Neurodevelopmental Outcomes of Neonatal Rotavirus-Associated Leukoencephalopathy.

Rotavirus infection has been reported to be associated with neonatal seizures with a diffuse and symmetrical diffusion restriction of periventricular white matter, namely, neonatal rotavirus-associated leukoencephalopathy. The extensive white matter injury seen in this cohort raises concerns about the long-term neurodevelopmental outcomes. In the present study, we prospectively assessed the neurodevelopmental outcomes of 13 patients with neonatal rotavirus-associated leukoencephalopathy at a median age of 26 months (range, 23-68 months). Neurodevelopmental outcomes were evaluated using a neurological examination, developmental evaluations, and magnetic resonance imaging (MRI) of the brain. Overall, 6 of the 13 patients (46%) had abnormal neurodevelopmental outcomes: 1 patient had mental retardation, visual-motor integration (VMI) dysfunction, cerebral palsy, and epilepsy; 1 patient had cerebral palsy and VMI dysfunction; remaining 4 patients had VMI dysfunction. Follow-up MRI in 12 of 13 patients showed an increased signal intensity on periventricular white matter in all patients. These findings suggested that neonatal rotavirus-associated leukoencephalopathy could not be assumed to be benign in long-term neurodevelopment, particularly in VMI function. Early intervention and long-term follow-up are necessary for these patients. Our findings raise caution for rotavirus infection in this vulnerable population for infants.

Changes in Seroprevalence of Helicobacter pylori Infection over 20 Years in Jinju, Korea, from Newborns to the Elderly.

BACKGROUND: The objective of this study was to examine changes in the prevalence of cytotoxic-associated gene A (CagA) positive Helicobacter pylori infection in Jinju, Korea, over the last 20 years. METHODS: Three cross-sectional analyses were conducted concurrently. A total of 1,305 serum samples were collected from 1994-1995, 2004-2005, and 2014-2015, respectively. The presence of immunoglobulin (Ig) G, IgA, and IgM antibodies against H. pylori CagA protein was examined by western blotting. RESULTS: Overall, seropositivity for anti-CagA IgG antibody was significantly decreased from 63.2% to 42.5% over the last 20 years (P < 0.001). Anti-CagA IgG seropositivities in children and young adults aged 10-29 years decreased from 1994 (60.0%-85.0%) to 2015 (12.5%-28.9%). The age when plateau of increasing IgG seropositivity was reached in each study period shifted from the 15-19 year-old group in 1994-1995 (85.0%) to the 40-49 year-old group in 2014-2015 (82.5%). Overall seropositive rates of anti-CagA IgA and IgM antibodies did not change significantly either over the last 20 years. CONCLUSION: H. pylori infection rate in children and young adults declined over 20 years in Jinju, probably due to improved sanitation, housing, or economy.

Monocyte Chemoattractant Protein (MCP)-1 in Rotavirus-Associated White Matter Injury in Newborns.

Recent reports have suggested an association between rotavirus infection and a distinctive pattern of white matter injury (WMI) in neonates with seizures; however, the connection between the two is not fully understood. To evaluate the underlying mechanism, we profiled and compared eight cytokines (IL [interleukin]-1ß, IL-6, IL-8, IL-10, IFN-γ [interferon-γ ], MCP-1 [monocyte chemoattractant protein-1], MIP-1ß [macrophage inflammatory protein-1ß], and TNF-α [tumor necrosis factor-α]) in the cerebrospinal fluid (CSF) of 33 neonates with seizures who had no other well-known causes of seizures and 13 control patients (rotavirus-induced gastroenteritis but without seizures). Among the 33 neonates with seizures, 9 showed WMI and all were infected with rotavirus (R + W + ). Among the 24 patients without WMI, 11 were infected with rotavirus (R + W - ) and 13 were not (R - W - ).Only MCP-1 and MIP-1ß were different between the groups. MCP-1 was increased in R+ W+ compared with R + W- (p < 0.01), R - W- (p < 0.01), and control (p = 0.03) patients. MIP-1ß was decreased in R + W+ compared with R - W- (p < 0.01) and control (p < 0.01), but not R + W- (p = 0.23) patients. MCP-1 and MIP-1ß are C-C chemokines that recruit immune cells to the site of inflammation. Our pilot study suggests MCP-1-mediated monocyte recruitment may be linked with this complication caused by rotavirus.

Immunohistochemical Expressions of MUC2, MUC5AC, and MUC6 in Normal, Helicobacter pylori Infected and Metaplastic Gastric Mucosa of Children and Adolescents.

