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.

Maternal pandemic-related stress during pregnancy associates with infants' socio-cognitive development at 12 months: A longitudinal multi-centric study.

BACKGROUND: Prenatal maternal stress is a key risk factor for infants' development. Previous research has highlighted consequences for infants' socio-emotional and cognitive outcomes, but less is known for what regards socio-cognitive development. In this study, we report on the effects of maternal prenatal stress related to the COVID-19 pandemic on 12-month-old infants' behavioral markers of socio-cognitive development. METHODS: Ninety infants and their mothers provided complete longitudinal data from birth to 12 months. At birth, mothers reported on pandemic-related stress during pregnancy. At infants' 12-month-age, a remote mother-infant interaction was videotaped: after an initial 2-min face-to-face episode, the experimenter remotely played a series of four auditory stimuli (2 human and 2 non-human sounds). The auditory stimuli sequence was counterbalanced among participants and each sound was repeated three times every 10 seconds (Exposure, 30 seconds) while mothers were instructed not to interact with their infants and to display a neutral still-face expression. Infants' orienting, communication, and pointing toward the auditory source was coded micro-analytically and a socio-cognitive score (SCS) was obtained by means of a principal component analysis. RESULTS: Infants equally oriented to human and non-human auditory stimuli. All infants oriented toward the sound during the Exposure episode, 80% exhibited any communication directed to the auditory source, and 48% showed at least one pointing toward the sound. Mothers who reported greater prenatal pandemic-related stress had infants with higher probability of showing no communication, t = 2.14 (p = .035), or pointing, t = 1.93 (p = .057). A significant and negative linear association was found between maternal prenatal pandemic-related stress and infants' SCS at 12 months, R2 = .07 (p = .010), while adjusting for potential confounders. CONCLUSIONS: This study suggests that prenatal maternal stress during the COVID-19 pandemic might have increased the risk of an altered socio-cognitive development in infants as assessed through an observational paradigm at 12 months. Special preventive attention should be devoted to infants born during the pandemic.

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.

Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: A longitudinal study.

The COVID-19 pandemic is a global traumatic experience for citizens, especially during sensitive time windows of heightened plasticity such as pregnancy and neonatal life. Pandemic-related stress experienced by mothers during pregnancy may act as an early risk factor for infants' regulatory capacity development by altering maternal psychosocial well-being (e.g., increased anxiety, reduced social support) and caregiving environment (e.g., greater parenting stress, impaired mother-infant bonding). The aim of the present longitudinal study was to assess the consequences of pandemic-related prenatal stress on infants' regulatory capacity. A sample of 163 mother-infant dyads was enrolled at eight maternity units in northern Italy. They provided complete data about prenatal stress, perceived social support, postnatal anxiety symptoms, parenting stress, mother-infant bonding, and infants' regulatory capacity at 3 months of age. Women who experienced emotional stress and received partial social support during pregnancy reported higher anxious symptoms. Moreover, maternal postnatal anxiety was indirectly linked to the infants' regulatory capacity at 3 months, mediated by parenting stress and mother-infant bonding. Dedicated preventive interventions should be delivered to mothers and should be focused on protecting the mother-infant dyad from the detrimental effects of pandemic-related stress during the COVID-19 healthcare emergency.

Sex-dependent association between variability in infants' OXTR methylation at birth and negative affectivity at 3 months.

BACKGROUND: Sex-specific differences in DNA methylation of the oxytocin receptor gene (OXTR) have been shown in adults and are related to several mental disorders. Negative affectivity early in life is a trans-diagnostic risk marker of later psychopathology and is partly under genetic control. However, sex-specific variations in OXTR methylation (OXTRm) in infants and their associations with negative affectivity are still unknown. AIMS: Here, we explored sex differences in the association between infant OXTRm at birth and negative affectivity at 3 months of age. METHODS: Infants and their mothers (N = 224) were recruited at delivery. Infants' methylation status was assessed in 13 CpG sites within the OXTR gene intron 1 region (chr3: 8810654-8810919) in buccal cells at birth while 3-month-old infants' negative affectivity was assessed by mothers using a well-validated temperament questionnaire. RESULTS: OXTRm at 12 CpG sites was higher in females than in males. Moreover, higher infants' OXTRm at 6 specific CpG sites was associated with greater negative affectivity in males, but not in females. CONCLUSIONS: These results provide new insights into the role of sex-dependent epigenetic mechanisms linking OXTRm with early infants' emotional development. Understanding the degree to which epigenetic processes relate to early temperamental variations may help inform the etiology of later childhood psychopathological outcomes.

