Vitamin D Supplementation in Neonatal and Infant MIS-C Following COVID-19 Infection.

To date, the SARS-CoV-2 pandemic still represents a great clinical challenge worldwide, and effective anti-COVID-19 drugs are limited. For this reason, nutritional supplements have been investigated as adjuvant therapeutic approaches in disease management. Among such supplements, vitamin D has gained great interest, due to its immunomodulatory and anti-inflammatory actions both in adult and pediatric populations. Even if there is conflicting evidence about its prevention and/or mitigation effectiveness in SARS-CoV-2 infection, several studies demonstrated a strict correlation between hypovitaminosis D and disease severity in acute COVID-19 and MIS-C (multisystem inflammatory syndrome in children). This narrative review offers a resume of the state of the art about vitamin D's role in immunity and its clinical use in the context of the current pandemic, specially focusing on pediatric manifestations and MIS-C. It seems biologically reasonable that interventions aimed at normalizing circulating vitamin D levels could be beneficial. To help clinicians in establishing the correct prophylaxis and/or supportive therapy with vitamin D, well-designed and adequately statistically powered clinical trials involving both adult and pediatric populations are needed. Moreover, this review will also discuss the few other nutraceuticals evaluated in this context.

Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose. METHODS: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). We randomly assigned the infants in a 2:1 ratio to receive nirsevimab, at a dose of 50 mg in a single intramuscular injection, or placebo at the start of an RSV season. The primary end point was medically attended RSV-associated lower respiratory tract infection through 150 days after administration of the dose. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after administration of the dose. RESULTS: From November 2016 through November 2017, a total of 1453 infants were randomly assigned to receive nirsevimab (969 infants) or placebo (484 infants) at the start of the RSV season. The incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower (95% confidence interval [CI], 52.3 to 81.2) with nirsevimab prophylaxis than with placebo (2.6% [25 infants] vs. 9.5% [46 infants]; P<0.001) and the incidence of hospitalization for RSV-associated lower respiratory tract infection was 78.4% lower (95% CI, 51.9 to 90.3) with nirsevimab than with placebo (0.8% [8 infants] vs. 4.1% [20 infants]; P<0.001). These differences were consistent throughout the 150-day period after the dose was administered and across geographic locations and RSV subtypes. Adverse events were similar in the two trial groups, with no notable hypersensitivity reactions. CONCLUSIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Funded by AstraZeneca and Sanofi Pasteur; ClinicalTrials.gov number, NCT02878330.).

Neonatal Outcomes of Water Delivery versus Land Delivery: A Retrospective Propensity Score Weighted Study.

OBJECTIVE: Recent evidence has shown that water delivery is safe for the mother, but high-quality evidence is not available for the newborn. Therefore, obstetric guidelines do not support it. This retrospective study aimed to contribute to the available evidence on maternal and neonatal outcomes associated with water delivery. STUDY DESIGN: Retrospective cohort study from prospectively collected birth registry data from 2015 to 2019. A total of 144 consecutive water deliveries and 265 land deliveries eligible for waterbirth were identified. The inverse probability of treatment weighting (IPTW) method was applied to address for confounders. RESULTS: We identified 144 women who delivered in water (water group) and 265 women who delivered on land (land group). One (0.7%) neonatal death was observed in the water delivery group. After IPTW adjustment, water delivery was significantly associated with a higher risk of maternal fever in puerperium (odds ratio [OR]: 4.98; 95% confidence interval [CI]: 1.86-17.02; p = 0.004), of neonatal cord avulsion (OR: 20.73; 95% CI: 2.63-2,674; p = 0.001), and of positive neonatal C-reactive protein (CRP > 5 mg/L; OR: 2.59; 95% CI: 1.05-7.24; p = 0.039); delivering in water was associated with lower maternal blood loss (mean difference: 110.40 mL; 95% CI: 191.01-29.78; p = 0.007), a lower risk of major (≥1,000 mL) postpartum hemorrhage (OR: 0.96; 95% CI: 0.92-0.99; p = 0.016), lower risk of manual placenta delivery (OR: 0.18; 95% CI: 0.03-0.67; p = 0.008) and curettage (OR: 0.24; 95% CI: 0.08-0.60; p = 0.002), lower use of episiotomy (OR: 0.02; 95% CI: 0-0.12; p < 0.001), and lower risk of neonatal ward admission (OR: 0.35; 95% CI: 0.25-0.48; p < 0.001). CONCLUSION: The present study showed that differences are present between water and land delivery, and among them is the risk of cord avulsion, a severe and potentially fatal event. In women choosing to deliver in water, a trained staffmust be present and immediate recognition of cord avulsion is key for a prompt management to avoid possible serious complications. KEY POINTS: · High-quality evidence is not available for neonatal safety of waterbirth; therefore, retrospective studies still represent the main body of evidence.. · Differences are present between water and land delivery, and among them, the increased risk of cord avulsion is a potentially fatal event.. · A trained staff must assist women who chose to deliver in water and cord avulsion must be promptly recognized and managed to avoid severe neonatal complications..

