Large Neonatal Intensive Care Unit Research Articles

Affordable Implementation of a Point-of-Care Ultrasound Program in a Large Tertiary Neonatal Intensive Care Unit to Assess Umbilical Venous Catheter Tips and Aid Central Placement.

This study aimed to implement a point-of-care ultrasound (POCUS) program into a large neonatal intensive care unit (NICU) to enhance care by improving (1) umbilical venous catheter (UVC) tip identification and (2) central placement. A POCUS program was established with core providers who received training from external and internal experts. A prospective study (n = 94) compared the accuracy of UVC identification between neonatology-performed ultrasound (NeoUS) and X-ray relative to a referent of radiology-interpreted ultrasound. Finally, an ultrasound-guided UVC insertion protocol was introduced to rescue noncentral traditionally placed catheters (n = 37). Program implementation trained six providers for a total cost of approximately $10,500 USD. NeoUS was more accurate than X-ray at identifying UVC location (81.9 vs. 60.6%) with improved sensitivity and specificity (80.0 and 84.6 vs. 52.5 and 66.7%, respectively). POCUS guidance was able to rescue 89.2% of catheters that were originally noncentral. POCUS implementation in a large NICU is feasible, affordable, and can improve quality of care. · POCUS implementation is feasible and affordable.. · POCUS is more accurate than X-ray at monitoring UVCs.. · Central UVC placement can be increased with POCUS..

Oropharyngeal administration of colostrum targeting gut microbiota and metabolites in very preterm infants: protocol for a multicenter randomized controlled trial

BackgroundOropharyngeal administration of colostrum (OAC) has an immune-stimulating effect on oropharyngeal-associated lymphoid tissue, and can promote the maturation of the gastrointestinal tract. However, how OAC promotes intestinal maturation in preterm infants by altering gut microbiota remains unclear. We aim to assess changes in gut microbiota and metabolites after OAC in very preterm infants.MethodsA multicenter, double-blind, randomized controlled trial will be conducted in three large neonatal intensive care units in Shenzhen, China, with preterm infants with gestational age less than 32 weeks at birth and birth weight less than 1500 g. It is estimated that 320 preterm infants will be enrolled in this study within one year. The intervention group will receive oropharyngeal administration of 0.2 ml colostrum every 3 h, starting between the first 48 to 72 h and continued for 5 consecutive days. Following a similar administration scheme, the control group will receive oropharyngeal administration of sterile water. Stool samples will be collected at the first defecation, as well as on the 7th, 14th, 21st and 28th days after birth for analysis of effect of OAC on gut microbiota and metabolites through 16sRNA gene sequencing and liquid chromatography-mass spectrometry.DiscussionThis proposal advocates for the promotion of OAC as a safe and relatively beneficial protocol in neonatal intensive care units, which may contribute to the establishment of a dominant intestinal flora. Findings of this study may help improve the health outcomes of preterm infants by establishment of targeted gut microbiota in future studies.Trial registrationNCT05481866 (registered July 30, 2022 on ClinicalTrials.gov).

The Implementation of a Multidisciplinary Lactation Program and the Subsequent Influence of Coronavirus Disease 2019: Observations of One Large Neonatal Intensive Care Unit.

The Implementation of a Multidisciplinary Lactation Program and the Subsequent Influence of Coronavirus Disease 2019: Observations of One Large Neonatal Intensive Care Unit.

Video laryngoscopy-assisted less-invasive surfactant administration quality improvement initiative

ObjectiveTo describe the use of quality improvement methodology in transitioning from delivery of surfactant by INSURE (INtubation–SURfactant administration–Extubation) to video laryngoscope-assisted LISA (less-invasive surfactant administration) for infants with respiratory distress...

Octyl-butyl-cyanoacrylate glue for securement of peripheral intravenous catheters: A retrospective, observational study in the neonatal population.