Post-partum Women's Anxiety and Parenting Stress: Home-Visiting Protective Effect During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic resulted in a particularly adverse and stressful environment for expecting mothers, possibly enhancing feelings of anxiety and parenting stress. The present work assesses mothers' anxiety levels at delivery and parenting stress after 3 months as moderated by home-visiting sessions. METHODS: Women (n = 177) in their second or third trimester of pregnancy during the COVID-19 lockdown were enrolled in northern Italy and split into those who did and did not receive home visits. After 3 months, the association between anxiety at delivery and parenting stress was assessed with bivariate correlations in the whole sample and comparing the two groups. RESULTS: Higher anxiety at birth correlated with greater perceived stress after 3 months. Mothers who received at least one home-visiting session reported lower parenting stress at 3 months than counterparts who did not receive home visits. CONCLUSIONS FOR PRACTICE: The perinatal period is a sensitive time window for mother-infant health, especially during a critical time like the COVID-19 pandemic. We suggest that home-visiting programs could be beneficial during global healthcare emergencies to promote maternal well-being after delivery.

Is Brain-Derived Neurotropic Factor Methylation Involved in the Association Between Prenatal Stress and Maternal Postnatal Anxiety During the COVID-19 Pandemic?

Background: The COVID-19 pandemic is a collective trauma that may expose susceptible individuals to high levels of stress. Pregnant women represent a high-risk population, considering that pregnancy is a period of heightened neuroplasticity and susceptibility to stress through epigenetic mechanisms. Previous studies showed that the methylation status of the BDNF gene is linked with prenatal stress exposure. The goals of this study were (a) to assess the association between pandemic-related stress and postnatal anxiety and (b) to investigate the potential role of maternal BDNF methylation as a significant mediator of this association. Methods: In the present study, we report data on the association among pandemic-related stress during pregnancy, maternal BDNF methylation, and postnatal anxiety symptoms. Pandemic-related stress and postnatal anxiety were assessed through self-report instruments. BDNF methylation was estimated in 11 CpG sites in DNA from mothers' buccal cells. Complete data were available from 108 mothers. Results: Results showed that pandemic-related stress was associated with an increased risk of postnatal anxiety, r = 0.20, p < 0.05. CpG-specific BDNF methylation was significantly associated with both prenatal pandemic-related stress, r = 0.21, p < 0.05, and postnatal maternal anxious symptoms, r = 0.25, p = 0.01. Moreover, a complete mediation by the BDNF CpG6 methylation emerged between pandemic-related stress during pregnancy and postnatal maternal anxiety, ACME = 0.66, p < 0.05. Conclusion: These findings suggest that BDNF epigenetic regulation by pandemic-related stress might contribute to increase the risk of anxiety in mothers. Policymakers should prioritize the promotion of health and wellbeing in pregnant women and mothers during the present healthcare emergency.

Pulmonary embolism in children, a real challenge for the pediatrician: a case report and review of the literature.

Venous thromboembolism (VTE) is a coagulopathic disease that may appear with deep vein thrombosis (DVT), pulmonary embolism (PE), or both and is responsible for increased mortality and morbidity in children. We report a case of PE in a male teenager obese boy in the setting of a thrombophilic genetic disorder, infective condition, and immobility. Our experience underlines as PE in childhood is a multifactorial disease in which clinical risk factors and inherited thrombophilia contribute to the development. It is crucial to identify one or more risk factors leading to the most appropriate diagnostic workup.

Depression and Anxiety in Mothers Who Were Pregnant During the COVID-19 Outbreak in Northern Italy: The Role of Pandemic-Related Emotional Stress and Perceived Social Support.

