ABSTRACT
BACKGROUND: Use of standardized feeding protocols and donor breast milk (DBM) have been studied primarily in infants born <1500 g and not examined exclusively in infants born >1500 g. METHODS: In this retrospective pre-post-implementation cohort study, we evaluated a protocol for preterm infants born >1500 g that was implemented clinically to standardize feeding advancements at 30 mL/kg/day, with infants born <33 weeks eligible to receive DBM. We compared placement of peripherally inserted central catheters for parenteral nutrition, feeding tolerance, growth, and maternal milk provision in the 18 months before/after implementation. The association between DBM intake and growth was evaluated using multivariable linear regression. RESULTS: We identified 133 and 148 eligible infants pre/post-implementation. Frequency of peripherally inserted central catheters and rate of maternal milk provision was not statistically different. While there was no difference in median days to full enteral volume, there was a narrower distribution post-implementation (p < 0.001). Growth was similar between eras, but each 10% increase in DBM was associated with 1.0 g/d decrease in weight velocity (p < 0.001). CONCLUSIONS: A feeding protocol for preterm infants >1500 g is associated with more consistent time to full enteral volume. Further investigation is needed to clarify DBM's impact on growth in this population. IMPACT: Despite practice creep, no study has examined the use of standardized feeding protocols or pasteurized donor breast milk exclusively in infants >1500 g. A feeding protocol in this population may achieve full enteral feedings more consistently. With appropriate fortification, donor breast milk can support adequate growth in infants born >1500 g but warrants further study.
ABSTRACT
Immune checkpoint inhibitors are effective first-line therapy for solid cancers. However, low response rate and acquired resistance over time has led to the need for additional therapeutic options. Here, we evaluated synergistic antitumor efficacy of EGFR × MET targeting bispecific antibody, amivantamab with PD-L1 immunotherapy, pembrolizumab in head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma tumor-bearing humanized patient-derived xenograft (PDX) models. We demonstrated that pembrolizumab or amivantamab alone was ineffective and that combination treatment induced a significant reduction of tumor growth in both models (P < 0.0001 and P < 0.01, respectively). It appeared that combination of amivantamab and pembrolizumab significantly enhanced infiltration of granzyme B-producing CD8 T cells was in the TME of HNSCC PDX (P < 0.01) and enhanced neoantigen-associated central memory CD8 T cells in circulating immune cells. Analysis of single-cell RNA transcriptomics suggested that the tumor cells dramatically upregulated EGFR and MET in response to PD-L1 immunotherapy, potentially creating a metabolic state fit for tumor persistence in the tumor microenvironment (TME) and rendered pembrolizumab ineffective. We demonstrated that EGFRHIGHMETHIGH subcluster displayed an increased expression of genes implicated in production of lactate [SLC16A3 and lactate dehydrogenase A (LDHA)] compared to the EGFRLOWMETLOW cluster. Accumulation of lactate in the TME has been associated with immunosuppression by hindering the infiltration of tumor killing CD8 T and NK cells. This study proved that amivantamab reduced glycolytic markers in the EGFRHIGHMETHIGH subcluster including SLC16A3 and LDHA and highlighted remodeling of the TME by combination treatment, providing rationale for additional therapy of amivantamab with PD-1 immunotherapy. SIGNIFICANCE: Amivantamab in synergy with pembrolizumab effectively eradicated EGFRHIGHMETHIGH tumor subcluster in the tumor microenvironment of head and neck squamous cell carcinoma and overcame resistance against anti-PD-1 immunotherapy.
Subject(s)
Antibodies, Monoclonal, Humanized , Lung Neoplasms , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/pathology , Animals , Mice , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/immunology , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/immunology , Xenograft Model Antitumor Assays , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , B7-H1 Antigen/metabolism , Cell Line, TumorABSTRACT
OBJECTIVE: Preterm infants need enrichment of human milk (HM) for optimal growth. This study evaluated a novel, point-of-care human milk concentration (HMC) process for water removal from fresh HM samples by passive osmotic concentration. STUDY DESIGN: Nineteen fresh HM samples were concentrated by incubation with the HMC devices for 3 h at 4 °C. Pre- and post-concentration HM samples were compared by HM properties for: pH, osmolality, macronutrients, enzyme activity, bioactive, and total cell viability. RESULTS: Passive osmotic concentration reduced HM volume by an average of 16.3% ± 3.8% without a significant effect on pH or cell viability. Ten of the 41 HM components did not differ significantly (p > 0.05) between pre- and post-concentration samples. Twenty-three increased within the expected range by volume reduction. Six increased more than expected, two less than expected, and none decreased significantly. CONCLUSION: Passive osmotic concentration of fresh HM can concentrate HM components by selective removal of water. HM osmolality and pH remained within neonatal feeding parameters.
