Lumbar Puncture and Meningitis in Infants with Proven Early- or Late-Onset Sepsis: An Italian Prospective Multicenter Observational Study.

Background: To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design: We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli, diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results: LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions: Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

Timing of Symptoms of Early-Onset Sepsis after Intrapartum Antibiotic Prophylaxis: Can It Inform the Neonatal Management?

The effectiveness of "inadequate" intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003-2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined "active" when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an "inactive" IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP "adequate" seems the pathogen's antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis.

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00-0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00-0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02-0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics.

Prognostic Risk Factors for Severe Outcome in the Acute Phase of Neonatal Hypoxic-Ischemic Encephalopathy: A Prospective Cohort Study.

In the first days after birth, a major focus of research is to identify infants with hypoxic-ischemic encephalopathy at higher risk of death or severe neurological impairment, despite therapeutic hypothermia (TH). This is especially crucial to consider redirection of care, according to neonatal outcome severity. We aimed to seek associations between some neonatal routine parameters, usually recorded in Neonatal Intensive Care Units, and the development of severe outcomes. All consecutive patients prospectively recruited for TH for perinatal asphyxia, born between February 2009 and July 2016, were eligible for this study. Severe outcome was defined as death or major neurological sequelae at one year of age. Among all eligible neonates, the final analysis included 83 patients. Severe outcome was significantly associated with pH and base excess measured in the first hour of life, mode of delivery, Apgar score, Sarnat and Sarnat score, electroencephalogram-confirmed neonatal epileptic seizures, and antiepileptic therapy. Studying univariate analysis by raw relative risk (RR) and 95% confidence intervals (CI), severe outcome was significantly associated with pH (p = 0.011), Apgar score (p = 0.003), Sarnat score (p < 0.001), and Caesarian section (p = 0.015). Conclusions. In addition to clinical examination, we suggest a clinical-electroencephalographic protocol useful to identify neonates at high neurological risk, available before rewarming from TH.

Understanding Factors in Group B Streptococcus Late-Onset Disease.

Group B streptococcus (GBS) infection remains a leading cause of sepsis, pneumonia, and meningitis in infants. Rates of GBS early onset disease have declined following the widcespread use of intrapartum antibiotic prophylaxis; hence, late-onset infections (LOGBS) are currently a common presentation of neonatal GBS dicsease. The pathogenesis, mode of transmission, and risk factors associated with LOGBS are unclear, which interfere with effective prevention efforts. GBS may be transmitted from the mother to the infant at the time of delivery or during the postpartum period via contaminated breast milk, or as nosocomial or community-acquired infection. Maternal GBS colonization, prematurity, young maternal age, HIV exposure, and ethnicity (Black) are identified as risk factors for LOGBS disease; however, further studies are necessary to confirm additional risk factors, if any, for the implementation of effective prevention strategies. This narrative review discusses current and previous studies that have reported LOGBS. Few well-designed studies have described this condition; therefore, reliable assessment of maternal GBS colonization, breastfeeding, and twin delivery as risk factors for LOGBS remains limited.

[Un neonato con un ginocchio congenito recurvato.] / A newborn with isolated congenital genu recurvatum.

Riassunto. Descriviamo un caso di un neonato con un ginocchio congenito recurvato. Il neonato non aveva altre malformazioni. Il trattamento precoce con fisioterapia ha risolto il problema.

Prevalence of celiac disease serological markers in a cohort of Italian rheumatological patients.

AIM: To assess the prevalence of celiac disease (CD) serological markers in a cohort of patients referred to an Italian rheumatological outpatient clinic. BACKGROUND: Current guidelines do not suggest CD screening in patients with rheumatological diseases and these subjects are not considered to be at high risk for CD. METHODS: A total of 230 sera of rheumatological patients referred to the Division of Internal Medicine at the Department of Medical and Surgical Sciences between January 2005 and December 2013 were screened for CD by testing IgA antitransglutaminase (TTG IgA), IgG deamidated gliadin peptides (DGP IgG) and IgA antiendomysium (EMA) antibodies. Of the 230 patients tested, 67 had a diagnosis of rheumatoid arthritis (RA), 52 Sjögren's syndrome (SjS), 42 systemic sclerosis (SCL), 35 systemic lupus erythematosus (SLE), 15 mixed connective tissue disease, 11 polymyositis and 10 dermatomyositis. RESULTS: TTG IgA antibodies were identified in 7/230 cases (3%), 3 in SjS (3/42 - 5.8%), 2 in SCL (2/42 - 4.8%), 1 in RA (1/67 - 1.5%) and 1 in SLE sera (1/35 - 2.8%). All the seven sera were also positive for DGP IgG and EMA IgA. DGP IgG were the most frequent antibody detected, being found in 16 (7%) sera. CONCLUSION: This study identified a high prevalence of CD antibodies in adult patients referred to a rheumatology outpatient clinic. These results highlight the importance of CD screening in subjects presenting with rheumatological features.

Corrigendum to "Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress".

[This corrects the article DOI: 10.1155/2015/591783.].