The COVID-19 pandemic is a collective trauma that is threatening citizens' mental health resulting in increased emotional stress, reduced social support, and heightened risk for affective symptoms. The present study aimed to investigate the effects of antenatal pandemic-related emotional stress and perceived social support on the symptoms of depression and anxiety of mothers who were pregnant during the initial COVID-19 outbreak in northern Italy. A sample of 281 mothers was enrolled at eight maternity units in the first hotspot region of the COVID-19 outbreak in northern Italy. Participants filled out online questionnaires assessing the direct or indirect exposure to the SARS-CoV-2 virus, pandemic-related stress, perceived social support, as well as symptoms of depression and anxiety. Depressive and anxious symptomatology was above clinical concern, respectively, in 26 and 32% of the respondents. Mothers who reported no exposure to SARS-CoV-2 during pregnancy and those who reported at least one direct or indirect exposure did not differ in terms of affective symptoms. Continuous scores and risk for severe depression and anxiety were positively associated with prenatal pandemic-related emotional stress and negatively linked with perceived social support during pregnancy. Women who become mothers during the COVID-19 emergency may be at high risk for affective problems. Dedicated preventive programs are needed to provide adequate preventive support and care for maternal mental health during and after the COVID-19 pandemic.

Hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants' temperament at 3 months.

The COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants' behavioral development. In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in thirteen CpG sites in mothers and infants' buccal cells. Infants' temperament was assessed at 3-month-age. Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants' SLC6A4 methylation in seven CpG sites. SLC6A4 methylation at these sites predicted infants' temperament at 3 months.

Oral vitamin A supplementation for ROP prevention in VLBW preterm infants.

Vitamin A administration may decrease any stage of retinopathy of prematurity (ROP) in preterm infants. To evaluate whether vitamin A oral supplementation could be preventive in ROP incidence and severity in VLBW infants, we compared results from 31 preterm infants, (< 1500 g or < 32 weeks) who, during a previous investigation, prospectively received 3000 UI/kg/die oral retinol palmitate drops, for 28 days, with 31 matching preterm newborns hospitalized in our NICU the same period, as control group. Although ROP incidence was similar, in the supplemented group, we had 9 cases of ROP grade 1, no ROP grade ≥ 2, in the un-supplemented group, 4 cases of ROP grade 1 and 6 ROP grade ≥ 2 (p = 0.018). The percentage of babies requiring treatment for ROP was 0 in treated and 16.6 in the un-treated group (p = 0.020). Moreover, Vitamin A administration showed a protective effect with an 88% risk reduction of developing severe ROP. Since vitamin A parenteral/IM administration presents some awareness, the results of this investigation may be important to plan further trials to confirm the usefulness of oral administration in mitigating the ROP severity of VLBW infants.ClinicalTrials.gov NCT02102711; may 03/06/2014.

Measuring the Outcomes of Maternal COVID-19-related Prenatal Exposure (MOM-COPE): study protocol for a multicentric longitudinal project.

INTRODUCTION: COVID-19 is a highly infectious respiratory disease that rapidly emerged as an unprecedented epidemic in Europe, with a primary hotspot in Northern Italy during the first months of 2020. Its high infection rate and rapid spread contribute to set the risk for relevant psychological stress in citizens. In this context, mother-infant health is at risk not only because of potential direct exposure to the virus but also due to high levels of stress experienced by mothers from conception to delivery. Prenatal stress exposure associates with less-than-optimal child developmental outcomes, and specific epigenetic mechanisms (eg, DNA methylation) may play a critical role in mediating this programming association. METHODS AND ANALYSIS: We present the methodological protocol for a longitudinal, multicentric study on the behavioural and epigenetic effects of COVID-19-related prenatal stress in a cohort of mother-infant dyads in Northern Italy. The dyads will be enrolled at 10 facilities in Northern Italy. Saliva samples will be collected at birth to assess the methylation status of specific genes linked with stress regulation in mothers and newborns. Mothers will provide retrospective data on COVID-19-related stress during pregnancy. At 3, 6 and 12 months, mothers will provide data on child behavioural and socioemotional outcomes, their own psychological status (stress, depressive and anxious symptoms) and coping strategies. At 12 months, infants and mothers will be videotaped during semistructured interaction to assess maternal sensitivity and infant's relational functioning. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Pavia). Results will be published in peer-reviewed journals and presented at national and international scientific conferences. TRIAL REGISTRATION NUMBER: NCT04540029; Pre-results.