Evidence-based insertion and maintenance strategies for neonatal vascular access devices (VAD) exist to reduce the causes of VAD failure and complications in neonates. Peripheral intravenous catheter failure and complications including, infiltration, extravasation, phlebitis, dislodgement with/without removal, and infection are majorly influenced by catheter securement methods. A retrospective, observational study using routinely collected data on intravenous device use in a large neonatal intensive care unit in Qatar. A 6-month historical cohort was compared with a 6-month cohort after the introduction of an octyl-butyl-cyanoacrylate glue (CG). In the historical cohort, the catheter was secured using a semi-permeable transparent membrane dressing while in the CG cohort, CG was applied at the insertion site on initial insertion and after any dressing change. This was the only variable intervention between both groups. A total of 8330 peripheral catheters were inserted. All catheters were inserted and monitored by members of the NeoVAT team. 4457 (53.5%) were secured with just a semi-permeable transparent dressing and 3873 (46.5%) secured a semi-permeable transparent dressing with the addition of CG. The odds ratio for premature failure after securement with CG was 0.59 (0.54-0.65) when compared to the catheters secured with a semi-permeable transparent dressing, which was statistically significant (p < 0.001). The correlation between the occurrence of a complication and the use of CG for device securement was significant (p < 0.001). The risk of developing device-related phlebitis and premature device removal, increased significantly if CG was not used for adjunct catheter securement. In parallel with the currently published literature, this study's findings support the use of CG for vascular device securement. When device securement and stabilization concerns are most pertinent CG is a safe and effective adjunct to reducing therapy failures in the neonatal patient population.

A Prospective Evaluation of Arrhythmias in a Large Tertiary Neonatal Intensive Care Unit.

Arrhythmias in the neonatal period are common and can be classified as bradyarhythmias and tachyarrhythmias and as benign or non-benign. Neonatal arrhythmias are further differentiated between those with abnormalities in generation (non-sinus) and those with abnormalities in propagation. Because the neonatal myocardium is immature and operates at the peak of the Starling curve, significant changes in heart rate can result in a decline in cardiac output and compromise end-organ perfusion. This is especially true for premature neonates, those critically ill, or those with concomitant congenital heart disease. While sustained arrhythmias are frequently witnessed and recorded in tertiary neonatal intensive care units (NICU) very little data exist on the observance of non-sustained brady- or tachyarrhythmias in this cohort. No prospective study has been performed on all neonates admitted to a large tertiary NICU throughout their entire stay. The purpose of this study was to prospectively evaluate the prevalence and type of arrhythmias in a large NICU population from admission to discharge. All neonates admitted to the NICU at Inova Children's Hospital at Inova Fairfax Medical Campus between January 1, 2021 and April 1, 2021 were prospectively evaluated from admission to hospital discharge via continuous bedside monitoring reviewed every 24h. Concerning telemetry strips were reviewed by two team members as well as the senior electrophysiologist. Two-hundred and one neonates (mean gestational age = 344/7weeks) were enrolled in the study. Admission length ranged from 1 to 195days (total of 5624 patient days, median 16days). Overall, 68% (N = 137) of admissions had one or more arrhythmias, the most common of which was sinus tachycardia (65%, N = 130), followed by sinus bradycardia (30%, N = 60). Clinically relevant arrhythmias were diagnosed in 6.5% of neonates. During the study period there were four deaths, none of which were directly attributable to a primary arrhythmia. Approximately 68% of neonates exhibited at least one arrhythmia. Although the vast majority of these arrhythmias were benign, clinically relevant arrhythmias were observed in 6.5%. Patients admitted to the NICU appear to have a relatively high burden of benign arrhythmias, but a relatively low burden of pathologic arrhythmias.

Implementation of a Bedside Point-of-Care Ultrasound Program in a Large Academic Neonatal Intensive Care Unit.