Two mutations in surfactant protein C gene associated with neonatal respiratory distress.

Multiple mutations of surfactant genes causing surfactant dysfunction have been described. Surfactant protein C (SP-C) deficiency is associated with variable clinical manifestations ranging from neonatal respiratory distress syndrome to lethal lung disease. We present an extremely low birth weight male infant with an unusual course of respiratory distress syndrome associated with two mutations in the SFTPC gene: C43-7G>A and 12T>A. He required mechanical ventilation for 26 days and was treated with 5 subsequent doses of surfactant with temporary and short-term efficacy. He was discharged at 37 weeks of postconceptional age without any respiratory support. During the first 16 months of life he developed five respiratory infections that did not require hospitalization. Conclusion. This mild course in our patient with two mutations is peculiar because the outcome in patients with a single SFTPC mutation is usually poor.

Feeding intolerance in the preterm infant.

Feeding intolerance (FI), defined as the inability to digest enteral feedings associated to increased gastric residuals, abdominal distension and/or emesis, is frequently encountered in the very preterm infant and often leads to a disruption of the feeding plan. In most cases FI represents a benign condition related to the immaturity of gastrointestinal function, however its presentation may largely overlap with that of an impending necrotizing enterocolitis. As a consequence, individual interpretation of signs of FI represents one of the most uncontrollable variables in the early nutritional management of these infants, and may lead to suboptimal nutrition, delayed attainment of full enteral feeding and prolonged intravenous nutrition supply. Strategies aimed at preventing and/or treating FI are diverse, although very few have been validated in large RCT and systematic reviews. The purpose of this paper is to summarize the existing information on this topic, spanning from patho-physiological and clinical aspects to the prevention and treatment strategies tested in clinical studies, with specific attention to practical issues.

Strategies to improve feeding tolerance in preterm infants.

Postnatal growth restriction and failure to thrive is a major issue in preterm, especially extremely low-birth-weight infants. Optimization of enteral nutrition, without increasing the risk of necrotizing enterocolitis (NEC), has thus become a priority for the neonatologist, who often has to face the challenge of interpreting the clinical and prognostic significance of common and aspecific signs of feeding intolerance (FI). The neonatologist often prescribes enteral nutrition as if walking on a tightrope between the purposed attainment of full enteral feeding and the fear of NEC. Despite advances in neonatal intensive care, NEC still remains one of the leading causes of mortality (15-30%) and morbidity in very-low-birth-weight infants. However, the relationship between FI and NEC remains unknown. Feeding intolerance often leads to discontinuation of enteral feeds, delayed attainment of full enteral feeding and prolongation of hospitalization. Strategies aimed at preventing and/or treating episodes of feeding intolerance are diverse and not always supported by scientific evidence.

Blood transfusion in infants: techniques and adverse events.

High risk infants, especially preterm ones, often require the administration of blood products. Specific guidelines and recommendations on this topic are continually issued and updated and their clinical application is strongly supported, in order to optimize the transfusion practice in neonatal and pediatric patients. Blood transfusion in infants has, in fact, specific indications, requires special considerations on technical procedures, and deserves particular awareness of possible errors and potential adverse reactions.

Fortification of maternal milk for very low birth weight (VLBW) pre-term neonates.

Human milk is the best food for all neonates; however, in pre-term infants, especially those with a very low birth weight, it may lead to insufficient intake of protein and energy. The use of fortified human milk produces adequate growth in premature infants and satisfies the specific nutritional requirements of these babies. To improve the nutritional management of pre-term infants < or =35 weeks' gestational age, an individualised human milk fortification system based on the analysis of maternal milk was evaluated.

Different pre-term formulas for different pre-term infants.

Optimal nutrition is one of the most important aspects in the care of pre-term infants, especially for the gestationally youngest ones. These infants should receive a supply of nutrients that can sustain growth similar to that of a third trimester normal foetus. Traditional pre-term formulas do not ensure an optimal protein supply except when fed at high volumes, with an excess of fat and carbohydrates. Formulas with a protein content of 2-2.5 g 100ml(-1) and a protein/energy (P:E) ratio of less than 3g 100 kcal(-1) are not the best choice for the very low birth weight (VLBW) infants. We have tested a new formulation designed for the nutrition of the VLBW infants that is characterised by a protein content of 2.9 g 100ml(-1) and a P:E ratio of 3.5 g 100 kcal(-1). The milk formula was well tolerated and associated with better weight gain compared with fortified breast milk (18.1 vs. 15.2 g kg(-1)day(-1); p=0.0015). These results were obtained with a noticeably lower fluid supply (157 vs. 177 ml kg day(-1); p<0.0001) and lower energy intake (130 vs. 151 kcal kg(-1)day(-1); p<0.0001). Infant length and head circumference did not differ significantly between groups. Currently, the use of a formula with a P:E ratio of 3.5 g 100 kcal(-1) appears to be safe and to represent the best choice available for the gestationally youngest infants.

Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind randomized multicenter study.