Rapid detection of bacteria in bloodstream infections using a molecular method: a pilot study with a neonatal diagnostic kit.

Neonatal sepsis is a life-threatening condition and its early diagnosis is crucial for infant survival. Identifying responsible pathogens is a key step. Blood culture (BC) is the gold standard, but more rapid and specific diagnostic methods are needed. We evaluated the reliability and utility of 3 h turnaround time diagnostic molecular kit, "EuSepScreen lattanti "CE IVD marked, (EuSepScreen lattanti, Eurospital Spa Trieste, Italy) specifically targeted to detect 4 pathogens in neonatal sepsis: Klebsiella pneumoniae (KP), Escherichia coli (EC), Streptococcus agalactiae (GBS), and Lysteria monocytogenes. We evaluated 69 neonates, 40 full term and 29 preterm infants, with suspected bloodstream infection, who, overall the routine clinical procedures, were tested using the molecular kit. Kit results were compared to BC outcomes. Nineteen cases for early onset sepsis (EOS) were evaluated, 2 of them resulted positive to a molecular kit and to BC (both for GBS and EC). In the 50 cases of suspected late onset sepsis (LOS), 7 infants reported positive and coincident results to both the methods, in 3 further cases the molecular kit identified pathogens (EC) in neonates with negative BC result; in 10 cases BC revealed etiological pathogens exceeding the molecular kit possibility of identification. In case of EOS, results of the molecular kit were coincident to these of BC, but available in 3 h turnaround time, which is an advantage, so the kit may actually be an "add-on tool" for EOS, with reference to EC and GBS, but a larger study with a greater number of EOS cases are needed to validate its usefulness in the NICU. Regarding LOS the restricted panel of identifiable microorganisms failed to provide timely information for sepsis diagnosis, highlighting the need of enlarged number microorganisms for the diagnosis of LOS.Trial registration number: NCT03884894.

Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials.

BACKGROUND: Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis (LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain. AIM: To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk. STUDY DESIGN: This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM. RESULTS: (A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64; p < 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96; p = 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (p = 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96; p = 0.01). CONCLUSION: Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS.

Anomalous Fusion of Right Pulmonary Artery to Aortic Arch: Case Report of a Rare and Fatal Congenital Malformation in a Newborn and a Literature Review.

BACKGROUND We present a report of a rare cardiac malformation case as well as a review of the literature. In addition, the diagnostic features are discussed. CASE REPORT The case of a female newborn who died on her third day of life was studied at the Institute of Legal Medicine, University of Chieti-Pescara (Italy). The investigations around her death revealed a cardiac congenital malformation, seen as a rare variant of a common arterial trunk, in which the aorta was fused with the right branch of the pulmonary artery. The ascending aorta showed hypoplasia, while the coronary arteries were free of any pathological findings. The atrial septum showed a closed foramen ovale and the ventricular septum did not show any defect. Only an isolated right ventricular hypertrophy and dilation with no other cardiac abnormalities was found. The cause of death was acute respiratory failure on the third day of extrauterine life when the ductus Botalli closed. The karyotype analysis performed in this case was normal, and the fluorescent in situ hybridization analysis did not show the 22q11.2 microdeletion suggestive of the DiGeorge syndrome. CONCLUSIONS These findings underline the value of 3-dimensional/4-dimensional ultrasound imaging when added to a fetal cardiology screening program, and the need for improvements in postnatal screening routines by using pulse oximetry in order to discover isolated vascular defects before circulatory collapse occurs, as well as to reduce the medico-legal disputes in cases of missed diagnosis. We found the relevant literature search lacked a description of this congenital malformation, which supports our deeper perinatal investigation.

Levels and effectiveness of oral retinol supplementation in VLBW preterm infants.

