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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
https://doi.org/10.1186/s13052-022-01374-8
REVIEW
New insights inpediatrics in2021: choices
inallergy andimmunology, critical care,
endocrinology, gastroenterology, genetics,
haematology, infectious diseases, neonatology,
neurology, nutrition, palliative care, respiratory
tract illnesses andtelemedicine
Carlo Caffarelli1* , Francesca Santamaria2, Ettore Piro3, Simona Basilicata2, Valeria Delle Cave2,
Marilena Cipullo2, Sergio Bernasconi4 and Giovanni Corsello3
Abstract
In this review, we report the developments across pediatric subspecialties that have been published in the Italian
Journal of Pediatrics in 2021. We highlight advances in allergy and immunology, critical care, endocrinology, gastroen-
terology, genetics, hematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract
illnesses and telemedicine.
Keywords: Allergy, Immunology, Critical care, Endocrinology, Gastroenterology, Genetics, Hematology, Infectious
diseases, Neonatology, Neurology, Nutrition, Palliative care, Respiratory tract illnesses, Telemedicine
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Introduction
Amid the persistence of the pandemic, the scientific
community pushed ahead innovative studies on the
conditions apart from Covid-19, most managed by
pediatricians. So, in this review, we have looked back
on the 2021 most accessed and innovative papers from
the Italian Journal of Pediatrics. ey offer remarkable
advancements in allergy and immunology, critical care,
endocrinology, gastroenterology, genetics, hematology,
infectious diseases, neonatology, neurology, nutrition,
palliative care, respiratory tract illnesses, and telemedi-
cine to improve care of children.
Allergy andimmunology. 1‑ House dust mite
immunotherapy; 2‑ Eosinophilic esophagitis; 3‑ Kawasaki
disease
House dust mite immunotherapy
e heterogeneity of asthma has long been recognized.
e allergic asthma is often associated with atopic dis-
eases [1] with eosinophil inflammation [2, 3] acidifica-
tion [4] and oxidative stress [5] in the airways. Allergen
immunotherapy, both subcutaneous immunotherapy
and sublingual immunotherapy, remains the only effec-
tive treatment for IgE-mediated allergic rhinoconjunc-
tivitis and asthma [6]. It has also been used in skin
diseases [7]. e subcutaneous route is recommended
in children > 5years of age because less adherence and
Open Access
*Correspondence: carlo.caffarelli@gmail.com
1 Department of Medicine and Surgery, Clinica Pediatrica, Azienda
Ospedaliera-Universitaria, University of Parma, Via Gramsci 14, Parma, Italy
Full list of author information is available at the end of the article
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
lack of quick reporting symptoms of adverse reactions.
However, early allergen immunotherapy may have bet-
ter efficacy. Yang etal. [8] studied safety of house dust
mite subcutaneous immunotherapy in children aged 3
to 5years, with respiratory allergies. e rate of sys-
temic reactions was low. In addition, they were mild,
and no anaphylaxis occurred. ese findings suggest
that subcutaneous immunotherapy appears safe in pre-
school children.
Eosinophilic esophagitis
Both IgE and non-IgE mediated food allergy are frequent
[9]. e definitive mean for diagnosing food allergy is the
oral food challenge [10], that is risky [11] and time con-
suming. Predictors of reactions included specific IgE lev-
els and skin tests to the food [12, 13]. Other biomarkers
such as intestinal permeability has been proposed [14].
In eosinophilic esophagitis, Barni etal. [15] reported that
proton pump inhibitors, corticosteroids and elimina-
tion diets are the first option for treatment. However, the
identification of causal foods to be eliminated from the
diet presents a diagnostic challenge. Elimination diet can
be based on allergy testing results. Another possibility is
an empiric restrict diet that eliminate the most frequent
foods causing allergic reactions, for example the six-food
elimination diet (cow’s milk, egg, soy, wheat, peanuts/
tree nuts, and fish/shellfish). An elemental diet without
allergenic proteins is the most successful diet and it is
also more effective than other first option of treatment.
e choice of treatment should be taken after consider-
ing preferences of parents. Biologics such as dupilumab
seems to be a promising future option for treating eosin-
ophilic esophagitis.
Kawasaki disease
Italian guideline on Kawasaki Disease has been updated
last year [16]. It recommends against waiting more
than 10days before starting treatment with intravenous
immunoglobulin plus medium–high dosage of acetylsa-
licilic acid that has an antinfiammatory effect. Children
at high risk are better defined. ey include: < 12month
of age, PCR > 200mg/L at onset, ipertransaminasemia,
albumin < 2.5 g/dL), severe anemia at onset, coronary
artery aneurysms, macrophage activation syndrome or
septic shock. High risk children should be treated with
intravenous immunoglobulin (plus low dose acetylsa-
licilic acid) and IV methylprednisolone (30mg/kg/day).
Among medication to achieve control, evidence on the
efficacy of infliximab [17], anakinra [18] and canaki-
numab in children with resistant Kawasaki Disease have
been provided.
Critical care. 1‑ Cardiopulmonary resuscitation; 2‑
Psychosomatic pain
Cardiopulmonary resuscitation
ere is a long-standing debate on the survival fol-
lowing discharge from hospital in pediatric patients
who performed cardiopulmonary resuscitation for in-
hospital cardiac arrest with cardiac activity cessation
[19]. Bimerew etal. [20] undertook a systematic review
and meta-analysis on this uncommon event [21]. ey
included 25 studies with 28,479 patients. e preva-
lence of survival was 48%. Living in Asiatic countries
and in low- or middle-income countries was associated
with decreased survival. Caution on the evidence pro-
vided by the study, is justified by high heterogeneity on
the reported prevalence of survival and by lack of con-
sidering factors such as chest compression depth and rate
that were found to be associated with survival outcomes
[22]. Nonetheless, the study showed that most pediatric
patients with in-hospital cardiopulmonary resuscitation
procedures failed to survive after hospital discharge. e
Authors suggest that new strategies are warranted for
cardiopulmonary resuscitation in children.
Psychosomatic pain
Several papers have recently elucidated the clinical care
related to psychosomatic pain [23]. e PIPER (Pain in
Paediatric Emergency Room) group comprises pediatri-
cians, emergency physicians, and anesthesiologists from
52 Italian emergency departments [24]. It presented an
evidence-based approach on clinical features and man-
agement of patients with psychosomatic pain in the
pediatric emergency department. e paper highlighted
differences in clinical manifestations between patients.
Psychosomatic pain is often localized at head or abdo-
men. It can also be simultaneously present in differ-
ent sites or be migrant. It is often every day associated
with marked fatigue, limiting daily activities. It persists
for months or years. e treatment still relies upon psy-
chological assistance for both patients and families [25].
An effective analgesic is lacking. Pharmacological treat-
ment should be used only for psychiatric comorbidities.
e Authors conclude that standardization of care in the
emergency department is warranted.
Endocrinology. 1‑ Faltering growth; 2‑ Phelan‑McDermid
syndrome
Faltering growth
e meaning of the term Failure to thrive is discussed.
Numerous definitions have been given, generally based
on the evaluation of anthropometric parameters (in par-
ticular on a significant decrease in the growth rate) which
do not agree with each other and therefore there does not
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
seem to be a specific parameter to identify patients to be
included in this diagnostic category. It is also hypoth-
esized that failure to thrive cannot constitute a true
category but that it is a clinical signal of an insufficient
nutritional intake to guarantee growth. e term “falter-
ing growth” has recently begun to be proposed to replace
failure to thrive [1]. e etiology of faltering growth is
very heterogeneous and traditionally two categories
of causes are distinguished: organic and non-organic,
although sometimes this distinction is considered
obsolete because there may be an interplay of organic,
behavioural, nutritional and psychosocial factors [26].
However, there is a trend to deepen the multifactorial
links between faltering growth and malnutrition consid-
ered as a signal of imbalance between nutritional intakes
and macro and micronutrient requirements [27]. Gen-
erally, the presence of an organic cause is suspected on
the basis of a detailed medical history and the presence
of specific signs and symptoms and confirmed by specific
tests. It is interesting to note that in large series of hospi-
talized patients diagnosed with failure to thrive in which
patients with recognized organic disease were excluded
the most common final diagnosis was “purely nutrition”
failure to thrive because of inadequate caloric intake,
and that extensive diagnostic workup was rarely helpful
to reveal the etiology [28] In conclusion: 1) an important
diagnostic role is played by the family pediatrician who
can, with a few targeted tests, make an initial diagnosis;
2) hospitalization should be reserved for patients with
specific characteristics and it is useful for the diagnostic
procedure to follow specific flow charts step by step to
avoid unnecessary laboratory and / or radiological inves-
tigations [29]; 3) in most cases the therapy involves the
collaboration of a team that can intervene on the nutri-
tional and behavioral aspects.
Phelan‑McDermid syndrome
Phelan-McDermid syndrome (is a rare genetic syndrome
originally considered to be the expression of a 22q13 dele-
tion and more specifically of alterations in the SHANK3
gene. More recently it has been proposed to include into
this classification also patients with interstitial deletions
close to the locus of this gene and not involving SHANK3
[30]. In fact, these patients present a clinical picture
largely overlapping with that of SHANK3 involvement
[31, 32]. e syndrome is characterized by intellectual
disability, hypotonia, delayed or absent speech, motor
impairment, behavioral anomalies, and dysmorphic fea-
tures [31]. Moreover, autism spectrum disorders may be
present in over 75% of patients. Various pharmacological
substances (intranasal insulin, lithium) have been used in
clinical trials and among these we must mention the insu-
lin-like growth factor-1. Based on the results obtained
with the latter, Xie et al. [32] verified the efficacy of a
treatment with recombinant human growth hormone in
one patient demonstrating that with this hormone it is
possible to obtain results similar to those obtained with
the insulin-like growth factor in the absence of significant
side effects. In particular, an improvement in motor skills
and autism-like behaviors is reported. is positive effect
was subsequently confirmed in an open-label, cross-over
study on a small series of patients [33]. Furthermore,
these results are in line with experimental models in the
rat that have shown that insulin-like growth factor-1 may
increase synaptic plasticity and improve both motor and
behavioral deficits characteristic of Phelan-McDermid
syndrome. Even if the results are not definitive, a new
therapeutic perspective is opening which could be based
on single pharmacological products or on the joint or
serial use of some of them.
Gastroenterology. 1‑Oral ulcers; 2‑ Haemolytic uremic
syndrome; 3‑ Inammatory bowel disease andglycogen
storage disease
Oral ulcers
Aphthous stomatitis is a common disease in childhood
[34]. Legeret et al. [35] have performed a systematic
review to explore causes and treatment of oral ulcers.
e pathogenesis has been found to be multifactorial
and they can be elicited by infections, autoimmune dis-
eases, drugs, immunosuppression, gastrointestinal dis-
eases, nutritional deficiency or local trauma. ere is
controversy about the optimal treatment. Avoidance and
prevention of exposure to triggering agents are neces-
sary as well as supplementation of vitamins and nutrients
when needed. Pain can be relieved by local anesthetics
such as lidocaine and benzocaine, especially at meals.
Chlorhexidine and topical antibiotics can be effective in
controlling infections, especially secondary [36]. Topical
corticosteroids are a useful first-line option for reduc-
ing ulcers [36]. When topical treatment is not effective,
a course of oral corticosteroids may be of benefit [37].
Montelukast, colchicine, dapsone and thalidomide have
been also proposed as second-line options.
Haemolytic uremic syndrome
Hemolytic uremic syndrome (HUS) is a rare disorder
caused by strains of Escherichia coli (E. coli) releas-
ing Shiga-like toxin in up to 90% of cases. e condi-
tion is characterized by microangiopathic hemolytic
anemia, thrombocytopenia, and acute kidney injury.
Central nervous system involvement is the most com-
mon extra-renal disorder in typical hemolytic uremic
syndrome. Major symptoms such as seizures, impaired
consciousness, and stroke were seen in 33% of cases
while minor symptoms in 14% [38]. Eculizumab, an
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
anti-C5-convertase monoclonal antibody, seems to be
helpful for treating children with central nervous sys-
tem symptoms [39]. Peripheral nerve involvement is very
rare. Santangelo etal. [40] showed patients with typical
hemolytic uremic syndrome with late onset inflammatory
polyneuropathy after acute treatment with eculizumab
and renal replacement therapy and resolution of central
nervous system (injury. ese children received meth-
ylprednisolone pulses (and immunoglobulins or plasma
exchange, followed by a prolonged multidisciplinary neu-
rorehabilitation program. A full functional improvement
occurred after intensive 8months of rehabilitation. e
delayed occurrence of peripheral symptoms [40] might
indicate that lack of nutrients (i.e., probiotics or vitamins)
[41] may lead to peripheral neuropathy [42]. Authors
concluded that neuro-rehabilitation may significantly
improve the outcome of children with polyneuropathy
during hemolytic uremic syndrome.
Inammatory bowel disease andglycogen storage disease
Glycogen storage disease type Ib is an autosomal reces-
sive disorder due to microsomal glucose-6-phosphate
transporter deficiency. Glycogen storage disease type Ib
patients [43] present hypoglycemia, glycogen accumula-
tion in liver and kidney, neutropenia, neutrophil dysfunc-
tion, and increased risk of inflammatory bowel disease
(i.e., Crohn disease-like enterocolitis). Treatment is based
on frequent intake of uncooked cornstarch and granulo-
cyte-colony stimulant factor for improving neutropenia
and bacterial infection. Granulocyte-colony stimulant
factor is associated with severe side effects such as acute
myeloid leukemia, myelodysplasia. Granulocyte-colony
stimulant factor is useful on IBD in some patients with
glycogen storage disease type Ib [44]. Empagliflozin is
useful in type 2 diabetes. It reduces renal 1,5-anhydroglu-
citol resorption leading to decrease accumulation in neu-
trophils that impairs survival and function in glycogen
storage disease type Ib [45]. In glycogen storage disease
type Ib and severe IBD, Rossi etal. [46] has found that
empagliflozin improved gastrointestinal symptoms in a
week and granulocyte-colony stimulant factor dose was
reduced by one third. Abdominal magnetic resonance
imaging showed amelioration of disease activity after
3 months. Authors concluded that empagliflozin was
effective with no side effects.
