Early parenting intervention promotes 24-month psychomotor development in preterm children.

AIM: Although parenting is key to promoting healthy development of at-risk preterm infants, parents have often restricted access to neonatal intensive care units (NICUs). This study aimed to assess the effect of an early parenting intervention on the psychomotor outcome in preterm children at 24 months of corrected age. METHODS: Forty-two preterm children and their parents were consecutively recruited at a level III NICU in Northern Italy and randomly allocated to early intervention (two educational peer-group sessions and four individual infant observation sessions) or care as usual (no educational or infant observation sessions). During NICU stay, parents provided information on daily holding and skin-to-skin. Psychomotor development was measured at 24 months of corrected age using the Griffith Mental Development Scales. RESULTS: There were no significant differences in socio-demographic and clinical variables between early intervention (n = 21; 13 females) and care as usual (n = 21; 12 females) groups. At 24 months of corrected age, children in the early intervention arm had greater scores for global psychomotor development as well as for Hearing-Speech and Personal-Social sub-scales, compared to those in the care as usual group. CONCLUSION: The present NICU parenting intervention was found to be associated with better psychomotor outcomes in preterm children at 24-month age. The effects were especially evident for domains related to language and socio-emotional functioning. Results are promising and should be retested with more heterogeneous and representative preterm sample.

Inherited human IRAK-1 deficiency selectively impairs TLR signaling in fibroblasts.

Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear. We describe here a boy with X-linked MECP2 deficiency-related syndrome due to a large de novo Xq28 chromosomal deletion encompassing both MECP2 and IRAK1 Like many boys with MECP2 null mutations, this child died very early, at the age of 7 mo. Unlike most IRAK-4- or MyD88-deficient patients, he did not suffer from invasive bacterial diseases during his short life. The IRAK-1 protein was completely absent from the patient's fibroblasts, which responded very poorly to all TLR2/6 (PAM2CSK4, LTA, FSL-1), TLR1/2 (PAM3CSK4), and TLR4 (LPS, MPLA) agonists tested but had almost unimpaired responses to IL-1ß. By contrast, the patient's peripheral blood mononuclear cells responded normally to all TLR1/2, TLR2/6, TLR4, TLR7, and TLR8 (R848) agonists tested, and to IL-1ß. The death of this child precluded long-term evaluations of the clinical consequences of inherited IRAK-1 deficiency. However, these findings suggest that human IRAK-1 is essential downstream from TLRs but not IL-1Rs in fibroblasts, whereas it plays a redundant role downstream from both TLRs and IL-1Rs in leukocytes.

Vertical Transmission of SARS-CoV-2 (COVID-19): Are Hypotheses More than Evidences?

In spite of the increasing, accumulating knowledge on the novel pandemic coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), questions on the coronavirus disease-2019 (COVID-19) infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending and have not been addressed so far. SARS-CoV-2, a RNA single-stranded virus, has been detected in the amniotic fluid, in the cord blood and in the placentas of the infected women. In the light of these findings, the theoretical risk of intrauterine infection for fetuses, or of peripartum infection occurring during delivery for neonates, has a biological plausibility. The extent of this putative risk might, however, vary during the different stages of pregnancy, owing to several variables (physiological modifications of the placenta, virus receptors' expression, or delivery route). This brief review provides an overview of the current evidence in this area. Further data, based on national and international multicenter registries, are needed not only to clearly assess the extent of the risk for vertical transmission, but also to ultimately establish solid guidelines and consistent recommendations. KEY POINTS: · Questions on the COVID-19 infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending so far.. · The theoretical risk of intrauterine infection for fetuses, or of neonatal infection during delivery for neonates, has a biological plausibility.. · A caution is recommended in the interpretation of clinical and laboratory data in neonates..

Neonatal vesiculopustular eruption in Down syndrome and transient myeloproliferative disorder: A case report and review of the literature.

Transient myeloproliferative disorder (TMD) is a spontaneously resolving clonal myeloid proliferation characterized by circulating megakaryoblasts in the peripheral blood that is restricted to neonates with Down syndrome (DS) or those with trisomy 21 mosaicism. Cutaneous manifestations of TMD are observed in only 5% of affected neonates and present as a diffuse eruption of erythematous, crusted papules, papulovesicles, and pustules, often with prominent and initial facial involvement. We describe the case of a male infant with DS and TMD, associated with a vesiculopustular eruption, which appeared on day 36 of life, and review previous cases.

New Diagnostic Possibilities for Neonatal Sepsis.