OBJECTIVES: The aim of this study was to investigate expression of gastric mucins in children and adolescents and to assess their relations with age and Helicobacter pylori (H. pylori) infection. METHODS: Gastric biopsies were collected from 259 pediatric and adulthood patients with gastrointestinal symptoms among all of patients undergone gastroduodenoscopy from 1990 to 2004 at Gyeongsang National University hospital and assorted based on H. pylori infection, age, and intestinal metaplasia as follows; H. pylori infection before 5 years of age or not, H. pylori infection between 5 and 9 years of age or not, H. pylori infection between 10 and 14 years of age or not, H. pylori infection between 20 and 29 years of age or not and intestinal metaplasia between 21 and 35 years of age. Total 810 tissue slides from the subjects were examined regarding expressions of Mucin2 (MUC2), Mucin5AC (MUC5AC), and Mucin6 (MUC6) in nine groups using immunohistochemical stains. A semiquantitative approach was used to score the staining extent of tissue slide. RESULTS: Increased expressions of MUC2, MUC5AC, and MUC6 were noted in intestinal metaplasia compared with subjects infected with H. pylori between 20 and 29 years. Gastric expressions of MUC5AC were decreased in older than 5 years with H. pylori compared with in older than 5 years without H. pylori (p < .001). Expressions of MUC2 and MUC6 did not change significantly by H. pylori status. Some nuclear expressions of MUC2 and MUC6 were noted in children without intestinal metaplasia. CONCLUSIONS: MUC5AC might be affected by chronic H. pylori infection. In addition to biomarkers for intestinal metaplasia or prognostic factors for gastric cancer in adults, MUC2 and MUC6 in children might have an another role, based on ectopic gastric nuclear expressions of MUC2 and MUC6 in children without intestinal metaplasia.

Correlation between positive rate and number of biopsy samples on urease test in childhood Helicobacter pylori infection.

To identify the correlation between the number of gastric biopsy samples and the positive rate, we compared the results of urease test using one and three biopsy samples from each 255 children who underwent gastroduodenoscopy at Gyeongsang National University Hospital. The children were divided into three age groups: 0-4, 5-9, and 10-15 yr. The gastric endoscopic biopsies were subjected to the urease test. That is, one and three gastric antral biopsy samples were collected from the same child. The results of urease test were classified into three grades: Grade 0 (no change), 1 (6-24 hr), 2 (1-6 hr), and 3 (<1 hr). The positive rate of urease test was increased by the age with no respect to the number of gastric biopsy samples (one biopsy P = 0.001, three biopsy P < 0.001). The positive rate of the urease test was higher on three biopsy samples as compared with one biopsy sample (P < 0.001). The difference between one and three biopsy samples was higher in the children aged 0-9 yr. Our results indicate that the urease test might be a more accurate diagnostic modality when it is performed on three or more biopsy samples in children.

Relationship between headache and mucosal mast cells in pediatric Helicobacter pylori-negative functional dyspepsia.

BACKGROUND: Although many patients with functional dyspepsia experience headache concurrently with dyspeptic symptoms, studies suggesting mechanisms underlying this phenomenon are limited. Herein, we explore the relationship between gastrointestinal inflammatory cells and presence of headache associated with dyspeptic symptoms in children with HELICOBACTER PYLORI -negative functional dyspepsia. METHODS: Fifty-six patients with H. PYLORI -negative functional dyspepsia underwent upper endoscopy with biopsy to investigate recurrent epigastric pain or discomfort. Patients were divided into two groups according to self-reported presence of headache associated with dyspeptic symptoms. Inflammatory cells including mast cells, and enteroendocrine cells in the gastroduodenal mucosa were evaluated. Associations between headache presence and cellular changes in the gastroduodenal mucosa were examined. RESULTS: Headache was not associated with the grade of lymphocytes, neutrophil infiltration, or enteroendocrine cell density in the gastroduedenal mucosa. However, headache was significantly associated with high mast cell density in the body (27.81 ± 8.71 vs. 20.30 ± 8.16, P < 0.01) and duodenum (23.16 ± 10.40 vs. 14.84 ± 5.88, P < 0.01). CONCLUSIONS: Presence of headache associated with dyspeptic symptoms is strongly related to mucosal mast cell density in pediatric patients with H. PYLORI -negative functional dyspepsia. Thus, our results may help clinicians understand and treat headache during dyspeptic symptoms in such pediatric patients.