Genetics. 1‑ White‑Sutton syndrome; 2‑ Aromatic L‑amino
acid decarboxylase deciency; 3‑ 15q26 deletion
White‑Sutton syndrome
e report on White-Sutton syndrome [47] is part of the
interesting line of research on genetic causes underlying
developmental anomalies [48]. Specifically, the clinical
contribution expanding the neurological and behavioral
phenotype refers to a patient with White-Sutton syn-
drome, related to a novel heterozygous pogo transposable
element with znf domain (POGZ) mutation [49]. e
patient showed a moderate intellectual impairment, mild
autistic traits and the never described co-existence of
both paroxysmal not-epileptic events and abnormal EEG
without clinical seizures. An important aspect of the arti-
cle is, for those involved in clinical research on genetic
syndromes associated with neurodevelopmental involve-
ment, the wide and updated arsenal of specific diagnostic
techniques relating to the different developmental areas
that the authors have explored to define the patient’s
profile.
Aromatic L‑amino acid decarboxylase deciency
A modified Delphi consensus method, based on the
selection of items drawn from synthesized reviews of the
literature rather than open-ended questions, has been
adopted as main stage of development of the identifica-
tion process concerning presentation, diagnosis, and
treatment of Aromatic L-amino Acid Decarboxylase defi-
ciency [50]. It is an untreatable rare autosomal recessive
neurometabolic disorder, is characterized by a severe
impairment of serotonin, dopamine, norepinephrine, and
epinephrine biosynthesis causing more often early onset
of a severe and progressive neurodevelopmental impair-
ment, although a milder clinical expression has also been
described. In relation to the difficulties of early diagnosis
the Italian working group and a patients’ association have
expressed consensus with high rates of agreement on a
series of statements paving the way to disseminate clear
messages concerning disease presentation, diagnosis [51]
and treatment [52, 53] as well as strategic interventions
to disseminate knowledge at different levels.
15q26 deletion
A patient had a complex phenotype characterized by
developmental, growth and heart involvement. Array
analysis, following a high-resolution R-banded karyo-
gram, identified a 9.15Mb deletion within the 15q26.1-
q26.3 region that was not previously reported [54].
Following the Hugo gene nomenclature committee, the
deleted segment encompassed 36 genes, 19 of whom
were referenced in the OMIM database, and among
which only IGF1R, NR2F2, CHD2 and MEF2A, were
consistent with the described patient’s phenotype [55,
56]. Following the authors’ opinion, 15q26 monosomy
should be taken in consideration in the differential diag-
nosis process when growth retardation is associated with
congenital heart defect, mainly atrioventricular septal
defects and /or aortic arch anomaly [57].
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
Hematology. 1‑ Thalassemia major; 2‑ Hemoglobin
life‑threatening levels
Thalassemia major
Endocrine complications are very common in
multi-transfused thalassemia major patients. For this
reason, international organizations such as the Inter-
national Network on Endocrine Complications in
alassemia (I - CET) have published guidelines for the
monitoring of endocrine diseases in thalassemia major
patients [58]. Most studies on the incidence of endo-
crinopathies in thalassemia major patients are retro-
spective and performed on adult patient populations. It
may therefore be interesting to evaluate this situation
in a pediatric population with the aim both of better
understanding the natural history of the various endo-
crine diseases and of implementing appropriate preven-
tive measures as soon as possible. In the survey carried
out by Mahmood etal. on 120 patients the presence of
endocrine disorders was observed in 23.33% of them.
Subclinical or clinical hypothyroidism, abnormalities
in glucose homeostasis and hypoparathyroidism are
the three endocrine pathologies found [59]. e abnor-
malities in glucose homeostasis which in perspective
can lead to an overt diabetes mellitus deserve a par-
ticular comment, suboptimal iron chelation and pres-
ence of hepatitis C infection may be a risk factor for the
development of insulin glucose intolerance through the
induction of insulin resistance [60]. However, it is inter-
esting that 70% of the patients studied showed signs
of malnutrition [59]. is aspect deserves to be inves-
tigated because recent research leads to consider that
malnutrition at any postnatal age can have both acute
and long-term adverse effects on pancreas function
[61].
Hemoglobin life‑threatening levels
Overall, WHO [62] reported anemia in 42% of children
under 5years-old of age. Parodi etal. [63] provided new
information concerning good clinical condition with only
slowly increasing asthenia despite of unanticipated severe
microcytic anemia (hemoglobin 1.9g/dL, mean corpus-
cular value 64fl) and iron deficiency (iron binding capac-
ity 6%, reticulocyte hemoglobin content 15.2pg) in a girl
of African origin aged 5years. e condition was deter-
mined by iron deficiency [64]
and homozygous sickle cell disease [65]. e patient
received intravenous packed red blood cells (15ml/kg) to
get 7.3g/dL hemoglobin level and after a few days, she
was discharged with 9.8g/dL hemoglobin concentration.
e findings show that life-threatening hemoglobin val-
ues are practically asymptomatic when anemia gradually
get worse.
Infectious diseases. 1‑Acute myositis; 2‑ Hookworm
infection; 3‑ Hematogenous osteomyelitis; 4‑ Nasal
inuenza vaccine; 5‑ Gentamicin; 6‑ Epstein‑Barr virus
andhemophagocytic syndrome
Acute myositis
Limited studies on cohort of children with benign acute
myositis are available. It is overlooked since there is com-
monly spontaneous resolution and occurrence of rhab-
domyolysis, and kidney impairment has been hardly ever
described [66]. Brisca etal. [67] identified 113 children
diagnosed with benign acute myositis from database of
two pediatric Emergency Departments. All patients had
normal neurological findings, and no one developed
myoglobinuria, or renal failure, accordingly with previ-
ous studies [68]. Creatine kinase ranged from 257–12,858
U/L, normal values < 150 U/L. In 51/74 cases (69%) an
association with viral infection was found. In agreement
with previous findings, influenza viruses were the com-
monest (37 cases) [68]. Myositis can be a complications
of severe acute respiratory syndrome coronavirus-2 and
more cases with this virus are expected [69]. Ten percent
of children had recurrent episodes. e median serum
creatine kinase levels were significantly higher in “recur-
rent” type than in “non-recurrent” type. Authors con-
cluded that most patients can be treated at home with
correct fluid intake, analgesics, and resting period.
Hookworm infection
Hookworm infection is common in rural areas of devel-
oping countries. In infancy it is rarely reported [70].
Umbrello etal. [71] reported their experience with an
Italian 2-month-old infant with vomiting, weight loss,
anemia, eosinophilia, and eggs of Ancylostoma duode-
nale in stools. Treatment with oral mebendazole was
successful. Hookworm infection was not reported in the
area where infant lived [72]. e mother travelled in an
endemic country during pregnancy and had gastrointes-
tinal symptoms. However, parents’ stools resulted nega-
tive. So, Authors suggested that vertical transmission of
Ancylostoma infection during pregnancy may explain the
parasitic disease. Although the response to mebendazole
was excellent without side effects [73], the best clinical
management needs to be elucidated.
Hematogenous osteomyelitis
A multidisciplinary experts reach a consensus by Del-
phi method on acute hematogenous osteomyelitis [74].
A systematic review retrieved 53 relevant articles that
were included in the Consensus. Regarding intravenous
antibiotics, the Panel recommended that the first option
was ampicillin-sulbactam or cephazolin + gentamycin
in infants under 3months of age; cephazolin in children
aged 3months—5years to cover K. kingae [75]; oxacillin
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
or cephazolin or clindamycin in children > 5 years. the
switch from intravenous to oral therapy is still a matter
of debate. Defervescence or decreasing body tempera-
ture for 24–48h, improvement of local symptoms, lack
of complication, 30–50% decrease of CRP and pathogens
sensible to antibiotic may be considered for switching
after 2–4days of intravenous antibiotics. In infants and
children > 3 months of age, the panel recommended to
switch to oral therapy within 5–7 days of intravenous
antibiotics. Oral treatment with cephalexin or amoxicil-
lin-clavulanic acid, possibly associated with rifampicin
should be given. Among the antistaphylococcal penicil-
lin, flucloxacillin, should be the first choice. e length of
anticrobial treatment may vary from 3 to 6weeks, mean
4weeks [76, 77].
Nasal inuenza vaccine
e availability of live attenuated influenza vaccine
(LAIV) for intranasal administration has given clinicians
choices for individual patients. It seems more effective
than intramuscular one in children [78, 79]. Gasparini
et al. [80] assessed efficacy and parent’s satisfaction of
LAIV in 9292 children. ey confirmed that rate of
adverse events was 24.8%: 80.6% mild, 18.1% moderate
and 1.3% significant [81]. Cold (52.5%) and fever (24.4%)
were the most frequent. Most parents (83.3%) were very
satisfied of LAIV, and they would give further jabs. Most
health professional found that LAIV administration was
easy. e authors concluded that LAIV is a safe and suit-
able option.
Gentamicin
Gentamicin is a bactericidal aminoglycoside to aerobic
Gram-negative bacilli and some Gram-positive cocci
with potential risk of nephrotoxicity and ototoxicity [82].
Ghoneim et al. [83] studied MICs of intravenous gen-
tamicin in subjects, aged from 1month to 12years of age,
using Monte Carlo simulation. ey found that a MIC of
2mg/L is reached using once daily dose of 6–7 mg/kg/
day in infants aged 1month – 12months and of 4–5mg/
kg/day in children > 1year of age. ese findings extend
previous results [84] on effective gentamicin level with-
out toxicity.
Epstein‑Barr virus andhemophagocytic syndrome
In patients with Epstein-Barr virus (EBV) infection, mon-
onucleosis and hemophagocytic syndrome (HLH), can
develop [85]. e most common secondary HLH in chil-
dren is linked to viral infection, especially EBV [86]. Shi
etal. [87] determined the clinical, and laboratory char-
acteristics of the 31 EBV-HLH compared to 61 mononu-
cleosis cases. ey noted that cellular immune function
was significantly impaired in in the HLH group [88].
Increased D-Dimer level is a predictor of HLH in chil-
dren with EBV.
Neonatology. 1‑ Sepsis; 2‑ Intravenous sodium
bicarbonate; 3‑ Neonatal seizures; 4‑ Umbilical venous
catheter; 5‑ Retinopathy ofprematurity; 6‑ Glucose
infusion inpreterm infants; 7‑ Respiratory distress
syndrome; 8‑ Delayed cord clamping: 9‑ Hypercalcemia
andhypophosphatemia; 10‑ Necrotizing enterocolitis;
11‑ Hypertrophic cardiomyopathy; 12‑ Asymptomatic
hypoglycemia; 13‑ Congenital hypothyroidism screening
Sepsis
Since several studies have showed multiple short and
long-term adverse health effects in infants undergoing
prolonged antibiotic treatments, reduction of antibiot-
ics administration during the early post-natal period
has become a fundamental need. One of the strategies
developed to rationalize the use of antibiotics has been
the development of tools such as the early onset sepsis
risk calculator [89, 90]. In this single-center retrospec-
tive study Laccetta etal. [91], assuming an incidence of
early-onset sepsis of 2/1000 live births, enrolled a total of
265/1667 (15.9%) newborns ≥ 34 weeks’ gestational age
and compared the number of patients for which antibiot-
ics would have been needed, based on early-onset sepsis
calculator, and the number of the same patients treated
with antibiotics during the study period. e comparison
showed in the newborns selected using the early-onset
sepsis calculator a lower antibiotic use (12.1%) than the
expected (20.7%). e results of this study highlight the
need to pursue the best possible antibiotic stewardship,
based on a continuous evidence-based update of local
guidelines, to further decrease their administration in
newborns [92].
Intravenous sodium bicarbonate
Intravenous sodium bicarbonate corrects metabolic aci-
dosis, but it is not without potential risks such as fluc-
tuations in cerebral and cardiovascular hemodynamic,
increased rates of severe intraventricular hemorrhage
and mortality [93]. Massenzi etal. [94] conducted a sur-
vey regarding treatment of metabolic acidosis and intra-
venous sodium bicarbonate prescription habits, involved
117 neonatal intensive care units. e authors used a
14-item questionnaire developed by the Neonatal Phar-
macology Study Group of the Italian Society of Neona-
tology (SIN), that is filled and sent in about 15min. e
study showed that intravenous sodium bicarbonate is
a commonly used treatment for metabolic acidosis in
more than half of Italian neonatal intensive care units,
with significantly variable indications and prescription
criteria across centers. ey concluded that intravenous
sodium bicarbonate should be given to selected cases [95,
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
96], also considering the severity of intravenous sodium
bicarbonate adverse effects and the lack of evidence
about its efficacy.
Neonatal seizures
e authors of this systematic review deepen the contro-
versies about therapy of neonatal seizures [97]. In recent
years, advances in the diagnosis [98] and etiological
definition of neonatal seizures have allowed more pre-
cise therapeutic approaches [99]. New pharmacological
approaches are nowadays available, like sodium channel
blockers for genetic early-onset epilepsies as well as the
overall good response to levetiracetam of neonatal sei-
zures [100]. Nevertheless, the World Health Organiza-
tion (WHO) recommends the use of phenobarbital and
phenytoin as first-line treatment yet. e authors con-
clude, that owing to the heterogeneity of the variables
considered in the different studies, such as the gestational
or postmenstrual age of the samples and the terms of def-
inition of the therapeutic response among the main ones,
a persistence of limited available evidence regarding the
best pharmacological treatments for neonatal seizures
still exist.
Umbilical venous catheter
Standard umbilical venous catheter insertion distance is
assessed by anthropometric measures or formulas and
nomograms usually based on birth weight. Recent guide-
lines advocate the use of real-time ultrasound to locate
umbilical venous catheter tip [101–103]. Rubortone etal.
[104] reported on a pre/post interventional study on fifty-
four patients to evaluate the efficacy of a training proto-
col in using ultrasound. A significative improvement in
the correct placement of the tip of the catheters was get
after the training (75% vs 30.7%, p = 0.0023). Interest-
ingly 50% of the positioned catheters underwent migra-
tion, as demonstrated by serial scans evaluation included
in the protocol. is article offers a valid contribution to
the topic and provides useful iconography and detailed
description of the protocol used.
Retinopathy ofprematurity
Dani et al. [105] conducted a study to assess inci-
dence [106] and risk factors [107, 108] for retinopa-
thy of prematurity (ROP) development in preterm
infants < 30 weeks gestational age, involving two neo-
natal intensive care units (NICUs) and 178 infants of
which 67 (38%) developed any grade of ROP. Compari-
son of both the unaffected and affected by ROP sample
(stage 1–2-3), using univariate and multivariable logistic
regression analyses, allowed to identify maternal milk
as protective and intraventricular hemorrhage and RBC
transfusion as increasing risk factors for the development
of ROP. e occurrence of ROP was similar to that pre-
viously reported. Limitations of this study, reported by
the authors, are mainly due to the heterogeneity of the
samples in relation to several not included concomitant
maternal and neonatal risk factors, and the lack of severe
ROP (stage 4 and 5) cases.