In the adult and pediatric critical care population, point-of-care ultrasound (POCUS) can aid in diagnosis, patient management, and procedural accuracy. For neonatal providers, training in ultrasound and the use of ultrasound for diagnosis and management is increasing, but use in the neonatal intensive care unit (NICU) is still uncommon compared with other critical care fields. Our objective was to describe the process of implementing a POCUS program in a large academic NICU and evaluate the role of ultrasound in neonatal care during early adaption of this program. A POCUS program established in December 2018 included regular bedside scanning, educational sessions, and quality assurance, in collaboration with members of the cardiology, radiology, and pediatric critical care divisions. Core applications were determined, and protocols outlined guidelines for image acquisition. An online database included images and descriptive logs for each ultrasound. A total of 508 bedside ultrasounds (76.8% diagnostic and 23.2% procedural) were performed by 23 providers from December 2018 to December 2020 in five core diagnostic applications: umbilical line visualization, cardiac, lung, abdomen (including bladder), and cranial as well as procedural applications. POCUS guided therapy and influenced clinical management in all applications: umbilical line assessment (26%), cardiac (33%), lung (14%), abdomen (53%), and cranial (43%). With regard to procedural ultrasound, 74% of ultrasound-guided arterial access and 89% of ultrasound-guided lumbar punctures were successful. Implementation of a POCUS program is feasible in a large academic NICU and can benefit from a team approach. Establishing a program in any NICU requires didactic opportunities, a defined scope of practice, and imaging review with quality assurance. Bedside clinician performed ultrasound findings can provide valuable information in the NICU and impact clinical management. · Use of point-of-care ultrasound is increasing in neonatology and has been shown to improve patient care.. · Implementation of a point-of-care ultrasound program requires the definition of scope of practice and can benefit from the support of other critical care and imaging departments and providers.. · Opportunities for point-of-care ultrasound didactics, imaging review, and quality assurance can enhance the utilization of bedside ultrasound..

Rapid Point-of-Care Genotyping to Avoid Aminoglycoside-Induced Ototoxicity in Neonatal Intensive Care

Aminoglycosides are commonly prescribed antibiotics used for the treatment of neonatal sepsis. The MT-RNR1 m.1555A>G variant predisposes to profound aminoglycoside-induced ototoxicity (AIO). Current genotyping approaches take several days, which is unfeasible in acute settings. To develop a rapid point-of-care test (POCT) for the m.1555A>G variant before implementation of this technology in the acute neonatal setting to guide antibiotic prescribing and avoid AIO. This pragmatic prospective implementation trial recruited neonates admitted to 2 large neonatal intensive care units between January 6, 2020, and November 30, 2020, in the UK. Neonates were tested for the m.1555A>G variant via the rapid POCT on admission to the neonatal intensive care unit. The primary outcome assessed the proportion of neonates successfully tested for the variant of all infants prescribed antibiotics. Secondary outcomes measured whether implementation was negatively associated with routine clinical practice and the performance of the system. The study was statistically powered to detect a significant difference between time to antibiotic administration before and after implementation of the MT-RNR1 POCT. A total of 751 neonates were recruited and had a median (range) age of 2.5 (0-198) days. The MT-RNR1 POCT was able to genotype the m.1555A>G variant in 26 minutes. Preclinical validation demonstrated a 100% sensitivity (95% CI, 93.9%-100.0%) and specificity (95% CI, 98.5%-100.0%). Three participants with the m.1555A>G variant were identified, all of whom avoided aminoglycoside antibiotics. Overall, 424 infants (80.6%) receiving antibiotics were successfully tested for the variant, and the mean time to antibiotics was equivalent to previous practice. The MT-RNR1 POCT was integrated without disrupting normal clinical practice, and genotype was used to guide antibiotic prescription and avoid AIO. This approach identified the m.1555A>G variant in a practice-changing time frame, and wide adoption could significantly reduce the burden of AIO.

Maintaining Normothermia in Preterm Babies during Stabilisation with an Intact Umbilical Cord.

