Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study.

Background: The first phase of the GAIL study ("Girls treated with an Aromatase Inhibitor and Leuprorelin," ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm). Objectives and hypotheses: In the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH. Methods: We measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 (n = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 (n = 10) and group B (n = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH. Results: AH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH-PAH group A1, +3.85 cm (+0.62 SDS, p = 0.01); group A2, +1.6 cm (+0.26 SDS, p = 0.26); and group B, +1.7 cm (+0.3 SDS, p = 0.08). The gain in group A1 was significantly greater than that in group A2 (p = 0.04) and in group B (p = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1. Conclusions: In early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.

SARS-CoV-2 seroprevalence among children in Greece during Omicron variant period.

The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. This study aims to evaluate SARS-CoV-2 seroprevalence in children during the different variants' subperiods. A prospective multicenter seroprevalence study was conducted in 7 University public hospitals in Greece from November 2021 to August 2022 (3 subperiods: November 2021-February 2022, March 2022-May 2022, June 2022-August 2022). Children from different age groups, admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 were enrolled. Neutralizing antibodies (Nabs), anti-Spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 IgG in serum were evaluated. A total of 2127 children (males:57,2%; median age:4,8years) were enrolled. Anti-N IgG seropositivity increased from 17,8% in the first sub-period to 40,7% in the second sub-period and then decreased in the third sub-period (36,7%). Anti-S IgG seropositivity appeared to have an increasing trend over the study period, starting from 34,8% and reaching 80,7%. Children aged 1-4 years old have significantly higher anti-N IgG titers compared to children aged 0-1 years old (p < 0,001). Infants have significantly lower anti-S IgG titers compared to all other age groups (p < 0,001). Immunocompromised children and infants have the lowest seropositivity for NAbs.Conclusions During the Omicron period, seropositivity significantly increased, as a result of higher transmissibility. Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1-4 years old present higher antibody titers, suggesting that this age group may mount a higher antibody response. Continuous surveillance seroprevalence studies are needed in children, in order to identify the true extent of SARS-CoV-2 and guide the planning of adequate public health measures.

WHAT IS KNOWN: • Seroprevalence surveys among children may be extremely useful, in order to properly monitor the immunity, either natural or acquired, through the quantification of IgG antibodies and to plan further immunization policies. • There are variations in the seroprevalence of COVID-19 between the different periods, according to the vaccination rates, the type of circulating variant and the transmissibility of the virus. • The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. WHAT IS NEW: • In this large multicenter seroepidemiological study, SARS-CoV-2 seroprevalence rate in children is higher during the Omicron period in comparison to the previous pandemic waves, due to the high transmissibility of the virus and the increased rates of reinfection. • Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1­4 years old present higher antibody titers, indicating that the children of this age group mount a higher antibody response. • This study provides essential information about immunity and the level of protection in the pediatric population, as neutralizing antibodies were evaluated, in addition to the anti-N and anti-S IgG antibodies.

Multisystem inflammatory syndrome in children (MIS-C): A nationwide collaborative study in the Greek population.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition that may occur following SARS-CoV-2 infection. This retrospective, descriptive study of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) in 12 tertiary care centers from 3/11/2020 to 12/31/2021. Demographics, clinical and laboratory characteristics, treatment and outcomes are described. Among 145 patients (95 males, median age 8.2 years) included, 123 met the WHO criteria for MIS-C, while 112 (77%) had serological evidence of SARS-CoV-2 infection. Fever was present in 99%, gastrointestinal symptoms in 77%, mucocutaneous involvement in 68% and respiratory symptoms in 28%. Fifty-five patients (38%) developed myocarditis, 29 (20%) pericarditis and 19 (13%) coronary aneurysms. Among the above cases 11/55 (20%), 1/29 (3.4%) and 5/19 (26.3%), respectively, cardiac complications had not fully resolved at discharge. Underlying comorbidities were reported in 18%. Median CRP value was 155 mg/l, ferritin 535 ng/ml, PCT 1.6 ng/ml and WBC 14.2 × 109/mm3. Most patients had elevated troponin (41.3%) and/or NT-pro-BNP (49.6%). Intravenous immunoglobulin plus corticosteroids were used in 117/145 (80.6%), monotherapy with IVIG alone in 13/145 (8.9%) and with corticosteroids alone in 2/145 (1.3%). Anti-IL1 treatment was added in 15 patients (10.3%). Thirty-three patients (23%) were admitted to the PICU, 14% developed shock and 1 required ECMO. Mortality rate was 0.68%. The incidence of MIS-C was estimated at 0.69/1000 SARS-CoV-2 infections. Patients who presented with shock had higher levels of NT-pro-BNP compared to those who did not (p < 0.001). Acute kidney injury and/or myocarditis were associated with higher risk of developing shock. CONCLUSION: MIS-C is a novel, infrequent but serious disease entity. Cardiac manifestations included myocarditis and pericarditis, which resolved in most patients before discharge. Timely initiation of immunomodulatory therapy was shown to be effective. NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. Further research is required to elucidate the pathogenesis, risk factors and optimal management, and long-term outcomes of this clinical entity. WHAT IS KNOWN: • MIS-C is an infrequent but serious disease entity. • Patients with MIS-C present with multi-organ dysfunction, primarily involving the gastrointestinal and cardiovascular systems. WHAT IS NEW: • NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. • Acute kidney injury and/or myocarditis were associated with higher risk of developing shock.