Early Biomarkers of Bronchopulmonary Dysplasia: A Quick Look to the State of the Art.

Bronchopulmonary dysplasia (BPD) is one of the most common pulmonary sequelae of extreme preterm birth, with long-lasting respiratory symptoms and reduced lung function. A reliable predictive tool of BPD development is urgent and its search remains one of the major challenges for neonatologists approaching the upcoming arrival of possible new preventive therapies. Biomarkers, identifying an ongoing pathogenetic pathway, could allow both the selection of preterm infants with an evolving disease and potentially the therapeutic targets of the indicted pathogenesis. The "omic" sciences represent well-known promising tools for this objective. In this review, we resume the current laboratoristic, metabolomic, proteomic, and microbiomic evidence in the prediction of BPD. KEY POINTS: · The early prediction of BPD development would allow the targeted implementation of new preventive therapies.. · BPD is a multifactorial disease consequently it is unlikely to find a single disease biomarker.. · "Omic" sciences offer a promising insight in BPD pathogenesis and its development's fingerprints..

Real-World Studies of Respiratory Syncytial Virus Hospitalizations among Moderate/Late Preterm Infants Exposed to Passive Immunoprophylaxis with Palivizumab.

This article aims to assess the real-world effectiveness of palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-associated hospitalization (RSVH) rates in otherwise healthy moderate/late preterm infants and discuss the role of palivizumab in preventing acute and long-term outcomes. We identified studies in the PubMed and Embase databases that reported patient-level data on (1) exposure to palivizumab in preterm infants born between 29 and 35 weeks of gestational age (or subsets within this range) ≤ 2 years of chronological age, and (2) the outcome of RSVH. Six studies assessed RSVH in infants this gestational age who had been exposed or not to palivizumab and reported patient-level data. Exposure was associated with a reduction in RSVH rates that was comparable to the reduction seen in controlled clinical trials (weighed mean 4.0-fold reduction). RSV immunoprophylaxis in preterm infants within 29 to 35 weeks of gestational age is associated with a considerably lower burden of RSVH. KEY POINTS: · RSV is the leading cause of lower respiratory tract infection hospitalization in infants.. · Palivizumab prevents RSVH in a real-world scenario.. · Immunoprophylaxis should be used in high-risk infants..

