Real-time investigation of an influenza A(H3N2) virus outbreak in a refugee community, November 2022.

OBJECTIVES: To report epidemiological and virological results of an outbreak investigation of influenza-like illness (ILI) among refugees in Northern Italy. STUDY DESIGN: Outbreak investigation of ILI cases observed among nearly 100 refugees in Northern Italy unvaccinated for influenza. METHODS: An epidemiological investigation matched with a differential diagnosis was carried out for each sample collected from ILI cases to identify 10 viral pathogens (SARS-CoV-2, influenza virus type A and B, respiratory syncytial virus, metapneumovirus, parainfluenza viruses, rhinovirus, enterovirus, parechovirus, and adenovirus) by using specific real-time PCR assays according to the Centers for Disease Control and Prevention (CDC) protocols. In cases where the influenza virus type was identified, complete hemagglutinin (HA) gene sequencing and the related phylogenetic analysis were conducted. RESULTS: The outbreak was caused by influenza A(H3N2): the attack rate was 83.3% in children aged 9-14 years, 84.6% in those aged 15-24 years, and 28.6% in adults ≥25 years. Phylogenetic analyses uncovered that A(H3N2) strains were closely related since they segregated in the same cluster, showing both a high mean nucleotide identity (100%), all belonging to the genetic sub-group 3C.2a1b.2a.2, as those mainly circulating into the general population in the same period. CONCLUSIONS: The fact that influenza outbreak strains as well as the community strains were genetically related to the seasonal vaccine strain suggests that if an influenza prevention by vaccination strategy had been implemented, a lower attack rate of A(H3N2) and ILI cases might have been achieved.

Thyroid-stimulating hormone levels in the first days of life and perinatal factors associated with sub-optimal neuromotor outcome in pre-term infants.

AIM: To identify perinatal factors associated with sub-optimal neuromotor outcome in infants without evident central nervous system lesions (intraventricular hemorrhage/ periventricular leukomalacia), with gestational age ≤30 (group I) and of 31-32 weeks (group II). PATIENTS AND METHODS: A total of 102 premature infants admitted to the Neonatal Intensive Care Unit of Pisa, at 26-32 weeks of gestation, were studied. Data about perinatal factors and TSH values at 3-4 days of life were collected. The assessment of neuromotor development was performed at 18 months of corrected age, using the locomotor subscale of the Griffiths Scales of Mental Development. RESULTS: Risk factors supposed to be predictive of sub-optimal neuromotor outcome (odds ratio >1) were at ≤30 weeks: male sex, small for gestational age, patent duct arterious, respiratory distress syndrome, and at 31-32 weeks: Apgar at 5 min <7, respiratory distress syndrome, patent duct arterious and birth weight <1500 g. A strong correlation was also found between TSH screening values >4,3 mU/l and suboptimal neuromotor outcome in both groups. CONCLUSIONS: Several perinatal factors, acting on an immature and more vulnerable nervous system, such as the pre-term one, different for different gestational ages, are associated with a sub-optimal neuromotor outcome. Higher, but within the normal range, TSH values at screening seem to be a strong risk factor for neuromotor outcome in preterm infants without intraventricular hemorrhage or periventricular leukomalacia.

Neonatal outcome in newborns from mothers with endocrinopathies.

INTRODUCTION: Hypothyroidism and gestational diabetes are common endocrine disorders in pregnancy. Our aim is to evaluate the outcome of newborns from mothers with hypothyroidism and from mothers with gestational diabetes. PATIENTS AND METHODS: The study analysed 216 newborns: 112 from mothers with gestational diabetes and 104 from mothers with hypothyroidism. For each case, we included as a control a newborn of same sex and gestational age from a mother without diabetes or thyreopathy. RESULTS: In newborns from mothers with gestational diabetes there was an increased frequency of hypoglycaemia and hypocalcaemia, of lower head circumference and of small-for-gestational age (SGA) birth or macrosomy (LGA) than controls. The newborns from mothers with hypothyroidism are more frequently SGA or LGA and they have a slightly increased risk of hypoglycaemia. CONCLUSIONS: Newborns from mothers with diabetes mellitus or hypothyroidism have an increased risk of being SGA or LGA, and to develop a mild transient hypoglycaemia. Newborns from mothers with diabetes mellitus have also an increased risk to develop hypocalcaemia and to have a lower head circumference than controls. Thus, to prevent SGA or LGA births, it is very important an early diagnosis and treatment, and a strict metabolic control of these conditions.