Knowledge and attitudes of medical students about clinical aspects of congenital cytomegalovirus infection in newborns: A nationwide cross-sectional study in Greece.

Introduction: Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide causing severe morbidity in newborns, infants, and children. Despite the clinical importance of congenital CMV (cCMV) infection, studies conducted so far indicate that there is limited awareness in the medical community in the field. The aim of this study was to assess Greek medical students' knowledge on cCMV infection. Methods: We performed a questionnaire-based nationwide cross-sectional study. A convenience sample of medical students from seven medical schools was enrolled. Results: Of the 562 respondents, 54,8% considered themselves undereducated on cCMV infection. However, almost half of the participants could correctly recognize some basic principles of cCMV infection including ways of transmission, diagnosis and treatment, while there were aspects of cCMV infection with knowledge deficit. The year of study had a positive impact on the level of knowledge with students of higher years of study being of more sufficient education on the specific topic. Conclusion: Overall, our study indicates a discrepancy between self-reported awareness and the level of knowledge among medical students in Greece. Further educational opportunities about cCMV should be offered, particularly in areas of the curriculum involving the care of women and children. Establishing medical students' solid background on the disease burden and educating them about preventative strategies for at-risk populations, should be the main pillars of such efforts in order to promote confidence in managing these cases in their future professional careers.

Extrauterine Growth Restriction and Optimal Growth of Very Preterm Neonates: State of the Art.

Over the last few decades, there has been an ongoing debate over both the optimal feeding mode for very premature neonates (VPN) as well as what their optimal growth should be. Despite the American Academy of Pediatric declaring since 1997 that the growth of VPN should follow the trajectory of intrauterine fetal growth, differences of opinion persist, feeding policies keep changing, and the growth and development of VPN remains extremely variable not only between countries, but even between neighboring neonatal units. Even the appropriate terminology to express poor postnatal growth (extrauterine growth restriction (EGR) and postnatal growth failure (PGF)) remains a subject of ongoing discussion. A number of recent publications have shown that by implementing breast milk fortification and closely following growth and adjusting nutrition accordingly, as per the consensus guidelines of the major Neonatal Societies, we could achieve growth that closely follows birth centiles. A recent position paper from EPSGAN recommending targeted nutritional support to cover the energy and protein deficits sustained by VPN during periods of critical illness further strengthens the above findings. Conclusion: We can promote better growth of VPN by ensuring a stable administration of sufficient calories and protein, especially in the first 2 weeks of life, implementing breast milk fortification, covering energy and protein deficits due to critical illness, and increasing feeding volumes as per the latest guidelines. The adoption of universal protocol for nutrition and growth of VPN is essential and will enable better monitoring of long-term outcomes for this population.

HPV-Based Self-Sampling in Cervical Cancer Screening: An Updated Review of the Current Evidence in the Literature.

