Giancarlo Gargano

The burden of early-onset sepsis in Emilia-Romagna (Italy): a 4-year, population-based study.

Abstract Objective: To provide the first Italian data on pathogens causing early-onset sepsis (EOS) and their antimicrobial susceptibility, after the successfully prevention of Group B streptococcus (GBS) EOS. Methods: Retrospective area-based cohort study from Emilia-Romagna (Italy). Cases of EOS registered (from 2009 to 2012) in all gestational age neonates were reviewed. Results: Live births (LB) numbered 146 682. Ninety neonates had EOS and 12 died (incidence rates of 0.61 and 0.08/1000 LB, respectively). EOS and mortality were the highest among neonates with a birth weightu2009<1000u2009g (20.37/1000 LB and 8.49/1000 LB, respectively). The most common pathogens were GBS (nu2009=u200927, 0.18/1000 LB) and Escherichia coli (nu2009=u200919, 0.13/1000 LB). Most infants affected by E. coli EOS were born preterm (nu2009=u200913), had complications (nu2009=u20094) or died (nu2009=u20097). Among 90 isolates tested, only 3 were resistant to both first line empirical antibiotics. Multivariate logistic regression analysis showed that low gestational age, caesarean section and low platelet count at presentation were significantly associated with death or brain lesions (area under ROC curveu2009=u20090.939, H-Lu2009=u20090.944, sensitivity 76.0%, specificity 90.7%). Conclusions: GBS slightly exceeds E. coli as a cause of EOS. However, E. coli is the prominent cause of death, complications and in most cases affects preterm neonates. Empirical antimicrobial therapy of EOS seems appropriate.

Kernicterus Associated with Hereditary Spherocytosis and UGT1A1 Promoter Polymorphism

Introduction: An apparent re-emergence of kernicterus has been recently reported, with some cases occurring in otherwise healthy breastfed newborn. Methods: We describe a case of kernicterus in a term Caucasian newborn. Results: An exceptional polymorphism of UGT1A1 gene promoter co-existed with asymptomatic inherited spherocytosis, due to erythroid anion exchange (band-3) deficiency. Both concurred to the development of severe neonatal hyperbilirubinaemia. Conclusion: As some cases of kernikterus remain unresolved, haemolytic diseases and bilirubin metabolism disorders should be carefully investigated in unexplained severe neonatal hyperbilirubinaemia.

Simpson–Golabi–Behmel syndrome type 1 in a 27-week macrosomic preterm newborn: The diagnostic value of rib malformations and index nail and finger hypoplasia†

The Simpson–Golabi–Behmel syndrome type 1 (SGBS1, OMIM #312870) is an X‐linked overgrowth condition comprising abnormal facial appearance, supernumerary nipples, congenital heart defects, polydactyly, fingernail hypoplasia, increased risk of neonatal death and of neoplasia. It is caused by mutation/deletion of the GPC3 gene. We describe a macrosomic 27‐week preterm newborn with SGBS1 who presents a novel GPC3 mutation and emphasize the phenotypic aspects which allow a correct diagnosis neonatally in particular the rib malformations, hypoplasia of index finger and of the same fingernail, and 2nd–3rd finger syndactyly.

Hydrops fetalis in a preterm newborn heterozygous for the c.4A>G SHOC2 mutation

Fetal hydrops is a condition resulting from interstitial fluid accumulation in fetal compartments secondary to increased capillary permeability and characterized by high rates of perinatal mortality and morbidity. Clinical features include skin edema, hydrothorax, pericardial effusion, ascites with or without polyhydramnios, and placental edema. While it may occur as associated feature in multiple disorders, it has been documented to recur in Noonan syndrome, the most common disorder among RASopathies, but also in cardiofaciocutaneous and Costello syndromes. Here, we report on the occurrence of severe hydrops in a newborn heterozygous for the invariant c.4A>G missense change in SHOC2 which underlies Noonan‐like syndrome with loose anagen hair, documenting that it represents a clinically relevant complication in this condition, shared by RASopathies.

Intrapartum fetal heart rate monitoring: evaluation of a standardized system of interpretation for prediction of metabolic acidosis at delivery and neonatal neurological morbidity.

Abstract Objective: To assess the ability of the intrapartum fetal heart rate interpretation system developed in 2008 by the National Institute of Child Health and Human Development (NICHD) to predict fetal metabolic acidosis at delivery and neonatal neurological morbidity. Methods: We analyzed the intrapartum fetal heart rate tracings of 314 singleton fetuses at ≥37 weeks using the NICHD three-tier system of interpretation: Category I (normal), Category II (indeterminate) and Category III (abnormal). Category II was further divided into Category IIA, with moderate fetal heart rate variability or accelerations, and Category IIB, with minimal/absent fetal heart rate variability and no accelerations. The presence and duration of the different patterns were compared with several clinical neonatal outcomes and with umbilical artery acid-base balance at birth. Results: The mean values of pH and base excess decreased proportionally as tracings worsened (pu2009<u20090.001). The duration of at least 30u2009min for Category III tracings was highly predictive of a pH <7.00 and a base excess ≤−12u2009mmol/L. The same was true for the duration of Category IIB tracings that lasted for at least 50u2009min. Conclusions: Our study demonstrates that the interpretation of fetal heart rate tracings based on a strictly standardized system is closely associated with umbilical artery acid-base status at delivery.

