Vitamin K insufficiency and the prophylaxis strategy in term healthy infants: A multicentre study.

BACKGROUND/AIM: Late vitamin K deficiency bleeding (VKDB) during early infancy is a serious problem worldwide. Vitamin K (VK) deficiency commonly occurs in newborns who are exclusively breastfed. Protein Induced by VK Absence (PIVKA-II) has been identified as an early indicator of subclinical VK deficiency in neonates, surpassing prothrombin time. To assess PIVKA-II levels at 48 h, 1 and 3 months of age in full-term newborns who were exclusively breastfed and received varying VKDB prophylaxis regimens. METHODS: A prospective observational study was conducted in four hospitals, enrolling 105 newborns. PIVKA-II levels were measured using a sandwich-type enzyme-linked immunosorbent assay. RESULTS: At 48 h of age, there was no significant difference in PIVKA-II concentrations between newborns who received intramuscular administration of 1 mg of phylloquinone (VK1) and those who received oral administration of 2 mg of VK1 at birth. At 1 and 3 months of life, infants who received any supplementation regimen between 2 and 14 weeks exhibited significantly lower PIVKA-II concentrations compared to infants who received only 1 mg of intramuscular VK1 at birth. The prophylaxis involving a dose of 1 mg of intramuscular VK1 at birth followed by oral administration of 150 µg/day of VK1 from the 2nd to the 14th week of life showed the lowest PIVKA-II blood concentrations. CONCLUSIONS: Oral supplementation of VK1 after discharge significantly reduced PIVKA-II concentrations in exclusively breastfed term infants. These findings suggest the importance of oral VK1 supplementation in exclusively breastfed infants during their first 3 months of life to avoid the risk of VK insufficiency.

Brain Damage in Preterm and Full-Term Neonates: Serum Biomarkers for the Early Diagnosis and Intervention.

The Brain is vulnerable to numerous insults that can act in the pre-, peri-, and post-natal period. There is growing evidence that demonstrate how oxidative stress (OS) could represent the final common pathway of all these insults. Fetuses and newborns are particularly vulnerable to OS due to their inability to active the antioxidant defenses. Specific molecules involved in OS could be measured in biologic fluids as early biomarkers of neonatal brain injury with an essential role in neuroprotection. Although S-100B seems to be the most studied biomarker, its use in clinical practice is limited by the complexity of brain damage etiopathogenesis and the time of blood sampling in relation to the brain injury. Reliable early specific serum markers are currently lacking in clinical practice. It is essential to determine if there are specific biomarkers that can help caregivers to monitor the progression of the disease in order to active an early neuroprotective strategy. We aimed to describe, in an educational review, the actual evidence on serum biomarkers for the early identification of newborns at a high risk of neurological diseases. To move the biomarkers from the bench to the bedside, the assays must be not only be of a high sensitivity but suitable for the very rapid processing and return of the results for the clinical practice to act on. For the best prognosis, more studies should focus on the association of these biomarkers to the type and severity of perinatal brain damage.

Prenatal and Neonatal Bone Health: Updated Review on Early Identification of Newborns at High Risk for Osteopenia.

Bone health starts with maternal health and nutrition, which influences bone mass and density already in utero. The mechanisms underlying the effect of the intrauterine environment on bone health are partly unknown but certainly include the 'foetal programming' of oxidative stress and endocrine systems, which influence later skeletal growth and development. With this narrative review, we describe the current evidence for identifying patients with risk factors for developing osteopenia, today's management of these populations, and screening and prevention programs based on gestational age, weight, and morbidity. Challenges for bone health prevention include the need for new technologies that are specific and applicable to pregnant women, the foetus, and, later, the newborn. Radiofrequency ultrasound spectrometry (REMS) has proven to be a useful tool in the assessment of bone mineral density (BMD) in pregnant women. Few studies have reported that transmission ultrasound can also be used to assess BMD in newborns. The advantages of this technology in the foetus and newborn are the absence of ionising radiation, ease of use, and, above all, the possibility of performing longitudinal studies from intrauterine to extrauterine life. The use of these technologies already in the intrauterine period could help prevent associated diseases, such as osteoporosis and osteopenia, which are characterised by a reduction in bone mass and degeneration of bone structure and lead to an increased risk of fractures in adulthood with considerable social repercussions for the related direct and indirect costs.

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.

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.

Report of a series of healthy term newborns from convalescent mothers with COVID-19.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmittable virus associated with a significantly increased risk of complications among the infected population. Few data are available for the outcome of pregnancy complicated by serious respiratory disease due to SARS-CoV-2 infection. AIM: We herein report a series of four neonates whose mothers had recovered from new coronavirus 2019 disease (COVID-19) diagnosed in the third trimester of pregnancy. METHODS: pregnant women with documented COVID-19 infection during their pregnancy, who gave birth in Parma Hospital, University of Parma, Italy, in March and April 2020, during the peak of incidence of COVID-19 in Italy. Clinical records and laboratory tests were retrospectively reviewed. RESULTS: All neonates were delivered at term in good conditions without congenital COVID-19 infection. CONCLUSIONS: Findings from our series of cases indicated that adverse effects on foetuses from pregnancies complicated by COVID-19 infection in late pregnancy are unlikely.