Glucose infusion inpreterm infants
In newborns, especially if preterm [109], persistent
altered blood glucose values (hypoglycemia and hyper-
glycemia [110] can be responsible for serious short
and long-term consequences [111]. In preterm infants
weighing < 2500 gr, the link between parenteral nutri-
tion with three different glucose infusion rates 5- < 7,
7–13 and > 13–15g/Kg/day, and selected neonatal mor-
bidities and mortality, was studied [112]. Main results
from univariate and multivariate logistic regression ana-
lyzes showed that glucose infusion of 5- < 7g/kg/day in
the first week, was an independent variable that signifi-
cantly increased the risk of hypoglycemia (P = 0.010) and
reduced the risk of sepsis (P = 0.026).
Respiratory distress syndrome
Term neonates can present neonatal respiratory dis-
tress syndrome (NRDS) with well described maternal
and neonatal risk factors [113–115]. In this prospective
case–control study, the authors compare 55 newborns
with NRDS diagnosis and 79 non-NRDS as controls
[116]. Main risk factors associated with the incidence and
severity of NRDS were male gender (p = 0.045), elective
caesarean section (p = 0.01) and early-onset infection
(p = 0.055), while hypotension and pulmonary hyperten-
sion were associated with longer duration of parenteral
nutrition and higher rate of blood transfusions. Main
strength of this study is the prospective recruitment of
participants and related data collection, while main limit
is not have included information or correlation with
severity predictive tools as Clinical Risk Index for Babies.
Delayed cord clamping
Delayed cord clamping (DCC) [117] is recommended for
both preterm [118] and vigorous term neonates [119].
In a retrospective study [120] on 796 women and their
term neonates delivered by cesarean section, the authors
compare the effects of early versus DCC (< 30, 30–60 and
61–120s), on short-term neonatal hematological status
(hemoglobin and hematocrit) and jaundice (transcuta-
neous bilirubin levels on 0 to 5days of life and the rate
of phototherapy). e results showed that in the whole
DCC cohort (30–120s), clamping merely increased the
transcutaneous bilirubin level of neonates on the day of
birth and in the DCC at 30–60 is a higher neonatal hemo-
globin level on day 3 and an increased rate of neonatal
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
polycythemia, without a higher rate of phototherapy.
e authors conclude that DCC at 30–60s should be an
optimal time in cesarean section, which could benefit the
neonates in the long term.
Hypercalcemia andhypophosphatemia
Both hypercalcemia and hypophosphatemia could be
deleterious in newborns [121, 122]. Improda etal. [123]
describe a premature infant presenting with early severe
hypercalcemia. In this patient, after a careful evaluation
of the various pathogenetic hypotheses, according to the
most compatible with laboratory data and the response
to the therapeutic interventions, the authors ascribe
to hypophosphatemia the key pathogenic factor [124].
e etiopathogenetic mechanism by which hypophos-
phatemia should have act was the inhibition of the secre-
tion of FGF23, leading to increased activity of 1-alfa
hydroxylase with production of 1,25(OH)2D, responsible
for hypercalcemia. is article enriches the knowledge
for the reader by providing useful and interesting insights
into the correct monitoring and supplementation of
phosphate and calcium in the first week of life in prema-
ture infants.
Necrotizing enterocolitis
Savarino et al. [125] described the clinical characteris-
tics and the different therapeutic paths undertaken of
18 preterm infants with necrotizing enterocolitis. ey
reported age of onset, duration of previous enteral, as
well as total parenteral feeding following surgery. In this
population 77.8% received surgery and the overall sur-
vival rate was 55.5%. e absence of infants with stage I
necrotizing enterocolitis may be related, to a failure of
early diagnosis, being some of them out born, while the
high prevalence of necrotizing enterocolitis at stage III
(78%) to the presence of a Pediatric Surgery Ward in the
same hospital. e discussion provides updates and con-
siderations on enteral and parenteral feeding as well as
medical and surgical treatment for necrotizing enterocol-
itis [126–128].
Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy accounts for 25 to 40%
of all pediatric cardiomyopathy cases with the highest
incidence in pediatric population in children < 1 year.
e authors [129] take a cue from two newborns of dia-
betic mother suffering from hypertrophic cardiomyopa-
thy to address the diagnostic and therapeutic approach.
Hypertrophic cardiomyopathy may be characterized by
recovery [130] or by progressive worsening [131, 132]
that require skills in genetic and metabolic diagnosis
along with a careful follow-up, as reported in the neo-
nate with Pompe disease. An important message for the
neonatologist is that early onset hypertrophic cardiomy-
opathy shows a high incidence of inborn errors of metab-
olism and neuromuscular disorders and that about 50%
of hypertrophic cardiomyopathy cases under one year of
age remains idiopathic.
Asymptomatic hypoglycemia
Asymptomatic hypoglycemia is a very dangerous condi-
tion, since it may cause, if prolonged, potential short and
long-term adverse outcomes [133]. In a retrospective/
prospective study on asymptomatic hypoglycemia in neo-
nates > 35weeks’ gestational age, Meneghin et al. [134]
compared a previous standard approach [135] based on
human or artificial milk and in selected cases on glucose
infusion, and administration of 40% oral dextrose gel at
200mg/kg followed by breast-feeding, squeezed human
milk or artificial milk. Advantages of the latter approach
were evident for both primary outcomes specifically
occurrence of NICU admission (p = 0.001) and require-
ment of intravenous glucose (p = 0.01), as well as for the
secondary outcome of exclusive breastfeeding at dis-
charge (p = 0.02). e paper included clear and informa-
tive flow charts describing the two approaches that can
be considered a valid starting point for a more adequate
management of neonatal hypoglycemia [136].
Congenital hypothyroidism screening
Congenital hypothyroidism is an endocrine disease
affecting 1:2000–1:3000 newborns in Italy. Early iden-
tification of congenital hypothyroidism [137] is based
on the neonatal screening [138], and the choice of the
TSH cutoff value is the discriminating element [139]. In
this retrospective analysis of neonatal screening data,
Maggio etal. [140] compared the number of congenital
hypothyroidism diagnosis if the TSH cutoff was consid-
ered as ≥ 6—< 7 mU/L , ≥ 7—< 10 mU/L and ≥ 10 mU/L .
Main conclusion of the study was that adopting a TSH
cutoff ≥ 6mU/L allowed recognizing 20.7% of neonates
with confirmed high TSH levels, otherwise not recruited
by the employed TSH cutoff > 7 mU/L. e authors
detected additional cases of permanent congenital hypo-
thyroidism, a number of which showed defects of thyroid
embryogenesis and severe hypothyroidism at the confir-
mation of the diagnosis by serum levels of fT4, fT3 and
TSH and by ultrasound and/or scintigraphy.
Neurology. 1‑ Autism; 2‑Plagiocephaly; 3‑ Post‑infectious
neurological syndromes; 4‑ Neuroblastoma; 5‑ Anorexia
nervosa; 6‑ Epilepsy; 7‑ Fetal alchool spectrum disorder; 8‑
Cognitive functions
Autism
Autism spectrum disorder is a neurodevelopmental
disorder displaying individual impairments in social
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
interaction, communication skills, interest, and behav-
iours [141]. e autism can be diagnosed through e
Autism Diagnostic Observation Schedule-Generic, a
standardized assessment of social interaction, commu-
nication, play, and imaginative use of materials which
considers the level of expressive language [142]. Most
children who undergo the correct treatment at preschool
age, after some months can greatly improve and do not
show the initial behaviors, typical of the autism spec-
trum disorders. It has been increasingly recognized that
it is important to evaluate the presence of positive pre-
dictive factors of outcome. Di Rienzo etal. [143] showed
that the indicators were IQ, emotional contagion, under-
standing of others’ intentions and level of play achieved.
To achieve a good outcome at least 3 predictive indica-
tors must be present. Better verbal ability predicted bet-
ter communication, socialization and daily living skills,
global adaptive functioning, while better nonverbal abil-
ity predicted better motor skills. Autism spectrum disor-
der symptom severity has not proven to be a predictor of
outcome [144]. Klinger etal. [145] found that treatment
characteristics, including intensity and duration, are the
most universally agreed upon predictors of treatment
outcome, whereas an additional predictor of outcome
which demonstrates congruent findings across studies is
parental involvement. In conclusion, at preschool age, a
therapeutic path for autism spectrum disorders must be
considered fundamental for intervening in the affective-
relational component, since at that age the brain has the
potential to change structurally and functionally.
Plagiocephaly
Positional plagiocephaly, or non-synostotic plagioceph-
aly, is the most common cranial asymmetry. It results
from mechanical factors applied, over a period in utero,
at birth, or postnatally. It is often associated with exces-
sive time in supine and with congenital muscular torticol-
lis. Children with positional plagiocephaly are more likely
to develop several conditions such as postural compen-
sations, muscle flexibility and balance alterations, visual
dysfunctions, temporomandibular dysfunctions, man-
dibular and occlusal asymmetries, neurodevelopmental
alterations, lower cognitive and academic results, and
language acquisition deficit. For this reason, it is impor-
tant to start treatment early, when children are younger
than 6.5months [146]. Rogers etal. [147] showed that
there was a restriction of active cervical rotation in all the
cases of plagiocephaly studied, even without a previous
diagnosis of congenital muscular torticollis, thus it is use-
ful to use manual manouvres. e first line treatment rec-
ommended in the guidance reviewed for both positional
plagiocephaly and congenital muscular torticollis include
parent education and support, positioning/tummy-time,
and physical therapy, followed by helmet therapy as a sec-
ond line of treatment for infants with moderate to severe
and persisting asymmetry. e Congress of Neurological
Surgeons’ guidance recommended to use manual therapy
and repositioning rather than positioning pillows [148].
A recent randomized controlled trial shows that adding
manual therapy to a caregiver educational program is
associated with a better outcome in terms of neck move-
ment in positional plagiocephaly. e technique applied
consists in letting the baby’s head rest on the hands of the
practitioner. Both fourth and fifth fingers were positioned
on the condylar area of the occipital bone, the middle fin-
ger on the articular processes of the axis, the index fin-
gers on the articular processes of the cervical vertebrae
below C2. e thumbs were placed on the anterior side of
the transverse processes of the atlas to cause a very gen-
tle dorsal positioning of the atlas, following the active and
spontaneous movements of the baby [149].
Post‑infectious neurological syndromes
Post-infectious neurological syndromes are heterogene-
ous neurological disorders with post or para-infectious
(within 15days from the infectious event) onset. ese
include the Acute Disseminated Encephalomyelitis, the
Mild Encephalitis/Encephalopathy with Reversible Sple-
nial Lesion, the Clinically Isolated Syndrome, and the
Autoimmune Encephalitis and Necrotizing Encephalitis.
ese syndromes are characterized by demyelination,
caused by immune-mediated reactions against cerebral,
spinal cord and optic nerves white matter. e diagnosis
may be difficult because there are no officially recognized
guidelines. e only existing criteria have been published
by the IPMSSG (reviewed in 2013) [150] and include
pediatric multiple sclerosis and immune-mediated cen-
tral nervous system demyelinating disorders. Tardieu
etal. published a consensus definition for pediatric mul-
tiple sclerosis and other demyelinating disorders in child-
hood and propose to incorporate in IPMSSG criteria the
2010 McDonald criteria, when specific features are pre-
sent [151]. Nevertheless, post-infectious neurological and
multiple sclerosis show different clinical, neurobiological,
and magnetic resonance imaging features [152]. No doc-
uments have ever mentioned specifically the post infec-
tious neurological syndrome. Bozzola etal. [153] tried to
provide with some indications and criteria for establish-
ing a correct diagnosis. ey suggested to consider the
following parameters: neurological symptoms, timing
of disease onset, blood and cerebral spinal fluid labora-
tory tests (positive for pathogenic IgM/IgG as a previous
infection; positivity of autoantibodies; negative blood
culture; negative cerebral spinal fluid culture, to exclude
meningitis or acute infections), magnetic resonance
imaging (which seems fundamental, even in the absence
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
of clinical or laboratory diagnostic findings). Magnetic
resonance imaging remains the most important criteria,
even though other laboratory tests demonstrating the
previous infection should be considered.
Neuroblastoma
Neuroblastoma is a heterogeneous solid tumor that
arises in the sympathetic nervous system. Neuroblas-
toma tumors most commonly develop in the abdomen
and are most frequently localized in the adrenal glands
[154]. Clinical symptoms vary, depending on the site
of the primary tumor and may include an abdominal
mass, abdominal pain, respiratory distress, or neuro-
logical symptoms due to spinal cord involvement [155].
It has high heterogeneity, hidden onset, and poor prog-
nosis [156]. A previous clinical study has demonstrated
that 50% of children with metastatic neuroblastoma had
chromosome abnormalities concerning chromosome 21,
10, or 11, with abnormalities on chromosome 10 being
the most frequent [157]. Jang etal. [158] described the
clinical characteristics of children with neuroblastoma
and abnormal chromosome 10. e study showed that
the overall survival rate of neuroblastoma children with
abnormal chromosome 10 was significantly lower than
that children with normal chromosome 10. e site
10q22 was linked to all structural abnormalities. is
indicates that the site 10q22 may have tumor suppres-
sor or oncogenic genes. Neuroblastoma patients with
abnormal chromosome 10 were prone to orbital metas-
tases. is study demonstrates that chromosome 10 can
be used as a novel prognostic marker for neuroblastoma.
Anorexia nervosa
Over the past few decades, research has suggested
a relationship between anorexia nervosa and autism
spectrum disorder [159]. Autism spectrum disorder
traits are present in approximately one third of cases
with anorexia nervosa, and there is some evidence that
autism spectrum disorder traits are associated with
more severe eating disorder psychopathology [160].
Although anorexia nervosa and autism spectrum disor-
der refer to separate and diverse diagnostic categories,
an underlying genetic vulnerability between the two
disorders was proposed [161]. It is well established that
certain neuropsychological functions are impaired in
individuals with autism spectrum disorder (e.g., cogni-
tive flexibility, such as set-shifting, and central coher-
ence) and that those impairments are often recognised
in the clinical presentation of anorexia nervosa [162].
