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Background and aim: A measles outbreak occurred in Greece during 2017–2018 affecting mainly pediatric population. The aim of the study was to describe the epidemiological and clinical characteristics of the cases diagnosed in the major pediatric tertiary hospital of Athens, where 26.5% of national pediatric measles cases were diagnosed and treated. Methods: This is a retrospective study of children 0–16 years old, who presented at the emergency department and/or were hospitalized with clinical presentation compatible with measles and diagnosis was confirmed with molecular detection of the measles RNA in pharyngeal swabs. Epidemiological, clinical and laboratory characteristics were retrieved from medical records and analyzed. Results: A total of 578 children with measles were identified during the study period. 322 (55.7%) were male with median age 36 months (range:1–193), while the largest number of documented cases (251; 43.4%) were children aged 1–5 years. Most children (429/578; 74.2%) belonged to the Roma minority and only 64 (11.1%) had Greek origin. 497 (91.5%) children were unvaccinated and 37 (6.8%) were partially vaccinated with measles vaccine. Hospitalization was required for 342 (59.2%) children, whereas one or more complications were reported in 230 (67.2%) of them. Most frequent complications were elevated transaminases (139; 40.6%), acute otitis media (72; 21%), dehydration (67; 19.6%) and pneumonia (58; 16.9%). 11 children (3.2%) required intensive care admission for altered mental status/status epilepticus (3), sepsis (2) and ARDS (6). 119/342 (34.8%) children were treated with antibiotics because of possible or confirmed bacterial coinfection. One death was reported, concerning an 11-month-old unvaccinated infant, with underlying dystrophy, who died of sepsis. Conclusion: Measles is not an innocent viral infection, as it is still characterized by high morbidity and complications rates. Unvaccinated or partially vaccinated populations could trigger new outbreaks, resulting in significant cost in public health. To avoid future measles outbreaks, high vaccination coverage should be achieved, as well as closing immunity gaps in the population and ensuring high-quality measles surveillance. [ABSTRACT FROM AUTHOR]

The recent economic crisis has been linked with declines in population health. Evidence on the impact of the crisis on stillbirth rates is scarce. The aim of this study was to assess trends of stillbirth rates in Greece during the pre-crisis (2004-2008) and crisis period (2009-2015) and explore risk factors. Nationwide data (n = 1,276,816 births; 5023 stillbirths) were used to assess rates and trends through Poisson and joinpoint regressions. Multivariable Poisson regressions by nationality were fitted. The overall annual stillbirth rate was 3.9/1000 births with higher rates among non-Greeks (5.0/1000) than Greeks (3.7/1000). Non-significant decreasing trends were noted for Greeks (- 0.5%, 95% confidence interval [CI] - 1.4, 0.4%) versus non-significant increasing trends in non-Greeks (1.4%, 95% CI - 0.5, 3.3%). After adjusting for possible confounders, the relative stillbirth risk (RR) increased during the crisis versus the pre-crisis period (RRGreeks 1.61, 95% CI 1.50, 1.74; RRnon-Greeks 1.92, 95% CI 1.64, 2.26). Multiplicity, birth order, birth size, maternal education, marital status, and parental age were risk factors.Conclusions: Bidirectional stillbirth trends were observed among Greeks and non-Greeks, whereas the RR increased by 2-fold during the crisis. Persisting disparities require tailored employment of preventive measures ensuring optimal quality of the child's and maternal health.What is Known:• Stillbirth rate is a key population health indicator reflecting economic development and health care services within a population.• The recent economic crisis has been linked with declines in population health.What is New:• Economic crisis, ethnic minorities, and several modifiable factors seem to be significant determinants of stillbirth risk. [ABSTRACT FROM AUTHOR]

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder, associated with inactivating mutations of the calcium-sensing receptor (CaSR). To evaluate the functional significance of a CaSR mutation, identified in a young infant who presented with hypercalcemia and hypocalciuria. The CaSR gene coding sequences were analyzed by polymerase chain reaction amplification and direct sequencing analysis. The mutation identified was introduced by site-directed mutagenesis into a wild-type (WT) CaSR plasmid, and human embryonic kidney 293 T cells were transfected with either the WT or mutant CaSR. The function of the mutated CaSR protein was analyzed by evaluating the free intracellular calcium [(Ca2+)i] response after challenge with extracellular calcium (Ca2+). We identified a heterozygous mutation c.772_773delGTinsA in exon 4 resulting in the substitution of amino acid valine (Val) with amino acid arginine (Arg) and the premature pause of the translation 46 amino acids later (Val258ArgfsTer47). Functional assay showed that cells transfected with the mutant CaSR had a significantly poorer response to extracellular Ca2+ stimulation compared with the WT. We have shown that the c.772_773delGTinsA mutation causes a significant alteration of CaSR function leading to features of FHH in an affected young infant since the first months of life. [ABSTRACT FROM AUTHOR]

