Cytomegalovirus DNA Detection by Polymerase Chain Reaction in Cerebrospinal Fluid of Infants With Congenital Infection: Associations With Clinical Evaluation at Birth and Implications for Follow-up.

BACKGROUND: DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) is a marker of central nervous system (CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is unknown. METHODS: A multicenter, retrospective study was performed using the Spanish Congenital Cytomegalovirus Infection Database (REDICCMV; http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed were included and classified according to their hCMV-PCR in CSF result (positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma viral load, and audiological and neurological outcomes of both groups were compared. RESULTS: A total of 136 neonates were included in the study: 21 (15.4%) with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen patients (81%) in the positive group were symptomatic at birth compared with 52.2% of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.28-14.1; P = .01). Only 4 asymptomatic newborns (6.8%) had a positive CSF hCMV-PCR. There were no differences between groups regarding the rate of microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age, or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P = .04), although no association was found at 6 months of age. CONCLUSIONS: A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV.

Unusual congenital goiter due to maternal Hashimoto thyroiditis: a case report.

Congenital hypothyroidism (CH) is the most common cause of endocrinopathy in the newborn Its incidence lies between 1 in 3,000 and 1 in 2,000, However, congenital goiter is a rare form of presentation. Hypothyroidism secondary to autoimmune etiology is extremely rare, with an incidence of 1:84.700-1:31.000 newborns. Anti-thyroid peroxidase antibodies (TPOAb) are able to cross the placenta but rarely induce hypothyroidism in the newborn, much less goiter. A case of congenital goiter in a male newborn secondary to maternal high TPOAb levels is reported. The mother was diagnosed of Hashimoto thyroiditis prior to the pregnancy. At birth, a grade 3 goiter was detected in the newborn. Laboratory testings revealed hypothyroidism with free thyroxine of 7.6 pmol/L, thyroid-stimulating hormone of 108 mUI/L and high TPOAb levels. Treatment with Levothyroxine was started the second day of life with progressive thyroid function normalization. Neurological development has been normal until the date.

Antiviral Treatment and Risk of Hearing Loss in Asymptomatic and Mild Symptomatic Infants With Congenital Cytomegalovirus.

BACKGROUND: To assess hearing outcomes at 24 months of age in infants with mild congenital cytomegalovirus (cCMV) infection, depending on whether they have received antiviral treatment or not. METHODS: A retrospective study within the European Registry of Children with cCMV was performed. Included children had cCMV diagnosed in utero/in the first 21 days of life, with normal physical examination, alanine aminotransferase <80 U/L and platelets >100,000 cs/mm3 and absence of hearing loss (HL) at birth. Cranial ultrasound (cUS) and/or cranial magnetic resonance imaging was normal or with minor findings (isolated lenticulostriate vasculopathy and/or germinolysis/caudothalamic or subependymal cysts, and/or focal/multifocal white matter involvement). The main outcome was the presence of HL at 24 months of age. RESULTS: One hundred ninety-six patients met inclusion criteria. A total of 34.7% received antiviral treatment with valganciclovir/ganciclovir. Children treated had lower gestational age, birth weight and head circumference, and maternal primary infection was less frequent. Among treated children, 21.3% presented minor findings in cUS versus 6.3% in nontreatment group (P = 0.003). Nine patients (4.6%) developed HL at 24 months. Among children with HL, 20% presented minor findings in cUS versus 11.3% in non-HL group (P = NS). HL rate was similar in treated and nontreated groups (4.6% vs. 6.3%; P = 0.6). CONCLUSIONS: One-third of the children were treated with antivirals and infants with minor neuroimaging findings at birth were more likely to receive antiviral. There were no differences in the prevalence of HL at 2 years of age between treated and not-treated children. Minor neuroimaging findings were not clearly associated with an increased risk of delayed onset HL.

Characteristics of enterovirus infection associated neurologic disease associated in a pediatric population in Spain.