Changes in anti-group a rotavirus antibody seroprevalence and levels in the Western Gyeongnam province of Korea over 16 years.

To observe how anti-group A rotavirus antibody seropositivity rates and levels have changed in the western region of Gyeongnam Province, 2,030 serum samples collected at four collection periods (1989-1990, 1994-1995, 1999-2000, and 2004-2005) were tested by Enzyme-Linked Immunosorbent Assay for IgG, and IgA antibodies reacting to recombinant VP6 protein. The seroprevalences exhibit no regular patterns over a 16-yr period. For all four collection periods, the anti-rVP6 IgG levels rose steadily during the first 5 months of life, after which they remained high. However, the 2-9 yr and 10-39 yr groups had significantly higher IgG levels in 1999-2000 and 2004-2005, respectively, than in the other collection periods. The 1-5 mo, 40- ≥ 60 yr, and 4-29 yr groups had significantly higher IgA levels in 1989-1990, 1999-2000, and 2004-2005, respectively. The 4 yr (25.0%), 5-9 yr (18.8%), 10-14 yr (41.1%), 20-29 yr (35.0%), and 30-39 yr (20.0%) groups in 2004-2005 had significant higher IgA seropositivity rate compared to the other three collection periods. These observations suggest that in the western region of Gyeongnam Province since the late 1990s, rotavirus reinfection has occurred more frequently than previously, with all ages being at risk.

Risk factors and neonatal outcomes of pulmonary air leak syndrome in extremely preterm infants: A nationwide descriptive cohort study.

Most extremely preterm infants (EPIs), who were born before 28 weeks of gestation, with pulmonary air leak syndrome (ALS) are symptomatic, often severe, and require drainage. EPIs with severe air leak syndrome (sALS) that require tube drainage or needle aspiration are at high risk of morbidities and mortality. This study aimed to investigate perinatal characteristics, morbidities, and mortality in EPIs with sALS, and to estimate the risk of mortality according to gestational age (GA). A prospective cohort study conducted from 2013 to 2020 compiled the Korean Neonatal Network database to evaluate the incidence, perinatal characteristics, and outcomes of sALS in EPIs born before 28 weeks of gestation. Among 5666 EPIs, the incidence of sALS was 9.4% and inversely related to GA. From this cohort, we compared 532 EPIs with sALS to 1064 EPIs without sALS as controls, matching the subjects by GA and birth weight. Preterm premature rupture of membranes, oligohydramnios, resuscitation after birth, low Apgar scores, repeated surfactant administration, persistent pulmonary hypertension of the newborn, and pulmonary hemorrhage were associated with the development of pneumothorax. The sALS group required a higher fraction of inspired oxygen and more invasive respiratory support at both 28 days of life and 36 weeks of postmenstrual age. The sALS group had a higher incidence of bronchopulmonary dysplasia and major brain injury. The mortality rate was higher in the sALS group than in the control group (55.3% vs 32.5%, P < .001), and the ALS group had a 1.7 times risk of mortality than the control group. More attention should be paid to sALS in EPIs because the frequency of sALS increased as GA decreased, and the risk of mortality was more significant at lower GA.

The Optimal Time for Initiating Probiotics for Preterm and Very-Low-Birth-Weight Infants: A 10-Year Experience in a Single Neonatal Intensive Care Unit.

Purpose: The starting time for probiotic supplementation in preterm infants after birth varies widely. This study aimed to investigate the optimal time for initiating probiotics to reduce adverse outcomes in preterm or very low birth weight (VLBW) infants. Methods: Medical records of preterm infants born at a gestational age (GA) of <32 weeks or VLBW infants in 2011-2020 were reviewed respectively. The infants who received Saccharomyces boulardii probiotics within 7 days of birth were grouped into an early introduction (EI) group, and those who received supplemented probiotics after 7 days of birth were part of the late introduction (LI) group. Clinical characteristics were compared between the two groups and analyzed statistically. Results: A total of 370 infants were included. The mean GA (29.1 weeks vs. 31.2 weeks, p<0.001) and birth weight (1,235.9 g vs. 1491.4 g, p<0.001) were lower in the LI group (n=223) than in the EI group. The multivariate analysis indicated that factors affecting the LI of probiotics were GA at birth (odds ratio [OR], 1.52; p<0.001) and the enteral nutrition start day (OR, 1.47; p<0.001). The late probiotic introduction was associated with a risk of late-onset sepsis (OR, 2.85; p=0.020), delayed full enteral nutrition (OR, 5.44; p<0.001), and extrauterine growth restriction (OR, 1.67; p=0.033) on multivariate analyses after adjusting for GA. Conclusion: Early supplementation of probiotics within a week after birth may reduce adverse outcomes among preterm or VLBW infants.