ABSTRACT
BACKGROUND AND OBJECTIVES: Neonatal endotracheal tube (ETT) size recommendations are based on limited evidence. We sought to determine data-driven weight-based ETT sizes for infants undergoing tracheal intubation and to compare these with Neonatal Resuscitation Program (NRP) recommendations. METHODS: Retrospective multicenter cohort study from an international airway registry. We evaluated ETT size changes (downsizing to a smaller ETT during the procedure or upsizing to a larger ETT within 7 days) and risk of procedural adverse outcomes associated with first-attempt ETT size selection when stratifying the cohort into 200 g subgroups. RESULTS: Of 7293 intubations assessed, the initial ETT was downsized in 5.0% of encounters and upsized within 7 days in 1.5%. ETT downsizing was most common when NRP-recommended sizes were attempted in the following weight subgroups: 1000 to 1199 g with a 3.0 mm (12.6%) and 2000 to 2199 g with a 3.5 mm (17.1%). For infants in these 2 weight subgroups, selection of ETTs 0.5 mm smaller than NRP recommendations was independently associated with lower odds of adverse outcomes compared with NRP-recommended sizes. Among infants weighing 1000 to 1199 g: any tracheal intubation associated event, 20.8% with 2.5 mm versus 21.9% with 3.0 mm (adjusted OR [aOR] 0.62, 95% confidence interval [CI] 0.41-0.94); severe oxygen desaturation, 35.2% with 2.5 mm vs 52.9% with 3.0 mm (aOR 0.53, 95% CI 0.38-0.75). Among infants weighing 2000 to 2199 g: severe oxygen desaturation, 41% with 3.0 mm versus 56% with 3.5mm (aOR 0.55, 95% CI 0.34-0.89). CONCLUSIONS: For infants weighing 1000 to 1199 g and 2000 to 2199 g, the recommended ETT size was frequently downsized during the procedure, whereas 0.5 mm smaller ETT sizes were associated with fewer adverse events and were rarely upsized.
Subject(s)
Intubation, Intratracheal , Resuscitation , Humans , Infant, Newborn , Cohort Studies , Intubation, Intratracheal/methods , OxygenABSTRACT
OBJECTIVE: To determine the factors associated with second attempt success and the risk of adverse events following a failed first attempt at neonatal tracheal intubation. DESIGN: Retrospective analysis of prospectively collected data on intubations performed in the neonatal intensive care unit (NICU) and delivery room from the National Emergency Airway Registry for Neonates (NEAR4NEOS). SETTING: Eighteen academic NICUs in NEAR4NEOS. PATIENTS: Neonates requiring two or more attempts at intubation between October 2014 and December 2021. MAIN OUTCOME MEASURES: The primary outcome was successful intubation on the second attempt, with severe tracheal intubation-associated events (TIAEs) or severe desaturation (≥20% decline in oxygen saturation) being secondary outcomes. Multivariate regression examined the associations between these outcomes and patient characteristics and changes in intubation practice. RESULTS: 5805 of 13 126 (44%) encounters required two or more intubation attempts, with 3156 (54%) successful on the second attempt. Second attempt success was more likely with changes in any of the following: intubator (OR 1.80, 95% CI 1.56 to 2.07), stylet use (OR 1.65, 95% CI 1.36 to 2.01) or endotracheal tube (ETT) size (OR 2.11, 95% CI 1.74 to 2.56). Changes in stylet use were associated with a reduced chance of severe desaturation (OR 0.74, 95% CI 0.61 to 0.90), but changes in intubator, laryngoscope type or ETT size were not; no changes in intubator or equipment were associated with severe TIAEs. CONCLUSIONS: Successful neonatal intubation on a second attempt was more likely with a change in intubator, stylet use or ETT size.
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Unaddressed health-related social needs (HRSNs) and parental mental health needs in an infant's environment can negatively affect their health outcomes. This study examines the challenges and potential technological solutions for addressing these needs in the neonatal intensive care unit (NICU) setting and beyond. In all, 22 semistructured interviews were conducted with members of the NICU care team and other relevant stakeholders, based on an interpretive description approach. The participants were selected from three safety net hospitals in the U.S. with level IV NICUs. The challenges identified include navigating the multitude of burdens families in the NICU experience, resource constraints within and beyond the health system, a lack of streamlined or consistent processes, no closed-loop referrals to track status and outcomes, and gaps in support postdischarge. Opportunities for leveraging technology to facilitate screening and referral include automating screening, initiating risk-based referrals, using remote check-ins, facilitating resource navigation, tracking referrals, and providing language support. However, technological implementations should avoid perpetuating disparities and consider potential privacy or data-sharing concerns. Although advances in technological health tools alone cannot address all the challenges, they have the potential to offer dynamic tools to support the healthcare setting in identifying and addressing the unique needs and circumstances of each family in the NICU.