Background. Only a few studies have been conducted with the objective of creating norms of the Alberta Infant Motor Scale (AIMS) for the assessment of gross motor development of preterm infants. The AIMS performance of preterm infants has been compared with that of the Canadian norms of full-term infants, but not with that of full-term infants of the same nationality. Moreover, the possible impact of prematurity-related morbidity factors on AIMS performance is unknown. Objectives. The aims of this study were: (1) to evaluate AIMS trajectory in a large population of Greek preterm infants and create norms, (2) to compare it with the AIMS trajectory of Greek full-term infants, and (3) to examine the possible influence of neonatal morbidity on AIMS scores in the preterm sample. Design. This was a cross-sectional study. Methods. Mean AIMS scores were compared, per month (1-19), between 403 preterm infants (≤32 weeks of age, corrected for prematurity) and 1,038 full-term infants. In preterm infants, the association of AIMS scores with respirator)' distress syndrome (RDS), intraventricular hemorrhage (IVH) of grade ≤III, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and sepsis was assessed by hierarchical regression analysis. Results. Alberta Infant Motor Scale scores were significantly lower in preterm infants than in full-term infants. Mean AIMS scores in preterm infants were significantly associated with RDS (b= -1.93; 95% CI= -2.70, -1.16), IVH (b=-0.97; 95% CI=-1.69, -0.25), and ROP (b= -1.12; 95% CI= -1.99, -0.24) but not with BPD or sepsis in hierarchical regression analysis. Conclusions. Alberta Infant Motor Scale norms were created for Greek preterm infants. This study confirms that AIMS trajectories of preterm infants are below those of full-term infants of the same nationality. The influence of morbidity factors, including RDS, IVH, and ROP, should be taken into account when administering the AIMS in preterm infants. [ABSTRACT FROM AUTHOR]

Hb Agrinio [α29(B10)Leu→Pro] is a highly unstable variant, classified as a nondeletional α-thalassemia (α-thal) mutation. To date it has only been described in individuals of Greek and Cypriot origin. Evaluation of the phenotypic presentation of 12 Hb Agrinio homozygotes or compound heterozygotes, diagnosed in a single center in Greece during a 15-year period, found a wide clinical expression, ranging from thalassemia intermedia (with or without transfusion requirement) to Hb H hydrops fetalis, with some phenotype-to-genotype correlation. The often severe clinical presentation of Hb Agrinio homozygotes or Hb Agrinio compound heterozygotes, coinheriting severe α-thal determinants, indicates that molecular identification of carriers of the Hb Agrinio mutation should be considered within the context of screening programs involving individuals of Greek and Cypriot origin. Selective molecular investigation of candidate carriers is facilitated by the observation that all heterozygotes for the Hb Agrinio mutation present with at least one hematological parameter implicating an α-thal carrier state. [ABSTRACT FROM AUTHOR]

Early-term birth (37+0 to 38+6 gestational weeks) may have a negative impact on infants' neurodevelopment compared to delivery at 39 weeks or beyond. The purpose of this study was to evaluate the gross motor development of early-term infants using the Alberta Infant Motor Scale (AIMS). A total of 1087 healthy infants (559 early-term and 528 full-term infants born at 39+0 to 41+6 weeks of gestation) were studied. Mean AIMS scores were compared between the two groups at monthly intervals. The impact of gestational age on total AIMS scores was assessed by linear regression, after adjustment for chronological age, sex and SGA. Mean total AIMS scores, albeit within normal range, were significantly lower in early-term than full-term infants at the 2nd, 6th, 7th, 8th and 12th month of age; differences between groups were within three points. In multivariate regression analysis, a longer gestation by one week had a positive impact on total AIMS score during the first year of life (β = 0.90; 95% CI 0.45, 1.35). In conclusion, early-term infants exhibit worse gross motor performance during the first year of life in comparison with their full-term peers; however, the differences between the two groups are small. [ABSTRACT FROM AUTHOR]

