Long-term clinical and serological follow-up of paediatric patients infected by SARS-CoV-2.

Studies concerning Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in paediatrics are limited to children mainly selected from hospitals, where patients with complications and co-morbidities are managed. We aimed to describe the course of the Coronavirus Disease 2019 (COVID-19) in a population of children enrolled by place of residence, from diagnosis to recovery, with a long-term clinical and serological follow-up. We identified patients aged <14 years old living in the Turin Health District 3 who had SARS-CoV-2 detected in at least one nasopharyngeal swab from 1st March to 1st June 2020. Epidemiological and clinical features of SARS-CoV-2 infection were collected by way of a telephone inquiry. Enrolled patients were tested for SARS-CoV-2 serology in order to provide evidence of seroconversion and persistence of specific antibodies some time after the infection. A total of 46 patients with SARS-CoV-2 infection/COVID-19 were identified. The main pattern of viral transmission was intra-family. Eleven children were totally asymptomatic. If symptoms appeared, the disease had a mild course. A single case of COVID-19-related respiratory insufficiency was registered. Among children who underwent serological evaluation, 84% had seroconversion. No significant differences in antibody development were found according to the age and the burden of the disease. Children tested farther from the primary infection had lower antibody index titre values than the others. In conclusion, COVID-19 has a good prognosis in paediatric age. Children are able to develop a valid immune response, although their index titres seem to decrease a long time after the disease.

Gastrointestinal involvement in paediatric COVID-19 - from pathogenesis to clinical management: A comprehensive review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the first pandemic of the 21st century. As found in adults, signs and symptoms related to the disease mainly involve the respiratory tract in the paediatric population. However, a considerable number of children present with gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. The purpose of this review is an accurate description, from pathogenesis to clinical presentation, diagnosis and treatment, of COVID-19 effects on the gastrointestinal system at a paediatric age. SARS-CoV-2 can be identified in stool specimens of affected children by real-time polymerase chain reaction techniques. Positivity can last for several weeks after the end of the symptomatic phase. Gastrointestinal signs and symptoms are generally self-limited, can correlate with blood tests and imaging alterations, and may require supportive treatment such as hydration. However, they can precede severe disease manifestations such as the COVID-19-related multisystem inflammatory syndrome. Children belonging to risk categories such as those affected by celiac disease, inflammatory bowel disease, and hepatic disease seem to not have a more severe course than the others, even if they are undergoing immunosuppressant treatment. Medical follow-ups of patients with chronic diseases need to be revised during the pandemic period in order to postpone unnecessary tests, mainly endoscopic ones.

Apparent Life-Threatening Events: Helping Infants Help Themselves.

OBJECTIVES: Apparent life-threatening event (ALTE) refers to a constellation of unexpected events suddenly occurring in infants that extremely alarm the observers. The objectives of this study were to evaluate 1) intervention of Emergency Service (ES) at home, 2) parental behavior before ES intervention, 3) patients' outcome at follow-up of a minimum of 6 months. METHODS: Retrospective study of infants younger than 12 months whose parents called ES and were evaluated for ALTE from 2005 to 2014. Tactile stimulation (TS) was defined as any maneuver performed by parents or ES staff aimed at rescuing patients without cardiopulmonary resuscitation attempts. Cardiopulmonary resuscitation was defined according to American Heart Association Guidelines 2010. RESULTS: One hundred eighty-eight patients were eligible. Emergency Service provided intervention for 178 infants (10 were assisted only by phone). All patients received TS by parents before ES arrival. Mean time for ES to reach patient location was 15 ± 10 minutes. On examination, 136 patients (76.5%) seemed normal and 42 symptomatic. One hundred sixty-three patients were brought to the emergency department where 23 patients were found symptomatic. One hundred six of 163 patients underwent capillary blood gas determination and, in 28 (26%) of 106, alterations were found. No infant had subsequent cardiopulmonary arrest or clinically evident adverse neurological outcome. Six were found to be epileptic. No infant died during the episode or during follow-up. CONCLUSIONS: Our findings suggest that ALTE is an alarming but self-limiting phenomenon that can be resolved either spontaneously or by simple TS in most cases. Emergency Service should solicit patients' physiological responses through TS first while considering a cardiopulmonary resuscitation maneuver.

Quantitative ultrasound applied to metacarpal bone in infants.