The Essentials about Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Coronavirus Disease: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can occur in neonates as the virus can be transmitted both horizontally (from the environment) and vertically (during the pregnancy or at the delivery). Compared to the adult outbreak, neonatal infections do not represent a public health problem. Nonetheless, severe and life-threatening cases may rarely occur and both obstetricians and neonatologists should have a good knowledge of perinatal SARS-CoV-2 infection and related consequences. A high suspicion index must be applied and ruling out neonatal SARS-CoV-2 infection must become a part of the routine clinical workout. Moreover, neonates may be affected by the multisystem inflammatory syndrome, due to a dysregulated host response in the absence of any SARS-CoV-2 infection. We performed a narrative review to summarize here the available literature describing the essentials that should be known by every neonatologist and obstetrician, starting from what has been discovered in 2020 and adding what has been learned in the following years. The paper describes the mechanisms of transmission, clinical features, diagnostic tools, and criteria, as well as possible treatment and prevention strategies. The goal is to provide the practical points to be remembered at the bedside while caring for a pregnant woman or a neonate with suspected or proven coronavirus disease 2019 or multisystem inflammatory syndrome. KEY POINTS: · SARS-CoV-2 neonatal infections occur both vertically (30%) and horizontally (70%).. · Approximately, half of patients do not have clinical manifestations; clinical and laboratory signs are similar to those of adults but usually milder.. · Remdesivir and steroids can be used as a treatment..

Maternal Origins of Neonatal Infections: What Do Obstetrician-Gynecologist Should/Could Do?

Neonatal infections are responsible for 20% of neonatal deaths yearly. In this review, we focused on the origins of the commoner neonatal infections, and we define the role of obstetricians. Regarding group B Streptococcus, a key measure for the prevention of neonatal infection is the vaginal-rectal culture screening at term pregnancy. Intravenous penicillin is the first-line prophylaxis at the start of labor, with intravenous ampicillin as an alternative. First-generation cephalosporins or clindamycin are recommended in case of penicillin allergy. Concerning urinary tract infections (UTIs), guidelines recommend complete urinalysis and urine culture in the first trimester of pregnancy for the screening of asymptomatic bacteriuria. For lower UTIs, guidelines recommend nitrofurantoin as first-choice antibiotic. Amoxicillin or cefalexin are second-line antibiotics. For upper UTIs, guidelines recommend cephalexin per os as first line. Candida spp. colonization affects 20% of pregnant women; however, congenital fetal candidosis and Candida amnionitis are rare. First-line treatment in case of symptomatic vaginitis during pregnancy or asymptomatic colonization during the third trimester is vaginal clotrimazole. Fluconazole is not approved in pregnancy, especially during the first trimester. Genital mycoplasmas colonization during pregnancy is usually asymptomatic and associated with bacterial vaginosis. Colonization is related to neonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), pneumonia, chorioamnionitis, and sepsis. Macrolides are the first-line treatment along with lactobacillus supplementation. In cases of preterm premature rupture of membranes or preterm labor, ceftriaxone, clarithromycin, and metronidazole are required to prevent intra-amniotic infection. Intra-amniotic infection affects 1 to 5% of deliveries at term and one-third of preterm ones and is associated with perinatal death, early-onset neonatal sepsis, RDS, BPD, pneumonia, meningitis, and prematurity-related diseases. Guidelines recommend a combination of ampicillin and gentamicin, and in case of caesarean section, an additional dose of clindamycin or metronidazole is required. In conclusion, obstetricians should be aware that the treatment of maternal infection during pregnancy can prevent potentially lethal infections in the newborn. KEY POINTS: · Part of neonatal infections starts from maternal infections that must be treated during pregnancy.. · Streptococcus group B and asymptomatic bacteriuria should be investigated in pregnancy and treated.. · Mycoplasma and ureaplasma vaginal colonization during pregnancy is related to negative neonatal outcomes..

A Randomized Controlled Trial of Osteopathic Manipulative Therapy to Reduce Cranial Asymmetries in Young Infants with Nonsynostotic Plagiocephaly.