OBJECTIVES: The primary objective of this study was to determine the bifidogenic effect of galacto-oligosaccharides (GOS) in a follow-on formula and the effects on other intestinal bacteria. Secondary objectives were the effects on stool characteristics, growth, and general well-being. PARTICIPANTS AND METHODS: In a multicenter, double-blind study, 159 healthy infants, formula-fed at enrollment (at 4-6 months), were randomized to an experimental follow-on formula supplemented with 5 g/L (GOS) (77 infants), or to a standard follow-on formula (control, 82 infants). Infants were evaluated at enrollment (study day 1 = sd1), after 6 weeks (study day 2 = sd2), and after an additional 12 weeks (study day 3 = sd3). At each study day, a fresh stool sample for the bacterial counts was collected, and the growth parameters were measured. At sd2, urinary specimens were collected for the evaluation of urinary osmolarity. RESULTS: At sd2 and sd3, the GOS group had a higher median number (colony-forming units per gram of stool) of bifidobacteria than did the control group (sd2 GOS 9.2 x 10(9) vs control 4.4 x 10(9), P = 0.012); (sd3 GOS 7.2 x 10(9) vs control 2.4 x 10(9), P = 0.027). Other bacteria did not show any significant differences between the 2 groups at all study days. The GOS produced softer stools but had no effect on stool frequency. The urinary osmolarity (mOsm/L) at sd2 was comparable in both groups. Supplementation had no influence on the incidence of gastrointestinal side effects or on the growth of the infants. CONCLUSIONS: These data indicate that the addition of GOS (5 g/L) to a follow-on formula positively influences the bifidobacteria flora and the stool consistency in infants during the supplementation period at weaning. No local or systemic side effects were recorded.

Which role for prebiotics at weaning?

It is now generally recognized that the intestinal microflora plays a key role for human health and well being. In fact, the gut ecosystem is involved in a number of biologic functions, such as direct and indirect antipathogen activity (nutritive competition, reduction of pH, production of short-chain fatty acids, maturation and protection of the mucosal barrier, etc), synthesis of vitamins, detoxification of potentially harmful substances, and maturation and regulation of the immune system. Weaning represents a crucial step in the development of the intestinal flora and, at the same time, corresponds to a very delicate phase of immunologic maturation. A safe and effective way to beneficially influence the intestinal microflora is the administration of prebiotics, which selectively promote the growth and/or activity of beneficial bacteria, such as bifidobacteria. Some of the studies, which investigated the microbiologic and clinical effectiveness of prebiotics have been conducted at weaning, reporting interesting results. Anyway, many of the promising beneficial effects evidenced still need to be confirmed by further large randomized trials.

Neonatal onset intestinal failure: an Italian Multicenter Study.

OBJECTIVE: To describe the natural course of intestinal failure with onset in the neonatal period to provide data regarding the occurrence and to provide a population-based survey regarding the spectrum of underlying diseases. STUDY DESIGN: We performed a retrospective chart review including infants admitted to the neonatal intensive care unit of 7 Italian tertiary care centers. Intestinal failure was defined as a primary intestinal disease that induces the need of total parenteral nutrition (PN) for more than 4 weeks or the need of partial PN for more than 3 months. RESULTS: The total number of live births during the study time within the enrolled institutions was 30 353, and the number of newborns admitted to the neonatal intensive care unit was 5088. Twenty-six patients satisfied the definition of intestinal failure; thus the occurrence rate of intestinal failure was 0.1% among live-birth newborns and 0.5% among infants at high risk. The main underlying diseases leading to intestinal failure in neonatal age were congenital intestinal defects (42.3%), necrotizing enterocolitis (30.8%), severe intestinal motility disorder (11.5%), intestinal obstruction (7.7%), structural enterocyte defects (3.8%), and meconium peritonitis (3.8%). After a follow-up of 36 months, 84.6% of patients achieved intestinal competence, 1 patient was still receiving home PN, 1 patient underwent transplantation, and 2 patients died. Cholestatic liver disease was diagnosed in 54% of observed children. CONCLUSION: An understanding of the incidence, causes, and natural history of intestinal failure would be helpful to appropriately allocate resources and to plan clinical trials.

Brain maturation of preterm newborn babies: new insights.

Preterm birth still results in a high number of neurodevelopmental sequelae, although major forms of brain lesions--such as periventricular leukomalacia and intraventricular hemorrhage--are significantly reduced in this population of babies compared with a few years ago. This paper focuses on the possible reasons for this phenomenon. Some brain lesions, such as those affecting the periventricular white matter and the cerebellum, may be underestimated if magnetic resonance imaging is not used. In addition, a functional neurological consequence is not necessarily due to a recognized brain lesion, but may simply derive from an abnormally or suboptimally developed brain structure. The quality of nutrition given to a preterm baby could play a crucial role in such cases. In fact, nutrition is known to affect brain function; a case in point is the improvement in visual function resulting from dietary essential fatty acids. Finally, research in this area should aim at both reducing potential hazards and improving the quality of perinatal care, including the quality of nutrition.