Aim. To provide bone status assessment in infancy using quantitative ultrasound (QUS) applied to second metacarpus. Methods. 103 healthy term infants and 3 patients with rickets, aged ≤ 12 months, underwent metacarpal QUS evaluation using QUS DBM Sonic Aurora IGEA (MO, Italy), which measures speed of sound (mcSOS) and bone transmission time (mcBTT). Results. In the total sample, median (interquartile range) of mcSOS was 1640.00 (26.0) m/s and mcBTT 0.82 (0.21) µs. Moreover, reference values for age were obtained based on estimation of the lower and upper percentiles. We observed a statistical significant difference between groups of age for mcSOS (p = 0.016). In a multiple linear regression model, we found a relation between age at enrolment and mcSOS (ß = -0.608; p = 0.000) and mcBTT (ß = -0.819; p = 0.001). A positive correlation between mcSOS and mcBTT has been observed (r = 0.631; p = 0.000). All the patients with rickets showed values of mcSOS and mcBTT lower than the 10th percentile. Conclusion. Our findings show that this new simple technique appears to be a promising tool for monitoring bone mineral status in pediatric clinical practice and in early life. Furthermore, it could be considered a useful method to investigate and to monitor the role of different factors on programming of bone health and it should be tested as a new method for monitoring subjects with rickets during therapy.

Resistin and leptin in breast milk and infants in early life.

BACKGROUND: The role of adipokines in early life is considered an emerging topic issue in nutritional researches. AIMS: To evaluate serum resistin and leptin concentrations and their relations in infants and in breast milk. STUDY DESIGN: We enrolled 41 term, AGA, healthy infants, of which 23 exclusively breast-fed (BF) and 18 formula-fed (FF), aged less than 6 months. Breast milk (BM) samples were collected from 23 breastfeeding mothers of the infants enrolled. Resistin concentration in serum and BM was determined by ELISA test (Human-Resistin-ELISA, Mediagnost, Reutlingen, Germany). Leptin concentration was determined by Radioimmunoassay method (LEP-R40, Mediagnost, Reutlingen, Germany). Infants weight, length and body mass index were measured. We used Mann-Whitney test. Spearman correlation was applied. Statistical significance was set at p<0.05. Data are reported as median and interquartile range (IR). RESULTS: Infants serum resistin concentration was 9.30 (5.02) ng/ml. Breast milk resistin concentration (n=23) was 0.18 (0.44) ng/ml. Leptin concentration was 3.04 (3.68) ng/ml in infants serum and in BM was 2.34 (5.73) ng/ml. Serum resistin concentrations in BF infants correlated positively with BM resistin (r=0.636, p=0.035). We have shown a positive correlation between resistin and leptin in total group of infants (r=0.44, p=0.05), confirmed in breastfed subjects (r=0.65, p=0.02). No correlations were found between serum hormones and anthropometric parameters of infants. CONCLUSION: Our findings show interestingly a positive correlation between resistin concentrations in BF infants serum and in BM and between resistin and leptin in infants.

Ghrelin and feeding behaviour in preterm infants.

The importance of early life events in the development of metabolic diseases is well recognized. Early postnatal environment, including nutrition, is key to future health, and this is particularly true for preterm infants. It is important that these infants receive sufficient nutrients to prevent growth restriction and promote neurodevelopment, while minimizing predisposition to metabolic diseases later in life. Feeding habits are the fundamental elements of nutrition and are influenced by many factors, including personal and familial habits, socioeconomic status, and cultural environment. In the last decades, there has been an important scientific interest toward the comprehension of the molecular and neural mechanisms regulating appetite. In these networks, act many peptide hormones produced in brain or gut, among which ghrelin is important because of its action in the short-term regulation of food intake and the long-term regulation of body weight. Ghrelin stimulates appetite and plays a role in regulating feeding behaviour. Ghrelin levels vary from fetal life through to early adulthood, with the highest levels observed in the very early years. Cord ghrelin levels have been evaluated in term and preterm newborns and high ghrelin levels have been observed in small-for-gestational age newborns and in newborns with intrauterine growth restriction. Moreover, ghrelin has been detected in term and preterm human breast milk, suggesting that it may play a role in the development of neuroendocrine pathways regulating appetite and energy homeostasis in early life. However, more research is required to better define ghrelin's role in breast milk and on feeding behaviour.

Assay of ghrelin concentration in infant formulas and breast milk.