Low testosterone levels in pre-term newborns born small for gestational age.

Previous studies showed that small for gestational age (SGA) newborns have an increased prevalence of hypospadias and other congenital defects of external genitalia. We observed that in the first days of life, SGA male pre-term newborns have reduced testosterone levels compared with adequate for gestational age pre-term newborns, independently from the presence of abnormalities of the external genitalia.

Retinol-binding protein 4 in neonates born small for gestational age.

BACKGROUND: Retinol-binding protein 4 (RBP4) is an adipocyte-derived 'signal' that may contribute to the pathogenesis of insulin resistance and Type 2 diabetes. The relationship of RBP4 with insulin resistance and metabolic risk in human beings has been the subject of several studies. Subjects born small for gestational age (SGA) are at risk of insulin resistance and Type 2 diabetes. Though RBP4 could represent an early marker of insulin resistance, to date, none have determined RBP4 in SGA children. AIM: Our aim was to measure RBP4 concentrations in cord blood of SGA newborns compared with those in children born with a birth weight appropriate for gestational age (AGA) and to determine whether serum RBP4 levels at birth correlate with insulin sensitivity markers. SUBJECTS AND METHODS: Sixty-four newborns, 17 born SGA (mean gestational age: 36.4+/-2.1 weeks), and 47 born AGA (mean gestational age: 37.0+/-3.6 weeks) were studied. The main outcome measures included anthropometry, lipid profile, insulin, homeostasis model assessment, quantitative insulin-sensitivity check index, adiponectin, and RBP4. RESULTS: RBP4 concentrations were significantly reduced in SGA newborns (p<0.002). No relationship was found between RBP4 and insulin sensitivity parameters. Stepwise regression analysis revealed that birth weight was the major predictor of RBP4 serum concentrations (p<0.001). CONCLUSION: RBP4 is reduced in SGA newborns, birth weight representing the major determinant of RBP4 concentrations, and is not related to insulin sensitivity. No significant difference in adiponectin levels and insulin sensitivity markers was found between SGA and AGA neonates.

Distribution of sleep and wakefulness EEG patterns in 24-h recordings of preterm and full-term newborns.

The aim of this study was to evaluate the organisation of EEG patterns in 24-h recordings of preterm and near-term neonates. In particular, the distribution of the different EEG codes at different postmenstrual ages (PMA) and the variations of sleep-related EEG pattern organisation was studied, during day (8.00 a.m.-8.00 p.m.) and night (8.00 p.m.-8.00 a.m.) time. The age of appearance of different neonatal EEG patterns, previously described in literature for short lasting records, was confirmed in this 24-h study. The medium-voltage continuous EEG pattern (pattern "3") was less represented approaching term age, in coincidence with the appearance of the two low-voltage continuous patterns ("1" and "2"), which are also related to active sleep and wakefulness. Discontinuous pattern ("7") was also less represented with age, but in day-time only. The percentage of time occupied by this pattern, related to quiet sleep, was significantly higher during day-time hours, than at night.

Serum iodothyronines in the human fetus and the newborn: evidence for an important role of placenta in fetal thyroid hormone homeostasis.

UNLABELLED: The pattern of circulating iodothyronines in the fetus differs from that in the adult, being characterized by low levels of serum T3. In this study, concentrations of various iodothyronines were measured in sera from neonates of various postconceptional age (PA). Results obtained in cord sera at birth (PA, 24-40 weeks), reflecting the fetal pattern, were compared with those found during extrauterine life in newborns of 5 days or more of postnatal life (PA, 27-46 weeks). The main findings are: Starting at 30 weeks of PA, serum levels increase linearly during extrauterine life; and at 40 weeks, they are more than 200% of those measured in cord sera from newborns of equivalent PA. Serum reverse T3 (rT3) levels during fetal life are higher than those measured during extrauterine life; but they significantly decrease, starting at 30 weeks of PA. Serum T3 sulfate (T3S) does not significantly differ between the two groups, showing the highest values at 28-30 weeks of PA, and significantly decreasing at 30-40 weeks. T3S levels are directly correlated with rT3, both in fetal and extrauterine life, whereas a significant negative correlation between T3S and T3 is found only during extrauterine life. IN CONCLUSION: 1) changes in serum concentrations of iodothyronines in umbilical cord and during postnatal life indicate that maturation of extrathyroidal type I-iodothyronine monodeiodinase (MD) accelerates, starting at 30 weeks of PA; 2) high levels of type III-MD activity in fetal tissues prevent the rise of serum T3, whereas they maintain high levels of rT3 during intrauterine life; 3) an important mechanism leading to the transition from the fetal to the postnatal thyroid hormone balance is a sudden decrease in type III-MD activity; iv) because placenta contains a high amount of type III-MD, it is conceivable that placenta contributes to maintain low T3 and high rT3 serum concentrations during fetal life and that its removal at birth is responsible for most changes in iodothyronine metabolism occurring afterwards.