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and -resource intervention to reduce antibiotic use in Greek NICUs implementing a "low-hanging fruit" approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016–06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase (p = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend (p = 0.002); a monthly decrease rate of 28.96 DOT/1000 patient-days (p = 0.001, 95%CI [−45.33, −12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a "low-hanging fruit" approach. In resource-limited settings, similar targeted stewardship interventions can be applied. [ABSTRACT FROM AUTHOR]

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0–16 years) with suspected meningitis–encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray® ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1–60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (n = 45/50), pharyngeal swabs (n = 15/29) and stools (n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates. [ABSTRACT FROM AUTHOR]

Abstract: Young infants are at increased risk for influenza-associated serious illness, onset of complications, utilization of health-care services, and hospitalization. We investigated the feasibility and acceptance of an influenza vaccination (cocooning) strategy by household contacts implemented in a maternity hospital and the neonatal unit of a pediatric hospital in Athens. A total of 224 mothers (mean age: 30.2 years) who gave birth to 242 neonates were studied. Of them, 165 (73.7%) mothers were vaccinated. Multiple logistic regression revealed that statistically significant factors associated with increased vaccination rates among mothers were: being of Roma origin (p-value=0.002), being an immigrant (p-value=0.025), giving birth to a neonate with birth weight <2500g (p-value=0.012), and residing in a family with ≥4 family members (p-value=0.017). Of the 224 fathers, 125 (55.8%) received the influenza vaccine. Fathers of neonates whose mothers were vaccinated had 6-fold higher vaccination rates compared to fathers of neonates whose mothers refused vaccination (p-value<0.001). Overall, influenza vaccine was administered to 348 (46.9%) of a total of 742 household contacts of the 242 neonates. Upon entering the 2011–2012 influenza season, 51 (22.7%) of 224 families had all household contacts vaccinated against influenza (complete cocoon). Among parents, the statement “I do not want to receive the vaccine” was the prevalent reason for declining influenza vaccination, followed by the misconception “I am not at risk for contacting influenza” (41.1% and 38.2%, respectively). [Copyright &y& Elsevier]

The COVID-19 pandemic modified the epidemiology and the transmission of respiratory syncytial virus (RSV). We collected data on RSV positivity and incidence from children hospitalized in the largest tertiary paediatric hospital in Greece before (2018-2020, period A), during (2020-2021, period B), and after (2021-2023, period C) the COVID-19 lockdown. A total of 9,508 children were tested for RSV. RSV positivity (%) was 17.6% (552/3,134) for period A, 2.1% (13/629) for period B, and 13.4% (772/5,745) for period C (p < 0.001). The mean age (±SD) of RSV-positive children among the three periods was A: 5.9(±9.3), B: 13.6 (±25.3), and C: 16.7 (±28.6) months (p < 0.001). The peak of RSV epidemiology was shifted from January-March (period A) to October-December (period C). RSV in-hospital incidence per 1,000 hospitalizations in paediatric departments was A:16.7, B:1.0, and C:28.1 (p < 0.001), and the incidence in the intensive care unit was A: 17.3, B: 0.6, and C: 26.6 (p < 0.001). A decrease in RSV incidence was observed during the COVID-19 lockdown period, whereas a significant increase was observed after the lockdown. A change in epidemiological patterns was identified after the end of the lockdown, with an earlier seasonal peak and an age shift of increased RSV incidence in older children.

The aim of the study was to evaluate the impact of the use of BioFire® FilmArray® meningitis/encephalitis(FA-ME) panel which enables rapid automated CSF testing for 14 common viral, bacterial, and yeast pathogens that cause CNS infections, in the management of children with suspected CNS infection. A prospective cohort study was performed on children admitted to a tertiary pediatric hospital, over a period of 1 year, with possible CNS infection and CSF pleocytosis (> 15 cells/mm 3 ). Children were randomized 1:1, either to use FA-ME or separate molecular CSF microbiological tests according to usual pediatric practice in the hospital. Length of hospital stay, duration of antimicrobials, and total cost of hospitalization were compared between groups. A total of 142 children were included in the study (71 cases). A pathogen was detected in 37/71(52.1%) children with the use of FA-ME and in 16/71(22.5%) in the control group (P value < 0.001). In aseptic meningitis cases a virus was detected in 27/61(44.2%) and in 11/66(16.7%) controls (P value < 0.001). Median (IQR) length of stay in cases and controls with aseptic meningitis was 5(4-8) and 8(6-10) days, respectively (P value < 0. 001). The median (IQR) duration of antimicrobials in cases and controls was 4(2-5.7) and 7(5-10) days, respectively (P value < 0.001). The hospitalization cost was calculated in cases and controls 1042€ (932-1372) and 1522€ (1302-1742), respectively (P value < 0.001). The use of FA-ME was able to reduce significantly the use of antimicrobials, the hospitalization days, and the total cost comparing to the control group in children with suspected CNS infection.

