Ana Alarcon

Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK-cell subset distribution in children.

Human cytomegalovirus (HCMV) has been reported to reshape the NK‐cell receptor (NKR) distribution, promoting an expansion of CD94/NKG2C+ NK and T cells. The role of NK cells in congenital HCMV infection is ill‐defined. Here we studied the expression of NKR (i.e., NKG2C, NKG2A, LILRB1, CD161) and the frequency of the NKG2C gene deletion in children with past congenital infection, both symptomatic (n = 15) and asymptomatic (n = 11), including as controls children with postnatal infection (n = 11) and noninfected (n = 20). The expansion of NKG2C+ NK cells in HCMV‐infected individuals appeared particularly marked and was associated with an increased number of LILRB1+ NK cells in cases with symptomatic congenital infection. Increased numbers of NKG2C+, NKG2A+, and CD161+ T cells were also associated to HCMV infection. The NKG2C deletion frequency was comparable in children with congenital HCMV infection and controls. Remarkably, the homozygous NKG2C+/+ genotype appeared associated with increased absolute numbers of NKG2C+ NK cells. Moreover, HCMV‐infected NKG2C+/+ children displayed higher absolute numbers of NKG2A+ and total NK cells than NKG2C+/− individuals. Our study provides novel insights on the impact of HCMV infection on the homeostasis of the NK‐cell compartment in children, revealing a modulatory influence of NKG2C copy number.

Dynamics of the NK-cell subset redistribution induced by cytomegalovirus infection in preterm infants

Human cytomegalovirus (HCMV) infection promotes an expansion of NK-cells expressing the CD94/NKG2C receptor. We prospectively monitored the effects of HCMV on the NK-cell receptor (NKG2C, NKG2A, KIR, LILRB1) distribution in preterm infants. As compared to non-infected moderately preterm newborns (n=19, gestational age: 32-37 weeks), very preterm infants (n=5, gestational age: <32 weeks) suffering symptomatic postnatal HCMV infection displayed increased numbers of NKG2C+, KIR+ NK-cells, encompassed by a reduction of NKG2A+ NK-cells. A similar profile was observed in HCMV-negative newborns (n=4) with asymptomatic infection, during follow-up at ~4 and 10 months of age. Of note, viremia remained detectable in three symptomatic cases at ~10 months despite the persistent expansion of NKG2C+ NK-cells. Our study provides original insights on the dynamics of the imprint exerted by primary HCMV infection on the NK-cell compartment, revealing that the expansion of NKG2C+ NK-cells may be insufficient to control viral replication in very preterm infants.

Neonatal neurological morbidity associated with uterine rupture.

Abstract Aims: To compare neonatal neurological morbidity associated with uterine rupture with morbidity associated with a non-reassuring fetal status. Methods: We conducted a retrospective cohort analysis. Twenty-one cases of term infants delivered after a symptomatic uterine rupture were analyzed and compared with a randomly selected group of 63 infants born after a non-reassuring fetal heart rate pattern. Results: Prevalence of uterine rupture was 0.058%. Maternal factors and infant general data were similar in both groups. Infants delivered after a uterine rupture had lower Apgar scores at 1 and 5 min, lower umbilical blood pH, and required more advanced resuscitation than infants delivered after a non-reassuring fetal status. Prevalence of hypoxic-ischemic encephalopathy in the uterine rupture group was 33%, compared with 5% in the other group (P<0.01, relative risk 3.7). Four infants in the uterine rupture group (19%) had moderate or severe encephalopathy; all of them had also multisystem dysfunction and an adverse outcome. No infant in the non-reassuring fetal status group showed moderate or severe encephalopathy. Conclusions: Uterine rupture is a considerable sentinel event that involves a high rate of early and late neurological morbidity in the newborn infant.