Pharmacological activation of gamma-aminobutyric acid-system blunts prolactin response to mechanical breast stimulation in puerperal women.

To evaluate whether the gamma-aminobutyric acid (GABA)ergic system participates in the control of PRL secretion during the puerperium, different doses of sodium valproate (DPA), a drug that increases endogenous GABA activity, were administered orally to puerperal women who did not wish to breast feed their infants. Two groups of five women were each given DPA in doses of 400 and 800 mg, respectively. PRL levels were measured in plasma samples collected before and after drug administration. Another group of five puerperal women was treated with 800 mg DPA 60 min before mechanical breast stimulation using an electric breast pump for 15 min. Circulating PRL levels were measured in samples obtained before, during, and after breast stimulation. No drug-associated side effects were observed. After placebo administration, no significant variations in plasma PRL levels occurred in any subject. The lower dose of DPA (400 mg) induced a slight decrease in plasma PRL levels, but 800 mg of the drug induced a significant fall (P less than 0.05 vs. baseline values) in PRL, with a maximum percent decrease (68.2 +/- 4%) 180 min after DPA treatment. Mechanical breast stimulation performed after placebo treatment induced a significant increase (P less than 0.01) in plasma PRL levels, with peak values (37 +/- 10% above baseline values) 10 min after the onset of stimulation. When DPA was administered to the same women, a significant decrease (23 +/- 3%) in plasma PRL occurred during breast stimulation. Thereafter, PRL values continued to fall in spite of breast stimulation. PRL levels were significantly decreased after DPA treatment compared to both basal values (P less than 0.01) and the levels found in the same patients during control tests (P less than 0.05). These results demonstrate that enhancement of endogenous GABAergic tone induced by DPA significantly decreases basal PRL levels and blunts PRL release after mechanical breast stimulation. In agreement with animal data, a possible physiological role of GABA in the control of PRL release during puerperium may be suggested.

Neuroimaging and functional outcome of neonatal leukomalacia.

Leukomalacia is a major cause of neurological impairment in the high-risk newborn. It can be identified during the early postnatal period by means of ultrasound (US) imaging of the brain, through the anterior fontanel. Magnetic resonance imaging (MRI) permits an optimal differentiation of brain tissue and of its abnormalities, without resorting to ionizing radiation or intravenous contrast. It is particularly appropriate for following the evolution of leukomalacia, after fontanel closure. Ninety-five fullterm and preterm infants with cystic and non-cystic leukomalacia, documented by US, were clinically followed-up until at least 12 months of corrected age. Thirty-two had a severe neurological outcome (mainly cerebral palsy, sometimes associated with mental retardation and/or cerebral visual impairment). The prognosis was worse in cystic leukomalacia than in prolonged flare. Electroencephalogram (EEG) carried out in the first 2 weeks of life provided valuable indexes of further outcome, especially for US findings of more uncertain prognosis. MRI was carried out at around 12 months of corrected age, by means of an apparatus operating at 0.5 Tesla. The main categories of abnormalities observed were the following: cystic lesions, enlarged ventricles with irregular outlines, delayed myelination, high intensity areas in the long TR (repetition time) images within the white matter, cortical atrophy. MRI findings correlated well with the results of US imaging and often with motor, cognitive and visual impairments. Nevertheless, clinical features cannot be predicted by neuroimaging alone and a comprehensive approach, including longitudinal functional and electrophysiological testing, is highly recommended.

