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Original Investigation |

Postnatal Cytomegalovirus Infection and the Risk for Bronchopulmonary Dysplasia Online Only

Matthew S. Kelly, MD, MPH1,2; Daniel K. Benjamin, PhD3; Karen M. Puopolo, MD, MPH4; Matthew M. Laughon, MD, MPH5; Reese H. Clark, MD6; Sagori Mukhopadhyay, MD, MMSc4; Daniel K. Benjamin Jr, MD, PhD1,2; P. Brian Smith, MD, MPH, MHS1,2; Sallie R. Permar, MD, PhD2
[+] Author Affiliations
1Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
2Division of Pediatric Infectious Diseases, Duke University School of Medicine, Durham, North Carolina
3Department of Economics, Clemson University, Clemson, South Carolina
4Division of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
5Division of Neonatal-Perinatal Medicine, The University of North Carolina at Chapel Hill
6Pediatrix-Obstetrix Center for Research and Education, Sunrise, Florida
JAMA Pediatr. 2015;169(12):e153785. doi:10.1001/jamapediatrics.2015.3785.
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Importance  Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but in very low-birth-weight (VLBW) infants can cause pneumonitis and sepsislike illness. Whether postnatal CMV infection results in long-term pulmonary sequelae in these infants is unknown.

Objective  To investigate the association between postnatal CMV infection and bronchopulmonary dysplasia (BPD) and mortality in a large multicenter cohort of VLBW infants.

Design, Setting, and Participants  Conducted between October 2014 and June 2015, this propensity-matched retrospective cohort study involved 101 111 hospitalized VLBW (<1500 g) infants at 348 neonatal intensive care units in the United States from 1997 to 2012. We matched infants with postnatal CMV infection 1:1 to comparison infants using propensity scores, and we used Poisson regression to examine the effect of postnatal CMV on the combined risk for death or BPD at 36 weeks’ postmenstrual age. To describe features of postnatal CMV infection, we extracted clinical and laboratory data from 7 days before until 7 days after infants met criteria for postnatal CMV.

Exposures  Postnatal CMV infection was defined as a diagnosis of CMV or detection of CMV from blood, urine, cerebrospinal fluid, or respiratory secretions on or after day of life 21. Infants with a CMV diagnosis or virologic detection of CMV prior to day of life 21 were not considered to have postnatal infection.

Main Outcomes and Measures  The primary outcome was death or BPD at 36 weeks’ postmenstrual age.

Results  Of 101 111 infants, 328 (0.3%) had postnatal CMV infection. We matched a comparison infant to 303 CMV-infected infants (92%) for a final cohort of 606 infants. The median gestational age and birth weight of this cohort were 25 weeks and 730 g, respectively. Postnatal CMV infection was associated with an increased risk for death or BPD at 36 weeks’ postmenstrual age (risk ratio, 1.21; 95% CI, 1.10-1.32) and BPD (risk ratio, 1.33; 95% CI, 1.19-1.50). Changes in cardiorespiratory status associated with postnatal CMV infection included a new requirement for vasopressor medications (9%; n = 29), intubation for mechanical ventilation (15%; n = 49), a new oxygen requirement (28%; n = 91), and death (1.2%; n = 4).

Conclusions and Relevance  In VLBW infants, postnatal CMV infection was associated with increased risk for BPD. Further studies are needed to determine the role of preventive measures against CMV in this population.

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Participant Flow Diagram

Inclusion criteria were cytomegalovirus (CMV) diagnosis on day of life (DOL) 21 or later or positive CMV culture/polymerase chain reaction (PCR) on DOL 21 or later. Exclusion criteria were intracranial calcifications, positive CMV culture/PCR before DOL 21, CMV diagnosis before DOL 21, microcephaly before DOL 21, anti-CMV treatment before DOL 21, and transaminitis before DOL 21. VLBW indicates very low birth weight.

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