Progress in neonatal care has decrease morbidity and mortality due to neonatal sepsis (NS). Although diagnosis of sepsis continues to rely on blood culture, this method is too slow and limited by false-negative results. There are numerous sepsis biomarkers that have been evaluated for the early diagnosis of NS, but, to date, there is no single ideal biomarker, though novel biomarkers are becoming more sophisticated and specific in their clinical applications. This review provides an overview of the current diagnostic approaches available or under development for diagnosing NS.

Novel Approaches to the Study of Neonatal Infections.

The pathogenesis of neonatal infection is incompletely understood. Neonatal immune immaturity and the microbial factors of virulence only partially explain the interindividual differences in the protective responses to the most common neonatal pathogens. Stratification of infants into high- and low-risk groups through epidemiological studies has been invaluable in designing preventive strategies and reducing the burden of neonatal infection. The discovery of the role of maternal antibodies (Abs) as, for instance, anti-capsular polysaccharide group B streptococcal (GBS) Abs, in protecting newborn infants against neonatal GBS sepsis, has been a milestone in the unraveling of the molecular underpinnings of susceptibility to infection in the neonatal age. Future work should aim at defining the cellular and molecular differences in the neonatal immune responses that account for individual susceptibility and resistance to common neonatal pathogens. The interplay between the genetic and immune backgrounds of the infant, changes in the infant's microbiome, maternal factors, and the pathogen's characteristics needs to be accurately described through human studies. Precise phenotyping and dissection of the clinical heterogeneity of neonatal infection should identify cohorts that can be studied through different study methodologies. Term and preterm infants should be investigated according to the most likely underlying mechanism, single-gene disorders and multifactorial predisposition, respectively. Novel technologies, including genotyping studies, exome and genome sequencing, analysis of the microbiome, and the study of the metabolome, are nowadays established and available and can be integrated to gain a better insight into the unexplained bases of individual susceptibility to neonatal infections.

The Mother-Child Relationship during the First Months of Life: Preliminary Considerations in Preterm as Compared with Term Mother-Infant Dyads.

INTRODUCTION: From the prognostic perspective, the quality of the mother-child relationship during the first months of life has been variously associated with different factors such as the child's psychomotor/cognitive development and emotional-behavioral disorders. METHODS: The main aim of this study was to describe, at term age and 3 months of corrected age, the features and the prevalent patterns of the mother-child relationship in a group of 20 mother-preterm infant dyads and to compare them with those of a group of 20 mother-term infant dyads. RESULTS: A relatively high rate of inadequate dyadic synchrony was found in our sample of preterms at 40 weeks of gestational age (half of the sample analyzed). The quality of the dyadic relationship and the prevalent patterns of the mother-child relationship were found to differ between the two groups we studied; moreover, the subjects at risk of relational problems remained substantially the same during the first 3 months of life. DISCUSSION: These data underline that in preterm children, the first weeks of life, coinciding with their hospitalization, represent a crucial time for establishing a valid dyadic relationship and for considering and planning any preventive interventions; after all, the earlier the risk of relational problems becomes a real possibility, the more likely it is to negatively impact on a child's overall development.

Impact of Early Postnatal Nutrition on the NMR Urinary Metabolic Profile of Infant.

NMR-based metabolomics was used to compare the metabolic urinary profiles of exclusively breast-fed term infants (n = 11) with those of a double-blinded controlled trial with 49 formula-fed term newborns randomized to receive either an infant formula enriched by functional ingredients (n = 24) or a standard formula (n = 25). Anthropometric measurements and urine samples were taken at enrollment (within the first month of life), at around 60 days of life, and at the end of study period (average age of 130 days). The metabolic profiles were examined in relation to time and diet strategy. A common age-dependent modification of the urine metabolome was observed for the three types of nutrition, mainly characterized by similar temporal trends of choline, betaine, myoinositol, taurine, and citrate. Contrariwise, differences in the metabolic profiles were identified according to the type of diet (human versus formula milk), while no significant difference was observed between the two formulas. These modifications are discussed mainly in terms of the different milk compositions. Despite the low number of enrolled infants (n = 60), these findings pointed out the potential of the metabolomics approach for neonatal nutritional science, in particular to provide important contributions to the optimization of formula milk.

Near-Infrared Spectroscopy Monitoring, Superior Vena Cava Flow, and Neurodevelopmental Outcome at 2 years in a Cohort of Very Low-Birth-Weight Infants.