INTRODUCTION: Enteroviruses are a type of RNA-strained virus with more than 100 different genotypes. Infection can be asymptomatic, and, if any, symptoms can range from mild to severe. Some patients can develop neurological involvement, such as aseptic meningitis, encephalitis, or even cardiorespiratory failure. However, in children, the risk factors for developing severe neurological involvement are not well understood. The aim of this retrospective study was to analyze some characteristics associated with severe neurological involvement in children hospitalized for neurological disease after enterovirus infection. METHODS: retrospective observational study analyzing clinical, microbiological and radiological data of 174 children hospitalized from 2009 to 2019 in our hospital. Patients were classified according to the World Health Organization case definition for neurological complications in hand, foot and mouth disease. RESULTS: Our findings showed that, in children between 6 months old and 2 years of age, the appearance of neurological symptoms within the first 12h from infection onset-especially if associated with skin rash-was a significant risk factor for severe neurological involvement. Detection of enterovirus in cerebrospinal fluid was more likely in patients with aseptic meningitis. By contrast, other biological samples (e.g., feces or nasopharyngeal fluids) were necessary to detect enterovirus in patients with encephalitis. The genotype most commonly associated with the most severe neurological conditions was EV-A71. E-30 was mostly associated with aseptic meningitis. CONCLUSIONS: Awareness of the risk factors associated with worse neurological outcomes could help clinicians to better manage these patients to avoid unnecessary admissions and/or ancillary tests.

Retinopathy of Prematurity and Possible Relation Between Postnatal Cytomegalovirus Infection.

Retinopathy of prematurity (ROP) is an eye disorder characterized by abnormal development of retinal blood vessels in premature infants. It has been associated with several risk factors, but the main factor is gestational age. Several studies have recently reported a possible link between ROP and postnatal cytomegalovirus (CMV) infection. The authors present 4 patients who developed severe ROP following postnatal CMV infection. ROP was successfully resolved with antiviral treatment in all 4 cases. Postnatal CMV infection could be responsible for the worsening of ROP. Antiviral therapy may improve the prognosis of ROP and avoid the need for more aggressive therapies.

Morbidity and mortality of very low birth weight multiples compared with singletons.

BACKGROUND: Previous studies comparing the neonatal outcome of very low birth weight (VLBW) multiples and singletons have suggested a worse outcome for multiples at gestational ages on the limits of viability. OBJECTIVES: The objective of this study is to determine the neonatal mortality and morbidity of VLBW multiples compared to singletons. METHODS: This is a retrospective study including all infants registered in the Spanish network for infants under 1500 g (SEN1500), over a 12-year period (from 2002 to 2013). Mortality and major morbidities were compared between singletons and multiples. RESULTS: About 32,770 infants were included: 21,123 singletons (64.5%) and 11,647 multiples (35.5%), with a mean gestational age of 29.5 weeks (22-38), and mean birth weight of 1115 g (340-1500). When adjusted by other perinatal factors, multiple pregnancy has a significantly higher risk of mortality than singleton pregnancy (odds ratio (OR) 1.15; IC 95% 1.05-1.26, p = .002), but not a higher risk of major morbidity or composite adverse outcome. In the subgroup of infants born before 26 weeks, multiples showed a higher risk of mortality (63.9% versus 51%, OR 1.7; 95% CI 1.47-1.96) and a higher risk of composite adverse outcome (88.9% versus 81.5%, OR 1.82, 95% CI 1.28-2.24). CONCLUSIONS: In preterm infants born with less than 1500 g, multiple pregnancy is a prognostic factor that can slightly increase mortality. Extremely preterm infants born before 26 weeks have a greater risk of mortality and major morbidity if they come from a multiple pregnancy.

Breastfeeding Disparities between Multiples and Singletons by NICU Discharge.

Multiple pregnancy increases the risk of a range of adverse perinatal outcomes, including breastfeeding failure. However, studies on predictive factors of breastfeeding duration in preterm twin infants have a conflicting result. The purpose of this observational study was to compare feeding practices, at hospital discharge, of twin and singleton very low birth weight infants. The study is part of a prospective survey of a national Spanish cohort of very low birth weight infants (SEN1500) that includes 62 neonatal units. The study population comprised all infants registered in the network from 2002 to 2013. They were grouped into singletons and multiples. The explanatory variables were first analyzed using univariate models; subsequently, significant variables were analyzed simultaneously in a multiple stepwise backward model. During the twelve-year period, 32,770 very low birth weight infants were included in the database, of which 26.957 were discharged alive and included in this analysis. Nine thousand seven hundred and fifty-eight neonates were multiples, and 17,199 were singletons. At discharge, 31% of singleton infants were being exclusively breastfed, 43% were bottle-fed, and 26% were fed a combination of both. In comparison, at discharge, only 24% of multiple infants were exclusively breastfed, 43% were bottle-fed, and 33% were fed a combination of both (p < 0.001). On multivariable analysis, twin pregnancy had a statistically significant, but small effect, on cessation of breastfeeding before discharge (OR 1.10; 95% CI: 1.02, 1.19). Risks of early in-hospital breastfeeding cessation were also independently associated with multiple mother-infant stress factors, such as sepsis, intraventricular hemorrhage, retinopathy, necrotizing enterocolitis, intubation, and use of inotropes. Instead, antibiotic treatment at delivery, In vitro fertilization and prenatal steroids were associated with a decreased risk for shorter in-hospital breastfeeding duration. Multiple pregnancy, even in the absence of pathological conditions associated to very low birth weight twin infants, may be an impeding factor for in-hospital breastfeeding.