Background: We had experienced an increase in admission hypothermia rates during implementation of deferred cord clamping (DCC) in our unit. Our objective was to reduce the number of babies with a gestation below 32 weeks who are hypothermic on admission, whilst practising DCC and providing delivery room cuddles (DRC). Method: A 12 month quality improvement project set, in a large Neonatal Intensive Care Unit, from January 2020 to December 2020. Monthly rates of admission hypothermia (<36.5 °C) for all eligible babies, were tracked prospectively. Each hypothermic baby was reviewed as part of a series of Plan, Do, Study Act (PDSA) cycles, to understand potential reasons and to develop solutions. Implementation of these solutions included the dissemination of the learning through a variety of methods. The main outcome measure was the proportion of babies who were hypothermic (<36.5 °C) on admission compared to the previous 12 months. Results: 130 babies with a gestation below 32 weeks were admitted during the study period. 90 babies (69.2%) had DCC and 79 babies (60%) received DRC. Compared to the preceding 12 months, the rate of hypothermia decreased from 25/109 (22.3%) to 13/130 (10%) (p = 0.017). Only 1 baby (0.8%) was admitted with a temperature below 36 °C and 12 babies (9.2%) were admitted with a temperature between 36 °C and 36.4 °C. Continued monitoring during the 3 months after the end of the project showed that the improvements were sustained with 0 cases of hypothermia in 33 consecutive admissions. Conclusions: It is possible to achieve low rates of admission hypothermia in preterm babies whilst providing DCC and DRC. Using a quality improvement approach with PDSA cycles is an effective method of changing clinical practice to improve outcomes.

Ten-Year Trend of Retinopathy of Prematurity Among Extremely Preterm Infants in One Neonatal Intensive Care Unit in China.

Background: Extremely preterm (EP) infants are at the highest risk of retinopathy of prematurity (ROP). With more EP infants survived in China, recent data of ROP is lacking. The aim of the study is to report the trend of incidence of ROP among EP infants in a large neonatal intensive care unit in China over the past 10-year period, in relation with the overall survival rate and the change of oxygen saturation targets.Methods: This retrospective cohort study enrolled all EP infants born before 28 weeks' gestation and admitted to one of the largest tertiary neonatal intensive care units in China from 2010 to 2019. Data were compared between two time periods according to different oxygen saturation targets: 2010–2014 (P1) with low saturation target and 2015–2019 (P2) with higher target.Results: Of 630 EP infants admitted during the 10 years, 447 (71.0%) infants survived to discharge. The survival rate increased significantly from 61.6% in P1 to 75.8% in P2 (P < 0.05). Of the 472 infants who had ROP data, 318 (67.4%) developed ROP of any stage, 67 (14.2%) developed severe ROP, and 44 (9.3%) received treatment. The incidence of any ROP increased significantly from 51.7% in P1 to 74.3% in P2 (P < 0.05). The incidence of severe ROP increased from 11.0% in P1 to 15.6% in P2, and ROP treatment increased from 6.9% in P1 to 10.4% in P2, but neither reached statistical significance (both P > 0.05).Conclusions: We observed an increasing trend in the incidence of ROP across the 10-year period in one of the largest neonatal care units in China. The increased survival rate and the use of high-target oxygen saturation in the later period may partly explain this trend. Further investigations are needed to improve the care practices and to reduce the incidence of severe ROP.

Relationship between intraventricular hemorrhage and acute kidney injury in premature infants and its effect on neonatal mortality

Intraventricular hemorrhage (IVH) and acute kidney injury (AKI) are important neonatal morbidities in premature infants. This study aimed to investigate the relationship between IVH and AKI in premature infants and whether this association affects the incidence of neonatal mortality. Infants [gestational age (GA) ≤ 32 weeks; birth weight (BW) < 1500 g] were retrospectively evaluated in a large tertiary neonatal intensive care unit. Of 710 premature infants, 268 (37.7%) developed AKI. Infants with IVH were more likely to have AKI than those without IVH. Infants with severe IVH had a higher incidence of AKI than infants with mild IVH. Infants younger than 28 weeks with IVH were more likely to have AKI than those without IVH. An association between IVH grades and AKI stages was observed in the overall study population, in infants with GA < 28 weeks, and in infants with GA between 28 and 32 weeks. Mortality was increased 1.5 times in infants with IVH and AKI compared with that in infants with IVH but without AKI. Furthermore, mortality was increased in infants with IVH and AKI compared with infants without IVH or AKI. This study shows a direct relationship between the severity of IVH and the degree of AKI; both IVH and AKI increase the incidence of neonatal mortality.

Neonatal donation: are newborns too young to be recognized?