Objective We aimed at assessing the association between superior vena cava flow (SVCf), regional (cerebral) tissue oxygen saturation (rSO2), and cerebral fractional oxygen extraction (CFOE) during the first 48 hours of life and 2-years neurodevelopmental outcome of very low-birth-weight infants (VLBW). Methods We prospectively studied 60 VLBW infants admitted to our neonatal intensive care unit; rSO2 was continuously monitored with near-infrared spectroscopy during the first 48 hours of life, SVCf was measured at 4 to 6, 12, 24, and 48 hours, and CFOE was calculated. Neurodevelopmental outcome was assessed at 24 months corrected age. Results The mean gestational age at birth was 27.9 weeks (standard deviation: 2.4); 8 infants died in the first 3 months of life, 6 were lost to follow-up, 46 survived and were followed up. At 24 months, 6 (13%) and 7 (15.2%) infants developed minor and major sequelae, respectively. Infants who died had higher CFOE (p < 0.001) and lower SVCf (p < 0.001) than infants surviving with sequelae. In turn, these had higher SVCf between 24 and 48 hours than those without sequelae (p < 0.001). Conclusion SVCf, rSO2, and CFOE patterns in the first days of life suggest cerebral hyperperfusion, related to loss of autoregulation and/or use of inotropic drugs, as a potential mechanism of cerebral injury.

Maternal and neonatal outcomes in pregnant women with autoimmune diseases in Pavia, Italy.

BACKGROUND: The increased number of childbearing women with autoimmune diseases leads to a growing interest in studying relationship among maternal disease, therapy, pregnancy and off-spring. The aim of this study was to determine the impact of autoimmune disease on pregnancy and on neonatal outcome, taking into account the maternal treatment and the transplacental autoantibodies passage. METHODS: We studied 70 infants born to 70 pregnant women with autoimmune disease attended in Fondazione IRCCS Policlinico San Matteo, Pavia, Italy from June 2005 to June 2012. Maternal and neonatal characteristics were collected and relevant clinical, laboratory, therapeutics, sonographic and electrocardiographic investigations were recorded and analyzed. RESULTS: We observed a high rate of spontaneous abortions in medical history, 29 %, and 18.6 % of preterm births and 22.9 % of low birth weight (< 2500 g). Transplacental autoantibodies passage wasn't related to maternal or obstetrical complication, but anti-Ro/SSA positive pregnancies correlated with abnormal fetal heart rate (P = 0.01). Pregnant women on therapy showed an higher incidence of maternal (p = 0.002), obstetric (p = 0.007) complications and an increased rate of intrauterine growth restriction (p = 0.01) than the untreated ones. CONCLUSIONS: Autoimmune diseases in pregnancy require to be carefully monitored to ensure the best possible management of mothers, fetuses and newborns due to the high rate of morbidity specially in case of maternal polytherapy and/or anti-Ro/SSA positivity.

Maternal, fetal, and neonatal parameters for prognosis and counseling of HCMV congenital infection.

To investigate retrospectively the prognostic significance of maternal, fetal, and neonatal parameters and clinical outcome in 150 HCMV congenital infections during the period 1995-2009. HCMV fetal infection was investigated in amniotic fluid and fetal blood samples. HCMV congenital infection was confirmed in newborn urine and blood samples. Symptomatic infection was defined in HCMV-infected fetuses and in infected newborns on the basis of physical and instrumental findings. Follow-up at 3, 6, 12 months, and then annually up to school age, included clinical evaluation, funduscopic, audiologic, neurologic, and cognitive assessment. Overall, 122/150 (81.3%) newborns were asymptomatic and 28/150 (18.7%) were symptomatic at birth. The best prognostic maternal parameter of symptomatic infection at birth was gestational age at infection (P = 0.037). The best fetal virological markers were HCMV DNA levels in amniotic fluid (P < 0.001), antigenaemia levels (P = 0.007), HCMV DNA levels in blood (P = 0.004), and HCMV-specific IgM index values (P = 0.002). The only significant neonatal parameter was HCMV DNA level in blood [P = 0.006; OR, 3.62 (95% CI, 1.46-8.97)]. Symptoms at birth correlated significantly with long-term sequelae (P = 0.021). A trend towards a risk of sequelae in early (n = 15/58 examined) versus late (n = 6/57 examined) maternal infection was documented. The risk of symptomatic congenital infection at birth increased linearly with the number of significant maternal, fetal, and neonatal parameters.

Malnutrition in pregnancy following bariatric surgery: three clinical cases of fetal neural defects.