Pruccoli et al. [163] have described the relationship
between autism spectrum disorder traits, eating disor-
der psychopathology and the body mass index (BMI) in
a population of young patients with anorexia nervosa at
an Italian Regional Centre for Eating Disorders. Autism
spectrum disorder traits and eating disorder psycho-
pathology were investigated administering the Autism
Diagnostic Observation Schedule-2, Autism Quotient
and Eating Disorder Inventory-3. e results showed
significant correlations between autism spectrum dis-
order trait and eating disorder psycopathology, that
were independent of BMI, obsessive compulsive disor-
der and anti-psychotic treatments.
Epilepsy Eating epilepsy is a form of reflex epilepsy
in which eating triggers seizures [164]. Eating epilepsy
includes patients who had more than 50% of fits dur-
ing or within 30min of eating breakfast, lunch, or din-
ner [165]. It is a rare condition, with high prevalence in
Sri Lanka [166]. e seizures can occur during any phase
of the meal, and are likely provoked by olfactory, auto-
nomic, or gustatory stimulus. As with other forms of
reflex epilepsy the pathophysiology of eating epilepsy is
unknown, but it is likely that the eating process triggers
cortical activity leads to subsequent brainstem activation
[167]; seizures usually arise in temporal limbic or perisyl-
vian regions and may progress to secondary generaliza-
tion [168]. Vercellino etal. [169] described two patients
with symptomatic eating epilepsy, i.e., a 13-years-old
boy with a bilateral perysilvian polymicrogyria and a
2-years-old boy with an underlying genetic disorder. In
the latter case, a relevant contribution to the neurological
phenotype is provided by de novo loss of function vari-
ants in CHD2, which can cause an early onset epileptic
encephalopathy, hypotonia and dysmorphic features. e
dysfunction of specific cortical regions in the contest of
germline genetic alteration can lead to a hyperexcitation
fostering the epileptogenesis.
Fetal alcohol spectrum disorders Fetal alcohol spec-
trum disorders (FASD) are a group of conditions result-
ing from prenatal alcohol exposure. e clinical picture
of FADS may vary, but the most affected brain functions
include cognition [170, 171], especially executive func-
tions [172] and social skills [173]. In this explorative
study, Dylag etal. [174] aimed at investigating the sleep
problems related to FASD. Forty patients were studied,
through both Child’s Sleep Habits Questionnaire and
polysomnography. e results show that a distorted sleep
pattern characterised by sleep onset delay, night waking,
parasomnias, sleep disordered breathing and daytime
sleepiness, together with apneic/hypopneic events is
often part of the clinical presentation of FADS. Further
studies are needed to understand better the correlation
between FADS and sleep problems.
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
Cognitive functions
Osika points up how the effects of technological
devices and television on cognitive functions in sev-
eral age groups [175], showing that spending time in
front of a television may decrease cognitive skills such
as language, concentration, but also emotional regu-
lations [176, 177]. Prolonged usage of mobile phones
can increase the risk of late language skills [178]. Fur-
thermore, it is well known that screen usage also plays
a major role in children’s sleep [179, 180] affecting it
both quantitatively (bedtime, sleep time, and total sleep
time) and qualitatively (restful sleep or not) [181, 182].
e unrestrained usage of the devices has an important
impact on essential parts of a child’s routine, such as
learning time, sleep time, physical activity, and free play
time. For all these reasons, it is fundamental to discour-
age screen exposure for very young children and advise
parents on a more responsible use of technology.
Nutrition. 1‑ Congenital chylothorax; 2‑ Formula feeding;3‑
Macronutrients andmicronutrients; 4‑ Breastfeeding
technique
Congenital chylothorax
Congenital chylothorax is the accumulation of lym-
phatic fluid in pleural space. The management con-
sists in respiratory support and dietary treatment.
Dietary treatment provides the use of protein-based
powdered formula with low long chain tryglicerides
and high medium chain triglycerides, like monogen or
basic fats. This takes away the possibility for the new-
born (especially if premature) to benefit from breast
milk. So, it was described in literature the possibil-
ity of skimming breast milk, to obtain a low-fat milk
preserving its nutritional, immunologic, and psycho-
social advantages [183]. A definitive guideline for
medical management and therapeutic dietary inter-
vention of congenital chylothorax is not available. A
recent study has shown the outcome of six patients
with chylothorax treated differently [184]. It showed
positive effects of skimmed breast milk after resolu-
tion of pleural effusions. Three patients received
skimmed breast milk: the first was associated with a
favourable outcome, no recurrence of pleural effusion,
adequate weight gain and a contented mother; the sec-
ond was difficult to evaluate due to a diagnosed Noo-
nan syndrome and the mother’s subsequent decision
to stop breastfeeding after two weeks; the third had
a relapse of pleural effusion after the administration
of skimmed milk. All patients started an additional
treatment with somatostatin to speed up healing.
Another positive effect is that in human milk soma-
tostatin is found in high concentrations, reducing
lymph production when breast feeding is continued
in infants with chylothorax [185]. Then the positive
effect on mother and child is proven, but a multicenter
study in a larger number will be helpful and necessary.
Formula feeding
All major health organizations recommend breast-
feeding as the optimal source of infant nutrition, with
exclusive breastfeeding recommended for the first six
months of life. After six months, complementary foods
can be introduced. Most organizations recommend
breastfeeding for at least one year, and the WHO rec-
ommends a minimum of 2years, but less than 40% of
infants below the 6months are exclusively breastfeed-
ing worldwide [186, 187]. Multiple investigations have
demonstrated that breast feeding not only reduces
the risk of death and disease in early life but has last-
ing health benefits through adult life [188, 189]. Taye
etal. [189] assessed the Authors found that the edu-
cational status of mothers, timing of initiation breast-
feeding, pre-lactal feeding, and delivery by cesarean
section were significantly associated with formula
feeding practice. erefore, early initiation of breast-
feeding, educating mothers about the risks associated
with pre-lacteal feeding and supporting mothers who
gave birth by cesarean section for exclusive breastfeed-
ing should be encouraged at the community and insti-
tutional levels. Prevalence of formula feeding practice
and its associated factors among mothers of an infant
aged 0–6months in Ethiopia.
Macronutrients and micronutrients Macronutri-
ents are mainly distinguished in carbohydrates, proteins,
and lipids [190]. Micronutrients are components that do
not provide a significant caloric intake and principally
include vitamins and minerals [191]. In this interesting
review, Savarino etal. [192] provided an up-to-date guide
about the importance of both macro and micronutrients
during paediatric age. During the first 6 months breast
milk is the main source of energy, macro and micronu-
trients [193]. During weaning, the risk of an unbalanced
diet increases, for this reason paediatricians should sup-
port the family during this process. Since preschool
age is characterised by constant growth, the diet of the
child should be checked by professionals that can ensure
a varied diet with adequate portions. During puberty, a
change in habits usually happens, with an increased risk
for “bad habits”, like choosing “junk food” during meals
“away from home”. In conclusion, each period of the pae-
diatric age has specific requirements and characteristics,
and clinicians should be able to ensure adequate support
to families for children’s nutrition.
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
Breastfeeding technique
Breastfeeding technique is explained as the mother’s and
baby’s positioning, baby’s attachment to the breast, and
suckling during breastfeeding, which are very impor-
tant for effective breastfeeding [194, 195]. Ineffective
breastfeeding technique is the leading cause of vari-
ous problems related to breastfeeding and significantly
affects both maternal and infants’ health [196]. Younger
and primiparous mothers usually perform poorly effec-
tive breastfeeding. But women having counseling during
antenatal care follow-up and immediately after delivery
and not having breast problems applied breastfeeding
effectively. In their observational study, Safayi etal. [197]
showed that counseling had a significant contribution to
effective breastfeeding. Moreover, it revealed that breast-
feeding technique is deficient in women giving birth for
the first time. In conclusion, authors recommend giving
particular emphasis especially to younger mothers and
primipara mothers to encourage adequate breastfeeding
technique.
Palliative care. 1‑ Medical complexity; 2‑ Cannabis
Medical complexity
Children with medical complexity are a population in
need of pediatric palliative care. ey have multiple
chronic health problems that affect multiple organs,
and they have high risk of adverse outcomes, both in the
psychological and medical fields. A recent retrospective
cross-sectional survey analysed prevalence and needs of
children with medical complexity from 14 local health
authorities of Emilia Romagna [198]. According to this
survey, 51% of the children had neurological conditions,
the single most frequent diagnosis was cerebral palsy.
is prevalence was found also in a recent review on
pediatric palliative care [199]. However, it is more com-
mon and faster to start palliative care to a child with can-
cer [200]. Children with medical complexity often need
assistance as they have higher access to health services
and assistance costs. Another data that emerges from the
study is that there should be more integration between
hospital and home care. e results in this literature
review include home-based care and community-based
services for children, which make it possible for children
in need of palliative care to stay at home [201]. In addi-
tion, it is important to selecting patients in need in the
most appropriate way possible and to give more attention
to patient’s family because the goal in both general and
specific paediatric palliative care is to improve quality of
life for both the child and his or her family [198].
Cannabis
Cannabis and cannabinoids preparations exert numer-
ous therapeutic effects. ey have antispastic, analgesic,
antiemetic, neuroprotective, and anti-inflammatory
actions, and are effective against certain psychiatric dis-
eases [202]. Overall, trials demonstrated that cannabis
significantly reduced the frequency of seizures compared
to placebo [203]. Children and young adults with cancer
reported using cannabis products for nausea and vom-
iting, depressed mood, sleep disturbances, pain, poor
appetite, and weight loss [204]. Divisic et al. described
a clinical experience of six patients in a pediatric pallia-
tive care who received a titrated plant extract of canna-
bis sativa for 1year [205]. All patients received cannabis
therapy for treatment-resistant epilepsy and chronic pain.
In this experience, only mild and transient adverse event
occurred: drownsiness, euphoria, restlessness, and tach-
ycardia: the resolution of symptoms were either spon-
taneous or obtained by modifying the administration
schedule. e experiences suggest that a titrated paint
extract preparation of medical cannabis may be useful to
control treatment-resistant paint and epilepsy in pediat-
ric palliative care patients.
Respiratory tract illnesses. 1‑ Cystic brosis;2‑ Recurrent
respiratory infections; 3‑ Respiratory syncytial virus;
4‑ Inhaled corticosteroids; 5‑ Foreign bodyaspiration; 6‑
Severe pneumonia
Cystic brosis
Cystic fibrosis (CF) is a multi-organ disease, which
mainly affects the respiratory and digestive systems. It is
a genetic disorder due to an altered gene, i.e., the CFTR
gene. e sweat test is the gold standard for the diagnosis
of CF, also used in newborn screening (NBS) programs
and to assess the response to treatment with new modu-
lators. Nevertheless, it is well known that sweat test may
give false negative or positive results, with a rate rang-
ing from 10 to 15% [206]. Patients with other underly-
ing disorders, i.e., celiac disease, Klinefelter Syndrome,
coprostasis in treatment with polyethylene glycol may
show false positive sweat test. Cimbalo et al. have tried
to explain the reason of this [207], discriminating false
positive and false negative sweat test results into 3 cat-
egories, i.e., ‘‘likely’’, ‘‘probable but needs validation,’’ and
‘‘unlikely’’ results based on the number of cases reported
and use of genetic testing to exclude CF. ey concluded
that clinicians must aware the possibility of other con-
ditions, such as adrenal insufficiency, even if two CFTR
mutations are identified [208]. ey also recommend
repeating the sweat test and/or genetic analyses twice,
possibly in specialized laboratories [209]. e mutated
protein produced by CFTR gene does not work prop-
erly and leads to the production of thick mucus and
sweat very rich in salts. e secretions of people with
CF contain purulent material, polymerized DNA, and
filamentous actin (F-actin) proteins derived from dead
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Caarellietal. Italian Journal of Pediatrics (2022) 48:189
inflammatory cells and epithelial cells and very little
mucin. is has important therapeutic implications. Ter-
lizzi etal. [210] have emphasized that at present sympto-
matic mucolytic treatment of patients with CF includes
the inhalation of DNase, hypertonic saline or mannitol
combined with chest physiotherapy. Several articles have
shown that there is no superiority of hypertonic saline
than other mucolytic agents, even if the benefits are that
it’s an inexpensive, safe, and effective additional therapy
[211, 212]. It is possible the use of more than one inhaled
solution at the same time, to achieve more benefit since
these agents have different mechanisms of action [213].
Accordingly, authors recommend the dornase alfa as
the first choice in routine treatment and if the clinical
response is inadequate, hypertonic saline is proposed
alone or in combination with dornase alfa.
Recurrent respiratory infections
Paediatric respiratory tract infections are one of the most
common reasons for physician visits and hospitalisa-
tion, and they are associated with significant morbidity
and mortality. In most cases, infections occur with mild
clinical manifestations and gradually improve by the age
of 12years old [214]. e diagnosis of recurrent respira-
tory infections (RRIs) is basically a diagnosis of exclusion
of other chronic conditions, such as genetic pathologies,
cystic fibrosis, congenital immunodeficiencies, malfor-
mations. Chiappini et al. [215] have promoted a con-
sensus document with the aim to propose an updated
definition and provide recommendations with the intent
of guiding the physician in the complex process of diag-
nosis, management, and prevention of RRIs. Main find-
ings are: 1) the use of oral probiotic formulations should
not be recommended for the prevention of RRIs; 2) the
routine vitamin C supplementation should not be used in
the prevention of RRIs; 3) evidence available to date does
not allow recommendation of the routine use of bacterial
lysates for the prevention of RRIs; 4) although there few
publications on the effects of influenza and anti-pneu-
mococcal vaccinations specifically for the prevention of
RRIs, they are strongly recommended; 5) nasal therapy
with hyaluronic acid, thermal waters for the prevention
of RRIs should not be discouraged; 6) the adeno-tonsil-
lectomy is not recommended for the reduction of RRIs;
7) no studies are available on the efficacy of antibiotic
prophylaxis in preventing RRIs.
Respiratory syncytial virus
Respiratory syncytial virus (RSV) is the most com-
mon respiratory agent in infants and young children
worldwide. It is by far the most frequent cause of
hospitalization in children younger than 2 years of
age, particularly in those born prematurely or who
have chronic lung disease or congenital heart disease
[216]. RSV can cause severe lower respiratory tract
infections, such as pneumonia and bronchiolitis, and
it is associated with an increased risk of developing
asthma and recurrent wheezing [217]. Azzari et al.