Identifying and reaching women at higher risk for cervical cancer is all-important for achieving the ambitious endpoints set in 2020 by the WHO for global cervical cancer control by 2030. HPV-based (vaginal) self-sampling (SS) represents a cost-effective screening strategy, which has been successfully implemented during the last decade both in affluent and constrained settings. Among other advantages, SS strategies offer convenience, diminished costs, flexibility to obtain a sample in the office or home, avoiding a pelvic exam and uncomfortable appointment with a healthcare professional, as well as social and cultural acceptability. SS implementation has been globally boosted during the COVID-19 pandemic. In pragmatic terms, social distancing, local lockdowns, discontinuation of clinics and reallocation of human and financial resources challenged established clinician-based screening; self-collection strategies apparently surpassed most obstacles, representing a viable and flexible alternative. With time, sufficient reassuring data has accumulated regarding specially designed SS devices, aspects of sample preparation, transport and storage and, importantly, optimization of validated PCR-based HPV testing platforms for self-collected specimens. Suboptimal rates of clinical follow-up post-SS screening, as well as overtreatment with reliance solely on molecular assays, have both been documented and remain concerning. Therefore, effective strategies are still required to ensure linkage to follow-up testing and management following positive SS results by trained health professionals with knowledge of HPV biology and management algorithms. Because of the prolonged SS screening intervals, implementation data are limited regarding subsequent screening rounds of SS-screened individuals; however, these are accumulating gradually. With further refinement of assays and validation of novel biomarkers in self-collected samples, there is a clear potential for increasing SS accuracy and PPV. The potential differentiation of self-collection protocols for vaccinated versus non-vaccinated individuals also represents an open issue. In conclusion, HPV-based self-collection techniques can effectively address limited uptake alongside other conventional cervical screening drawbacks; however, assays, logistics and infrastructures need further optimization to increase the efficacy, effectiveness and cost-effectiveness of SS approaches.

Polydactyly: Clinical and molecular manifestations.

Polydactyly is a malformation during the development of the human limb, which is characterized by the presence of more than the normal number of fingers or toes. It is considered to be one of the most common inherited hand disorders. It can be divided into two major groups: Non-syndromic polydactyly or syndromic polydactyly. According to the anatomical location of the duplicated digits, polydactyly can be generally subdivided into pre-, post-axial, and mesoaxial forms. Non-syndromic polydactyly is often inherited with an autosomal dominant trait and defects during the procedure of anterior-posterior patterning of limb development are incriminated for the final phenotype of the malformation. There are several forms of polydactyly, including hand and foot extra digit manifestations. The deformity affects upper limbs with a higher frequency than the lower, and the left foot is more often involved than the right. The treatment is always surgical. Since the clinical presentation is highly diverse, the treatment combines single or multiple surgical operations, depending on the type of polydactyly. The research attention that congenital limb deformities have recently attracted has resulted in broadening the list of isolated gene mutations associated with the disorders. Next generation sequencing technologies have contributed to the correlation of phenotype and genetic profile of the multiple polydactyly manifestations and have helped in early diagnosis and screening of most non-syndromic and syndromic disorders.

Decreasing Incidence of the Multisystem Inflammatory Syndrome in Children Over 3 Pandemic Waves.

In this nationwide retrospective study, a substantial decline in the incidence of multisystem inflammatory syndrome in children over 3 successive pandemic waves characterized by different severe acute respiratory syndrome coronavirus 2 variants was documented-from 3.4 of 1000 to 1.1 of 1000 and finally to 0.25 of 1000 confirmed severe acute respiratory syndrome coronavirus 2 positive cases (P < 0.0001), respectively, whereas clinical findings and severity did not significantly vary.

Seroprevalence of anti-SARS-CoV-2 antibodies among children and their parents in Greece.