OBJECTIVE: This study aimed to compare the efficacy of osteopathic manipulative therapy (OMTh) versus light touch therapy (LTT) in reducing cranial asymmetries in infants with nonsynostotic plagiocephaly (NSP). STUDY DESIGN: A prospective, parallel-group, single-center, LTT-controlled randomized clinical trial was conducted in the Department of Neonatology of Sant'Anna Hospital in Turin, Italy, from September 6, 2016 to February 20, 2020. We enrolled infants of 1 to 6 months of age with NSP, who were then randomly assigned to the study group (repositioning therapy plus six sessions of OMTh) or the control group (repositioning therapy plus six sessions of LTT). The outcome was the reduction of the oblique diameter difference index (ODDI) score <104%, which was assessed at the end of the intervention protocol (at 3 months) and at 1 year of age. RESULTS: A total of 96 infants were randomized, 48 in the OMTh group and 48 in the LTT group, with mean ages of 3.1 versus 3.2 months, and baseline ODDI score of 110.2 versus 108.7%. In the OMTh group, a significant reduction of the ODDI score <104%, compared with the LTT group, was observed in the intension-to-treat (ITT) and per-protocol (PP) analyses. The ITT analysis revealed an ODDI score <104% in the OMTh group at 3 months (risk difference: 0.41; 95% confidence interval [CI]: 0.25-0.53; p < 0.001) and at the follow-up at 1 year of age (risk difference: 0.47; 95% CI: 0.31-0.64; p < 0.001). The PP analysis at 3 months reported a risk difference of 0.44 (95% CI: 0.27-0.60; p < 0.001), and at 1 year of age, a risk difference of 0.54 (95% CI: 0.36-0.72; p < 0.001). CONCLUSION: In infants with NSP, a course of six OMTh sessions significantly reduced cranial asymmetries at both the 3-month and 1-year follow-up assessments, compared with LTT. This study is registered with ClinicalTrial.gov (identifier: NCT03970395; www. CLINICALTRIALS: gov ). KEY POINTS: · OMTh plus repositioning therapy significantly decreased the risk and severity of NSP compared with LTT.. · OMTh reduced mild and moderate cranial asymmetries.. · The role of OMTh in severe cranial asymmetries should be investigated in a multicenter trial..

Expert consensus on palivizumab use for respiratory syncytial virus in developed countries.

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalisation in early childhood and palivizumab is the only licensed intervention for prevention. Palivizumab guidelines should reflect the latest evidence, in addition to cost-effectiveness and healthcare budgetary considerations. RSV experts from Europe, Canada and Israel undertook a systematic review of the evidence over the last 5 years and developed recommendations regarding prophylaxis in industrialised countries. Almost 400 publications were reviewed. This group recommended palivizumab for: preterm infants (<29 and ≤31 weeks gestational age [wGA] and ≤9 and ≤6 months of age, respectively; high-risk 32-35wGA), former preterm children ≤24 months with chronic lung disease/bronchopulmonary dysplasia, children ≤24 months with significant congenital heart disease; and other high-risk populations, such as children ≤24 months with Down syndrome, pulmonary/neuromuscular disorders, immunocompromised, and cystic fibrosis. Up to 5 monthly doses should be administered over the RSV season. It is our impression that the adoption of these guidelines would help reduce the burden of RSV.

Evidence on the Link between Respiratory Syncytial Virus Infection in Early Life and Chronic Obstructive Lung Diseases.

There is growing evidence in medical literature to support an association between early-life respiratory syncytial virus lower respiratory tract-lower respiratory tract infection (RSV-LRTI) and recurrent wheezing/asthma-like symptoms. It has been estimated that children with a history of RSV-LRTI have a 2- to 12-fold higher risk of developing asthma. The connection between RSV infection and a developmental trajectory of reduced lung function remains throughout adolescence and early adulthood, suggesting a possible role for RSV even in the inception of chronic obstructive pulmonary disease. That is why the postnatal period appears to offer a specific window of opportunity for early intervention to prevent chronic obstructive lung diseases. The mechanisms by which RSV contributes to the onset of wheezing/asthma and lung function impairment are not fully understood but appear to relate to injury caused directly by the virus and/or to pre-existing predisposing factors. While awaiting a deeper understanding of the association between RSV and chronic lung diseases, the crucial role of pediatricians and physicians is to develop strategies to prevent RSV infections to try and protect children's lifelong respiratory health. KEY POINTS: · Several evidence suggest a link between RSV infection in early life and wheezing/asthma development.. · RSV infection appears to have long term respiratory effects.. · The prevention of RSV infections could reduce the incidence of chronic obstructive respiratory diseases..

COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach.

The novel coronavirus disease 2019 (COVID-19) pandemic has urged the development and implementation of guidelines and protocols on diagnosis, management, infection control strategies, and discharge planning. However, very little is currently known about neonatal COVID-19 and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections. Thus, many questions arise with regard to respiratory care after birth, necessary protection to health care workers (HCW) in the delivery room and neonatal intensive care unit (NICU), and safety of bag and mask ventilation, noninvasive respiratory support, deep suctioning, endotracheal intubation, and mechanical ventilation. Indeed, these questions have created tremendous confusion amongst neonatal HCW. In this manuscript, we comprehensively reviewed the current evidence regarding COVID-19 perinatal transmission, respiratory outcomes of neonates born to mothers with COVID-19 and infants with documented SARS-CoV-2 infection, and the evidence for using different respiratory support modalities and aerosol-generating procedures in this specific population. The results demonstrated that to date, neonatal COVID-19 infection is uncommon, generally acquired postnatally, and associated with favorable respiratory outcomes. The reason why infants display a milder spectrum of disease remains unclear. Nonetheless, the risk of severe or critical illness in young patients exists. Currently, the recommended respiratory approach for infants with suspected or confirmed infection is not evidence based but should include all routinely used types of support, with the addition of viral filters, proper personal protective equipment, and placement of infants in isolation rooms, ideally with negative pressure. As information is changing rapidly, clinicians should frequently watch out for updates on the subject. KEY POINTS: · Novel coronavirus disease 2019 (COVID-19) pandemic urged development of guidelines.. · Neonatal COVID-19 disease is uncommon.. · Respiratory outcomes in neonates seems favorable.. · Current neonatal respiratory care should continue.. · Clinicians should watch frequently for updates..

Management and Nutrition of Neonates during the COVID-19 Pandemic: A Review of the Existing Guidelines and Recommendations.

OBJECTIVE: We aimed at reviewing the currently available guidelines and scientific recommendations regarding the neonatal in-hospital management and feeding in the light of the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: We systematically searched the guideline databases, Medline, Embase, and nationale/international neonatal societies websites as of June 19, 2020, for guidelines on neonatal management and feeding during the COVID-19 pandemic, at the same time assessing the methodological quality using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: Eleven guidelines were included. The Chinese and American recommendations suggest separation of the mother and her neonate, whereas in French, Italian, UK, Canadian, and World Health Organization consensus documents the rooming-in is suggested, with Centers for Disease Control and Prevention guidelines suggesting to decide on a case-by-case basis. All the guidelines recommend breastfeeding or feeding with expressed maternal milk; the only exception is the Chinese recommendations, these last suggesting to avoid breastfeeding. CONCLUSION: This review may provide a useful tool for clinicians and organizers, highlighting differences and similarities of the existing guidelines on the management and feeding strategies in the light of the COVID-19 pandemic. KEY POINTS: · This study compares guidelines on management and nutrition of a newborn born to a mother with SARS-CoV-2 infection.. · Existing guidelines on neonatal management and nutrition during the SARS-CoV-2 pandemic show many differences.. · The majority of recommendations are mainly based on experts' opinion and are not evidence-based..

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..

Vaginal Birth after Two Previous Cesarean Sections versus Elective Repeated Cesarean: A Retrospective Study.