Retrospective analysis on the efficacy of corticosteroid prophylaxis prior to elective caesarean section to reduce neonatal respiratory complications at term of pregnancy: review of literature

PurposeOur purpose was to conduct a systematic review of the literature to determine whether synthetic pharmaceutical glucocorticoids (betamethasone and dexamethasone) are safe as well as effective in reducing neonatal respiratory morbidity at term of pregnancy prior to elective caesarean section. The overall incidence of respiratory disorders is estimated at 2.8xa0%, and the main risk factors are gestational age and mode of delivery. Newborns delivered by elective caesarean section (CS after 37xa0weeks) are more susceptible to serious respiratory complications than babies born by vaginal delivery. Neonatal respiratory morbidity at term of pregnancy is low but not negligible. Further, it is increasing due to a drastic decline in trial of labour in those pregnant women who underwent a caesarean section in the past. Because prophylaxis is inexpensive, easy to administer, and safe, other studies should be conducted to confirm its effectiveness.MethodsWe conducted a systematic review of literature since 1965 on the discovery of action mechanisms, pharmaceutical development, proper dosage, and potential side effects of corticosteroids on the mother and offspring to extrapolate their efficacy as no clinical trial has directly demonstrated it.ResultsWe extrapolated no negative effects on mother and foetus behaviour.ConclusionsHuman studies suggest that corticosteroid administration may become a proper clinical indication prior to caesarean section in the reduction of neonatal respiratory problems.

Multiple sulfatase deficiency with neonatal manifestation

Multiple Sulfatase Deficiency (MSD; OMIM 272200) is a rare autosomal recessive inborn error of metabolism caused by mutations in the sulfatase modifying factor 1 gene, encoding the formylglycine-generating enzyme (FGE), and resulting in tissue accumulation of sulfatides, sulphated glycosaminoglycans, sphingolipids and steroid sulfates. Less than 50 cases have been published so far. We report a new case of MSD presenting in the newborn period with hypotonia, apnoea, cyanosis and rolling eyes, hepato-splenomegaly and deafness. This patient was compound heterozygous for two so far undescribed SUMF1 mutations (c.191C > A; p.S64X and c.818A > G; p.D273G).

Fatal pneumonia following maternal HSV-1 viraemia in late pregnancy

Abstract Neonatal Herpes simplex virus (HSV) pneumonia without apparent accompanying disseminated infection is a rare condition. We describe a case of neonatal pneumonia following maternal HSV type 1 viraemia in late pregnancy. A review of the literature shows that cases of HSV presenting as pneumonia in the first week of life are the most severe form of neonatal HSV.

Massive thymic hemorrhage and hemothorax occurring in utero

Background Thymic enlargement is a common and physiological finding in children and neonates’ X-rays, but it is usually asymptomatic. Occasionally it can cause respiratory distress. In most cases the aetiology of this expansion remains unclear and it is diagnosed as a thymic hyperplasia. True thymic hyperplasia is defined as a gland expansion, both in size and weight, while maintaining normal microscopic architecture. Often it is a diagnosis of exclusion and prognosis is good.Thymic haemorrhage is an unusual condition related to high foetal and neonatal mortality.Case PresentationWe report a case of spontaneous massive thymic haemorrhage in a newborn developing at birth acute respiratory distress associated with severe bilateral haemothorax.Thymic enlargement was evident after pleural evacuation and confirmed by radiographic, Computed Tomography (CT) images and Magnetic Resonance Imaging (MRI) sequences. The spontaneous resolution of this enlargement seen with CT scan and MRI sequences suggested a thymic haemorrhage; surgery was not necessary.ConclusionThymic haemorrhage should be considered in newborn infants with pleural effusion, mediastinal space enlargement and Respiratory Distress.

Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

BackgroundSince 2010, array-CGH (aCGH) has been the first-tier test in the diagnostic approach of children with neurodevelopmental disorders (NDD) or multiple congenital anomalies (MCA) of unknown origin. Its broad application led to the detection of numerous variants of uncertain clinical significance (VOUS). How to appropriately interpret aCGH results represents a challenge for the clinician.MethodWe present a retrospective study on 293 patients with age range 1xa0month - 29xa0years (median 7xa0years) with NDD and/or MCA and/or dysmorphisms, investigated through aCGH between 2005 and 2016. The aim of the study was to analyze clinical and molecular cytogenetic data in order to identify what elements could be useful to interpret unknown or poorly described aberrations. Comparison of phenotype and cytogenetic characteristics through univariate analysis and multivariate logistic regression was performed.ResultsCopy number variations (CNVs) with a frequencyu2009<u20091% were detected in 225 patients of the total sample, while 68 patients presented only variants with higher frequency (heterozygous deletions or amplification) and were considered to have negative aCGH. Proved pathogenic CNVs were detected in 70 patients (20.6%). Delayed psychomotor development, intellectual disability, intrauterine growth retardation (IUGR), prematurity, congenital heart disease, cerebral malformations and dysmorphisms correlated to reported pathogenic CNVs. Prematurity, ventricular septal defect and dysmorphisms remained significant predictors of pathogenic CNVs in the multivariate logistic model whereas abnormal EEG and limb dysmorphisms were mainly detected in the group with likely pathogenic VOUS.A flow-chart regarding the care for patients with NDD and/or MCA and/or dysmorphisms and the interpretation of aCGH has been made on the basis of the data inferred from this study and literature.ConclusionOur work contributes to make the investigative process of CNVs more informative and suggests possible directions in aCGH interpretation and phenotype correlation.