Visual acuity of low- and high-risk neonates and acuity development during the first year.

Binocular grating acuity of 65 neonates was measured using Teller acuity cards. At the time of testing, age corrected for prematurity ranged from -3 weeks to 2 weeks. On the basis of clinical data, serial ultrasound scans and EEG recording newborns were divided into 4 subgroups: fullterm low-risk (FLR, n = 22); preterm low-risk (PLR, n = 20); preterm medium-risk (PMR, n = 9) and preterm high-risk (PHR, n = 14). Mean visual acuity of PLR infants (0.86 cy/deg; S.D. 0.34 oct) was not significantly different from that of FLR newborns (0.80 cy/deg; S.D. 0.71 oct); the lower variability of the PLR infants might possibly be caused by their longer postnatal experience. Within the preterm groups, mean visual acuity of PLR newborns was found to be significantly higher than that of PMR (0.73 cy/deg; S.D. 0.26 oct) and PHR infants (0.73 cy/deg; S.D. 0.35 oct). This difference can not be explained by dissimilarities in postnatal or corrected age. Brain impairment, as documented by US scans and EEG recording could account for these findings. Longitudinal data are needed in order to substantiate these findings and correlate them with later neurological and neuro-imaging outcome. Preliminary results of an ongoing longitudinal study suggest acuity development of most, but not all, PHR infants, in whom a cystic-periventricular leukomalacia had been diagnosed, to be worse than that of low- and medium-risk infants.

Constantly discontinuous EEG patterns in full-term neonates with hypoxic-ischaemic encephalopathy.

OBJECTIVES: Selected EEG features were evaluated in 21 constantly discontinuous tracings recorded on the same number of full-term neonates with hypoxic-ischaemic encephalopathy. METHODS: The tracings were examined without using interval amplitude as the basis for distinguishing between burst-suppression and nonburst-suppression patterns. RESULTS: The results were related to outcomes and other clinical parameters (severity of hypoxic-ischaemic encephalopathy, pO2 levels and drug intake). CONCLUSIONS: Features defining the grade of EEG discontinuity (i.e. maximum interval duration, minimum burst duration and interval amplitude) significantly related to outcome and, in most cases, to the grade of hypoxic-ischaemic encephalopathy. Other features (amplitude of slow waves within the burst and incidence of abnormal EEG transients) related to PO2 levels. The consumption of anticonvulsant drugs increased EEG discontinuity, but this effect did not seem dose-related. Finally, the persistence of a constantly discontinuous EEG pattern after the first week of life is a sign of unfavourable prognosis. In full-term neonates with hypoxic-ischaemic encephalopathy quantitative analysis of all constantly discontinuous EEGs seems more useful than only describing burst-suppression patterns on the basis of interval amplitude.

A clinician looks at androgen resistance.

Androgen resistance in genetic males occurs when gonadotropins and testosterone are normal, but the physiological androgen response in androgen target organs is absent or decreased. In androgen-dependent target tissues two main defects may be found: 1) defective testosterone metabolism (5 alpha-reductase type 2 deficiency) and 2) anomalies in androgen receptors (androgen insensitivity syndrome (AIS)). The clinical manifestations of these defects vary from subjects with female external genitalia to subjects with mild forms of impaired masculinization. In particular, in the complete form of AIS (CAIS) the phenotype is feminine, and in the partial form (PAIS) the external genitalia are ambiguous with an extremely variable phenotype. The diagnosis requires clinical, hormonal, genetic, and molecular investigation for appropriate gender assignation and treatment. In AIS, cloning of androgen receptor cDNA using the polymerase chain reaction, denaturing gradient gel electrophoresis, and nucleotide sequencing have enabled a variety of molecular defects in the androgen receptor to be identified. The complexity of phenotypic presentation of AIS probably reflects the heterogeneity of androgen receptor gene mutations, but to date a relationship between genotype/phenotype has been difficult to establish, with the same point mutation reported to be associated with different phenotypic expressions. Other factors must therefore also contribute to the clinical presentation of AIS, although none have yet been identified. Establishing the functional consequences of androgen receptor mutations in vitro systems and correlating them with clinical presentation may ultimately provide an explanation for the variable clinical presentation of AIS and perhaps enable prediction of the response to androgen therapy in infants with PAIS.