Can red cell distribution width in very low birth weight infants predict bronchopulmonary dysplasia?

ABSTRACT: Red cell distribution width (RDW) is a useful marker for assessing the severity and prognosis of various diseases in adults. However, whether it is applicable to children, especially in newborns, has not been determined.This study aimed to investigate the RDW values of preterm infants and evaluate whether RDW values in the early days of life can predict bronchopulmonary dysplasia (BPD) development.One hundred and eight infants born at <30 weeks of gestation with a birth weight of <1500 g participated in this retrospective study. RDW values measured at birth, 7 days (D7), and 28 days (D28) after birth were reviewed. The changes in RDW values in the first month of life were analyzed, and we evaluated the relationship between RDW and BPD.The mean RDW values at birth, D7, D28 and the change from birth to D7 were 16.2 ±â€Š0.1%, 17.5 ±â€Š0.2%, 17.6 ±â€Š0.2% and 1.3 ±â€Š1.8%, respectively. RDW at birth was lower in the infants born at <28 weeks' gestational age than in those born at ≥28 weeks' gestational age (15.7 ±â€Š0.3 vs 16.4 ±â€Š0.2, P = .024). RDW values of both groups increased during the first week after birth and did not differ significantly at D7. The levels remained similar at 1 month of age. RDW at birth, D7, and D28 and the changes in RDW from birth to D7 were not correlated with the development of BPD independent of its severity.The usefulness of RDW as a predictor of BPD development remains questionable and requires further study.

Thyroid Dysfunction and the Effect of Iodine-Deficient Parenteral Nutrition in Very Low Birth Weight Infants: A Nationwide Analysis of a Korean Neonatal Network Database.

Background: To investigate the impact of nutritional iodine deficiency on thyroid dysfunction (TD) in very low birth weight (VLBW) infants, we analyzed the association between iodine-deficient parenteral nutrition (PN) and TD requiring L-thyroxine (TD-LT4). Methods: Data of VLBW infants were obtained from the Korean Neonatal Network registry. Factors including duration of PN were analyzed according to TD-LT4. Results: TD-LT4 occurred in 490 (8.7%) of 5635 infants, and more frequently occurred in infants requiring PN for ≥4 weeks (10.2%). PN ≥ 4 weeks was one of the risk factors for TD-LT4, with an odds ratio (OR) of 1.346, p = 0.002. However, multivariate analysis showed that TD-LT4 was more of a risk for infants that were small for gestational age (OR 2.987, p < 0.001) and for other neonatal morbidities such as seizures (OR 1.787, p = 0.002) and persistent pulmonary hypertension (OR 1.501, p = 0.039) than PN ≥ 4 weeks (OR 0.791, p = 0.080). Conclusions: Prolonged iodine-deficient PN might affect TD-LT4 in VLBW infants. However, the effect of nutritional iodine deficiency on TD-LT4 risk was less than that of SGA or severe neonatal morbidities in Korean VLBW infants.

Difference in macrophage migration inhibitory factor between preterm and term newborns and associating clinical factors: Preliminary study.

This study aimed to investigate the macrophage migration inhibitory factor (MIF) and associated clinical factors in neonates. Clinical information and blood samples were obtained from 77 neonates. Clinical details were reviewed from medical records, and MIF was measured by enzyme-linked immunosorbent assay using blood samples acquired within a week after birth. Statistical analyses were performed between plasma MIF concentration and clinical factors. Among the 77 newborn infants, 25 were born at <34 weeks of gestation (preterm), 25 at 34 to 37 weeks (late preterm), and 27 at term gestation. The mean MIF was 9849.5 ± 7187.8 pg/mL in preterm, 5718.7 ± 4596.4 in late preterm, and 5361.1 ± 3895.7 in term infants (P = .016). Among 25 preterm infants born at <34 weeks of gestation, MIF was significantly higher in infants with necrotizing enterocolitis (NEC, 19,478.6 ± 8162.4 pg/mL, n = 5) than that in infants without NEC (feeding intolerance 7173.7 ± 4203.0 pg/mL, n = 12 and others 7844.9 ± 5311.2 pg/mL, n = 8, P = .020). Elevated plasma MIF levels in the transitional period were significantly associated with preterm birth before 34 weeks of gestation and the development of NEC.

aPTT prolongation and skin eruption possibly associated with lamotrigine monotherapy in a paediatric patient.