[218] have reviewed the global RSV epidemiological
data and current prevention strategies. Prevention
strategies include maternal vaccines which can pro-
tect neonates from birth and during the RSV epidemic
season. A prevention strategy based on passive immu-
noprophylaxis provide immediate protection of the
child and last up to 5months. Pediatric vaccines can
be administered to all children, provide longer-term
protection and limit RSV circulation within the pedi-
atric population. The possible cooperation between
maternal vaccination or passive immunoprophylxis to
protect neonates from birth and subsequent pediatric
vaccination to achieve more durable protection and
limit RSV circulation.
Inhaled corticosteroids
A consensus document for the use of inhaled corticos-
teroids [219] was provided by experts from eight scien-
tific societies, he Italian Society for Paediatrics (SIP),
the Italian Society of Paediatric Respiratory Diseases
(SIMRI), the Italian Society for Paediatric Allergy and
Immunology (SIAIP), the Italian Society for Preven-
tive and Social Paediatrics (SIPPS), the Italian Society
of Paediatric Primary Care (SICuPP), the Italian Society
of Adolescent Medicine (SIMA), the Italian Society of
Paediatric Emergency Medicine (SIMEUP) and the Ital-
ian Federation of Paediatricians (FIMP). rough clini-
cal questions and systematic review of the literature,
the expert panel provided recommendations on the
use of inhaled corticosteroids, in preschool wheezing,
asthma [220], allergic and non-allergic rhinitis [221],
acute and chronic rhinosinusitis [222], adenoid hyper-
trophy, laryngospasm. e panel recommended against
of inhaled corticosteroids administration in acute
infectious laryngitis, otitis media with effusion. is
article is useful guidance for paediatricians and general
practitioners.
Foreign body aspiration Foreign body aspiration
(FBA) is a common and possibly life-threatening event
[223], that could lead to serious clinical events such as
pneumonia, bronchiectasis, lung abscess, atelectasis, or
even death. e severity of the complications may be due
to missed or delayed diagnosis and management [224].
In this retrospective cohort study, Fasseeh et al. [225]
have proposed new criteria to predict FBA in children,
together with the elaboration of a clinical algorithm that
Page 14 of 20
Caarellietal. Italian Journal of Pediatrics (2022) 48:189
may help in decision making about the need and type of
bronchoscopy in children presenting with potential FBA.
Severe pneumonia
Pediatric community acquired pneumonia (CAP) is fre-
quently encountered by medical providers and is one
of the most common reasons for hospital [226] and the
major cause of pediatric mortality [227]. CAP is a pulmo-
nary infectious disease acquired outside of the hospital,
with viruses and bacteria as the most common pathogens
[228]. Previous studies were focused on the identification
of risk factors associated with severe CAP and thus facili-
tated the risk stratification of CAP patients [229]. Chen
etal. [230] have investigated the age-specific risk factors
for severe disease among children hospitalized with CAP.
Birth history, including premature birth and low birth
weight (< 2.5kg), is a significant predictor of severe CAP.
e breastfeeding acting is a protective factor for CAP,
whereas formula feeding was associated with increased
risk. e infants born within 6months demonstrated a
significantly higher risk of developing severe CAP than
older children. e risk factors predicting disease sever-
ity among children hospitalized with CAP vary with age.
An age-specific model should be developed for risk strat-
ification of pediatric CAP patients, which could better
guide the practice of precision medicine.
Telemedicine. 1‑ Paediatric inuencers
Paediatric inuencers
In this study, Bozzola et al. [231] have evaluated the
role of paediatric influencers in communicating infor-
mation about children’s and adolescents’ health [232].
e authors’ study shows the potential role of influenc-
ers: following specific guidelines and criteria spreading
health messages via paediatric influencers seems to be
a successful strategy to support correct communication
about children’s and adolescents’ health [233, 234]. In
conclusion, any medical doctor and health care profes-
sional could promote health messages among patients
and families, to achieve two significant results in one
shot: spreading correct information and contrasting the
spreading of fake news on sensible health topics.
Conclusions
We have offered major advancements in the growing field
of Pediatrics through the eyes of the Italian Journal of
Pediatrics. e past year’s papers have provided clear and
incisive information on how can change children care.
Impactful views and comprehensions will enhance the
quality of care for childhood diseases.
Abbreviations
CAP: Community acquired pneumonia; CF: Cystic fibrosis; DCC: Delayed
cord clamping; EBV: Epstein-Barr virus; FBA: Foreign body aspiration; HLH:
Hemophagocytic syndrome; LAIV: Live attenuated influenza vaccine; NICU:
Neonatal intensive care units; NRDS: Neonatal respiratory distress syndrome;
RRI: Recurrent respiratory infections; ROP: Retinopathy of prematurity; RSV:
Respiratory syncytial virus; WHO: World Health Organization.
Acknowledgements
Not applicable.
Authors’ contributions
CC, FS, SBe, GC conceived the study, participated in its design, carried out the
literature research and helped to draft the manuscript; MP, EP, VdC, SBa carried
out the literature research and helped draft the manuscript. All authors read
and approved the final manuscript.
Funding
Not applicable.
Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated or
analysed during the current study.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1 Department of Medicine and Surgery, Clinica Pediatrica, Azienda Ospe-
daliera-Universitaria, University of Parma, Via Gramsci 14, Parma, Italy. 2 Depart-
ment of Translational Medical Sciences, Federico II University, Naples, Italy.
3 Department of Sciences for Health Promotion and Mother and Child Care G.
D’Alessandro, University of Palermo, Palermo, Italy. 4 Microbiome Research Hub,
University of Parma, Parma, Italy.
Received: 30 September 2022 Accepted: 25 October 2022
References
1. Caffarelli C, Bacchini PL, Gruppi L, Bernasconi S. Exercise-induced
bronchoconstriction in children with atopic eczema. Pediatr Allergy
Immunol. 2005;16:655–61.
2. Riscassi S, Corradi M, Andreoli R, Maccari C, Mercolini F, Pescollderungg
L, et al. Nitric oxide products and aldehydes in exhaled breath conden-
sate in children with asthma. Clin Exp Allergy. 2022;52:561–4.
3. Manna A, Caffarelli C, Varini M, Povesi Dascola C, Montella S, Maglione
M, et al. Clinical application of exhaled nitric oxide measurement in
pediatric lung diseases. Ital J Pediatr. 2012;38:74.
4. Caffarelli C, Dascola CP, Peroni D, Ricò S, Stringari G, Varini M, et al.
Airway acidification in childhood asthma exacerbations. Allergy Asthma
Proc. 2014;35:51–6.
5. Caffarelli C, Calcinai E, Rinaldi L, Povesi Dascola C, Terracciano L, Corradi M.
Hydrogen peroxide in exhaled breath condensate in asthmatic children
during acute exacerbation and after treatment. Respir. 2012;84:291–8.
6. Caffarelli C, Mastrorilli C, Procaccianti M, Santoro A. Use of sublingual immuno-
therapy for aeroallergens in children with asthma. J Clin Med. 2020;9:3381.
7. Di Rienzo V, Cadario G, Grieco T, Galluccio AG, Caffarelli C, Liotta G, et al.
Sublingual immunotherapy in mite-sensitized children with atopic der-
matitis: a randomized, open, parallel-group study. Ann Allergy Asthma
Immunol. 2014;113:671-673.e1.
Page 15 of 20
Caarellietal. Italian Journal of Pediatrics (2022) 48:189
8. Yang Y, Ma D, Huang N, Li W, Jiang Q, Wang Y, et al. Safety of house dust
mite subcutaneous immunotherapy in preschool children with respira-
tory allergic diseases. Ital J Pediatr. 2021;47:101.
9. Caffarelli C, Coscia A, Ridolo E, Povesi Dascola C, Gelmett C, Raggi V,
et al. Parents’ estimate of food allergy prevalence and management in
Italian school-aged children. Pediatr Int. 2011;53:505–10.
10. Caffarelli C, Ricò S, Rinaldi L, Povesi Dascola C, Terzi C, Bernasconi
S. Blood pressure monitoring in children undergoing food chal-
lenge: association with anaphylaxis. Ann Allergy Asthma Immunol.
2012;108:285–6.
11. Povesi Dascola C, Caffarelli C. Exercise-induced anaphylaxis: a clinical
view. Ital J Pediatr. 2012;38:43.
12. Caffarelli C, Dondi A, Povesi Dascola C, Ricci G. Skin prick test to foods in
childhood atopic eczema: pros and cons. Ital J Pediatr. 2013;39:48.
13. Caglayan Sozmen S, Povesi Dascola C, Gioia E, Mastrorilli C, Rizzuti L,
Caffarelli C. Diagnostic accuracy of patch test in children with food
allergy. Pediatr Allergy Immunol. 2015;26:416–22.
14. Caffarelli C, Cavagni G, Menzies IS, Bertolini P, Atherton DJ. Elimination
diet and intestinal permeability in atopic eczema: a preliminary study.
Clin Exp Allergy. 1993;23:28–31.
15. Barni S, Arasi S, Mastrorilli C, Pecoraro L, Giovannini M, Mori F, et al. Pedi-
atric eosinophilic esophagitis: a review for the clinician. Ital J Pediatr.
2021;47:230.
16. Marchesi A, Rigante D, Cimaz R, Ravelli A, Tarissi de Jacobis I, Rimini
A, et al. Revised recommendations of the Italian society of pediatrics
about the general management of Kawasaki disease. Ital J Pediatr.
2021;47:16.
17. Burns JC, Capparelli EV, Brown JA, Newburger JW, Glode MP. Intrave-
nous gamma-globulin treatment and retreatment in Kawasaki disease
US/Canadian Kawasaki syndrome study group. Pediatr Infect Dis J.
1998;17:1144–8.
18. Ferrara G, Giani T, Caparello MC, Farella C, Gamalero L, Cimaz R. Anakinra
for treatment-resistant Kawasaki disease: evidence from a literature
review. Paediatr Drugs. 2020;22:645–52.
19. Tress EE, Kochanek PM, Saladino RA, Manole MD. Cardiac arrest in
children. J Emergencies Trauma Shock. 2010;3:267.
20. Bimerew M, Wondmieneh A, Gedefaw G, Gebremeskel T, Demis A, Getie
A. Survival of pediatric patients after cardiopulmonary resuscitation for
in-hospital cardiac arrest: a systematic review and meta-analysis. Ital J
Pediatr. 2021;47:118.
21. Martinez PA, Totapally BR. The epidemiology and outcomes of pediatric
in-hospital cardiopulmonary arrest in the USA during 1997 to 2012.
Resusc. 2016;105:177–81.
22. Talikowska M, Tohira H, Finn J. Cardiopulmonary resuscitation quality
and patient survival outcome in cardiac arrest: A systematic review and
meta-analysis. Resusc. 2015;96:66–77.
23. Cozzi G, Minute M, Ventura G, Barbi E. Mental health problems in chil-
drenand adolescents in the emergency department: “the times they are
AChangin.” Pediatr Emerg Care. 2017;33:e8.
24. Cozzi G, Lucarelli A, Borrometi F, Corsini I, Passone E, Pusceddu S, et al.
how to recognize and manage psychosomatic pain in the pediatric
emergency department. Ital J Pediatr. 2021;47:74.
25. Bonvanie IJ, Kallesøe KH, Janssens KAM, Schröder A, Rosmalen JGM,
Rask CU. Psychological interventions for children with functional
somatic symptoms: a systematic review and metaanalysis. J Pediatr.
2017;187:272–81.
26. Tang MN, Adolphe S, Rogers SR, Frank DA. Failure to thrive or growth
faltering: Medical, developmental/behavioral, nutritional, and social
dimensions. Pediatr Rev. 2021;42:590–603.
27. Lezo A, Baldini L, Asteggiano M. Failure to thrive in the outpatient clinic:
a new insight. Nutrients. 2020;12:2202.
28. Selbuz S, Kırsaçlıoğlu CT, Kuloğlu Z, Yılmaz M, Penezoğlu N, Sayıcı U,
et al. Diagnostic workup and micronutrient deficiencies in children
with failure to thrive without underlying diseases. Nutr Clin Pract.
2019;34:581–8.
29. Franceschi R, Rizzardi C, Maines E, Liguori A, Soffiati M, Tornese G. Failure
to thrive in infant and toddlers: a practical flowchart-based approach in
a hospital setting. Ital J Pediatr. 2021;47:62–70.
30. Phelan K, Boccuto L, Powell CM, Boeckers TM, van Ravenswaaij-Arts C,
Rogers RC, et al. Phelan-McDermid syndrome: a classification system
after 30 years of experience. Orphanet J Rare Dis. 2022;17:27–30.
31. Ricciardello A, Tomaiuolo P, Persico AM. Genotype-phenotype correla-
tion in Phelan-McDermid syndrome: a comprehensive review of chro-
mosome 22q13 deleted genes. Am J Med Genet A. 2021;185:2211–33.
32. Xie RJ, Li TX, Sun C, Cheng C, Zhao J, Xu H, et al. A case report of Phelan-
McDermid syndrome: preliminary results of the treatment with growth
hormone therapy. Ital J Pediatr. 2021;47:49.
33. Li T, Xie R, Zhao J, Xu H, Cui Y, Sun C. Effectiveness of recombinant
human growth hormone therapy for children with Phelan-McDermid
syndrome: An open-label, cross-over, preliminary study. Front Psychia-
try. 2022;13:763565.
34. Shulman JD. Prevalence of oral mucosal lesions in children and youths
in the USA. Int J Paediatr Dent. 2005;15:89–97.
35. Légeret C, Furlano R. Oral ulcers in children- a clinical narrative over-
view. Ital J Pediatr. 2021;47:144.
36. Belenguer-Guallar I, Jiménez-Soriano Y, Claramunt-Lozano A. Treatment
of recurrent aphthous stomatitis a literature review. J Clin Exp Dent.
2014;6:e168-74.
37. Brocklehurst P, Tickle M, Glenny AM, Lewis MA, Pemberton MN, Taylor J,
et al. Systemic interventions for recurrent aphthous stomatitis (mouth
ulcers). Cochrane Database Syst Rev. 2012;9:CD005411.
38. Keenswijk W, Raes A, Vande WJ. Is eculizumab efficacious in Shigatoxin-
associated hemolytic uremic syndrome? A narrative review of current
evidence. Eur J Pediatr. 2018;177:311–8.
39. Ylinen E, Salmenlinna S, Halkilahti J, Jahnukainen T, Korhonen L, Virkkala
T, et al. Hemolytic uremic syndrome caused by Shiga toxin-producing
Escherichia coli in children: incidence, risk factors, and clinical outcome.