Electroclinical correlation in neonatal seizures.

A dissociation between clinical and electroencephalographic phenomena is often observable in neonatal seizures. This finding raises important questions, including those related to the management of these patients. Another characteristic of neonatal convulsions is represented by their increased tendency towards status epilepticus. In order to examine the electroclinical correlation and its possible relationship to the occurrence of status epilepticus, recorded video-electroencephalograms of 17 newborns were submitted to detailed analysis. Time of onset, duration and other characteristics of all clinical and electrical events were noted. Five degrees of correlation were observed, from constant concurrence to complete dissociation. Examining the role of different parameters, it was observed that the incidence of electric discharges related significantly to the occurrence of electroclinical dissociation.

Correlation between visual function, neurodevelopmental outcome, and magnetic resonance imaging findings in infants with periventricular leucomalacia.

AIM: To evaluate the correlation between visual function and neurodevelopmental outcome in children with periventricular leucomalacia at 1 and 3 years. METHOD: Visual acuity, visual field, ocular motility, and optokinetic nystagmus were tested in 29 infants with periventricular leucomalacia by brain magnetic resonance imaging. All infants also had a structured neurological examination and a Griffiths developmental assessment. RESULTS: 21 of the infants showed at least one abnormality of visual function. The degree of visual impairment-that is, the number of visual tests showing abnormal results-correlated well with the results on developmental assessment at both ages. CONCLUSION: Multivariate analysis showed that visual impairment was the most important variable in determining the neurodevelopmental scores of these infants, more than their motor disability and the extent of their lesions on magnetic resonance imaging.

Electroencephalography in infants with periventricular leukomalacia: prognostic features at preterm and term age.

Cystic periventricular leukomalacia represents the most severe white-matter lesion in preterm infants and its occurrence accounts for most cases of neurologic impairment in these subjects. Electroencephalographic (EEG) findings and their prognostic value in relation to motor and cognitive outcome were investigated in a group of preterm infants affected by different degrees of cystic periventricular leukomalacia. EEG recordings were carried out in the early postnatal period (first 2 weeks of life) on 24 infants and at term age on 29. In the early postnatal period, background EEG abnormalities ("dysmaturity") were significantly more apparent in affected infants than in a control group, and, among infants with cystic periventricular leukomalacia, this parameter related to the occurrence of cerebral palsy; moreover, at the same age, the incidence of abnormal EEG transients seemed to show a correlation with cognitive outcome. At term age, these latter abnormalities were significantly more apparent in neonates with cystic periventricular leukomalacia than in control subjects, but they did not show any prognostic value. In conclusion, these data indicate that, during the early postnatal period, the EEG is a useful diagnostic and prognostic tool for preterm infants with white-matter lesions, whereas at term age, the role of EEG tracings appears secondary.

Universal screening and intensive metabolic management of gestational diabetes: cost-effectiveness in Italy.

This study retrospectively evaluated two groups of pregnant women. Group A women (n=1,338) were universally screened for gestational diabetes mellitus (GDM) and GDM patients were intensively treated. In Group B (n=4,035), screening was performed only in women at high risk for GDM and treatment was conventional. This study confirms the validity of a cost-effective screening program for the diagnosis of GDM and that selective screening may be an option only in a situation where healthcare resources are very scarce and/or universal screening of any kind is not feasible. Once the diagnosis of GDM has been made, metabolic management with an intensive approach is important to reduce maternal and fetal morbidity. Diagnosis of GDM and intensive treatment represent a cost for the public health system, but permit a significant monetary savings in terms of costs linked to maternal and neonatal morbidity.

Cerebral visual impairment in preterm infants with periventricular leukomalacia.