Subject(s)
Intensive Care Units, Neonatal , Mental Health , Infant, Newborn , Infant , Humans , Aftercare , Patient DischargeABSTRACT
Importance: Genomic testing in infancy guides medical decisions and can improve health outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal gene-sequencing test provides comparable molecular diagnostic yields and times to return of results. Objective: To compare outcomes of genomic sequencing with those of a targeted neonatal gene-sequencing test. Design, Setting, and Participants: The Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a prospective, comparative, multicenter study of 400 hospitalized infants younger than 1 year of age (proband) and their parents, when available, suspected of having a genetic disorder. The study was conducted at 6 US hospitals from June 2019 to November 2021. Exposure: Enrolled participants underwent simultaneous testing with genomic sequencing and a targeted neonatal gene-sequencing test. Each laboratory performed an independent interpretation of variants guided by knowledge of the patient's phenotype and returned results to the clinical care team. Change in clinical management, therapies offered, and redirection of care was provided to families based on genetic findings from either platform. Main Outcomes and Measures: Primary end points were molecular diagnostic yield (participants with ≥1 pathogenic variant or variant of unknown significance), time to return of results, and clinical utility (changes in patient care). Results: A molecular diagnostic variant was identified in 51% of participants (n = 204; 297 variants identified with 134 being novel). Molecular diagnostic yield of genomic sequencing was 49% (95% CI, 44%-54%) vs 27% (95% CI, 23%-32%) with the targeted gene-sequencing test. Genomic sequencing did not report 19 variants found by the targeted neonatal gene-sequencing test; the targeted gene-sequencing test did not report 164 variants identified by genomic sequencing as diagnostic. Variants unidentified by the targeted genomic-sequencing test included structural variants longer than 1 kilobase (25.1%) and genes excluded from the test (24.6%) (McNemar odds ratio, 8.6 [95% CI, 5.4-14.7]). Variant interpretation by laboratories differed by 43%. Median time to return of results was 6.1 days for genomic sequencing and 4.2 days for the targeted genomic-sequencing test; for urgent cases (n = 107) the time was 3.3 days for genomic sequencing and 4.0 days for the targeted gene-sequencing test. Changes in clinical care affected 19% of participants, and 76% of clinicians viewed genomic testing as useful or very useful in clinical decision-making, irrespective of a diagnosis. Conclusions and Relevance: The molecular diagnostic yield for genomic sequencing was higher than a targeted neonatal gene-sequencing test, but the time to return of routine results was slower. Interlaboratory variant interpretation contributes to differences in molecular diagnostic yield and may have important consequences for clinical management.
Subject(s)
Genetic Diseases, Inborn , Genetic Testing , Neonatal Screening , Sequence Analysis, DNA , Whole Genome Sequencing , Clinical Decision-Making/methods , Genetic Profile , Genomics , Prospective Studies , Genetic Testing/methods , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Humans , Infant, Newborn , Neonatal Screening/methods , Infant , Sequence Analysis, DNA/methods , MutationABSTRACT
Major improvements in preterm nutrition have taken place in the past 2 decades that have resulted in the successful survival of extremely preterm infants. Nutrition management for preterm infants traverses several different epochs during hospitalization. More standardization of practice has been evaluated during the early epochs (parenteral nutrition and enteral feeding advancement), whereas later epochs are opportunities for enhanced research to further standardize nutrition practices.
Subject(s)
Infant, Very Low Birth Weight , Intensive Care Units, Neonatal , Infant, Newborn , Humans , Infant , Parenteral Nutrition , Enteral Nutrition , Infant, Extremely PrematureABSTRACT
This study aims to examine the influence of hospital experience factors on parental discharge readiness, accounting for key background characteristics. Parents/guardians of infants 33 weeks of gestation or less at birth receiving neonatal intensive care at 6 sites were enrolled from April 2017 to August 2018. Participants completed surveys at enrollment, 3 weeks later, and at discharge. Multiple regression analysis assessed relationships between parental experience, well-being, and perceived readiness for infant discharge, adjusting for socioenvironmental, infant clinical, and parent demographic characteristics. Most (77%) of the 139 parents reported high levels of readiness for their infant's discharge and 92% reported high self-efficacy at discharge. The multiple regression model accounted for 40% of the variance in discharge readiness. Perceptions of family-centered care accounted for 12% of the variance; measures of parent well-being, anxiety, and parenting self-efficacy accounted for an additional 16% of the variance; parent characteristics accounted for an additional 9%; and infant characteristics accounted for less than 3% of the variance. Parental perceptions of the family-centeredness of the hospital experience, anxiety, and parenting self-efficacy accounted for a substantial proportion of the variance in readiness for discharge scores among parents of preterm infant. These influential perceptions are potentially modifiable by nursing-led interventions.