We report the case of a six-year-old female with childhood absence epilepsy who developed combined aPTT prolongation, not corrected by normal plasma, and atypical skin eruption six months after initiating lamotrigine treatment with dose increment. Two weeks after lamotrigine withdrawal, the skin eruption disappeared and aPTT normalised. To our knowledge, this is the first report of aPTT prolongation possibly due to factor inhibitors associated with lamotrigine monotherapy.

Factors associated with hypoxemia in children infected with pandemic H1N1 2009 influenza virus.

BACKGROUND: Hypoxemia was found to be a major cause of death from pandemic H1N1 2009 influenza (pH1N1) infection. There are limited data on factors associated with hypoxemia in children infected with pH1N1 influenza virus. METHODS: Factors associated with hypoxemia were investigated using univariate and multivariate analysis in 76 hospitalized pediatric patients with laboratory-confirmed H1N1 influenza virus infection at Gyeongsang National University Hospital in Jinju, South Korea, from August 2009 to January 2010 by retrospective chart review. RESULTS: Hypoxemia occurred in 17 children (22%), of whom three were admitted to an intensive care unit and one died. Hypoxemic patients were significantly more likely to have a higher respiratory rate, pulse rate, white blood cell count (WBC), and C-reactive protein level, as well as a longer hospital stay. Respiratory rate and WBC count at admission were independently associated with hypoxemia as determined on multivariate analysis, and this association was found to be clinically significant. CONCLUSION: Although a higher WBC count and respiratory rate may not be specific for pHINI but represent the degree of disease severity for any infectious respiratory disease in general, clinicians can use these parameters at admission as useful, early indicators of disease severity in pediatric pH1N1 infection.

Acinetobacter baumannii isolation in cerebrospinal fluid in a febrile neonate.

We report the isolation of multidrug-resistant Acinetobacter baumannii from the cerebrospinal fluid (CSF) of a neonate suffering from fever and irritability who was initially regarded as aseptic meningitis [CSF analysis: white blood cell (WBC), 14/mm3 (neutrophil 78%); glucose, 41 mg/dl; protein, 52 mg/dl]. The normal range of WBC counts in the CSF is fairly wide, and the symptoms of meningitis are nonspecific in this age group. This patient had several risk factors for Acinetobacter infection, including exposure to antibiotics and previous admission to a neonatal care unit; therefore, it was difficult to judge the import of the isolation of A. baumannii from the CSF in this case. With the increasing prevalence of Acinetobacter species in hospital environments, clinicians may thus be confronted with uncertainty regarding whether isolated A. baumannii is a true pathogen or a contaminant. Thus, clinicians should be familiar with the risk factors for Acinetobacter infection and clinical/laboratory findings of clinically significant CSF Acinetobacter isolates.

Preterm Twins Born to a Mother with Miliary Tuberculosis: Importance of Early Recognition and Prompt Response in Infection Control to Manage Congenital Tuberculosis Exposure in a Neonatal Intensive Care Unit.

Delayed diagnosis of congenital tuberculosis (TB) in the neonatal intensive care unit (NICU) is a serious problem in terms of infection control. Here, we report our preemptive infection control activities implemented after the diagnosis of miliary TB in a mother of preterm twins (index twins, NB1 and NB2) in the NICU. In addition, we reviewed previous case reports of congenital TB exposure in the NICU setting. Immediately after diagnosing miliary TB in the mother, the index twins were isolated before their TB diagnosis and received preemptive anti-TB medication; contact investigations were also conducted. Eventually, NB1 was diagnosed with congenital TB at 29 days of age, and NB2 showed no definite evidence of TB. Through contact investigation, 11 of the 16 exposed infants received isoniazid prophylaxis and no positive tuberculin skin test results were obtained after 3 months. One of the 31 exposed healthcare workers showed new interferon-gamma release assay conversion. Moreover, our case showed a much shorter contagious period compared to that in previous reports (8 versus 17-102 days). This suggests that a high index of suspicion and prompt measures can help prevent congenital TB outbreaks and reduce the burden of infection control activities in the NICU.

Risk Factors and Effects of Severe Late-Onset Hyponatremia on Long-Term Growth of Prematurely Born Infants.