Neonatal organ and tissue donation is not common practice in the Netherlands. At the same time, there is a transplant waiting list for small size-matched organs and tissues. Multiple factors may contribute to low neonatal donation rates, including a lack of awareness of this option. This study provides insight into potential neonatal organ and tissue donors and reports on how many donors were actually reported to the procurement organization. We performed a retrospective analysis of the mortality database and medical records of two largest neonatal intensive care units (NICUs) in the Netherlands. This study reviewed records of neonates with a gestational age >37 weeks and weight >3000g who died in the period from January 1, 2005 through December 31, 2016. During the study period, 259 term-born neonates died in the two NICUs. In total, 132 neonates with general contra-indications for donation were excluded. The medical records of 127 neonates were examined for donation suitability. We identified five neonates with documented brain death who were not recognized as potential organ and/or tissue donors. Of the remaining neonates, 27 were found suitable for tissue donation. One potential tissue donor had been reported to the procurement organization. In three cases, the possibility of donation was brought up by parents.Conclusion: A low proportion (2%) of neonates who died in the NICUs were found suitable for organ donation, and a higher proportion (12%) were found suitable for tissue donation. We suggest that increased awareness concerning the possibility of neonatal donation would likely increase the identification of potential neonatal donors.What is Known:• There is an urgent need for very small organs and tissues from neonatal donorsWhat is New:• A number of neonates who died in the NICU were suitable organ or/and tissue donors but were not recognized as donors.• Knowledge on neonatal donation possibilities is also important for proper counseling of parents who sometimes inquire for the possibility of organ and tissue donation.

Does Feeding Previously Frozen (Thawed) Fortified Human Milk Increase the Incidence of Lactobezoar (Milk Curd) Obstruction? A Retrospective Cohort Study in One Large Neonatal Intensive Care Unit

BackgroundCurrent recommendations suggest that it is appropriate to store human milk (HM) for up to 24 hours following fortification despite any changes that may occur in fortified HM over time. However, a recent publication suggested fortified frozen HM should be thawed and fed within 12 hours of fortification due to the risk of lactobezoar or milk curd obstruction. ObjectiveThis study investigated whether lactobezoar (milk curd) formation increased when frozen fortified HM was thawed and fed within 12 hours vs 12 to 24 hours postfortification in the neonatal intensive care unit (NICU) at Children’s Hospital of Orange County to determine if practice changes were warranted. DesignThis study was a retrospective cohort study. Participants/settingAll infants admitted to the Children’s Hospital of Orange County NICU for calendar years 2018-2019 who were fed fortified human milk (n = 802) were included in the study. Exposure variableFeedings using previously frozen (thawed) fortified HM. Main outcome measureLactobezoar or milk curd formation. Statistical analysisDescriptive analyses were used for statistical analysis. ResultsOf the 107,602 feedings prepared with fortified thawed HM, 68% (72,602) were used within 12 hours of preparation and 32% (34,499) were stored for 12 to 24 hours before administration. The NICU at Children’s Hospital of Orange County did not identify any lactobezoar formation or milk curd obstruction in either group. ConclusionsData from this study support recommendations for a maximum storage time for thawed, fortified HM of 24 hours.

The Role of a NICU Hepatology Consult Service in Assessing Liver Dysfunction in the Premature Infant

Liver dysfunction is common in the neonatal intensive care unit (NICU). Literature exists on the presentation of primary liver disease in the NICU but little has been published on general liver dysfunction in the NICU. This is a retrospective observational study of hepatology consultations and outcomes in a large referral NICU. 157 babies were evaluated by a single hepatologist and followed to resolution of disease, death, or lost to follow-up as outpatients. Infectious etiologies were the most common cause for liver dysfunction in the NICU, followed by shock, genetic abnormalities, cardiac disease, large heme loads, and hypothyroidism. Primary liver disease was rare. Liver dysfunction in the sick preterm infant was often multifactorial, and the distribution of diagnoses differs from that seen in the term baby. The liver dysfunction may last well beyond discharge from the NICU and may result in death.

Informing mothers of neonatal death and the need for family-centered bereavement care: A phenomenological qualitative study.