Aim: To validate the Greek version of Kennerley and Gath's Blues Questionnaire (BQ) and gather further knowledge on maternity blues (MB) associations with certain clinical and sociodemographic factors in Greek population. Material and methods: 116 postpartum women, who met the inclusion criteria, completed the Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the third day after delivery. Sociodemographic and clinical data were also collected. Results: Fifty women (43.1%) experienced severe MB on the third day postpartum. Lower number of previous births, fewer years of marriage, and husband's occupation were found to be associated with MB occurrence. Of them, years of marriage (odds 0.21, p  = .001) and husband's occupation in private sector (odds 1.21, p  = .04) were independent predictors of MB in logistic regression analysis. Cronbach's α for the total 28-item Greek version of BQ was 0.85. Cluster analysis in our data showed that the optimal number of clusters of BQ items was 4; these four clusters of items presented similarities with the Bartholomew and Horowitz's four-category model of attachment styles (avoidant - dismissing, preoccupied, secure, avoidant - fearful). Conclusions: The Greek version of Blues Questionnaire is a reliable tool for the detection and measurement of MB. Fewer years of marriage and the economic insecurity seem to have strong impact on the occurrence of MB. Further investigation is needed to evaluate whether the phenomenon of MB is associated with parental or mother-to-infant bonding disorders.

Objective: To study trends of infant mortality rate (IMR) and neonatal mortality rate in Greece during the period 2004-2016 and explore the role of sociodemographic factors in the years of crisis., Design: Nationwide individual data for live births and infant (0-11 months) deaths provided by the Hellenic Statistical Authority were examined using Poisson, joinpoint regression and interrupted time series (ITS) analyses., Setting: Greece., Participants: All infant deaths (n=4862) over the 13-year period, of which 87.2% were born to Greek mothers, and respective live births., Main Outcome Measures: Evolution of IMR (0-364 days), early (<7 days) neonatal mortality rate (ENMR), late (7-27 days) neonatal mortality rate (LNMR) and post neonatal (28-364 days) mortality rate (PNMR) trends, by maternal nationality, place of residence and Human Development Index (HDI)., Results: By Poisson regression, overall, during the study period, among infants of Greek mothers, IMR and PNMR declined significantly (-0.9%; 95% CI -1.7% to -0.1% and -1.6%; -3.0% to -0.2% annually, respectively), although differentially by place of residence (IMR urban : -2.1%; -2.9% to -1.3%, IMR rural : +10.6%; 7.6% to 13.6%). By contrast, among infants of non-Greek mothers, the low starting IMR/ENMR/LNMR/PNMR increased significantly (max ENMR:+12.5%; 8.6% to 16.5%) leading to a non-significant time-trend pattern overall in Greece. The inverse associations of HDI with IMR, ENMR and PNMR were restricted to Greek mothers' infants. Joinpoint regression analyses among Greek mothers' infants indicated non-significant increasing trends of IMR and ENMR following the crisis (+9.3%, 2012-2016, p=0.07 and +10.2%, 2011-2016, p=0.06, respectively). By contrast, the high (+17.1%; 8.1% to 26.9%, p=0.002) IMR increases among non-Greek infants were restricted to 2004-2011 and equalised to those of Greek mothers' infants thereafter. ITS analyses in preset years (2008, 2010, 2012) identified significantly increasing trends in IMR, LNMR and PNMR after 2012, and in ENMR after 2010, among Greek mothers' infants., Conclusions: HDI and rural residence were significantly associated with IMR. The strongly decreasing IMR trends among Greek-mothers' infants were stagnated after a lag time of ~4 years of crisis approximating the previously sharply increasing trends among non-Greeks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Rotavirus (RV) infection in neonatal age can be mild or even asymptomatic. Several studies have reported that RV is responsible for 31%-87% of pediatric nosocomial diarrhea and causes gastroenteritis outbreaks in pediatric and neonatal units., Objectives: Study clinical characteristics, genotypes and risk factors of RV infection in neonatal age., Methods: A prospective study was conducted from April 2009 till April 2013 in the neonatal special care unit of the largest tertiary pediatric hospital of Greece. Fecal samples and epidemiological data were collected from each neonate with gastrointestinal symptoms. RV antigen was detected with a rapid immunochromatography test. RV positive samples were further genotyped with RT PCR and sequencing using specific VP7 and VP4 primers., Results: Positive for RV were 126/415 samples (30.4%). Mean age of onset was 18 days. Seventy four cases (58%) were hospital acquired. Seasonality of RV infection did not differ significantly throughout the year with the exception of 4 outbreaks. Genotypes found during the study period were G4P[8] (58.7%), G1P[8] (14.7%), G12P[8] (9.3%), G3P[8] (9.3%), G12P[6] (5.3%), G9P[8] (1.3%) and G2P[4] (1.3%). RV cases presented with: diarrhea (81%), vomiting (26.2%), fever (34.9%), dehydration (28.6%), feeding intolerance (39.7%), weight loss (54%), whilst 19% of cases were asymptomatic. Comparing community with hospital acquired cases differences in clinical manifestations were found., Conclusions: Significant incidence of nosocomially transmitted RV infection in neonatal age including asymptomatic illness exists. Genotypes causing nosocomial outbreaks are not different from community strains. Circulating vaccines can be effective in prevention of nosocomial RV infection through herd immunity.