AIM: To test if total ghrelin is present in infant formulas. METHODS: Using a radioimmunoassay, we measured total ghrelin concentrations in 19 samples of commercial infant formulas and in 20 samples of human milk. We also determined ghrelin concentration in the serum of infants and lactating mothers. RESULTS: Ghrelin concentrations were significantly higher in artificial milk (2007.1 ± 1725.36 pg/mL) than in human milk (828.17 ± 323.32 pg/mL) (P = 0.005). The mean ghrelin concentration in infant serum (n = 56) was 1115.86 ± 42.89 pg/mL, and was significantly higher (P = 0.023) in formula-fed infants (1247.93 ± 328.07 pg/mL) than in breast-fed infants (1045.7 ± 263.38 pg/mL). The mean serum ghrelin concentration (mean ± SD) in lactating mothers (n = 20) was 1319.18 ± 140.18 pg/mL. CONCLUSION: This study provides evidence that total ghrelin is present in infant formulas. This finding raises diverse questions regarding the uptake, absorption and metabolic effects of this hormone.

Fulminant hepatitis after 10 days of acetaminophen treatment at recommended dosage in an infant.

Acetaminophen is considered a safe drug for children, although hepatotoxicity may develop after overdosing. Reports of liver failure after repeated therapeutic doses of the drug have been rare. Here we describe the case of an infant who developed acute liver failure after administration of acetaminophen for 10 days at a total dose of 720 mg/day (72 mg/kg per day). The patient had high levels of aspartate aminotransferase (11 735 U/L) and alanine aminotransferase (6611 U/L) accompanied by encephalopathy and an increased ammonium level (266 µg/dL). Intravenous N-acetylcysteine therapy resulted in rapid improvement of the child's clinical condition and laboratory test results. Health care providers should be aware that multiple doses of acetaminophen in infants may lead to acute hepatic failure. N-acetylcysteine therapy should be initiated in cases of drug-induced acute liver failure.

Adipokines in breast milk and preterm infants.

Studies have shown that the early life environment affects feeding behaviour, food intake and energy balance in later life, suggesting there is a link between foetal and infant growth and the risk of metabolic disorders in adulthood. Although there is an evident epidemiological association between low birth weight and adult-onset diseases, the incidence of metabolic diseases in adulthood among people who were born prematurely is still unknown. Considerable advances have been made during the last years in the scientific knowledge of the benefits of early nutrition, such as breastfeeding, on health and well-being later in life. Nutritional researchers have focussed their attention on the biological characteristics of human breast milk, which represents the main source of nutrients in the first months of life for breastfed infants. Recently, leptin and ghrelin have been detected in the breast milk of mothers of term and preterm infants. Adiponectin and resistin, present in term human milk, have not been investigated in the breast milk of mothers of preterm infants. These hormones are involved in the regulation of energy balance and may have a role in the regulation of growth and development in the neonatal period and infancy, as well as long-term effects on metabolic programming. Leptin, adiponectin and resistin have been found at lower levels in pre-term infants compared with term newborns, whereas there seems to be no difference in ghrelin levels. Future research is necessary to clarify the role of hormones present in breast milk for identifying potential short- and long-term effects of breastfeeding on the health of children born prematurely.

[Breast milk: biological constituents for health and well-being in infancy]. / II latte materno: costituenti biologici per il benessere del bambino.

Many factors are involved in infants' health; one of the most important of them may be the kind of early feeding. Recent evidences suggest that breastfeeding, in addition to its well-established beneficial effects during lactation period, provides also beneficial long-term effects, like the protection against infectious and immune-related diseases, a better cognitive development, a decreased risk of metabolic syndrome and of obesity. It has been reported that the early feeding mode affects growth and body composition and it could be considered a critical factor for metabolic development. Human milk is a source of different nutrients and bioactive factors, especially hormones and growth factors like leptin, ghrelin, insulin, insulin-like growth factor (IGF-I) playing a role in food intake regulation, metabolism and body composition. In particular breast milk leptin may provide a physiological explanation for a number of advantages seen in reaching proper growth and energy balance in breast-fed infants compared with formula fed ones. Etiopathogenesis and therapeutic approach in common minor gastrointestinal diseases in infants are important subject of study for pediatricians. Colic, constipation and regurgitation can be considered feeding problems and they might benefit from dietary treatment. Regarding infantile colic, dietary modifications seem to be more suitable than pharmacological treatment in resolving symptoms; also prebiotics and probiotics are useful for this aim. The occurence of constipation is related to the kind of feeding and it is lower in breastfed infants. Moreover formulas with probiotics and beta-palmitic acid could promote a regression of symptoms. A dietary approach may be useful also in regurgitation. Anyway we have to remember that breastfeeding require a supplementation of vitamin D and K for some months and a correct weaning program is needed from the 5th-6th months of life to prevent iron deficiency.