OBJECTIVE: Trial of labor after cesarean delivery (TOLAC) is a common practice worldwide but the evidence is still scant regarding this practice in women who underwent 2 previous cesareans. The purpose of this study is to retrospectively review our experience with vaginal birth after two previous cesarean sections (VBA2C), with specific attention to the indications for previous cesarean and to the women's motivation for attempting trial of labor. STUDY DESIGN: This was a retrospective cohort study conducted in a primary care hospital between January 2011 and December 2019. Inclusion criteria were: singleton pregnancies, absence of morphological abnormalities at ultrasonographic screening of the second trimester (or at any other stage of pregnancy), and two previous cesarean sections. RESULTS: The final analysis included 114 cases for maternal and neonatal outcomes. In total, 40.4% of women chose trial of labor after two cesarean delivery (TOLA2C group). TOLA2C was associated with a success rate of 76.1%, a higher gestational age at birth, and a shorter hospital stay, compared with elective repeated cesarean delivery group. There were no significant differences in the rate of Apgar scores at 5 minutes <7 between both groups. The percentage of successful TOLA2C in women with prior vaginal delivery was 92.8%. Factors related to failed TOLA2C included failure to progress (3/11, 27.3%), nonreassuring fetal heart rate (3/11, 27.3%), and no onset of spontaneous labor after premature rupture of membranes (5/11, 45.4%). In the group of TOLA2C, more than 70% accepted to travel more than 45 minutes to reach our hospital, with the aim to attempt VBA2C. CONCLUSION: TOLA2C is a possible option for both mothers and neonates in selected cases. Adequate counseling about pros and cons of TOLA2C is mandatory. The woman's motivation represents a key element to determine the success of VBA2C. KEY POINTS: · Selection of candidates and motivation of the patients represent key elements for successful TOLA2C.. · A careful record of obstetrical history and previous deliveries can provide clinicians useful information.. · Mode of delivery in women with two previous cesareans is strongly associated with doctor's counseling..

Neonatal Adrenal Hemorrhage: A Case Series.

Neonatal adrenal hemorrhage (NAH) in newborn infants is a rare event that is associated with specific anatomical and vascular characteristics. It is more common in term infants and occurs more often in neonates who feature perinatal asphyxia. Symptoms that more frequently prompt to diagnosis are prolonged jaundice, detection of an abdominal mass, anemia, scrotal discoloration and/or swelling, hypotonia, lethargy, and hypertension. However, NAH may also occur without symptoms with its detection being occasional. Imaging through ultrasound scans is the cornerstone of diagnosis and follow-up monitoring over time. Here we report on a small NAH case series comprising three full-term, macrosomic infants who were born by vaginal delivery. The first and second ones showed clear signs of birth asphyxia, whereas the third was completely asymptomatic. In all three patients, only the right adrenal gland was involved, in line with what happens in 70% of cases. NAH is usually self-limiting and prone to a progressive resolution in a time ranging between 3 weeks and 6 months and so did in our three patients. KEY POINTS: · NAH is caused by perinatal asphyxia.. · It is diagnosed with addominal ultrasound.. · It is usually self-limiting..

The Case of a Serous Borderline Ovarian Tumor in a 15-Year Old Pregnant Adolescent: Sonographic Characteristics and Surgical Management.

OBJECTIVE: This study aimed to describe a rare case of a serous borderline ovarian tumor (BOT) diagnosed during pregnancy in a 15-year old adolescent. RESULTS: The suspect of BOT was raised at a transvaginal ultrasound scan in early first trimester (at 5 weeks of amenorrhea), due to the presence of a moderately vascularized irregular papilla in the context of a unilocular low-level right ovarian cyst. The patient and her parents required termination of pregnancy, irrespective of the diagnosis of an ovarian lesion. After termination of pregnancy, the patient underwent laparoscopic enucleation of the ovarian mass, omentectomy, and peritoneal biopsies. No intra-abdominal spillage of the ovarian mass occurred, and the surgical specimens were put in an endobag and extracted transvaginally. Final pathological examination confirmed the diagnosis of a serous borderline ovarian tumor. The patient of free of disease after 8 months of follow-up. CONCLUSION: Although rare, borderline ovarian tumors can be diagnosed in an adolescent during pregnancy. The combination of specific sonographic assessment and minimally invasive conservative surgery appears as a very effective approach in this type of patient. KEY POINTS: · BOTs can occur in pregnant adolescents.. · Transvaginal ultrasound is crucial to suspect BOT.. · Laparoscopic conservative treatment is feasible..