School closures were enforced as measures to restrain the COVID-19 pandemic, based on the assumption that young children may play a key role in SARS-CoV-2 spread. This study aims to determine the prevalence of SARS-CoV-2 IgG antibodies in children and corresponding parents, in order to improve surveillance and estimate the prevalence of asymptomatic or subclinical COVID-19 cases. A prospective multicenter study was conducted between March and June 2021 in Greece. Children admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 and their parents were tested for anti-Spike SARS-CoV-2 IgG in serum. A questionnaire about clinical and demographic data was completed. The study included 823 participants: 427 children and 396 corresponding parents. The overall seroprevalence was 16.4% in parents and 13.8% in children. Among families with ≥ 1 seropositive child or parent, the combination of a seropositive parent and a corresponding seronegative child was 29.6%, a seronegative parent and a corresponding seropositive child was 24.7%, and a seropositive child with a corresponding seropositive parent was 45.7%. Age, level of education, and school or work attendance were not significantly associated with increased seropositivity. On the contrary, ethnic minority of Roma, close contact with known COVID-19 case, previous symptoms consistent with COVID-19, and mass gatherings were risk factors for seropositivity. CONCLUSION: The spread of SARS-CoV-2 during a period of lockdown in Greece was low in children and comparable to adults most likely due to intrafamilial transmission. Accordingly, it is unlikely that children have boosted virus transmission. WHAT IS KNOWN: • In the earliest months of the pandemic, it was demonstrated that children had significantly lower seroprevalence rates than the older age groups, due to the fact that children had decreased exposure to the virus, because of early public health interventions, such as school and day care closure. • Later, further studies reported that children have similar incidence rate of SARS-CoV-2 infection compared to adults in households and community settings. WHAT IS NEW: • In this seroprevalence study, the spread of SARS-CoV-2 infection during a period of lockdown in Greece with the predominance of the Alpha-variant was particularly low in children and comparable to adults, most likely due to intrafamilial transmission. • These study findings will be useful for decisions regarding non-pharmaceutical interventions during the pandemic, and especially, to guide in designing and implementing appropriate containment measures for schools and social gatherings.

Drug allergy evaluation in children with suspected mild antibiotic allergy.

Background: Adverse antibiotic reactions caused by an immunological mechanism are known as allergic reactions. The percentage of reported antibiotic allergies is likely to differ from the one validated after a drug provocation test (DPT) with the culprit antibiotic. This study aimed to compare the percentage of children who were thought to be allergic to a certain antibiotic with those who have a true allergy, as confirmed by DPTs. We also validated Skin Prick Tests (SPTs) and Intradermal Tests (IDTs) by assessing their sensitivity and specificity, in diagnosing antibiotic allergies using DPT as the gold standard. Furthermore, we investigated epidemiological risk factors such as personal and family history of atopic disease and eosinophilia. Methods: Children with a history of possible allergic reaction to an antibiotic underwent a diagnostic procedure that included: (1) Eosinophil blood count, (2) SPTs, (3) IDTs and (4) DPTs. The parameters were compared with Pearson's Chi-Square and Fisher's Exact Test. Several risk factors that were found significant in univariate analysis, such as personal and family history of atopic disease, and positive SPTs and IDTs were examined with multiple logistic regression analysis to see if they were related to a higher risk for a positive DPT. Results: Semi-synthetic penicillin was the most common group of antibiotics thought to cause allergic reactions in this study. Overall, 123 children with a personal history of an adverse reaction to a certain antibiotic, were evaluated. In 87.8% of the cases, the symptoms had occurred several hours after administration of the culprit antibiotic. Both SPTs and IDTs had low sensitivity but high specificity. Moreover, they had a high positive predictive value (PPV). In contrast, eosinophilia was not recognized as a risk factor. Seventeen patients (13.8%) had a true antibiotic allergy, as confirmed by a positive DPT. A positive IDT was a strong predictor of a positive DPT, along with a positive personal and family history of atopy. Conclusion: SPTs and IDTs are very reliable in confirming antibiotic allergy when found positive. A negative result of a SPT highly predicts a negative DPT. A positive IDT and a positive personal and family history of atopy were recognized as significant risk factors for antibiotic allergy.

Genetics of congenital anomalies of the hand.

Congenital anomalies of the hand are malformations occurring during the development of the human limb, and present as isolated disorders or as a part of a syndrome. During the last years, molecular analysis techniques have offered increasing knowledge about the molecular basis of hand malformations. Disturbances in the signaling pathways during the development of the upper limb result in malformations of the upper extremity. At present, several genes have been identified as responsible for hand anomalies and other have been recognized as suspect genes related to them. Different and new high throughput methods have been introduced for the identification of the gene mutations. In the current editorial, we summarize concisely the current molecular status of isolated hand genetic disorders and the recent progress in molecular genetics, including the genes related to the disorder. This progress improves the knowledge of these disorders and has implications on genetic counselling and prenatal diagnosis.

Scleral buckling surgery for stage 4A and 4B retinopathy of prematurity in critically ill neonates.

