Incidence and Risk Factors for Glucose Disturbances in Premature Infants.

Background and Objectives: There are limited data regarding the incidence and risk factors for hypoglycemia, hyperglycemia, and unstable glycemia in preterm infants. The aim of the present study was to determine the incidence and risk factors associated with neonatal hypoglycemia, hyperglycemia, and unstable glycemia in preterm infants during the first seven days of life. Materials and Methods: This prospective study included preterm infants <37 weeks of gestation, admitted to the Neonatal Intensive Care Unit between January 2018 and December 2020. Based on blood glucose levels in the first week of life, infants were divided into the following four groups: normoglycemic, hypoglycemic, hyperglycemic, and unstable. Blood glucose levels were measured from capillary blood at the 1st, 3rd, 6th, and 12th hour of life during the first 24 h, and at least once a day from days 2 to 7, prefeed. Results: Of 445 enrolled infants, 20.7% (92/445) were categorized as hypoglycemic, 9.9% (44/445) as hyperglycemic, and 2.9% (13/445) as unstable, respectively. Hypoglycemia was most commonly observed among infants ≥34 weeks (27.9%), and hyperglycemia was most common among preterm infants <28 weeks (50%). Female gender increased the chances of developing hypoglycemia by three times. The decrease in gestational age by one week increased the chance of developing hyperglycemia by 1.9 times. Sepsis increased the chance of developing hyperglycemia seven times, respiratory distress syndrome five times, and mechanical ventilation three times, respectively. Conclusions: Glucose disturbances in the early neonatal period in preterm infants are common and mostly asymptomatic. Therefore, careful blood glucose level monitoring is required in those infants, especially in late preterm infants, in order to prevent possible neurological complications.

GLUT1 Deficiency Syndrome-Early Treatment Maintains Cognitive Development? (Literature Review and Case Report).

Glucose transporter type 1 (GLUT1) is the most important energy carrier of the brain across the blood-brain barrier, and a genetic defect of GLUT1 is known as GLUT1 deficiency syndrome (GLUT1DS). It is characterized by early infantile seizures, developmental delay, microcephaly, ataxia, and various paroxysmal neurological phenomena. In most cases, GLUT1DS is caused by heterozygous single-nucleotide variants (SNVs) in the SLC2A1 gene that provoke complete or severe impairment of the functionality and/or expression of GLUT1 in the brain. Despite the rarity of these diseases, GLUT1DS is of high clinical interest since a very effective therapy, the ketogenic diet, can improve or reverse symptoms, especially if it is started as early as possible. We present a clinical phenotype, biochemical analysis, electroencephalographic and neuropsychological features of an 11-month-old boy with myoclonic seizures, hypogammaglobulinemia, and mildly impaired gross motor development. Using sequence analysis and deletion/duplication testing, deletion of an entire coding sequence in the SLC2A1 gene was detected. Early introduction of a modified Atkins diet maintained a seizure-free period without antiseizure medications and normal cognitive development in the follow-up period. Our report summarizes the clinical features of GLUT1 syndromes and discusses the importance of early identification and molecular confirmation of GLUT1DS as a treatable metabolic disorder.

Pregnancy exposome and child psychomotor development in three European birth cohorts.

Characterization of the exposome, the totality of all environmental factors that one is exposed to from conception onwards, has been recommended to better evaluate the role of environmental influences on developmental programming and life-course vulnerability to major chronic diseases. In the framework of the Health and Environment-wide Associations based on Large population Surveys (HEALS) project we considered the pregnancy exposome exploiting two databases (PHIME and REPRO_PL) that include birth cohorts from three EU countries (Croatia, Slovenia and Poland). The databases contained information on several chemical exposures, socio-demographic, lifestyle and health related factors from conception to child birth, and neuropsychological scores assessed by the Bayley Scales of Infant and Toddler Development in the first two years of life. Our main goal was to assess consistency of environmental influences on neurodevelopment, if any, across European countries differing for geographical, socio-demographic characteristics and levels of chemical exposures to metals such as lead (Pb), mercury (Hg), cadmium (Cd) and trace elements, including micronutrients such as zinc (Zn) and selenium (Se). To this aim, we first selected variables common to the different databases, then applied univariate and multivariate regression analyses to identify factors linked to neurodevelopment, and finally performed meta-analysis to detect potential heterogeneity among cohorts and pooled estimates. Significant differences in exposure levels among the three sub-cohorts were observed as for Hg and Se; exposure levels under study were relatively low and within the range described in existing EU biomonitoring studies. The univariate analyses did not show any common pattern of association as only in the Polish cohort chemical exposure had an impact on neuropsychological outcome. In the meta-analysis, some consistent trends were evident, relative to the adverse influence of Pb on children's language and cognition and the positive influence of Se on language abilities. The effects of the neurotoxic metal Hg positively influenced the motor scores in the Polish cohorts, while it decreased the motor scores in the Slovenia and Croatian sub-cohorts. The only socio-demographic factor consistently associated to the outcome among cohorts was child's sex, with females performing better than males on cognitive and language scores. These findings point to the need of harmonizing existing cohorts or creating prospective study designs that facilitate comparisons in the exposome over time, places and kind of environmental exposures.