Pediatr Nephrol. 2020;35:1749–59.
40. Santangelo L, Netti GS, Torres DD, Piscopo G, Carbone V, Losito L, et al.
Peripheral nervous system manifestations of Shiga toxin-producing
E. coli-induced haemolytic uremic syndrome in children. Ital J Pediatr.
2021;47:181.
41. Caffarelli C, Cardinale F, Povesi-Dascola C, Dodi I, Mastrorilli V, Ricci G.
Use of probiotics in pediatric infectious diseases. Expert Rev Anti Infect
Ther. 2015;13:1517–35.
42. Morel L, Domingues O, Zimmer J, Michel T. Revisiting the role of neuro-
trophic factors in inflammation. Cells. 2020;9:E865.
43. Sim SW, Weinstein DA, Lee YM, Jun HS. Glycogen storage disease type
Ib: role of glucose-6-phosphate transporter in cell metabolism and
function. FEBS Lett. 2020;594:3–18.
44. Rossi A, Miele E, Fecarotta S, Veiga-da-Cunha M, Martinelli M, Mollica
C, et al. Crohn disease-like enterocolitis remission after empagliflozin
treatment in a child with glycogen storage disease type Ib: a case
report. Ital J Pediatr. 2021;47:149.
45. Alsultan A, Sokol RJ, Lovell MA, Thurman G, Ambruso DR. Long term
G-CSF induced remission of ulcerative colitis-like inflammatory bowel
disease in a patient with glycogen storage disease Ib and evaluation of
associated neutrophil function. Pediatr Blood Cancer. 2010;55:1410–3.
46. Wortmann SB, Van Hove JLK, Derks TGJ, Chevalier N, Knight V, Koller
A, et al. Treating neutropenia and neutrophil dysfunction in glycogen
storage disease IB with an SGLT2-inhibitor. Blood. 2020;136:1033–43.
47. Donnarumma B, Riccio MP, Terrone G, Palma M, Strisciuglio P, Scala I.
Expanding the neurological and behavioral phenotype of White-Sutton
syndrome: a case report. Ital J Pediatr. 2021;47:148.
48. Savatt JM, Myers SM. Genetic testing in neurodevelopmental disorders.
Front Pediatr. 2021;9:526779.
49. Matsumura K, Seiriki K, Okada S, Nagase M, Ayabe S, Yamada I, et al.
Pathogenic POGZ mutation causes impaired cortical development and
reversible autism-like phenotypes. Nat Commun. 2020;11:859.
50. Fusco C, Leuzzi V, Striano P, Battini R, Burlina A, Delphi panel experts’
group, Spagnoli C. Aromatic L-amino acid decarboxylase (AADC) defi-
ciency: results from an Italian modified Delphi consensus. Ital J Pediatr.
2021;47:13.
51. Montioli R, Borri VC. Aromatic amino acid decarboxylase deficiency: the
added value of biochemistry. Int J Mol Sci. 2021;22:3146.
52. Pearson TS, Gupta N, San SW. Gene therapy for aromatic L-amino acid
decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC
to midbrain dopaminergic neurons. Nat Commun. 2021;12:4251.
53. Rossignoli G, Krämer K, Lugarà E, Alrashidi H, Pope S, De La Fuente
BC, et al. Aromatic L-amino acid decarboxylase deficiency: a
patient-derived neuronal model for precision therapies. Brain.
2021;144:2443–56.
Page 16 of 20
Caarellietal. Italian Journal of Pediatrics (2022) 48:189
54. Benbouchta Y, De Leeuw N, Amasdl S, Sbiti A, Smeets D, Sadki K, et al.
15q26 deletion in a patient with congenital heart defect, growth
restriction and intellectual disability: case report and literature review.
Ital J Pediatr. 2021;47:188.
55. MalaCards: The human disease database. Chromosome 15q26-Qter
deletion syndrome. Rehovot: Weizmann Institute of Science; 2022.
Available at https:// www. malac ards. org/ card/ chrom osome_ 15q26_
qter_ delet ion_ syndr ome. Accessed 22 Sept 2022.
56. Bruford EA, Braschi B, Denny P. Guidelines for human gene nomencla-
ture. Nat Genet. 2020;52:754–8.
57. Miksiunas R, Mobasheri A, Bironaite D. Homeobox genes and homeo-
domain proteins: new insights into cardiac development, degeneration
and regeneration. Adv Exp Med Biol. 2020;1212:155–78.
58. De Sanctis V, Soliman AT, Elsedfy H, Skordis N, Kattamis C, et al. Growth
and endocrine disorders in thalassemia: the international network on
endocrine complications in thalassemia (I-CET ) position statement and
guidelines. Indian J Endocr Metab. 2013;17:8–18.
59. Mahmoud RA, Khodeary A, Farhan MS. Detection of endocrine disor-
ders in young children with multi-transfused thalassemia major. Ital J
Pediatr. 2021;47:165–73.
60. De Sanctis V, Soliman A, Tzoulis P, Daar S, Fiscina B, Kattamis C.
The pancreatic changes affecting glucose homeostasis in transfu-
sion dependent β- thalassemia (TDT): a short review. Acta Biomed.
2021;92:e2021232.
61. Ferdous F, Filteau S, Schwartz NB, Gumede-Moyo S, Cox SE. Association
of postnatal severe acute malnutrition with pancreatic exocrine and
endocrine function in children and adults: a systematic review. Br J
Nutr. 2022;4:1–34.
62. World Health Organization. Haemoglobin concentrations for the
diagnosis of anaemia and assessment of severity. Geneve: World Health
Organization; 2011. Available at https:// apps. who. int/ iris/ bitst ream/
handle/ 10665/ 85839/ WHO_ NMH_ NHD_ MNM_ 11.1_ eng. pdf? seque
nce= 22& isAll owed=y. Accessed 22 Sept 2022.
63. Parodi E, Riboldi L, Ramenghi U. Hemoglobin life-threatening value
(1.9 g/dl) dl in good general condition: a pediatric case report. Ital J
Pediatr. 2021;47:200.
64. Wang M. Iron deficiency and other types of Anemia in infants and
children. Am Fam Physician. 2016;93:270.
65. Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease.
Lancet. 2017;390:311–23.
66. Nauss MD, Schmidt EL, Pancioli AM. Viral myositis leading to rhab-
domyolysis: a case report and literature review. Am J Emerg Med.
2009;27:372.e5-372.e6.
67. Rosenberg T, Heitner S, Scolnik D, Levin Ben-Adiva E, Rimon A, Glat-
stein M. Outcome of benign acute childhood myositis: The experi-
ence of 2 large tertiary care pediatric hospitals. Pediatr Emerg Care.
2018;34:400–2.
68. Brisca G, Mariani M, Pirlo D, Romanengo M, Pistorio A, Gaiero A, et al.
Management and outcome of benign acute childhood myositis in
pediatric emergency department. Ital J Pediatr. 2021;47:57.
69. Beydon M, Chevalier K, Al Tabaa O, Hamroun S, Delettre AS, Thomas
M, et al. Myositis as a manifestation of SARS-CoV-2. Ann Rheum Dis.
2021;80:e42.
70. Budhathoki S, Shah D, Bhurtyal KK, Amatya R, Dutta AK. Hookworm
causing melaena and severe anaemia in early infancy. Ann Trop Paedi-
atr. 2008;28:293–6.
71. Umbrello G, Pinzani R, Bandera A, Formenti F, Zavarise G, Arghittu M,
et al. Hookworm infection in infants: a case report and review of litera-
ture. Ital J Pediatr. 2021;47:26.
72. Silvestri C, Greganti G, Arzeni D, Morciano A, Castelli P, Barchiesi F, et al.
Intestinal parasitosis: data analysis 2006–2011 in a teaching hospital of
Ancona Italy. Infez Med. 2013;21:34–9.
73. Karra N, Cohen R, Berlin M, Dinavitser N, Koren G, Berkovitch M.
Mebendazole use during lactation: a case series report. Safety Drugs R
D. 2016;16:251–4.
74. Krzysztofiak A, Chiappini E, Venturini E, Gargiullo L, Roversi M, Mon-
tagnani C, et al. Italian consensus on the therapeutic management of
uncomplicated acute hematogenous osteomyelitis in children. Ital J
Pediatr. 2021;47:179.
75. Alcobendas R, Murias S, Remesal A, Calvo C. Oral treatment of osteoar-
ticular infections caused by Kingella kingae in children. Eur J Rheuma-
tol. 2018;5:147–8.
76. McNeil JC. Acute Hematogenous osteomyelitis in children: clinical
presentation and management. Infect Drug Resist. 2020;13:4459–73.
77. Congedi S, Minotti C, Giaquinto C, Da Dalt L, Donà D. Acute infectious
osteomyelitis in children: new treatment strategies for an old enemy.
World J Pediatr. 2020;16:446–55.
78. Smith KJ, Raviotta JM, DePasse JV, Brown ST, Shim E, Patricia Nowalk M,
et al. Cost effectiveness of influenza vaccine choices in children aged
2-8 years in the U.S. Am J Prev Med. 2016;50:600–8.
79. Shim E, Brown ST, DePasse J, Nowalk MP, Raviotta JM, Smith K J, et al.
Cost effectiveness of influenza vaccine for U.S. children. Am J Prev Med.
2016;51:309–17.
80. Gasparini C, Acunzo M, Biuso A, Roncaglia S, Migliavacca F, Borriello CR,
et al. Nasal spray live attenuated influenza vaccine: the first experience
in Italy in children and adolescents during the 2020–21 season. Ital J
Pediatr. 2021;47:225.
81. Carter NJ, Curran MP. Live Attenuated Influenza Vaccine (FluMist®;
Fluenz™). Drugs. 2011;71:1591–622.
82. Lopez SA, Mulla H, Durward A, Tibby SM. Extended-interval gentamicin:
population pharmacokinetics in pediatric critical illness. Pediatr Crit
Care Med. 2010;11(2):267–74.
83. Ghoneim RH, Thabit AK, Lashkar MO, Ali AS. Optimizing gentamicin
dosing in different pediatric age groups using population pharmacoki-
netics and Monte Carlo simulation. Ital J Pediatr. 2021;47:167.
84. Wang H, Sherwin C, Gobburu JVS, Ivaturi V. Population pharma-
cokinetic modeling of gentamicin in pediatrics. J Clin Pharmacol.
2019;59:1584–96.
85. Zhang SQ, Tang XY, Li YQ. Clinical characteristics comparison of children
EB virus correlation Hemophagocytic syndrome and infectious mono-
nucleosis. J Basic Clin Oncol. 2016;29(3):249–52.
86. Morimoto A, Nakazawa Y, Ishii E. Hemophagocytic lymphohistiocytosis:
Pathogenesis, diagnosis, and management. Pediatr Int. 2016;58:817–25.
87. Shi J, Chu C, Yu M, Zhang D, Li Y, Fan Y, et al. Clinical warning of
hemophagocytic syndrome caused by Epstein-Barr virus. Ital J Pediatr.
2021;47:3.
88. Toga A, Wada T, Sakakibara Y, Mase S, Araki R, Tone Y, et al. Clinical
significance of cloned expansion and CD5 down-regulation in Epstein-
Barr Virus (EBV)-infected CD8+ T lymphocytes in EBV-associated
hemophagocytic lymphohistiocytosis. J Infect Dis. 2010;201:1923–32.
89. Benitz WE, Achten NB. Technical assessment of the neonatal early-onset
sepsis risk calculator. Lancet Infect Dis. 2021;21:e134–40.
90. Deshmukh M, Mehta S, Patole S. Sepsis calculator for neonatal early
onset sepsis - a systematic review and meta-analysis. J Matern Fetal
Neonatal Med. 2021;34:1832–40.
91. Laccetta G, Ciantelli M, Tuoni C, Sigali E, Miccoli M, Cuttano A. Early-
onset sepsis risk calculator: a review of its effectiveness and compara-
tive study with our evidence-based local guidelines. Ital J Pediatr.
2021;47:73.
92. Glaser MA, Hughes LM, Jnah A, Newberry D. Neonatal sepsis: A review
of pathophysiology and current management strategies. Adv Neonatal
Care. 2021;21:49–60.
93. Patterson J, North K, Dempsey E, Ishoso D, Trevisanuto D, Lee AC, et al.
Optimizing initial neonatal resuscitation to reduce neonatal encepha-
lopathy around the world. Semin Fetal Neonatal Med. 2021;26:101262.
94. Massenzi L, Aufieri R, Donno S, Agostino R, Dotta A. Neonatal pharma-
cotherapy study group of the Italian Society of Neonatology (SIN). Use
of intravenous sodium bicarbonate in neonatal intensive care units in
Italy: a nationwide survey. Ital J Pediatr. 2021;47:63.
95. Vadakkencherry Ramaswamy V, Abiramalatha T, Weiner GM, Trevisanuto
D. A comparative evaluation and appraisal of 2020 American heart
association and 2021 European resuscitation council neonatal resusci-
tation guidelines. Resusc. 2021;167:151–9.
96. Wyckoff MH, Sawyer T, Lakshminrusimha S, Collins A, Ohls RK, Leone TA.
Resuscitation 2020: Proceedings from the NeoHeart 2020 International
conference. World J Pediatr Congenit Heart Surg. 2022;13:77–88.
97. Falsaperla R, Scalia B, Giugno A, Pavone P, Motta M, Caccamo M, et al.
Treating the symptom or treating the disease in neonatal seizures: a
systematic review of the literature. Ital J Pediatr. 2021;47:85.
Page 17 of 20
Caarellietal. Italian Journal of Pediatrics (2022) 48:189
98. Pressler RM, Cilio MR, Mizrahi EM, Moshé SL, Nunes ML, Plouin P, et al.
The ILAE classification of seizures and the epilepsies modification for
seizures in the neonate position paper by the ILAE task force on Neona-
tal seizures. Epilepsia. 2021;62:615–28.
99. Ramantani G, Schmitt B, Plecko B, Pressler RM, Wohlrab G, Kleber-
mass-Schrehof K, et al. Neonatal seizures-are we there yet? Neurope-
diatrics. 2019;50:280–93.
100. Samanta D. Recent advances in the diagnosis and treatment of
neonatal seizures. Neuropediatrics. 2021;52:73–83.
101. Yeung C-Y. Complications of umbilical venous catheters in neonates:
a safety reappraisal. Pediatr Neonatol. 2020;61:1–2.