Objective: The aims of this study were to investigate gross motor development in Greek infants and establish AIMS percentile curves and to examine possible association of AIMS scores with socioeconomic parameters., Methods: Mean AIMS scores of 1068 healthy Greek full-term infants were compared at monthly age level with the respective mean scores of the Canadian normative sample. In a subgroup of 345 study participants, parents provided, via interview, information about family socioeconomic status. Multiple linear regression analysis was performed to evaluate the relationship of infant motor development with socioeconomic parameters., Results: Mean AIMS scores did not differ significantly between Greek and Canadian infants in any of the 19 monthly levels of age. In multiple linear regression analysis, the educational level of the mother and also whether the infant was being raised by grandparents/babysitter were significantly associated with gross motor development (p=0.02 and p<0.001, respectively), whereas there was no significant correlation of mean AIMS scores with gender, birth order, maternal age, paternal educational level and family monthly income., Conclusions: Gross motor development of healthy Greek full-term infants, assessed by AIMS during the first 19months of age, follows a similar course to that of the original Canadian sample. Specific socioeconomic factors are associated with the infants' motor development., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Influenza is associated with an increased risk for serious illness, hospitalization, and mortality in infants aged <6 months. However, influenza vaccines are not licensed for administration in this age group. The study evaluated the effectiveness of postpartum influenza vaccination of mothers and household members in infants., Methods: The influenza vaccine was offered to mothers and household members of neonates born or hospitalized in 3 hospitals prior to the 2012-2013 season. Mothers were contacted every 2 weeks during the influenza season, and data regarding the onset of fever and/or respiratory symptoms in infants, healthcare seeking, hospitalization, and administration of antibiotics were collected., Results: The study group consisted of 553 mothers who delivered 573 neonates. The influenza vaccine was administered to 841 of 1844 (45.6%) household contacts. Vaccination coverage rates ranged between 41.9% for neonates siblings and 49% for mothers. Five hundred thirty infants were analyzed for vaccine effectiveness. For outcomes in the infant, postpartum maternal vaccination had 37.7% effectiveness against acute respiratory illness (ARI), 50.3% against a febrile episode, 53.5% against influenza-like illness (ILI), 41.8% against related healthcare seeking, and 45.4% against administration of antibiotics. Multiple logistic regression analyses showed that maternal influenza vaccination was significantly associated with a decreased probability for febrile episodes, ARIs, and/or ILIs in infants, related healthcare seeking, and/or administration of antibiotics during the influenza season. Vaccination of other household contacts had no impact., Conclusions: Maternal postpartum vaccination against influenza was associated with a significant reduction of influenza-related morbidity, healthcare seeking, and antibiotic prescription in infants during the influenza season.