Symptomatic Postnatal Cytomegalovirus Infection in Less than 32-Week Preterm Infants: 13-Year Retrospective Multicenter Case-Control Study

Abstract

<b><i>Introduction:</i></b> Reports on the influence of postnatal cytomegalovirus (pCMV) infection in neonatal outcomes of preterm babies vary while guidance on management including screening is lacking. We aim to determine the association between symptomatic pCMV infection and chronic lung disease (CLD) and mortality in preterm infants born less than 32 weeks gestation. <b><i>Methods:</i></b> We used data from the Neonatal Intensive Care Units’ (NICUS) population-based prospective data registry of infants in 10 neonatal units in New South Wales and the Australian Capital Territory, Australia. De-identified perinatal and neonatal outcome data for 40,933 infants were examined. We identified 172 infants <32 weeks gestation with symptomatic pCMV infection. Each was matched with one control infant. <b><i>Results:</i></b> Infants with symptomatic pCMV infection were 2.7 times more likely to develop CLD (OR 2.7, 95% CI: 1.7–4.5) and spend 25.2 days more in hospital (95% CI: 15.2–35.2). Seventy-five percent (129/172) of infants with symptomatic pCMV were extremely preterm (<28 weeks). The mean age of symptomatic pCMV diagnosis was 62.5 ± 20.5 days or 34.7 ± 3.6 weeks-corrected gestational age. Ganciclovir treatment did not decrease CLD and death. CLD was 5.5 times predictive of death in patients with symptomatic pCMV infection. Symptomatic pCMV infection did not influence mortality nor increase neurologic impairment. <b><i>Conclusion:</i></b> Symptomatic pCMV is a modifiable factor affecting extreme preterm infants with significant impact on CLD. Prospective study on screening and treatment will help unveil potential benefits in our already at-risk preterm infants.

Association between viral infection and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis

“…The population included in the studies was primarily preterm or low birth weight infants. Among the 17 incorporated studies, preterm infants in six investigations demonstrated gestational ages below 32 weeks [ 13 – 15 , 29 , 33 , 34 ], whereas those in eight studies exhibited birth weights under 1500 g [ 16 , 18 , 20 , 29 , 30 , 32 – 34 ]. One study did not report the birth weight of the infants studied [ 14 ].…”

“…One study diagnosed BPD relying solely on the results of chest imaging [ 27 ]. When selecting samples to confirm viral infection, eleven studies chose urine samples [ 15 – 18 , 27 – 29 , 31 – 34 ], nine used respiratory secretion samples [ 12 – 17 , 31 , 32 , 34 ], six used blood samples [ 15 , 16 , 20 , 31 , 32 , 34 ], three chose cerebrospinal fluid samples [ 16 , 32 , 34 ], and one took umbilical cord tissue samples [ 30 ]. In choosing the means of detecting viral infections, thirteen studies opted for nucleic acid testing by polymerase chain reaction (PCR) [ 12 – 17 , 20 , 28 – 31 , 33 , 34 ], seven took viral cultures [ 16 – 18 , 27 , 29 , 32 , 34 ], and two used immunological methods [ 20 , 31 ].…”

“…The meta-analysis was examined using a random-effects model. Tapawan et al [ 15 ] matched control infants by sex, birth gestational age, and birth weight. Kelly et al [ 34 ] adjusted for confounding variables including GA, BW, small for gestational age status, race/ethnicity, discharge year, NICU site, use of antenatal corticosteroids, days of breast milk exposure from postnatal days 15 to 21, days of aminoglycoside (gentamicin sulfate, tobramycin, and amikacin sulfate) and loop diuretic (furosemide and bumetanide) exposure, NEC, grade 3 or 4 intraventricular hemorrhage, patent ductus arteriosus, sepsis occurring on or before postnatal day 21, vasopressor medications (amrinone lactate, dobutamine hydrochloride, dopamine hydrochloride, epinephrine, milrinone lactate, and norepinephrine bitartrate), type of respiratory support, and fraction of inspired oxygen on postnatal day 21.…”

“…There are three routes of transmission of CMV infection in preterm infants, including congenital CMV via intrauterine transmission, transmission via cervical or vaginal secretions, and postnatal CMV via breast milk or blood transfusion [ 15 , 16 ]. Previous studies have defined congenital CMV infection using PCR or viral isolation (culture) for CMV DNA in body fluids (including saliva and/or urine) or blood obtained within 3 weeks of birth [ 44 ].…”

“…Certainly, cytomegalovirus (CMV) should be the most discussed viral infection in BPD research. Large multicenter studies in the USA and Australia have concluded that CMV is a risk factor for BPD [ 15 , 16 ].…”