102. Miller LE, Stoller JZ, Fraga MV. Point-of-care ultrasound in the neona-
tal ICU. Curr Opin Pediatr. 2020;32:216–27.
103. Meinen RD, Bauer AS, Devous K, Cowan E. Point-of-care ultrasound
use in umbilical line placement: a review. J Perinatol. 2020;40:560–6.
104. Rubortone SA, Costa S, Perri A, D’Andrea V, Vento G, Barone G.
Real-time ultrasound for tip location of umbilical venous catheter in
neonates: a pre/post intervention study. Ital J Pediatr. 2021;47:68.
105. Dani C, Coviello C, Panin F, Frosini S, Costa S, Purcaro V, et al. Inci-
dence and risk factors of retinopathy of prematurity in an Italian
cohort of preterm infants. Ital J Pediatr. 2021;47:64.
106. Hong EH, Shin YU, Cho H. Retinopathy of prematurity: a review of
epidemiology and current treatment strategies. Clin Exp Pediatr.
2022;65:115–26.
107. Arima A, Fujii Y, Koh-Hei Sonoda KH. Translational research in retin-
opathy of prematurity: from bedside to bench and back again. J Clin
Med. 2021;10:331.
108. Carroll L, Owen LA. Current evidence and outcomes for retinopathy
of prematurity prevention: insight into novel maternal and placental
contributions. Explor Med. 2020;1:4–26.
109. Wang N, Cui L, Liu Z, Wang Y, Zhang Y, Shi C, et al. Optimizing par-
enteral nutrition to achieve an adequate weight gain according to
the current guidelines in preterm infants with birth weight less than
1500 g: a prospective observational study. BMC Pediatr. 2021;21:303.
110. Beardsall K. Hyperglycaemia in the newborn infant Physiology verses
pathology. Front Pediatr. 2021;9:641306.
111. Rizzo V, Capozza M, Panza R, Laforgia N, Baldassarre ME. Macro-
nutrients and micronutrients in parenteral nutrition for preterm
newborns: a narrative review. Nutrients. 2022;14:1530.
112. Angelika D, Etika R, Utomo MT, Mirha S, Handayani KD, Ugrasena
IDG. The glucose infusion rate of parenteral nutrition in the first
week of life in preterm infants: an observational study. Ital J Pediatr.
2021;47:219.
113. Betts KS, Kisely S, Alati RJ. Predicting neonatal respiratory distress
syndrome and hypoglycaemia prior to discharge: Leveraging
health administrative data and machine learning. Biomed Inform.
2021;114:103651.
114. Tian T, Wang L, Ye R, Liu J, Ren A. Maternal hypertension, preeclamp-
sia, and risk of neonatal respiratory disorders in a large-prospective
cohort study. Pregnancy Hypertens. 2020;19:131–7.
115. Arruda A, Ormonde M, Stokreef S, Fraga B, Franco C, Dâmaso C, et al.
Is there a role for antenatal corticosteroids in term infants before
elective cesarean section? Rev Bras Ginecol Obstet. 2021;43:283–90.
116. Stylianou-Riga P, Boutsikou T, Kouis P, Kinni P, Krokou M, Ioannou
A, et al. Maternal and neonatal risk factors for neonatal respiratory
distress syndrome in term neonates in Cyprus: a prospective case-
control study. Ital J Pediatr. 2021;47:129.
117. Surak A, Elsayed YJ. Delayed cord clamping: Time for physiologic
implementation. Neonatal Perinatal Med. 2022;15:19–22.
118. Marrs L, Niermeyer S. Toward greater nuance in delayed cord clamp-
ing. Curr Opin Pediatr. 2022;34:170–7.
119. Bruckner M, Katheria AC, Schmölzer GM. Delayed cord clamping in
healthy term infants: More harm or good? Semin Fetal Neonatal Med.
2021;26:101221.
120. Shao H, Gao S, Lu Q, Zhao X, Hua Y, Wang X. Effects of delayed cord
clamping on neonatal jaundice, phototherapy and early hematologi-
cal status in term cesarean section. Ital J Pediatr. 2021;47:115.
121. Bergwitz C, Jüppner H. Regulation of phosphate homeostasis by PTH,
vitamin D, and FGF23. Annu Rev Med. 2010;61:91.
122. Rodd C, Schwieger-Briel A, Hagmann C. Newborn brain society
guidelines and publications committee Subcutaneous fat necrosis
associated with hypercalcemia in neonates with neonatal encepha-
lopathy treated with therapeutic hypothermia. Semin Fetal Neonatal
Med. 2021;26:101269.
123. Improda N, Mazzeo F, Rossi A, Rossi C, Improda FP, Izzo A. Severe hyper-
calcemia associated with hypophosphatemia in very premature infants:
a case report. Ital J Pediatr. 2021;47:155.
124. Höppner J, Lais S, Roll C, Wegener-Panzer A, Wieczorek D, Högler
W, et al. Case report: severe neonatal course in paternally derived
familial hypocalciuric hypercalcemia. Front Endocrinol (Lausanne).
2021;12:700612.
125. Savarino G, Carta M, Cimador M, Corsello A, Giuffrè M, Schierz IAM, et al.
Necrotizing enterocolitis in the preterm: newborns medical and nutri-
tional management in a single-center study. Ital J Pediatr. 2021;47:226.
126. Bellodas Sanchez J, Kadrofske M. Necrotizing enterocolitis. Neurogastro-
enterol Motil. 2019;31:e13569.
127. Meister AL, Doheny KK, Travagli RA. Necrotizing enterocolitis: It’s not all
in the gut. Exp Biol Med (Maywood). 2020;245:85–95.
128. Neu J. Necrotizing enterocolitis: The future. Neonatol. 2020;117:240–4.
129. Codazzi AC, Ippolito R, Novara C, Tondina E, Cerbo RM, Tzialla C.
Hypertrophic cardiomyopathy in infant newborns of diabetic mother:
a heterogeneous condition, the importance of anamnesis, physical
examination and follow-up. Ital J Pediatr. 2021;47:197.
130. Boyd SM, Riley KL, Giesinger RE, McNamara PJ. Use of vasopressin in
neonatal hypertrophic obstructive cardiomyopathy: case series. Perina-
tol. 2021;41:126–33.
131. Loomba RS, Flores S, Bronicki RJ. Vasopressin in neonatal hypertrophic
cardiomyopathy: do perceived benefits translate to clinical outcome?
Perinatol. 2021;41:905–6.
132. Giesinger RE, Boyd SM, Rios DR, McNamara PJ. Towards optimization
of cardiovascular stability in neonates with hypertrophic cardiomyo-
pathy: uniqueness of the neonatal cardiovascular system. Perinatol.
2021;41:907–8.
133. Hubbard EM, Hay WW Jr. The term newborn: Hypoglycemia. Clin Peri-
natol. 2021;48:665–79.
134. Meneghin F, Manzalini M, Acunzo M, Daniele I, Bastrenta P, Castoldi
F, et al. Management of asymptomatic hypoglycemia with 40% oral
dextrose gel in near term at-risk infants to reduce intensive care need
and promote breastfeeding. Ital J Pediatr. 2021;47:201.
135. Harding JE, Hegarty JE, Crowther CA, Edlin RP, Gamble GD, Alsweiler JM.
Evaluation of oral dextrose gel for prevention of neonatal hypoglyce-
mia (hPOD): a multicenter, double-blind randomized controlled trial.
hPOD study group. PLoS Med. 2021;18:e1003411.
136. Adamkin DH. Low blood sugar levels in the newborn infant: Do chang-
ing goal posts matter? Semin Fetal Neonatal Med. 2021;26:101202.
137. Yamaguchi T, Nakamura A, Nakayama K, Hishimura N, Morikawa S,
Ishizu K, et al. Targeted next-generation sequencing for congenital
hypothyroidism with positive neonatal TSH screening. Clin Endocrinol
Metab. 2020;105:dgaa308.
138. Cherella CE, Wassner AJ. Update on congenital hypothyroidism. Curr
Opin Endocrinol Diabetes Obes. 2020;27:63–9.
139. Léger J. Neonatal screening for congenital hypothyroidism. Med Sci
(Paris). 2021;37:474–81.
140. Maggio MC, Ragusa SS, Aronica TS, Granata OM, Gucciardino E, Corsello
G. Neonatal screening for congenital hypothyroidism in an Italian
centre: a 5-years real-life retrospective study. Ital J Pediatr. 2021;47:108.
141. Hyman SL, Levy SE, Myers SM. Council on children with disabilities, sec-
tion on developmental and behavioral pediatrics identification, evalu-
ation, and management of children with autism spectrum disorder.
Pediatr. 2020;145:e20193447.
142. Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, et al.
The autism diagnostic observation schedule-generic: a standard meas-
ure of social and communication deficits associated with the spectrum
of autism. J Autism Dev Disord. 2000;30:205–23.
143. Di Renzo M, di Castelbianco FB, Alberto V, Antonio DV, Giovanni C,
Vanadia E, et al. Prognostic factors and predictors of outcome in chil-
dren with autism spectrum disorder: the role of the paediatrician. Ital J
Pediatr. 2021;18(47):67.
144. Hodge MA, Boulton KA, Sutherland R, Barnett D, Bennett B, Chan E,
et al. Predictors of adaptive functioning in preschool aged children with
autism spectrum disorder. Autism Res. 2021;14:1444–55.
Page 18 of 20
Caarellietal. Italian Journal of Pediatrics (2022) 48:189
145. Klinger LG, Cook ML, Dudley KM. Predictors and moderators of treat-
ment efficacy in children and adolescents with autism spectrum
disorder. J Clin Child Adolesc Psychol. 2021;50:517–24.
146. Cabrera-Martos I, Valenza MC, Valenza-Demet G, Benítez-Feliponi A,
Robles-Vizcaíno C, Ruiz-Extremera A. Effects of manual therapy on
treatment duration and motor development in infants with severe non-
synostotic plagiocephaly: a randomised controlled pilot study. Childs
Nerv Syst. 2016;32:2211–7.
147. Rogers GF, Oh AK, Mulliken JB. The role of congenital muscular torticol-
lis in the development of deformational plagiocephaly. Plast Reconstr
Surg. 2009;123:643–52.
148. Olson JJ, Kalkanis SN, Ryken TC. Congress of Neurological Surgeons
systematic review and evidence-based guidelines on the treatment of
adults with vestibular schwannomas: Executive summary. Neurosurg.
2018;82:129–34.
149. Pastor-Pons I, Hidalgo-García C, Lucha-López MO, Barrau-Lalmolda M,
Rodes-Pastor I, Rodríguez-Fernández ÁL, et al. Effectiveness of pediatric
integrative manual therapy in cervical movement limitation in infants
with positional plagiocephaly: a randomized controlled trial. Ital J
Pediatr. 2021;47:41.
150. Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, et al.
International Pediatric Multiple Sclerosis Study Group criteria for pedi-
atric multiple sclerosis and immune-mediated central nervous system
demyelinating disorders: revisions to the 2007 definitions. Mult Scler.
2013;19:1261–7.
151. Tardieu M, Banwell B, Wolinsky JS, Pohl D, Krupp LB. Consensus defini-
tions for pediatric MS and other demyelinating disorders in childhood.
Neurol. 2016;87(9 Suppl 2):S8–11.
152. Marchioni E, Ravaglia S, Montomoli C, Tavazzi E, Minoli L, Baldanti F,
et al. Postinfectious neurologic syndromes: a prospective cohort study.
Neurol. 2013;80:882–9.
153. Bozzola E, Spina G, Valeriani M, Papetti L, Ursitti F, Agostiniani R, et al.
Management of pediatric post-infectious neurological syndromes. Ital J
Pediatr. 2021;47:17.
154. Zafar A, Wang W, Liu G, Wang X, Xian W, McKeon F, et al. Molecular
targeting therapies for neuroblastoma: progress and challenges. Med
Res Rev. 2021;41:961–1021.
155. Luksch R, Castellani MR, Collini P, De Bernardi B, Conte M, Gambini C,
et al. Neuroblastoma (Peripheral neuroblastic tumours). Crit Rev Oncol
Hematol. 2016;107:163–81.
156. Whittle SB, Smith V, Doherty E, Zhao S, McCarty S, Zage PE. Overview
and recent advances in the treatment of neuroblastoma. Expert Rev
Anticancer Ther. 2017;17:369–86.
157. Bilke S, Chen QR, Wei JS, Khan J. Whole chromosome alterations predict
survival in high-risk neuroblastoma without MYCN amplification. Clin
Cancer Res. 2008;14:5540–7.
158. Jiang CY, Xu X, Jian BL, Zhang X, Yue ZX, Guo W, et al. Chromosome 10
abnormality predicts prognosis of neuroblastoma patients with bone
marrow metastasis. Ital J Pediatr. 2021;47:134.
159. Westwood H, Tchanturia K. Autism spectrum disorder in anorexia
nervosa: an updated literature review. Curr Psychiatry Rep. 2017;19:41.
160. Kerr-Gaffney J, Halls D, Harrison A, Tchanturia K. Exploring relationships
between autism spectrum disorder symptoms and eating disorder
symptoms in adults with anorexia nervosa: a network approach. Front
Psychiatry. 2020;11:401.
161. Boltri M, Sapuppo W. Anorexia nervosa and autism spectrum disorder: a
systematic review. Psychiatry Res. 2021;306:114271.
162. Karjalainen L, Råstam M, Paulson-Karlsson G, Wentz E. Do autism spec-
trum disorder and anorexia nervosa have some eating disturbances in
common? Eur Child Adolesc Psychiatry. 2019;28:69–78.
163. Pruccoli J, Solari A, Terenzi L, Malaspina E, Angotti M, Pignataro V, et al.
Autism spectrum disorder and anorexia nervosa: an Italian prospective
study. Ital J Pediatr. 2021;47:59.
164. Patel M, Satishchandra P, Saini J, Bharath RD, Sinha S. Eating epilepsy:
phenotype, MRI, SPECT and video-EEG observations. Epilepsy Res.
2013;107:115–20.
165. Nakazawa C, Fujimoto S, Watanabe M, Tanaka M, Kageyama M, Ishikawa
T, et al. Eating epilepsy characterized by periodic spasms. Neuropediat-
rics. 2002;33:294–7.
166. Seneviratne U, Seetha T, Pathirana R, Rajapakse P. High prevalence of
eating epilepsy in Sri Lanka. Seizure. 2003;12:604–5.
167. Labate A, Colosimo E, Gambardella A, Leggio U, Ambrosio R, Loi M, et al.
Reflex periodic spasms induced by eating. Brain Dev. 2006;28:170–4.