Congenital syphilis: β2-microglobulin in cerebrospinal fluid and diagnosis of neurosyphilis in an affected newborn

Abstract Meningoencephalitis in neonatal congenital syphilis (CS) is a difficult diagnosis because of the limitation of standard cerebrospinal fluid (CSF) tests. This limitation means that new markers in CSF tests are needed to establish whether meningitis is present in presumptive cases of CS. β2-Microglobulin (β2-m) is raised in CSF recovered from neonates with central nervous system (CNS) infections, but it does not correlate with cellular count or proteins in the CSF. We present a preterm newborn with symptomatic CS. First-day CSF showed 50 cells/mm3, protein of 220 mg/dL and a β2-m concentration of 16.9 mg/dL (normal <2.25 mg/dL). Serial determinations of β2-m showed a marked reduction (76%) after 10 days of appropriate treatment. At 30 days of life, β2-m was already within the normal range (1.8 mg/dL). Cerebral ultrasonography showed ventricular dilatation, moderate periventricular echogenicity, subependimal hemorrhages, and linear hyperechoic areas in the thalamus and basal ganglia. We suggest that β2-microglobulin is very useful in the diagnosis of CNS involvement and in monitoring the response to treatment. In addition, infants with CS may exhibit CNS imaging findings similar to those observed in other intrauterine CNS infections.

A Prognostic Neonatal Neuroimaging Scale for Symptomatic Congenital Cytomegalovirus Infection

Background: Congenital cytomegalovirus (cCMV) can cause brain inflammation/destruction and teratogenic effects. The only validated neuroimaging prognostic categorization for symptomatic cCMV available is based on destructive lesions seen on computed tomography (CT). Objective: The aim of this study was to establish the predictive ability of a comprehensive neonatal neuroimaging scale in symptomatic cCMV. Methods: Twenty-six infants were studied by neonatal cranial ultrasound scans (US; n = 25), CT (n = 11) and magnetic resonance imaging (MRI; n = 9). A previously validated neuroimaging scale comprising calcifications, ventriculomegaly and atrophy was compared to a newly proposed system adding cerebral dysgenesis and white matter disease. The findings were graded from 0 to 3. Neurodevelopmental assessment included motor and cognitive functions, epilepsy, vision, hearing and behavioral disorders. Results: Both scales showed a significant association with outcome (p < 0.005). Our scale was more accurate in predicting death or moderate-severe disability (area under the curve for scores ≥2, 0.88 ± 0.06 vs. 0.80 ± 0.08). All 5 infants with normal neuroimaging survived with intact neurological function. While our scale was highly associated with outcome in patients studied by MRI, it was unable to predict unfavorable outcomes in 2 patients with mildly abnormal US and/or CT. Conclusions: A comprehensive scale based on US and MRI predicts neurodevelopment in symptomatic cCMV. Significant destructive lesions are associated with a poor prognosis. While a strictly normal cranial US predicts a favorable outcome, in case of subtle US abnormalities, MRI is crucial for prognostication.

Contents Vol. 110, 2016

K. Allegaert, Leuven S. Andersson, Helsinki E. Bancalari, Miami, Fla. D. Bassler, Zurich C. Bührer, Berlin W. Carlo, Birmingham, Ala. Y.-S. Chang, Seoul R. Christensen, Salt Lake City, Utah T. Curstedt, Stockholm C. Dani, Florence B. Darlow, Christchurch H. Hagberg, Gothenburg M. Hallman, Oulu J.E. Harding, Auckland W.W. Hay Jr., Aurora, Colo. H.H. Hummler, Ulm S.E. Juul, Seattle, Wash. M. Kaplan, Jerusalem B. Kramer, Maastricht R.J. Martin, Cleveland, Ohio W. McGuire, York J. Neu, Gainesville, Fla. P.C. Ng, Hong Kong W.S. Park, Seoul N.J. Robertson, London C. Roehr, Oxford E. Saliba, Tours O.D. Saugstad, Oslo M.P. Sherman, Columbia, Mo. E.S. Shinwell, Tsfat J. Smith, Tygerberg R.F. Soll, Burlington, Vt. (Cochrane Review Updates) J. Soul, Boston, Mass. B. Sun, Shanghai N. Takahashi, Tokyo B. Thébaud, Ottawa, Ont. D. Tibboel, Rotterdam N. Vain, Buenos Aires F. van Bel, Utrecht J.N. van den Anker, Washington, D.C. M. Vento Torres, Valencia F.J. Walther, Leiden J.A. Widness, Iowa City, Iowa T.F. Yeh, Taipei Fetal and Neonatal Research