To understand the lived experience of mothers surrounding the time of being informed of neonatal deaths in intensive care units. A phenomenological qualitative approach was employed. Twelve mothers (age 24-41 years) were identified from the neonatal mortality records of two large neonatal intensive care units with high neonate turnover rates in Amman, Jordan. Data were collected using semistructured interviews with the participants. Interpretive phenomenology was used to generate themes regarding the essence of the mother's experience. Critical analyses of mothers' accounts revealed three major themes: (a) Minimize the hurt, which described how mothers intuited overprotection by their families while the news was conveyed indirectly to them; (b) The striking reality of death, which captured mothers' distressing experiences while realizing the loss of their neonates; and (c) Farwell my baby, which accentuated mothers' needs and experiences while neonates' bodies were honored and prepared for burial per the cultural norms in Jordan. Our findings highlighted the complex dynamics of familial interactions and cultural influences on mothers' bereavement experiences at the time of neonatal death. The grieving mothers expressed unfulfilled needs of receiving professional bereavement support at the time of neonatal death. Strategies are needed to optimize the supportive role of specialized nurses in providing family-centered bereavement care to mothers and their families who experience neonatal death.

Personal resources associated with peripartum depression among mothers of NICU hospitalised preterm infants

Objective The high prevalence of peripartum depression (PPD) among mothers of preterm infants concerns health professionals due to its implications for mothers’ and infants’ health. A model for explaining PPD, consisting of four personal resources was examined: locus of control, intolerance to uncertainty, maternal self-efficacy, and quality of the couple relationship. Design In one of the largest Neonatal Intensive Care Unit (NICU) in Israel, 129 mothers of 215 preterm infants completed self-report questionnaires regarding their background variables, locus of control, intolerance to uncertainty, maternal self-efficacy and quality of couple relationship. Main Outcome Measures PPD symptoms and high risk for diagnosing clinical PPD. Results The examined personal resources explained 43.9% of the variance in PPD symptoms. Intolerance to uncertainty was positively associated with PPD symptoms, while internal locus of control, high levels of maternal self-efficacy, and high quality of couple relationships were found to be negatively associated with PPD symptoms. Additionally, these variables predicted the likelihood for clinical PPD. Conclusion The findings indicate a potential likelihood of reducing PPD through healthcare professional interventions, by strengthening personal resources. Associations between personal resources and PPD are discussed in light of the transactional theory of coping.

Retrospective study of short-term complications associated with early morphine use in intubated premature infants

Relieving neonatal pain is essential for the management of premature infants. Morphine is the most frequently used analgesic in neonatal intensive care. Here we report the relationship between early morphine infusion and the composite outcome of intraventricular hemorrhage and/or death in intubated premature infants. Infants (gestational age ≤ 32 weeks and birth weight < 1,500 g) intubated on admission were retrospectively evaluated in a large tertiary neonatal intensive care unit. Modified log-Poisson regression with robust variance estimator and Cox regression was applied to adjust the relative risk for infants’ outcomes. Of 420 premature infants, 230 (54.7%) received continuous morphine infusion in the first 72 h. Of these, 153 were < 28 gestational weeks; of the 190 patients who did not receive morphine, 63 were < 28 gestational weeks. The analysis revealed that infants < 28 gestational weeks who received morphine were significantly associated with an increased risk for IVH and/or death [adjusted relative risk (aRR) 1.37, 95% confidence interval (CI) 1.1–1.71)], and mortality (aRR 1.83, 95% CI 1.17–2.89). Moreover, in infants < 28 gestational weeks, survival was low in those infants who were exposed to morphine infusion in the first 72 h (hazard ratio 2.11; 95% CI 1.19–3.73). Early morphine infusion is associated with an increased risk for IVH and/or death; however, further studies are required to verify our findings.