168. Girges C, Vijiaratnam N, Wirth T, Tjoakarfa C, Idaszak J, Seneviratne U.
Seizures triggered by eating - a rare form of reflex epilepsy: a systematic
review. Seizure. 2020;83:21–31.
169. Vercellino F, Siri L, Brisca G, Scala M, Riva A, Severino M, et al. Symp-
tomatic eating epilepsy: two novel pediatric patients and review of
literature. Ital J Pediatr. 2021;47:137.
170. Mattson SN, Bernes GA, Doyle LR. Fetal alcohol spectrum disorders: a
review of the neurobehavioral deficits associated with prenatal alcohol
exposure. Alcohol Clin Exp Res. 2019;43:1046–62.
171. McDougall S, Finlay-Jones A, Arney F, Gordon A. A qualitative exami-
nation of the cognitive and behavioural challenges experienced
by children with fetal alcohol spectrum disorder. Res Dev Disabil.
2020;104:103683.
172. Kingdon D, Cardoso C, McGrath JJ. Research Review: Executive func-
tion deficits in fetal alcohol spectrum disorders and attention-deficit/
hyperactivity disorder - a meta-analysis. J Child Psychol Psychiatry.
2016;57:116–31.
173. Kully-Martens K, Denys K, Treit S, Tamana S, Rasmussen C. A review of
social skills deficits in individuals with fetal alcohol spectrum disorders
and prenatal alcohol exposure: profiles, mechanisms, and interventions.
Alcohol Clin Exp Res. 2012;36:568–76.
174. Dylag KA, Bando B, Baran Z, Dumnicka P, Kowalska K, Kulaga P, et al.
Sleep problems among children with Fetal Alcohol Spectrum Disorders
(FASD)- an explorative study. Ital J Pediatr. 2021;47:113.
175. Eric O. The negative effects of new screens on the cognitive func-
tions of young children require new recommendations. Ital J Pediatr.
2021;47:223.
176. Anderson DR, Subrahmanyam K. Cognitive impacts of digital media
workgroup digital screen media and cognitive development. Pediatr.
2017;140((Suppl 2)):S57–61.
177. Aishworiya R, Cai S, Chen HY, Phua DY, Broekman BFP, Daniel LM, et al.
Television viewing and child cognition in a longitudinal birth cohort in
Singapore: the role of maternal factors. BMC Pediatr. 2019;19:286.
178. Madigan S, McArthur BA, Anhorn C, Eirich R, Christakis DA. Associations
between screen use and child language skills: a systematic review and
meta-analysis. JAMA Pediatr. 2020;174:665–75.
179. van den Heuvel M, Ma J, Borkhoff CM, Koroshegyi C, Dai DWH,
Parkin PC, et al. Mobile media device use is associated with expres-
sive language delay in 18-month-old children. J Dev Behav Pediatr.
2019;40:99–104.
180. Cespedes EM, Gillman MW, Kleinman K, Rifas-Shiman SL, Redline S,
Taveras EM. Television viewing, bedroom television, and sleep duration
from infancy to mid-childhood. Pediatr. 2014;133:e1163–71.
181. Chen B, van Dam RM, Tan CS, Chua HL, Wong PG, Bernard JY, et al.
Screen viewing behavior and sleep duration among children aged 2
and below. BMC Public Health. 2019;19:59.
182. Council on communications and media. Media and young minds.
Pediatr. 2016;138:e20162591.
183. Gupta V, Mahendri NV, Tete P, Santhanam S. Skimmed milk prepa-
ration in management of congenital chylothorax. Indian Pediatr.
2014;51:146–8.
184. Höck M, Höller A, Hammerl M, Wechselberger K, Krösslhuber J, Kiechl-
Kohlendorfer U, et al. Dietary treatment of congenital chylothorax with
skimmed breast milk. Ital J Pediatr. 2021;47:175.
185. Goldstein A, Armony-Sivan R, Rozin A, Weller A. Somatostatin
levels during infancy, pregnancy, and lactation: a review. Peptides.
1995;16:1321–6.
186. Westerfield KL, Koenig K, Oh R. Breastfeeding: common questions and
answers. Am Fam Physician. 2018;98:368–73.
187. Section on Breastfeeding. Breastfeeding and the use of human milk.
Pediatr. 2012;129:e827–41.
188. Gartner LM, Morton J, Lawrence RA, Naylor AJ, O’Hare D, Schan-
ler RJ, et al. Breastfeeding and the use of human milk. Pediatr.
2005;115:496–506.
189. Taye AA, Asegidew W, Taderegew MM, Bizuwork YG, Zegeye B. Formula
feeding practice and associated factors among mothers with infants
0–6 months of age in Addis Ababa, Ethiopia: a community-based cross-
sectional study. Ital J Pediatr. 2021;47:55.
Page 19 of 20
Caarellietal. Italian Journal of Pediatrics (2022) 48:189
190. Shergill-Bonner R. Micronutrients. Paediatr Child Heal (United King-
dom). 2017;27:357–62.
191. Whitehead RG, Paul AA. Long-term adequacy of exclusive breast-
feeding: how scientific research has led to revised opinions. Proc Nutr
Soc. 2000;59:17–23.
192. Savarino G, Corsello A, Corsello G. Macronutrient balance and micro-
nutrient amounts through growth and development. Ital J Pediatr.
2021;47:109.
193. Eriksen KG, Johnson W, Sonko B, Prentice AM, Darboe MK, Moore SE.
Following the world health organization’s recommendation of exclu-
sive breastfeeding to 6 months of age does not impact the growth of
rural Gambian infants. J Nutr. 2017;147:248–55.
194. Gera T, Shah D, Garner P, Richardson M, Sachdev HS. Integrated man-
agement of childhood illness (IMCI) strategy for children under five.
Cochrane Database Syst Rev. 2016;6:CD010123.
195. Prajapati AC, Chandwani H, Rana B, Sonaliya KN. A community based
assessment study of positioning, attachment and suckling during
breastfeeding among 0–6 months aged infants in rural area of Gan-
dhinagar district, Gujarat, India. Int J Community Med Public Health.
2016;3:1921–6.
196. Degefa N, Tariku B, Bancha T, Amana G, Hajo A, Kusse Y, et al. Breast
feeding practice: positioning and attachment during breast feeding
among lactating mothers visiting health facility in Areka Town South-
ern Ethiopia. Int J Pediatr. 2019;2019:8969432.
197. Safayi BL, Assimamaw NT, Kassie DG. Breastfeeding technique and
associated factors among lactating mothers visiting Gondar town
health facilities, Northwest Ethiopia: observational method. Ital J
Pediatr. 2021;47:206.
198. Amarri S, Ottaviani A, Campagna A, De Panfilis L, Romagna E, Paedi-
atric palliative care working group. Children with medical complexity
and paediatric palliative care a retrospective cross-sectional survey of
prevalence and needs. Ital J Pediatr. 2021;47:110.
199. Lyons-Warren AM. Update on palliative care for pediatric neurology.
Am J Hosp Palliat Care. 2019;36:154–7.
200. Weaver MS, Heinze KE, Bell CJ, Wiener L, Garee AM, Kelly KP, et al.
Establishing psychosocial palliative care standards for children and
adolescents with cancer and their families: an integrative review.
Palliat Med. 2016;30:212–23.
201. Nilsson S, Ohlen J, Hessman E, Brännström M. Paediatric palliative
care: a systematic review. BMJ Support Palliat Care. 2020;10:157–63.
202. Grotenhermen F, Müller-Vahl K. The therapeutic potential of cannabis
and cannabinoids. Dtsch Arztebl Int. 2012;109:495–501.
203. Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial
of cannabidiol for drug-resistant seizures in the Dravet Syndrome. N
Engl J Med. 2017;376:2011–20.
204. Oberoi S, Protudjer JLP, Rapoport A, Rassekh SR, Crooks B, Siden H,
et al. Perspectives of pediatric oncologists and palliative care physi-
cians on the therapeutic use of cannabis in children with cancer.
Cancer Rep (Hoboken). 2021;5:e1551.
205. Divisic A, Avagnina I, De Tommasi V, Santini A, Brogelli L, Giacomelli L,
et al. The use of medical cannabis in pediatric palliative care: a case
series. Ital J Pediatr. 2021;47:229.
206. LeGrys VA, Wood RE. Incidence and implications of false-negative
sweat test reports in patients with cystic fibrosis. Pediatr Pulmonol.
1988;4:169–72.
207. Cimbalo C, Tosco A, Terlizzi V, Sepe A, Castaldo A, Salvadori L, et al.
Elevated sweat chloride test: is it always cystic fibrosis? Ital J Pediatr.
2021;47:112.
208. Com G, Uc A. Exercise intolerance, malnutrition, abnormal sweat
chloride levels, and two CFTR mutations: is it cystic fibrosis? J Pediatr
Health Care. 2015;29:201–4.
209. Brown A, Jenkins L, Reid A, Leavy A, McDowell G, McIlroy C, et al. How
to perform and interpret the sweat test. Arch Dis Child Educ Pract Ed.
2020;105:230–5.
210. Terlizzi V, Masi E, Francalanci M, Taccetti G, Innocenti D. Hypertonic
saline in people with cystic fibrosis: review of comparative studies
and clinical practice. Ital J Pediatr. 2021;47:168.
211. Wark P, McDonald VM. Nebulised hypertonic saline for cystic fibrosis.
Cochrane Database Syst Rev. 2018;(9):CD001506.
212. Yang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane
Database Syst Rev. 2021;3:CD001127.
213. Southern KW, Clancy JP, Ranganathan S. Aerosolized agents for
airway clearance in cystic fibrosis. Pediatr Pulmonol. 2019;54:858–64.
214. de Benedictis FM, Bush A. Recurrent lower respiratory tract infections
in children. BMJ. 2018;362:k2698.
215. Chiappini E, Santamaria F, Marseglia GL, Marchisio P, Galli L, Cutrera
R, et al. Prevention of recurrent respiratory infections : Inter-society
consensus. Ital J Pediatr. 2021;47:211.
216. Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila
T, et al. International union of immunological societies: 2017 primary
immunodeficiency diseases committee report on inborn errors of
immunity. J Clin Immunol. 2018;38:96–128.
217. Bont L, Checchia PA, Fauroux B, Figueras-Aloy J, Manzoni P, Paes B,
et al. Defining the epidemiology and burden of severe respiratory
syncytial virus infection among infants and children in Western
countries. Infect Dis Ther. 2016;5:271–98.
218. Azzari C, Baraldi E, Bonanni P, Bozzola E, Coscia A, Lanari M, et al.
Epidemiology and prevention of respiratory syncytial virus infections
in children in Italy. Ital J Pediatr. 2021;47:198.
219. Duse M, Santamaria F, Verga MC, Bergamini M, Simeone G, Leonardi L,
et al. Inter-society consensus for the use of inhaled corticosteroids in
infants, children and adolescents with airway diseases. Ital J Pediatr.
2021;47:97.
220. Expert Panel Working Group of the National Heart Lung, and Blood
Institute (NHLBI) Administered and coordinated National Asthma
Education and Prevention Program Coordinating Committee (NAEP-
PCC), Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens
T, et al. focused updates to the asthma management guidelines: a
report from the National Asthma Education and prevention program
coordinating committee expert panel working group. J Allergy Clin
Immunol. 2020;2020(146):1217–70.
221. Wise SK, Lin SY, Toskala E, Orlandi RR, Akdis CA, Alt JA, et al. Interna-
tional consensus statement on allergy and rhinology: allergic rhinitis.
Int Forum Allergy Rhinol. 2018;8:108–352.
222. Chong LY, Head K, Hopkins C, Philpott C, Burton MJ, Schilder AG. Dif-
ferent types of intranasal steroids for chronic rhinosinusitis. Cochrane
Database Syst Rev. 2016;26:4.
223. Montana A, Salerno M, Feola A, Asmundo A, Di Nunno N, Casella F,
et al. Risk management and recommendations for the prevention of
fatal foreign body aspiration: four cases aged 1.5 to 3 years and mini-
review of the literature. Int J Environ Res Public Health. 2020;17:4700.
224. Chen X, Zhang C. Foreign body aspiration in children: Focus on
the impact of delayed treatment. Int J Pediatr Otorhinolaryngol.
2017;96:111–5.
225. Fasseeh NA, Elagamy OA, Gaafar AH, Reyad HM, Abougabal MS,
Heiba DA, et al. A new scoring system and clinical algorithm for the
management of suspected foreign body aspiration in children: a
retrospective cohort study. Ital J Pediatr. 2021;47:194.
226. Posten S, Reed J. Pediatric community acquired pneumonia. S D Med.
2017;70:557–61.
227. Qin Q, Shen KL. Community-acquired pneumonia and its complica-
tions. Indian J Pediatr. 2015;82:745–51.
228. Johnson AW, Osinusi K, Aderele WI, Gbadero DA, Olaleye OD,
Adeyemi-Doro FA. Etiologic agents and outcome determinants of
community-acquired pneumonia in urban children: a hospital-based
study. J Natl Med Assoc. 2008;100:370–85.
229. Shan W, Shi T, Chen K, Xue J, Wang Y, Yu J, et al. Risk factors for severe
community-aquired pneumonia among children hospitalized with
CAP younger than 5 years of age. Pediatr Infect Dis J. 2019;38:224–9.
230. Chen L, Miao C, Chen Y, Han X, Lin Z, Ye H, et al. Age-specific risk fac-
tors of severe pneumonia among pediatric patients hospitalized with
community-acquired pneumonia. Ital J Pediatr. 2021;47:100.
231. Bozzola E, Staiano AM, Spina G, Zamperini N, Marino F, Roversi M,
et al. Social media use to improve communication on children and
adolescent’s health: the role of the Italian Paediatric Society influenc-
ers. Ital J Pediatr. 2021;47:171.
232. Moola F. The complexities of contagion: The experience of social iso-
lation among children and youth living with cystic fibrosis in Canada.
J Child Health Care. 2018;22:631–45.
Page 20 of 20
Caarellietal. Italian Journal of Pediatrics (2022) 48:189
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233. Bonnevie E, Rosenberg SD, Kummeth C, Goldbarg J, Wartella
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edge and positive attitudes toward the flu vaccine. PLoS ONE.
2020;15:e0240828.
234. Coates AE, Hardman CA, Halford JCG, Christiansen P, Boyland EJ. Social
media influencer marketing and children’s food intake: a randomized
trial. Pediatr. 2019;14:e20182554.
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