Prenatal selenium status, neonatal cerebellum measures and child neurodevelopment at the age of 18 months.

OBJECTIVES: The aim of this study was to evaluate the association of maternal blood selenium (Se) levels and cord blood Se levels with neonatal cerebellum measures and child neurodevelopment at the age of 18 months. Moreover, to investigate whether the neonatal cerebellum measures could be used as a potential biomarker for selenium homeostasis during pregnancy. STUDY GROUP AND METHODS: The study population consisted of 205 mother-child pairs from Croatian Mother and Child Cohort. Maternal blood and cord blood were obtained at delivery and selenium level was analyzed by Inductively Coupled Plasma Mass Spectrometry. Cranial ultrasonography examination was performed on 49 newborns - cerebellum length and width have been measured. Neurodevelopmental assessment of cognitive, language and motor skills were conducted on 154 children, using The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), at the age of 18 months. RESULTS: The mean levels of selenium in maternal blood and cord blood were 92.6 ng/g and 97.0 ng/g, respectively. Maternal blood selenium levels were moderately and negatively correlated (r = -0.372; p = 0.008) with cerebellum length, while cord blood selenium levels were positively correlated with cerebellum width (r = 0.613; p = 0.007) among female children group. Maternal blood selenium levels were weakly and positively correlated (r = 0.176; p = 0.029) with child's cognitive abilities. CONCLUSION: To the best of our knowledge, our study is the first one investigating the association between neonatal brain measures and selenium levels in mother-child pairs. Our results indicate that prenatal selenium intake correlated with cerebellum length and width measured by cranial ultrasonography. Hence, cerebellum may be used as a potential biomarker and a target "organ" for early detection of possible adverse effects of prenatal status to various micronutrients.

Prenatal mercury exposure and child neurodevelopment outcomes at 18 months: Results from the Mediterranean PHIME cohort.

INTRODUCTION: Neurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However, the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question about "safety" of fish-eating during pregnancy remain controversial. International comparisons of Hg concentrations in mother-child biological samples and neurodevelopmental scores embedded in birth cohort studies may provide useful evidence to explore this issue. MATERIALS AND METHODS: The Mediterranean (Italy, Slovenia, Croatia, and Greece) cohort study included 1308 mother-child pairs enrolled in the Public Health Impact of long-term, low-level, Mixed Element exposure in a susceptible population EU Sixth Framework Programme (PHIME). Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured. Demographic and socioeconomic information, lifestyles and nutritional habits were collected through questionnaires at different phases of follow-up. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multivariate linear and logistic regressions were performed, for each country, to assess the association between THg and BSID-III scores, obtaining adjusted ß coefficients and odds ratios (ORs). These values were used to conduct a meta-analysis, to explore possible heterogeneity among countries and to obtain combined estimates of the association between THg exposure and BSID-III scores. RESULTS: Median THg (ng/g) was: 704 in maternal hair, 2.4 in maternal blood, 3.6 in cord blood, and 0.6 in breast milk. THg concentrations were highest in Greece and lowest in Slovenia. BSID-III neurodevelopmental scores were higher in Croatia and Slovenia. The meta-analysis of multivariate linear models found an overall positive association between language composite score and receptive communication scaled score and increasing THg in maternal hair (n = 1086; ß = 0.55; 95%CI: 0.05-1.05 and n = 1075; ß = 0.12; 95%CI: 0.02-0.22, respectively). The meta-analysis of logistic regression models showed that the overall adjusted OR between THg in cord blood and suboptimal gross motor score was borderline significant (n = 882; OR = 1.03; 95%CI: 1.00-1.07). Heterogeneity was found across the four sub-cohorts for language composite score in maternal blood, and for fine motor scaled score in cord blood and breast milk. Language composite score and THg concentrations in maternal venous blood were positively related (n = 58; ß = 4.29; CI95% (-0.02, 8.60)) in Croatia and an increase of 1 ng/g of THg in maternal venous blood was associated with a reduced risk for children to fall in the lowest quintile of language score by 31% (n = 58; OR = 0.69; CI 95%: 0.37, 1.01). The comparison of ß coefficients obtained by multiple linear regression model showed an inverse association between fine motor score and THg concentrations in cord blood for Croatia (n = 54; ß = -0.53; CI 95%: -1.10, 0.04) and Slovenia (n = 225; ß = -0.25; CI 95%: -0.49, -0.01). In Slovenia THg level in breast milk was associated with suboptimal fine motor performance (n = 195; OR = 5.25; CI 95%: 1.36, 21.10). CONCLUSIONS: This study showed an inverse relation between THg levels and developmental motor scores at 18 months, although the evidence was weak and partially internally and externally inconsistent. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age.