Medical Exome As a First-Line Diagnostic Test in the Neonatal Intensive Care Unit: Experience in a Large Broad Cohort of 4,124 Neonates with Minimal Clinical Selection in China

Background: Rare genetic diseases underlie a significant portion of congenital anomalies and contribute to neonatal intensive care unit (NICU) admissions. A timely genetic diagnosis is important for medical decision making. Emerging evidence demonstrates the clinical utility of medical genomic applications in NICU patients with highly suspect genetic etiology. However, the diagnostic yield and utility of such applications remain unclear for large scale and non-selective NICU cohorts. Methods: Focused medical exome sequencing was used as a first-tier, singleton focused diagnostic tool for minimally selected 4,124 unrelated sick neonates from 2016 to 2018. Integrated analysis of single nucleotide variants, small insertions and deletions, and large copy number variants was performed on genes with established clinical validity and neonatal onset. Diagnostic yield, medically actionable incidental findings, and potential clinical predictors for a molecular diagnosis were analyzed. Findings: The overall diagnostic rate in this large NICU cohort is 7.1%, with an average turnaround time of 10 days and a cost of under $250 per patient. In addition, 2.0% patients had a reportable incidental finding. Multiple organ failure was the strongest positive predictor while hepatic/hyperbilirubinemia involvements were the strongest negative predictors for a diagnosis. Interpretation: Focused medical exome sequencing is a powerful first line test for timely molecular diagnosis and informed management of NICU patients. A genome-first approach such as medical exome sequencing can particularly benefit intensively ill neonates in a large patient population with a resource-constrained environment such as China, where well-trained clinical geneticists are scarce and comprehensive diagnostic tools are not readily available. Funding Statement: This work was supported by grants from the Shanghai Shen Kang Hospital Development Center (SHDC12017110), the Technology Major Project (2018SHZDZX01) and ZJLab, the Shanghai Municipal Commission of Health and Family Planning (GDEK201701), the Shanghai Municipal Science and Technology Major Project (2018SHZDZX05). Declaration of Interests: ZW, KM, TX, JZ, FC, LL, YD, CL, ST, and PF are employed by and receive a salary from WuXiNextCode Genomics. Medical exome testing is among the commercially available tests. All other authors declare no competing interests. Ethics Approval Statement: This study was approved by the ethics committees of Children’s Hospital of Fudan University (2015-169). The samples used in this study were collected with appropriate informed consent and approval of the ethics committee of Children’s Hospital, Fudan University. Written informed consent was obtained from parents or legal guardians of patients.

Early exposure to antibiotics in the neonatal intensive care unit alters the taxonomic and functional infant gut microbiome

Introduction The infant gut microbiome is thought to play a key role in developing metabolic and immunologic pathways. Antibiotics have been shown to disrupt the human microbiome, but the impact they have on infants during this key window of development remains poorly understood. Through this study, we further characterize the effect antibiotics have on the gut microbiome of infants by looking at metagenomic sequencing data over time. Materials and methods Stool samples were collected on infants from a large tertiary care neonatal intensive care unit. After DNA extraction, metagenomics libraries were generated and sequenced. Taxonomic and functional analyses were then performed. Further directed specimen sequencing for fungal species was also performed. Results A total of 51 stool samples from 25 infants were analyzed: seven infants were on antibiotics during at least one of their collection time points. Antibiotics given at birth altered the microbiome (PERMANOVA R 2 = 0.044, p = .002) but later courses did not (R 2 = 0.023, p = .114). Longitudinal samples collected while off antibiotics were more similar than those collected during a transition on or off antibiotics (mean Bray–Curtis distance 0.29 vs. 0.63, Wilcoxon p = .06). Functional analysis revealed four microbial pathways that were disrupted by antibiotics given at-birth (p < .1, folate synthesis, glycerolipid metabolism, fatty acid biosynthesis, and glycolysis). No functional changes associated with current antibiotic use were identified. In a limited sample set, we saw little evidence of fungal involvement in the overall infant microbiome. Conclusion Through this study, we have further characterized the role antibiotics have in the development of the infant microbiome. Antibiotics given at birth were associated with alterations in the microbiome and had significant impact on the functional pathways involved in folate synthesis and multiple metabolic pathways. Later courses of antibiotics led to stochastic dysbiosis and a significant decrease in Escherichia coli. Further characterization of the infant mycobiome is still needed.

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

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. 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). 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%). 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.