Use of Zoledronic Acid in a Neonate with Subcutaneous Fat Necrosis Complicated with Severe, Refractory Hypercalcemia.

OBJECTIVE: Subcutaneous fat necrosis (SCFN) is a rare condition that may occur in the neonatal period. SCFN is an inflammatory disorder of the adipose tissue, usually found in full-term healthy infants who have a history of intrauterine or perinatal distress. It is usually a self-limited condition; however, in some cases, it can get complicated, leading to severe hypercalcemia that may be life-threatening. STUDY DESIGN: We report and describe a classic presentation of SCFN that led to severe hypercalcemia refractory to standard treatment. The diagnosis of SCFN was made based on the finding of subcutaneous nodules and of hypercalcemia. The serum calcium level reached 16.6 mg/dL. Hypercalcemia was treated first with intravenous infusions of fluids and furosemide and then of methylprednisolone. This standard treatment was not effective; therefore, we administered a single low dose of zoledronic acid, which, in turn, was efficacious in ultimately managing the hypercalcemia. CONCLUSION: Our case shows how a single low dose of zoledronic acid was safe and effective in managing severe hypercalcemia unresponsive to conventional treatment while minimizing the risk of hypocalcemic rebounds.

Restricted Palivizumab Recommendations and the Impact on RSV Hospitalizations among Infants Born at > 29 Weeks of Gestational Age: An Italian Multicenter Study.

OBJECTIVE: Premature infants have the highest risk of being hospitalized with respiratory syncytial virus (RSV) infections. Palivizumab is the only licensed agent for RSVhospitalization (RSVH) prophylaxis in infants born at < 35 weeks of gestational age (wGA). In 2016, the Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) has restricted the eligibility for reimbursement to infants at high risk of RSVH, ruling out palivizumab administration for infants born at > 29 wGA. The aim of the present study was to compare the incidence of RSVH in two consecutive epidemic seasons (2015-2016 vs. 2016-2017), that is, before and after the new AIFA recommendations on palivizumab eligibility. STUDY DESIGN: This was a noninterventional retrospective cohort study conducted at three neonatal intensive care units (NICUs) in northern Italy. Infants born at 29 and 35 wGA between March 15, 2015 and March 14, 2017 were enrolled for this study. Electronic medical charts were reviewed and parents were interviewed by telephone. Data were collected on neonatal course during NICU stay, palivizumab administration, and hospitalizations related to respiratory infections during the 1st year of life, comparing the infants born in season 1 with season 2. RESULTS: Of 632 eligible infants, data were available for 536 (262 in season 1 and 274 in season 2). Overall, RSVH occurred 1.9 and 5.1% in infants in seasons 1 and 2, respectively (odds ratio [OR] = 2.77; 95% confidence interval [CI]: 0.98-7.8, p = 0.045). When the analysis was limited to patients not exposed to palivizumab, RSVHs were recorded for 1.8 and 5.9% infants in seasons 1 and 2, respectively (OR = 3.42; 95% CI: 0.96-12.20, p = 0.045). It is noteworthy that the incidence of hospital admissions for respiratory viruses other than RSV did not differ between the two seasons. CONCLUSION: Restricting eligibility for palivizumab reimbursement led to a significant increase in RSVH but had no impact on hospitalizations for other respiratory viruses. Future decisions on palivizumab prescription and coverage rules should be driven by a careful assessment of the cost-benefit ratio.

Pulmonary Recruitment Strategy in Preterm Neonates < 29 Weeks of Gestational Age to Reduce the Need for Intubation in the Delivery Room.