PURPOSE: To determine the efficacy of scleral buckling in eyes with stage 4A and 4B retinopathy of prematurity (ROP). METHODS: Seven eyes of five premature infants underwent scleral buckling for stage 4 ROP in zone II. Five eyes had stage 4A ROP, and two eyes had stage 4B ROP. Six eyes had previous diode laser photocoagulation, and one eye had received an intravitreal ranibizumab injection. Scleral buckling was the procedure of choice due to lack of access to specialized pediatric vitrectomy instrumentation. Average age at surgery was 3.4 months. Postoperative anatomic retinal status, visual acuity outcome and refractive error were assessed. RESULTS: The scleral buckle was removed on average 8 months after surgery. Retinal reattachment was achieved in all seven eyes. At final follow-up one eye had macular ectopia and disc dragging, one eye had a macular traction fold and two eyes had optic disc pallor. Average myopic error after buckle removal was -7.5 D. CONCLUSION: Scleral buckling can be performed safely and effectively in 4A and 4B stage ROP in critically ill infants, when access to specialized pediatric vitrectomy instrumentation is limited. This surgical technique may provide adequate relief of vitreoretinal traction with improved visual potential.

Kinematic and Temporospatial Changes in Children with Cerebral Palsy during the Initial Stages of Gait Development.

PURPOSE: To identify changes in the gait kinematics and temporospatial parameters of children with bilateral Cerebral Palsy (CP) at 8 months after the onset of independent walking and identify differences to Typical Development (TD) children at the onset of independent walking and at 8 months follow up. METHOD: Sixteen children with bilateral CP, GMFCS levels I and II, and 15 TD children were recruited. Gait kinematics and temporospatial parameters were recorded using a 3-D gait analysis system; the sagittal plane of the lower limb joints was analyzed. Baseline measurements were recorded at the individual's onset of independent walking and follow up was after 8 months. RESULTS: Compared to baseline, children with bilateral CP demonstrated increased (mean difference ± SE) plantar flexion (11.79 ± 2.96), single support (0.04 ± 0.01), step length (0.2 ± 0.05) and stride length (0.4 ± 0.09), at follow up; all p < .05. Compared to TD children, they also had lower gait speed (0.16 ± 0.05), higher single support (0.02 ± 0.01) and lower maximum knee extension (9.14 ± 4.49) during the swing phase, at baseline and follow up (0.1 ± 0.04, 0.05 ± 0.01, 23.04 ± 4.17, respectively); all p < .05. CONCLUSION: There are changes in the sagittal plane kinematics and temporospatial parameters of the gait during the first 8 months of independent walking. These indicate gait maturation changes and highlight the impact of walking experience on the gait characteristics of children with bilateral CP.

Molecular surveillance of pneumococcal carriage following completion of immunization with the 13-valent pneumococcal conjugate vaccine administered in a 3 + 1 schedule.

In a cross-sectional study, with the use of molecular methods, we aimed to gain insight into oropharyngeal pneumococcal colonization over time in 1212 Greek children recruited in general pediatric settings throughout the country; they were fully vaccinated with PCV13 (3 + 1 schedule). A single sample was obtained from each child at a time interval of 26 days to 70 months after administration of the 4th (booster) PCV13 dose; sampling time was divided into six time intervals. Carriage of Streptococcus pneumoniae was detected by real-time PCR targeting the lytA gene and isolates were serotyped by singleplex real-time PCR assays. Multiple control procedures to avoid false-positive results were applied. We showed an overall S. pneumoniae carriage rate of 48.6%. Serotyping identified typeable isolates in 82% of the total lytA-positive samples. Non-PCV13 serotypes represented 83.8% of total isolates when excluding serogroups with mixed PCV13 and non-PCV13 serotypes. In multivariate analysis daycare/school attendance emerged as the main contributing factor. Notably, serotypes 19A and 3 were the only two PCV13 serotypes the colonization rate of which increased over time (χ2 for trend P < 0.001 and P = 0.012, respectively). The application of the SP2020 gene on lytA-positive serotyped samples showed pneumococcal colonization in 97% of cases, and the overall colonization profile over time closely resembled that of the lytA gene. With the provisions of the methodological approach and age group of our study, the use of the oropharynx emerges as a reliable alternative to the nasopharynx in estimating pneumococcal carriage in epidemiological studies.

The Effect of a Structured Individualized Educational Intervention on Breastfeeding Rates in Greek Women.