Group B Streptococcus early-onset disease and observation of well-appearing newborns.

BACKGROUND: International guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy. METHODS: This is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks' gestation) registered in 2003-2009 (baseline period: 266,646 LBs) and in 2010-2016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs). RESULTS: There were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twenty-two (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%) at birth or within 6 hours. The median age at presentation was significantly earlier in the intrapartum antibiotic prophylaxis (IAP)-exposed than in the IAP-unexposed neonates (0 hours, IQR 0.0000-0.0000 vs 6 hours, IQR 0.0000-15.0000, p<0.001). High number of neonates (n = 531) asymptomatic at birth, exposed to intrapartum fever, should be treated empirically for each newborn who subsequently develops sepsis. IAP exposed neonates increased (12% vs 33%, p = 0.01), age at presentation decreased (median 6 vs 1 hours, p = 0.01), whereas meningitis, mechanical ventilation and mortality did not change in baseline vs intervention period. After implementing the SPEs, no cases had adverse outcomes due to the strategy, and no cases developed severe disease after 6 hours of life. CONCLUSIONS: Infants with EOS exposed to IAP developed symptoms at birth in almost all cases, and those who appeared well at birth had a very low chance of having EOS. The risk of EOS in neonates (asymptomatic at birth) exposed to intrapartum fever was low. Although definite conclusions on causation are lacking, our data support SPEs of asymptomatic newborns at risk for EOS. SPEs seems a safe and effective alternative to laboratory screening and empirical antibiotic therapy.

An area-based study on intrapartum antibiotic prophylaxis for preventing group B streptococcus early-onset disease: advances and limitations.

INTRODUCTION: The prevalence of maternal group-B-streptococcus (GBS) colonization and risk factors (RFs) for neonatal early-onset disease (EOD) in Europe are poorly defined. Large-scale information concerning adherence to recommendations for preventing GBS-EOD are lacking. MATERIALS AND METHODS: This was a 3-month retrospective area-based study including all regional deliveries ≥35 weeks' gestation (in 2012). The sensitivity, specificity, positive and negative predictive values, odds ratio and receiver operating characteristic (ROC) curve for intrapartum antibiotic prophylaxis (IAP) among full-term and preterm deliveries and prolonged membrane rupture (PROM) were calculated. RESULTS: Among 7133 women, 259 (3.6%) were preterm (35-36 weeks' gestation). Full-term women were 6874, and 876 (12.7%) had at least 1 RF. Most women (6495) had prenatal screening and 21.4% (1390) were GBS positive. IAP was given to 2369 (33.2%) women (preterm, n = 166; full term, n = 2203). Compared to full-term, preterm women were less likely to receive IAP when indicated (73.2% versus 90.3%, p < 0.01). Full-term women represented the largest area under the curve (AUC, 0.87). PROM showed the highest sensitivity (98.6%), but the lowest specificity (6.9%) and AUC (0.53). CONCLUSIONS: Large-scale prenatal screening and IAP are feasible. Women delivering preterm are less likely to receive IAP when indicated. Most unnecessary antibiotics are given in cases of PROM.

Serial physical examinations, a simple and reliable tool for managing neonates at risk for early-onset sepsis.

AIM: To investigate whether serial physical examinations (SPEs) are a safe tool for managing neonates at risk for early-onset sepsis (EOS). METHODS: This is a retrospective cohort study of neonates (≥ 34 wks' gestation) delivered in three high-volume level IIIbirthing centres in Emilia-Romagna (Italy) during a 4-mo period (from September 1 to December 31, 2015). Neonates at risk for EOS were managed according to the SPEs strategy, these were carried out in turn by bedside nursing staff and physicians. A standardized form detailing general wellbeing, skin colour and vital signs was filled in and signed at standard intervals (at age 3, 6, 12, 18, 36 and 48 h) in neonates at risk for EOS. Three independent reviewers reviewed all charts of neonates and abstracted data (gestational age, mode of delivery, group B streptococcus status, risk factors for EOS, duration of intrapartum antibiotic prophylaxis, postpartum evaluations, therapies and outcome). Rates of sepsis workups, empirical antibiotics and outcome of neonates at-risk (or not) for EOS were evaluated. RESULTS: There were 2092 live births and 1 culture-proven EOS (Haemophilus i) (incidence rates of 0.48/1000 live births). Most newborns with signs of illness (51 out of 101, that is 50.5%), and most of those who received postpartum antibiotics (17 out of 29, that is 58.6%) were not at risk for EOS. Compared to neonates at risk, neonates not at risk for EOS were less likely to have signs of illness (51 out of 1442 vs 40 out of 650, P = 0.009) or have a sepsis workup (25 out of 1442 vs 28 out of 650, P < 0.001). However, they were not less likely to receive empirical antibiotics (17 out of 1442 vs 12 out of 650, P = 0.3). Thirty-two neonates were exposed to intrapartum fever or chorioamnionitis: 62.5% (n = 20) had a sepsis workup and 21.9% (n = 7) were given empirical antibiotics. Among 216 neonates managed through the SPEs strategy, only 5.6% (n = 12) had subsequently a sepsis workup and only 1.9% (n = 4) were given empirical antibiotics. All neonates managed through SPEs had a normal outcome. Among 2092 neonates, only 1.6% (n = 34) received antibiotics; 1.4% (n = 29) were ill and 0.2% (n = 5) were asymptomatic (they were treated because of risk factors for EOS). CONCLUSION: The SPEs strategy reduces unnecessary laboratory evaluations and antibiotics, and apparently does not worsen the outcome of neonates at-risk or neonates with mild, equivocal, transient symptoms.