OBJECTIVE: Bariatric surgery results in decreased food intake and a variable degree of malabsorption. Without adequate supplementation, the most common complications of this surgery are nutritional disorders. Pregnancy following surgery for obesity is a particular condition requiring strict monitoring of nutrient intake necessary for fetal development and a favourable neonatal prognosis. PATIENTS: Malnutrition in pregnancy and congenital neural malformations are reported in three women who had previously undergone bariatric surgery (1, 5 and 18 years before pregnancy, respectively). Two patients underwent the Roux en Y bypass and one bilio-pancreatic diversion with gastroplasty. None of the three received pre-conceptional nutritional counselling. Patients 1 and 2 did not undergo postoperative nutritional surveillance; nutrient supplementation was started at 22 and 20 weeks gestation, respectively. In patient 3, supplementation was stopped at six weeks gestation. RESULTS: Newborns 1 and 2 presented with dorsal myelomeningocele and ventricular dilation. Both underwent surgery and a ventriculo-peritoneal shunt was inserted in the first month of life. Newborn 3 had microcephaly, bilateral microphthalmia and sensorineural deafness. CONCLUSIONS: Diet and nutritional status, before and during pregnancy, play an important role in the early processes of fetal development and neonatal outcome. Women of childbearing age who have had bariatric surgery, should be encouraged to follow a well-balanced diet as part of a weight management strategy. They should be advised to take recommended maternal supplements.

The early administration of Lactobacillus reuteri DSM 17938 controls regurgitation episodes in full-term breastfed infants.

Forty breastfed full-term infants were randomly, double blind assigned to receive orally Lactobacillus reuteri (L. reuteri) DSM 17938, 5 drops/daily (10(8) colony-forming units), for 4 weeks (n = 20) or an identical placebo (n = 20), starting before third day of life. They underwent basal and final visit to monitor growth parameters and gastrointestinal (GI) disease. Parents registered daily: crying minutes, stool frequency and consistency, numbers of regurgitations, adverse events. Secretory IgA (sIgA) has been measured in saliva on 28th day. Treated infants demonstrated a reduction in daily regurgitations at the end of treatment (p = 0.02), three neonates in the placebo group only needed simethicone for GI pain, sIgA level was similar in both groups. Random casualty produced an unbalanced gender distribution in the groups, but this bias did not affect the results. Therefore, early administration of L. reuteri DSM 17938 resulted beneficial in preventing regurgitation episodes during the first month of life.

Genomic alterations in human umbilical cord-derived mesenchymal stromal cells call for stringent quality control before any possible therapeutic approach.

BACKGROUND AIMS: The umbilical cord (UC) is a promising source of mesenchymal stromal cells (MSCs). UC-MSCs display very similar in vitro characteristics to bone marrow-MSCs and could represent a valuable alternative for cell-based therapies. However, it is still unclear whether UC-MSCs are prone or not to the acquisition of genomic imbalances during in vitro expansion. METHODS: With the use of array-comparative genomic hybridization, we compared copy number variations of early (P2-P3) and late (>P5) passages of in vitro-expanded UC-MSCs. RESULTS: In two of 11 long-term UC-MSCs cultures, we observed the appearance of clones carrying genomic imbalances, which generated genetic mosaicism at intermediate passages. Although still able to reach the senescence phase, the cells carrying the genomic imbalance acquired a proliferative advantage, as demonstrated by the increase in frequency during long-term culture. CONCLUSIONS: Altogether, our results suggest that UC-MSC-based clinical protocols should be designed with caution; their clinical use should be preceded by array-comparative genomic hybridization screening for the acquisition of genomic imbalances during in vitro expansion.

Diagnostic performance of triggering receptor expressed on myeloid cells-1 and CD64 index as markers of sepsis in preterm newborns.