Retinol palmitate oral administration is convenient, but it is difficult to assess/monitor its nutritional status in preterm infants and literature is controversial about the administration route and the effectiveness of vitamin A supplementation. We primarily evaluated retinol plasma levels to assess the vitamin A nutritional status in preterm infants (<1500 g; 32 weeks) after 28 days of oral supplementation (3000 IU/kg/day, retinol palmitate drops), in addition to vitamin A standard amount as suggested by European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines. We then observed the rate of typical preterm pathologies in the supplemented group (31 newborns) and in 10 matching preterm infants, hospitalized in neonatal intensive care unit (NICU) in the same period, who received neither vitamin A supplementation nor parents allowed plasma sampling. Oral integration resulted in constant retinol plasma concentration around the desired level of 200 ng/mL, but without statistical increase during the study period. Due to the complexity of vitamin A metabolism and the immaturity of preterm infant's organs, retinol supplementation may had first saturated other needy tissues; therefore, plasmatic measures may not be consistent with improved global vitamin A body distribution. Therefore, achieving a constant retinol concentration is a valuable result and supportive for oral administration: decreasing levels, even after parenteral/enteral supplementation, were reported in the literature. In spite of favourable trend and no adverse events, we did not report statistical difference in co-morbidities. This investigation confirms the necessity to perform further trials in preterm newborns, to find an index reflecting the complex nutritional retinol status after oral administration of vitamin A, highlighting its effectiveness/tolerability in correlated preterm infant's pathologies.

Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect.

OBJECTIVE: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. STUDY DESIGN: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. RESULTS: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. CONCLUSION: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. TRIAL REGISTRATION: isrctn.org: ISRCTN53107700.

Plasma lactoferrin levels in newborn preterm infants with sepsis.

INTRODUCTION: Lactoferrin (Lf) is one of the major proteins of all exocrine secretions with a role in the antinfective process. Our aim was to evaluate how plasma Fl levels may change in response to infection in newborn preterm infants. METHODS: A total of 15 (8 females, 7 males) newborn preterm infants with a postnatal age >72 h of life, underwent to blood culture and others markers of infection, for suspected sepsis, were enrolled in the study. RESULTS: We found that Lf serum concentration was significantly lowest in four neonates (26.7%) with confirmed sepsis than in 11 (73.3%) with clinical sepsis. The AUC was 0.90 (95%CI: 0.63-0.99). The optimal cutoff for Lf was <1.2 µg/ml with a sensibility of 100% and a specificity of 81.8%. Lf serum concentration was positively correlated with WBC or neutrophil (Spearman rho = 0.69 and 0.49, respectively). CONCLUSIONS: Serum Lf could prove a promising, sensitive and specific marker in the diagnostic approach to infants with suspected sepsis, thanks to its role in defense mechanisms and physiological functions of the immune system. Low levels of Lf in sepsis may suggest an immature response due to suboptimal leukocites activity in newborn preterm infants.

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.

Serum Calprotectin: A Potential Biomarker for Neonatal Sepsis.

INTRODUCTION: The correct diagnosis of neonatal sepsis is a relevant problem because sepsis is one of the most important causes of neonatal morbidity, mortality, and prolonged hospital stay. Calprotectin is an antimicrobial, calcium and zinc binding heterocomplex protein that could be used as a nonspecific marker for activation of granulocytes and mononuclear phagocytes. Calprotectin has been proposed for the diagnosis of inflammatory conditions. Our aim is to study serum calprotectin as a biomarker for neonatal sepsis diagnosis. METHODS: 41 (20 females, 21 males) infants who underwent blood culture due to suspected sepsis were enrolled in the study. Serum calprotectin was measured by a commercial ELISA assay (Calprest, Eurospital, Trieste, Italy). Statistical analysis was performed using the statistical software package Stata 13.1 (Stata Corporation, College Station, Texas, USA). RESULTS: 8 neonates (19.51%) showed sepsis with positive culture and 33 (80.49%) showed suspected sepsis. The optimal cut-off for calprotectin is 2.2 µg/mL with a sensitivity of 62.5% and a specificity of 69.7%. CONCLUSIONS: Calprotectin may be considered a promising early, sensitive, specific marker of sepsis thanks to the importance of calprotectin in defense mechanisms and physiological functions of the immune system.