Breastfeeding rates remain extremely low in Greece and women with gestational diabetes mellitus and hypothyroidism may experience additional difficulties. The aim of the study was to investigate the effect of a structured individualized lactation educational intervention by a midwife on increasing breastfeeding rates in women with endocrine disorders and low-risk women compared to women receiving standard care, 24 months after delivery. Two-hundred women made up the study population. Half of them were experiencing endocrine pregnancy disorders and 100 women constituted the low-risk pregnancy standard care control group. Women who were breastfeeding exclusively were significantly higher in the midwifery intervention group with endocrine disorders, namely breastfeeding continued at four months (breastfeeding: 20% vs. 12%, exclusive breastfeeding: 50% vs. 26%, p = 0.0228), and at six months after childbirth (breastfeeding: 54% vs. 28%, exclusive breastfeeding: 32% vs. 12%, p = 0.0011), compared to the standard care control group with endocrine disorder. The low-risk midwifery intervention group breastfed at four months (22% vs. 14%, p = 0.0428) and at six months (52% vs. 26%, p = 0.0018) at higher rates compared to the standard care control group. In addition, exclusive breastfeeding was significantly higher in the low-risk midwifery intervention group at four months (46% vs. 20%, p = 0.0102) and six months (38% vs. 4%, p < 0.0001) compared to the standard care control group. This study was the first attempt of a structured midwifery breastfeeding education in Greece and its major contribution reflects a significant positive impact on breastfeeding rates in terms of duration and exclusivity in women with gestational endocrine disorders as well as in low-risk women, and could possibly be applied and instituted in everyday clinical practice to increase the low breastfeeding rates in Greece.

"Aggressive" Feeding of Very Preterm Neonates and Body Mass Index at School Age.

INTRODUCTION: The effects of "aggressive" neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our "aggressive" nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. MATERIALS AND METHODS: Eighty four VPN, who received "aggressive" nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180-210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. RESULTS: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. CONCLUSIONS: "Aggressive" and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.

Val66Met polymorphism is associated with decreased likelihood for pediatric headache and migraine.

Background: Migraine is a complex multifactorial disorder and its pathogenesis still remains unclear. Evidence suggests the involvement of the activated trigeminovascular pathway, in which BDNF seems to play an important role. Therefore, BDNF polymorphisms are promising candidate susceptibility factors.Aim: BDNF rs6265 functional polymorphism was analyzed in order to determine its possible association with pediatric headache and migraine risk.Methods: The research included 120 consecutive pediatric patients who were diagnosed with headache and 120 healthy controls. The diagnosis was in compliance with the International Classification of Headache Disorders. Blood samples were collected from all participants and genotyped for rs6265.Results: BDNF rs6265 was significantly associated with decreased headache risk, particularly in the dominant model [Odds Ratio, OR (95% confidence interval, C.I.): 0.47 (0.26-0.85), p = 0.011] and the log-additive model [OR (95% C.I.): 0.48 (0.28-0.82), p = 0.0053]. During the sensitivity analysis, the associations were also maintained among patients with migraine.Conclusions: This is the first study to reveal a significant association of this BDNF variant with headache risk. Additionally, Val66Met was also for the first time related to decreased childhood migraine risk.

Gastric Volume Changes in Preterm Neonates during Intermittent and Continuous Feeding-GRV and Feeding Mode in Preterm Neonates.

Background: We aimed to evaluate gastric volume changes during intermittent milk feeds (IMF) and continuous milk feeds (CMF) in very premature neonates (VPN), with gastric residual volume (GRV) based on antral cross-sectional area (ACSA) measurements and to examine if there were differences in GRV between the two feeding methods. Methods: A randomized prospective clinical trial with crossover design was conducted in 31 preterm neonates (gestational age < 30 weeks). Gastric volume was assessed twice in each neonate (during IMF and CMF feeding), at 7 specific time points during a 2-h observation period by measuring ACSA changes via the ultrasound (U/S) method. Results: There was a significantly different pattern of gastric volume changes between the two feeding methods. GRV, expressed as the median percentage of ACSA measurement at 120 min relative to the higher ACSA measurement during IMF, was found to be 3% (range 0-25%) for IMF and 50% (range 15-80%) for CMF. Neonates fed with IMF had a shorter mean gastric emptying time compared to those fed with CMF (p = 0.0032). No signs of feeding intolerance were recorded in either group during the period of observation. Conclusions: Our results showed that gastric volume changes and gastric emptying time in VPN, based on ACSA measurement changes, depend on the milk feeding method. No gastrointestinal complications/adverse events were noted with GRV up to 80% with CMF.