BACKGROUND: The application of noninvasive ventilation (NIV) modalities from birth in the delivery room (DR) during fetal-neonatal transition reduces the need for invasive mechanical ventilation, mortality, and bronchopulmonary dysplasia (BPD). The use of a RAM nasal cannula (RAM NC) in the DR for resuscitation results in less need for intubation, chest compressions, and epinephrine administration when compared with using a face mask for PPV in the DR. OBJECTIVE: To evaluate the need for endotracheal intubation in the DR among extremely low gestational age neonates treated at birth with sustained inflation (SI) followed by a nasal continuous positive airway pressure (NCPAP) (range: 6-8 cm of H2O) delivered through the RAM NC. STUDY DESIGN: A retrospective study was conducted to compare the use of NIV techniques in the DR and the need for intubation in the DR in premature infants 23 to 28 weeks' gestational age from December 2016 to July 2018 (group A). These data were compared with those of premature inborn infants with similar GA born between April 2015 and November 2016 (group B). In the DR, immediately after birth, neonates in group A received SI through RAM NC followed by CPAP ranging from 6 to 8 cm H2O, whereas the neonates in group B were treated in the DR with SI administered through a face mask followed by the application of CPAP of 5 cm H2O delivered through a nasopharyngeal tube. RESULTS: A total of 65 preterm infants 23 to 28 weeks of gestational age, 31 in group A and 34 in group B, were included in the study. The percentage of neonates intubated in the DR was significantly lower in group A (p < 0.008). In both groups, no neonates died in the DR, and no one required epinephrine and/or chest compressions. For those neonates who did not require intubation in the DR, there was no significant difference in the average FiO2 on arrival in the neonatal intensive care unit, rate of intubation within 24 hours, and use of surfactant. The incidence of BPD was similar in the two groups. Only one infant in group A developed moderate BPD, and no one needed oxygen and/or ventilatory assistance at discharge. Mortality was similar in the two groups, with a slight prevalence in group B (27.7 vs. 19.2%). CONCLUSION: SI with RAM NC followed by NCPAP ranging from 6 to 8 cm H2O, administered with RAM NC resulted in a significant reduction of intubation in the DR.

Fungal Ecology in a Tertiary Neonatal Intensive Care Unit after 16 Years of Routine Fluconazole Prophylaxis: No Emergence of Native Fluconazole-Resistant Strains.

OBJECTIVE: We analyzed the fungal ecology of a neonatal intensive care unit (NICU) over a period of 20 consecutive years following the introduction of routine fluconazole prophylaxis for all very low birth weight (VLBW; <1,500 g at birth) preterm babies. The aim was to detect the possible appearance of any ecological shifts toward the emergence of native fluconazole-resistant (NFR) fungal species. STUDY DESIGN: This was a retrospective analysis of clinical and microbiological data of VLBW preterm neonates admitted to a large tertiary NICU in Italy from 1997 to 2016 and surviving more than 3 days. Colonization and infection incidence rates, both for fluconazole-sensitive Candida spp and NFR Candida spp, were calculated for each year. We compared the first 4-year period without prophylaxis (1997-2000) with the last 16-year period with use of routine fluconazole prophylaxis (2000-2016). RESULTS: Overall, the incidence of fungal colonization significantly decreased after the introduction of prophylaxis (from 43.4% to 16.5%) as well as the systemic fungal infection incidence (from 16% to 3.7%). The proportion of colonization and infection by NFR Candida spp, on the other hand, did not increase, remaining stable throughout the 16 years of exposure to fluconazole. During the prophylaxis period, 42 of 1,172 VLBW neonates were colonized by NFR species (3.6%), and of them 11 developed a systemic infection (0.9%). During the preprophylaxis period, colonization by these particular species affected 11 of 285 VLBW neonates (3.8%), and a systemic infection involved 4 neonates (1.4%). CONCLUSION: Fluconazole prophylaxis is effective in decreasing Candida colonization and systemic infections in preterm neonates in NICU and did not cause emergence or shifts toward NFR Candida spp over a 16-year surveillance period.