PURPOSE: Sodium is an essential nutritional electrolyte that affects growth. A low serum sodium concentration in healthy premature infants beyond 2 weeks of life is called late-onset hyponatremia (LOH). Here, we investigated the association between LOH severity and growth outcomes in premature infants. METHODS: Medical records of premature infants born at ≤32 weeks of gestation were reviewed. LOH was defined as a serum sodium level <135 mEq/L regardless of sodium replacement after 14 days of life. Cases were divided into two groups, <130 mEq/L (severe) and ≥130 mEq/L (mild). Characteristics and growth parameters were compared between the two groups. RESULTS: A total of 102 premature infants with LOH were included. Gestational age ([GA] 27.7 vs. 29.5 weeks, p<0.001) and birth weight (1.04 vs. 1.34 kg, p<0.001) were significantly lower in the severe group. GA was a risk factor of severe LOH (odds ratio [OR], 1.328, p=0.022), and severe LOH affected the development of bronchopulmonary dysplasia (OR, 2.950, p=0.039) and led to a poor developmental outcome (OR, 9.339, p=0.049). Growth parameters at birth were lower in the severe group, and a lower GA and sepsis negatively affected changes in growth for 3 years after adjustment for time. However, severe LOH was not related to growth changes in premature infants. CONCLUSION: Severe LOH influenced the development of bronchopulmonary dysplasia and developmental outcomes. However, LOH severity did not affect the growth of premature infants beyond the neonatal period.

Dynamic Changes of Fecal Calprotectin and Related Clinical Factors in Neonates.

Objective: Fecal calprotectin (FC) has been widely used for a clinical marker of intestinal inflammation in children and adults. However, the clinical usefulness has not been determined in neonates. The purpose of this study was to investigate the change of FC and associated clinical factors in neonates. Methods and Materials: In total, 146 neonates among 472 admissions to our NICU between 2018 and 2019 were included, and 242 stool samples were collected. FC was measured in the first, second, and third-fourth week after birth, respectively, using commercial ELISA. The clinical characteristics were reviewed from medical records. Statistical analyses were performed to analyze associated factors regarding on changes of fecal calprotectin. Results: A wide range from 5.5 to 6,000 mg/kg of FC was observed in neonates. FCs during neonatal period were not correlated with the gestational age at birth or birth weight. The meconial calprotectin was higher than FCs after 2 weeks of age (n = 134, 418.06 vs. 243.12 in the second week and 259.58 in the third week after birth). Meconial calprotectin was associated with birth weight and meconium stained amniotic fluid. FC during the neonatal period decreased with postnatal week (-464.93 ± 158.02 at third-fourth week after birth compared with the 1st week, P = 0.004) and breast milk (-337.27 ± 150.51 compared with formula milk, P = 0.026). Conclusion: Fecal calprotectin tended to decrease with postnatal week during the neonatal period, and breast milk could affect more decrease of FC.

Neonatal seizures and white matter injury: Role of rotavirus infection and probiotics.

BACKGROUND: Recent reports associate rotavirus infection with neonatal seizures of distinctive white matter injury (WMI) pattern, but evidence is lacking. We examined this association prospectively and analyzed factors related to occurrence of seizures and WMI pattern in neonates with rotavirus infection. METHODS: We prospectively included 228 neonates (≥34 gestational weeks) who were admitted to a regional neonatal intensive care unit between February 2015 and April 2016 and underwent rotavirus antigen testing using stool samples. Patients with neonatal seizures of other etiologies were excluded. RESULTS: Seventy-eight (34.2%) neonates were rotavirus-positive. Otherwise-unexplained seizures were more frequently observed among rotavirus-positive than among rotavirus-negative neonates (20.5% vs. 4.0%, p < 0.001). Rotavirus infection increased the risk of seizures (odds ratio [OR], 6.19; p < 0.001), even after adjustment for confounders (OR, 4.46; p = 0.007). After stratification according to probiotic administration immediately after birth, rotavirus infection remained a significant risk factor only in patients without probiotic medication (OR, 4.83; p = 0.01 vs. OR, 2.44; p = 0.49). The WMI pattern was observed in 9 of 22 neonates with seizures, and this subgroup was characterized by rotavirus infection (100% vs. 53.8%, p = 0.004) and seizure onset on days 4-6 of life (66.7% vs. 15.0%; p = 0.02). G9P[8] was the most common genotype in this subgroup but was also commonly detected in neonates without seizures. CONCLUSION: Rotavirus infection is an independent risk factor for neonatal seizures, and associated with the WMI. Immediate administration of probiotics after birth may reduce rotavirus-associated neonatal seizures.