Prenatal mercury exposure, neurodevelopment and apolipoprotein E genetic polymorphism.

The aim of the present study was to evaluate the association between prenatal exposure to mercury (Hg) and neurodevelopment of the child, taking into account genetic polymorphism of apolipoprotein E (Apoe) and other relevant confounders. Six hundred and one mother-child pairs were recruited from the central Slovenia region and 243 from Rijeka, on the Croatian coast of the northern Adriatic. The total Hg in cord blood, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessment at 18 months of age and Apoe genotyping was performed on 361 children; 237 of them were from Slovenia and 124 from Croatia. The results showed negative association between low-to-moderate Hg exposure in children with normal neurodevelopmental outcome and cognitive and fine motor scores at 18 months of age as assessed by Bayley III. The Hg-related decrease in cognitive score was observed only in children carrying at least one Apoe ε4 allele, while the decrease in fine motor scores was independent of the Apoe genotype. Adjusting for selenium (Se) and lead (Pb) levels, a positive association between Se and the language score and a negative association between Pb and the motor score was observed, but not in the subgroup of children carrying the ε4 allele.

Prenatal exposure to low-level methylmercury alters the child's fine motor skills at the age of 18 months.

OBJECTIVES: To compare motor, cognitive and language characteristics in children aged 18 months who were prenatally exposed to low-level methyl-mercury (MeHg), and to analyze the eventual differences in these characteristics in relation to cord blood THg concentration. PATIENTS AND METHODS: The total number of 205 child-mother pairs was included in the study, and total cord blood mercury was measured in 198 of them. Out of the 198 already measured samples, 47 of them have also been tested for methyl-mercury in cord blood. Data regarding the 47 samples of MeHg levels has been used for calculating the correlation between cord blood THg and cord blood MeHg. MeHg and THg showed a significant correlation (r=0.95, p<0.05). One month after the delivery, mothers were asked to complete the questionnaire regarding socioeconomic factors, breastfeeding of their infants, and dietary habits during pregnancy. Neurodevelopmental assessment of motor, cognitive and language skills were conducted on 168 children using The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Regarding the cord blood THg concentration, 135 children were divided in 4 quartile groups. Their neurodevelopmental characteristics have been compared. RESULTS: The cord blood THg concentration median and inter-quartile range was 2.98ng/g (1.41-5.61ng/g). There was a negative correlation between cord blood THg concentration and fine motor skills (rho=-0.22, p=0.01). It is evident that children grouped in 2nd ,3rd and 4th quartile had statistically significant lower fine motor skills assessment related to those grouped in 1st quartile (2nd quartile -1.24, p=0.03; 3rd quartile -1.28, p=0.03; 4th quartile -1.45, p=0.01). The differences in fine motor skills assessments between children in 2nd and 3rd and 3rd and 4th quartile were not statistically significant. CONCLUSION: Intrauterine exposure to low-level THg (MeHg) is associated with alterations in fine motor skills at the age of 18 months.

Croatian children's views towards importance of health care information.

The aim of research was to investigate: the need for health care information of Croatian adolescents aged from 13 to 18 years; the difference in evaluation of the frequency of receiving information between hospitalized and healthy children; if the hospitalized children expectations about the frequency of receiving health care information differed significantly from information they have actually received; whose information was most comprehensible to the hospitalized children (doctors, parents, other health care givers). The children were either hospitalized in the pediatrics departments or were high schools pupils (healthy children). The hospitalized children "Completely agreed" (92.7%) with the statement "When I am sick, I should receive information about my health" in comparison to the healthy children (85.1%). In comparison to healthy children, the hospitalized children assessed that doctors, other health care givers and parents should give them information more frequently. The experience of hospitalized children indicate that they received less information then they have actually excepted. The information received from doctors was mostly in correlation with the understanding of this information. We concluded that the children want to be informed about their health, especially hospitalized children. Health care professionals should offer understandable health care information according to the children's expectation.