Growth Patterns in Children With Congenital Cytomegalovirus Infection.

BACKGROUND: Congenital cytomegalovirus infection (CMVc) affects 0.7%-6% of recent births. Among its clinical manifestations are low weight and length at birth. OBJECTIVE: Describe the growth patterns of children with CMVc in their early years. METHODS: Observational, multicenter study of patients with CMVc. Anthropometric data were collected during the first 2 years of life and compared with World Health Organization standards. RESULTS: Anthropometric characteristics of 383 children with CMVc were studied, of which 198 (51%) were symptomatic at birth. At birth, 9% were small for gestational age (SGA) in terms of their weight and length and 17% had microcephaly. At 24 ± 3 months, 10% had a weight and length ≤2 SD, and 13% a head circumference ≤2 SD. Of those who were SGA at birth, at 24 ± 3 months >20% remained at ≤2 SD of their weight and length. Conversely, 75% of children with low weight or length at 24 ± 3 had not been SGA at birth. 20% of infants with microcephaly at birth remained with microcephaly, and 10% of those without microcephaly developed it at 24 ± 3 months. The average growth rate in length and weight was normal. Patients who were symptomatic at birth, premature and with motor and neurocognitive impairment had a significantly higher risk of low weight and length at 24 ± 3 months. CONCLUSION: Around 10% of children with CMVc are at ≤2 SD in weight, length and head circumference at 24 ± 3 months. The lack of adequate growth is associated with symptoms at birth, prematurity and motor and neurocognitive impairment. Growth impairment could be incorporated into the symptomatic spectrum of CMVc.

Physicochemical Stability and Sterility of Standard Parenteral Nutrition Solutions and Simulated Y-Site Admixtures for Neonates.

BACKGROUND: Parenteral nutrition (PN) is frequently needed in neonatal intensive care. The use of standard PN has emerged as an easy-to-prescribe approach that allows one to have on-site, ready-to-use PN. The aim of this study was to test the physicochemical stability and sterility of 2 specific PN solutions as well as simulate Y-site compatibility with lipid injectable emulsions (ILE). METHODS: Our study considered 2 standard ILE-free PN solutions according to neonatal weight. These solutions were prepared in duplicate and stored at 4°C. The following physicochemical parameters were tested: visual alterations, turbidity, pH, osmolarity, and calcium concentration. Sterility was assessed by means of agar blood culture and glucose concentration determination. In addition, we assessed the stability of simulated Y-site admixtures. For each standard ILE-free PN solution, 2 3-in-1 PN admixtures were designed, considering extreme values of fluid requirements (50 and 150 ml/kg/d) and a fat supply of 2 g/kg/24 h. The physicochemical parameters tested were phase separation and fat mean droplet size distribution. RESULTS: No alterations were detected by visual inspection. Calcium concentrations, turbidity, pH, and osmolarity values remained stable in all the determinations. All agar blood cultures were negative and glucose concentration was constant over time. Physical stability of simulated Y-site admixtures was considered acceptable as mean droplet size distribution remained below 500 nm in all the emulsions. CONCLUSION: The 2 tested standard ILE-free PN solutions for neonates are physicochemically stable and sterile for 31 days under refrigeration (4°C). These solutions are also stable in case of Y-site administration with ILE at the conditions tested.

Hydrops fetalis-associated congenital dyserythropoietic anemia treated with intrauterine transfusions and bone marrow transplantation.

Hydrops fetalis is rarely caused by congenital dyserythropoietic anemia (CDA). We report a patient with hydrops fetalis as a result of severe anemia. This patient needed intrauterine transfusions from 21 weeks of gestation until birth. The hematologic study showed an atypical CDA (hydrops fetalis-associated CDA) characterized by features resembling CDA type II, but negative acidified serum lysis test (HEMPAS negative). The patient was regularly transfused for a year, after which an allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling was successfully carried out. His actual hemoglobin is 127 g/L, and he has not received transfusions for more than a year. In conclusion, intrauterine transfusions and BMT could cure an otherwise lethal atypical CDA.