > .05). Conclusions In our small but well-characterized group, our results provide evidence for adverse effects of early postnatal CMV infection on overall cognitive functions in adolescents born preterm. If confirmed, these results support the implementation of preventive measures. (J Pediatr 2014;-:---). See editorial, p  W ith an estimated prevalence of 0.6% in newborn infants, human cytomegalovirus (CMV) is the most common congenital infection worldwide. 1 Such an infection can result in a wide range of brain abnormalities, 2,3 affecting both gray and white matter. A postnatal infection with CMV is defined as an infection (proven by virus detection) within the first year of life but later than 2 weeks after delivery. 4 In term born neonates, a postnatal infection (usually via CMV positive breast milk) is unlikely to cause severe illness because of the placental transmission of protective antibodies after about 28 weeks of gestation. 5 However, the situation is less clear in premature infants. 6 Because of its nutritional and non-nutritional benefits, human milk is recommended for both preterm and term-born in- fants. 7 At the same time, human milk is a prominent mode of CMV transmission in early postnatal life of preterm infants 8 because the incidence of CMV reactivation in mothers during lactation is high, particularly following premature birth. 4,9 As evidence for long-term neurobiological consequences of such an infection is inconclusive, prevention strategies are not imple- mented universally. Although we and others did not find evidence for specific neurologic impairment in the neonatal period and in early childhood, 10-12 our follow-up assessments revealed that cognitive deficits in children born preterm induced by an early postnatal CMV infection do exist and can be detected in later childhood. 13,14 This argues against overt neurologic impair- ment but suggests possible effect on complex cognitive skills. Because of the direct consequences for handling CMV-positive human milk in the neonatal intensive care unit (“to pasteurize or not to pasteurize”), examining long-term neurobiological consequences is of high relevance. For the present study, we hypothesized that compared with term-born controls (TERM), adolescents born preterm are impaired in general cognitive abilities, as well as in visuoperceptive abilities (independent of gen- eral cognitive abilities), and adolescents born preterm with an early postnatal CMV infection (PRE CMV+ ) are similarly, but more prominently, affected in both of these domains than adolescents born preterm without early postnatal CMV (PRE CMV ). From the Departments of 1 Pediatric Neurology and Developmental Medicine and 2 Neonatology, University Children’s Hospital, T€ ubingen, Germany Supported by the Deutsche Forschungsgemeinschaft (WI3630/1-1 and 1-2 [to M.W.]), and a Margarete von Wrangell Scholarship funded by the European Social Fund & Ministry of Science and the Arts, Baden- W€ urttemberg (to K.L.). The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.11.002 CMV Human cytomegalovirus DTVP-A Developmental Test of Visual Perception-Adolescent and Adult GVPI General visual perceptual index HAWIK-IV Hamburg-Wechsler-Intelligenztest f€ ur Kinder IV MRI Magnetic resonance imaging PCR Polymerase chain reaction PRE CMV+ Adolescents born preterm without postnatal CMV infection PRE CMV Adolescents born preterm with postnatal CMV infection TERM Term-born controls VCI Verbal comprehension index 1