Intrapartum antibiotic prophylaxis failure and group-B streptococcus early-onset disease.

OBJECTIVES: To determine factors influencing intrapartum antibiotic prophylaxis (IAP) failure in the prevention of group B streptococcus (GBS) early-onset disease (EOD). METHODS: GBS EOD case is defined as isolation of GBS from a normally sterile body site (e.g. blood or cerebrospinal fluid) in infants aged ≤7 days. During a consecutive 93-month period, GBS EOD cases and care data were reviewed. RESULTS: Seventy-nine GBS EOD cases were registered; 67 infants were born to women who received no i.v. antibiotics during labor. The 12 EOD cases exposed to IAP were more likely to be associated with emergency caesarean section (p = 0.0015), maternal obstetric risk factors (ORFs) (p = 0.0061), particularly intrapartum fever (p = 0.0002), and to present with signs of illness at birth (p = 0.0015). Correct dosages, agents, and timing were registered in three cases only; of which two were associated with intrapartum fever. CONCLUSIONS: ORFs, emergency caesarean section, and signs of illness at birth are significantly associated with GBS EOD in infants exposed to IAP. This study also suggests that recommended IAP agents, dosages, and timing are infrequently associated with EOD. Strict protocol adherence is recommended in all cases.

Group B Streptococcus early-onset disease in Emilia-romagna: review after introduction of a screening-based approach.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections. Early-onset infections have decreased in recent years but, despite considerable efforts poured into prevention, cases continue to occur. OBJECTIVES: To analyze trends and identify determining factors for the persistence of the GBS infections. To evaluate the impact of antenatal screening and intrapartum chemoprophylaxis on the clinical presentation of the infection. METHODS: A prospective cohort, population-based study has been ongoing in Emilia-Romagna (Italy) since 2003. Invasive GBS infections, observed between 2003 and 2008 in infants aged < 7 days were analyzed. RESULTS: Among 214,120 live births, 61 early-infections were observed. Fourteen infants (23.0%) were born preterm. Among 47 infants who were delivered at term, 28 were born to mothers who had no risk factors and 7 were born to mothers who had none other than GBS colonization. Forty-one women at term had been screened prenatally; among them, only 10 were documented as GBS culture-positive.Disease severity was highest in infants at lower gestational ages, but most meningitis cases were observed in term infants born to mothers who were GBS culture-negative at screening.Nine newborns had culture-proven infection despite having received intrapartum antibiotics. They were born to mothers with > or =1 obstetrical risk factors and 5 mothers had been treated during labor with macrolides. CONCLUSION: Most infections presented in infants whose mothers had been screened as GBS culture-negative. Missed opportunities for prevention contributed more than prophylaxis failures to the early-onset disease burden.

Group B streptococcal infections in a northern region of Italy.

BACKGROUND: Group B streptococcus is a leading cause of neonatal bacterial infections. Despite adoption of preventive strategies, cases of infection continue to occur and there is concern that widespread antimicrobial prophylaxis might delay rather than prevent disease onset, increasing the rates of late-onset diseases. OBJECTIVES: The purpose of this study was to determine the incidence and clinical features of early- and late-onset group B streptococcus disease in a northern region of Italy where a screening-based approach had been proposed. METHODS: A population-based study was prospectively conducted in Emilia-Romagna, Italy. Infections that occurred during 2003-2005 in infants aged <3 months were analyzed. RESULTS: Among 112,933 live births, 56 cases of invasive disease (30 early- and 26 late-onset disease) were observed, giving an annual group B streptococcus disease incidence of 0.50 per 1000 live births. Eleven infants with early-onset disease showed no signs of illness or were mildly ill, whereas 19 had moderate-to-severe symptoms, and culture-proven meningitis was found in 2. Risk factors were detected in 12 women. Twenty-two mothers had antenatal screening; 5 were group B streptococcus colonized, but 17 were culture-negative. Prophylaxis was administered in 3 women. Three infants with late-onset diseases were mildly ill, whereas 23 had moderate-to-severe symptoms. Risk factors were found in 7 mothers. Late-onset diseases were clinically more severe than early-onset diseases; meningitis was diagnosed in 12 infants, and 4 of 26 died. CONCLUSIONS: The incidence of early-onset disease was low. Some early infections were still observed because of negative screening results or missed opportunity for prevention. Late-onset diseases accounted for most meningitis cases and deaths. Strict adherence to protocols and adoption of optimal culture methods would further improve prevention of early-onset disease, but the aim of future strategies should be the prevention of all invasive diseases.