OBJECTIVE: CD64 index and triggering receptor expressed on myeloid cells-1 are biomarkers on neutrophil polymorphonuclear cells with crucial role in sepsis. The study aim is to assess diagnostic performance, individually and combined, of CD64 index and triggering receptor expressed on myeloid cells-1 (surface marker/soluble form), in late-onset sepsis of preterm infants. DESIGN: Observational study. SETTING: Neonatal ICU. PATIENTS: Sixteen septic and 16 control preterm infants, gestational age younger than 32 weeks and/or birth weigh less than 1500 g. MEASUREMENT AND MAIN RESULTS: Seventy preterm infants, free of sepsis were enrolled into the study. CD64 index and triggering receptor expressed on myeloid cells-1 were measured once between day 5 and 15 of life (T0) and once between day 16 and 25 (T1). At T1, 16 infants were assigned to septic group because of reported signs of sepsis and positive blood culture. From the remaining 54 infants, 16 of them who always remained free of sepsis had a blood sample at T1 and constituted the control group (n = 16). Comparing T1 vs T0, triggering receptor expressed on myeloid cells-1 polymorphonuclear cells percentage was significantly lower (p = 0.002) in septic group but not in control group; soluble triggering receptor expressed on myeloid cells-1 concentration did not show significant differences in both groups; CD64 index significantly increased (p = 0.0004) in septic group, while no difference was found in control group. Comparing septic with control group at T0, no differences were found in any markers. At T1, triggering receptor expressed on myeloid cells-1 polymorphonuclear cells percentage was significantly lower (p = 0.003) and CD64 index was higher (p = 0.00019) in septic infants. Triggering receptor expressed on myeloid cells-1 polymorphonuclear cells receiver operating characteristic curve indicated cutoff 62.12%, sensitivity 56.2%, specificity 93.5%, and area under the curve 0.8. CD64 index receiver operating characteristic curve indicated cutoff 2.85, sensitivity 87.5%, specificity 100%, and area under the curve 0.95. Combination of the two indexes was not useful in increasing individual diagnostic power. CONCLUSIONS: Despite limited sample size, CD64 index demonstrated to be a promising biomarker, with high specificity, to diagnose late-onset sepsis. Further investigations are needed to substantiate these findings. Triggering receptor expressed on myeloid cells-1 showed less valuable diagnostic role.

Prevention of nosocomial infections in neonatal intensive care units.

Neonatal sepsis causes a huge burden of morbidity and mortality and includes bloodstream, urine, cerebrospinal, peritoneal, and lung infections as well as infections starting from burns and wounds, or from any other usually sterile sites. It is associated with cytokine - and biomediator-induced disorders of respiratory, hemodynamic, and metabolic processes. Neonates in the neonatal intensive care unit feature many specific risk factors for bacterial and fungal sepsis. Loss of gut commensals such as Bifidobacteria and Lactobacilli spp., as occurs with prolonged antibiotic treatments, delayed enteral feeding, or nursing in incubators, translates into proliferation of pathogenic microflora and abnormal gut colonization. Prompt diagnosis and effective treatment do not protect septic neonates form the risk of late neurodevelopmental impairment in the survivors. Thus prevention of bacterial and fungal infection is crucial in these settings of unique patients. In this view, improving neonatal management is a key step, and this includes promotion of breast-feeding and hygiene measures, adoption of a cautious central venous catheter policy, enhancement of the enteric microbiota composition with the supplementation of probiotics, and medical stewardship concerning H2 blockers with restriction of their use. Additional measures may include the use of lactoferrin, fluconazole, and nystatin and specific measures to prevent ventilator associated pneumonia.

Human parechovirus infections in patients admitted to hospital in Northern Italy, 2008-2010.

Human parechoviruses (HPeVs) infection is associated with a wide range of clinical syndromes such as respiratory, gastrointestinal, neurologic diseases, and neonatal sepsis-like illness. The main objective of this study was to investigate the epidemiology of HPeVs infection in hospitalized patients in a period of 2 years. Respiratory samples from 3,525 patients with respiratory syndrome, cerebrospinal fluid (CSF) from 340 patients with neurologic syndrome as well as CSF and plasma samples from five neonatal patients with sepsis-like illness collected from October 2008 to 2010 were tested retrospectively using HPeV-specific real-time RT-PCR. Phylogenetic analysis of VP3/VP1 region was performed on the positive samples. Fourteen out of 3,525 (0.4%) patients with respiratory syndrome and five out of five patients with sepsis-like illness were positive for HPeV. In 3/5 patients with sepsis-like illness multiple samples (e.g., stool, plasma, CSF, or respiratory samples) were available, and HPeV was found in all specimens. In contrast, no positive CSF was detected among the 340 patients with neurologic syndromes. Eleven patients (57.9%) were infected with HPeV1 strain, 7 (36.8%) with HPeV3, and 1 (5.3%) with HPeV6 strains. Ten of the 14 HPeV patients with respiratory syndrome were co-infected with other respiratory viruses (eight with rhinovirus and two with coronavirus OC43). All five patients with sepsis-like illness were less than 1 month of age and were infected with HPeV3. Although not circulating at high frequency and unlikely to cause respiratory syndrome, HPeV was associated with severe clinical syndromes in a minority of newborns.

Central venous catheters in premature babies: radiological evaluation, malpositioning and complications.

Central venous catheters are important in the care for prematurely born children in the neonatal intensive care unit. The purpose of this pictorial essay is to illustrate correct positioning, malpositioning and possible complications of such devices.