Neonatal brain lesions are the main cause of cerebral visual impairment in infancy, i.e., of a visual deficit caused by damage to posterior visual pathways. Visual outcome of preterm infants with periventricular leukomalacia (PVL) was investigated in 14 subjects affected by severe cystic PVL, another 34 with moderate PVL (prolonged periventricular echodensities), and 18 control preterm infants. All cases with significant ocular abnormalities (such as retinopathy of prematurity state III or upwards, optic nerve atrophy, or major refraction problems) were excluded. Visual acuity, visual field, eye alignment, fixation and following, optokinetic nystagmus, and visual threat were tested at 1 year of corrected age. A high incidence of cerebral visual impairment, consisting mainly of low visual acuity, severe oculomotor disorders, and reduced visual field, was found in infants with severe PVL. Visual defects were less frequent and less severe in the moderate PVL group, and very rare in the control group. The results of neuroimaging, and especially of magnetic resonance imaging, correlated with the visual outcome and indicate lesions at the level of optic radiations as the main anatomic substrate of the visual impairment. All infants with PVL need a visual follow-up, from the first months of life, the results of which are important both for visual and motor rehabilitation of these cases and for their daily care.

Rhythmical leg movements in low-risk and brain-damaged preterm infants.

The characteristics of rhythmical kicking movements of preterm infants with documented brain damage (BD), who later showed a severe motor impairment, are described and compared with those of low-risk (LR) preterm infants. Spontaneous movements were videotaped for 60 min in the incubator or in a warmer. A first group of 6 BD and 6 LR infants was observed at 31-35 weeks of postmenstrual age (PMA) and a second group (6 BD, 6 LR) at 37-39 weeks. Bouts of rhythmical kicks, defined as leg movements repeated in the same form at least three times at regular short intervals, were analysed during periods of activity. The results indicated non-significant differences between BD and LR infants at 31-35 weeks of PMA. In contrast, some differences were observed at 37-39 weeks. These differences were not due to leg movement frequency, but to inter-leg coordination and to temporal organisation of the kicking cycles. LR infants exhibited more alternate-leg movements and fewer semi-both-leg movements (simultaneous flexion and non-simultaneous extension) than BD infants. In LR cases the duration of the pause between flexion and extension was shorter, whereas flexion and extension periods were similar for all infants. Although there were significant differences, quantitative analysis of kicking characteristics was not clinically useful because of the large overlap in findings between the two groups. On the other hand Gestalt evaluation of general movements of the same videorecordings showed a closer correlation with the presence of brain lesions and with neurological outcome.

Differences and variations in the patterns of early independent walking.

The early development of walking was investigated in 25 normal fullterm and in 25 low-risk preterm infants. All subjects were videorecorded within 3-4 weeks of the beginning of independent walking and again 4 months later. Analysis of the videos was carried out according to a predetermined list of items, with a semiquantitative score for each. The results indicate wide interindividual differences in normal infants in the form of independent walking. Several items seemed to be associated in different ways in different individuals. Age of onset, as long as the corrected age was considered, did not differ between preterm and fullterm infants, neither did their walking patterns. Gait asymmetries were often observed in both groups and they were related with asymmetries observable in prewalking locomotor behaviour. Toe-strike often occurred at the beginning of walking, but not after 4 months; in preterm infants the toe strike pattern correlated significantly with certain motor characteristics observed during the first weeks of life.

Kinematic and qualitative analysis of lower-extremity movements in preterm infants with brain lesions.

BACKGROUND AND PURPOSE: The purposes of this study were to evaluate the effects of preterm birth, severe brain lesions, and postterm age on kicking movements of young infants and to compare the prognostic value of kinematic analysis of kicking with a qualitative assessment of infants' spontaneous movements. SUBJECTS: The subjects were 12 full-term infants without brain injury, 12 low-risk preterm infants without brain injury, and 11 preterm infants with severe brain lesions (periventricular leukomalacia). METHODS: Videotape recordings of each infant's motor behavior in a supine position were made at 1 and 3 months postterm age. Kicking frequency, temporal organization of the kick cycle, coordination among different joints, and interlimb coordination were measured. A qualitative assessment for lower-extremity movements and a Gestalt judgment of general movement quality according to Prechtl's method were made from the same videotape recordings. RESULTS: Kinematic analysis showed only mild differences among the 3 groups of infants. Qualitative assessment of the lower-extremity movements, however, showed that preterm infants with brain lesions, and particularly those who later were found to have cerebral palsy, consistently had fewer segmental movements of the foot and abnormal general movements at both ages. CONCLUSION AND DISCUSSION: The data suggest that the mechanisms responsible for kicking movements in newborns and young infants do not appear to be influenced by the extrauterine environment or by brain lesions, at least at the ages studied. Qualitative assessment of lower-extremity and general movements seems to be more appropriate for clinical purposes.