Subject(s)
Infant, Premature , Intensive Care Units, Neonatal , Infant , Infant, Newborn , Humans , Patient Discharge , Parents , Intensive Care, NeonatalABSTRACT
BACKGROUND: Lipid-injectable emulsions (ILEs) are a necessity for neonates dependent on parenteral nutrition (PN). In this manuscript, we describe the patterns of ILE use in neonatal intensive care units (NICUs) in the United States (US). METHODS: An electronic survey was sent to 488 NICUs across the US between December 2020 and March 2021. Survey fields included availability and utilization of various ILE in neonates. RESULTS: The response rate was 22% (107 out of 488). Soybean oil ILE (SO-ILE) and soybean oil, medium-chain triglycerides, olive oil, fish oil ILE (SO, MCT, OO, FO-ILE) had similar availability (87% vs 86%, respectively), and SO, MCT, OO, FO-ILE was more commonly used (SO-ILE, 71% vs SO, MCT, OO, FO-ILE, 86%). Fish oil-ILE (FO-ILE) was used by 55% of centers. SO-ILE was most frequently used with PN and needs <4 weeks without cholestasis (79%). The most common reason for SO, MCT, OO, FO-ILE use was cholestasis (71%). ILE minimization was used by 28% of SO-ILE and 22% of SO, MCT, OO, FO-ILE users; 95% of these centers restrict SO, MCT, OO, FO-ILE to doses ≤2 g/kg/day. Twenty-two percent of centers started FO-ILE at direct bilirubin of >5 mg/dl. CONCLUSION: The results of this survey reveal significant variability in ILE usage across the US. Lipid minimization with SO, MCT, OO, FO-ILE and initiation of FO-ILE for cholestasis at higher bilirubin thresholds are prevalent. Such reports are crucial for a better understanding of ILE use in the NICU and in future ILE development.
Subject(s)
Cholestasis , Fat Emulsions, Intravenous , Humans , Infant, Newborn , United States , Soybean Oil , Intensive Care Units, Neonatal , Fish Oils , Olive Oil , Bilirubin , TriglyceridesABSTRACT
BACKGROUND: Social support is associated with decreased symptoms of postpartum mood and anxiety disorders (PMAD) in mothers of healthy infants, but less is known about social support and PMADs in mothers with preterm infants. The purpose of this study was to examine the relationship between social support and symptoms of PMADs reported by mothers in the months following hospital discharge of their preterm infant. METHODS: Mothers of infants less than 33 weeks gestational age were enrolled from neonatal intensive care units (NICU) at 6 sites. Mothers completed PMAD measures of depression, anxiety and post-traumatic stress approximately 3 months following their infant's discharge. Multivariable regression was used to evaluate relationships between social support and PMAD measures. RESULTS: Of 129 mothers, 1 in 5 reported clinically significant PMAD symptoms of: depression (24%), anxiety (19%), and post-traumatic stress (20%). Social support was strongly inversely associated with all 3 PMADs. Social support explained between 21% and 26% of the variance in depression, anxiety and post-traumatic stress symptoms. CONCLUSION: Increased social support may buffer PMAD symptoms in mothers of preterm infants after discharge. Research is needed to determine effective screening and interventions aimed at promoting social support for all parents during and following their infant's hospitalisation.
Subject(s)
Infant, Premature , Puerperal Disorders , Female , Infant , Infant, Newborn , Humans , Infant, Premature/psychology , Mothers/psychology , Patient Discharge , Mental Health , Aftercare , Social SupportABSTRACT
The dramatic technologic advancements seen in ultrasound have accelerated the growth of point-of-care ultrasound (POCUS) in medicine. Neonatology has lagged behind other pediatric and adult specialties in incorporating POCUS into clinical practice despite there being numerous applications in cardiac and non-cardiac arenas. Widely available training programs are aiding in improving this situation but significantly more structure and orchestration for neonatal POCUS dissemination will be needed to fully actualize the potential for POCUS to augment its widespread clinical application.
Subject(s)
Neonatology , Point-of-Care Systems , Infant, Newborn , Adult , Humans , Child , UltrasonographyABSTRACT
The importance of nutrition in managing critically ill infants with congenital heart disease (CHD) is foundational to optimizing short- and long-term health outcomes. Growth failure and malnutrition are common in infants with CHD. The etiology of growth failure in this population is often multifactorial and may be related to altered metabolic demands, compromised blood flow to the intestine leading to nutrient malabsorption, cellular hypoxia, inadequate energy intake, and poor oral-motor skills. A dearth of high-quality studies and gaps in previously published guidelines have led to wide variability in nutrition practices that are locally driven. This review provides recommendations from the nutrition subgroup of the Neonatal Cardiac Care Collaborative for best evidence-based practices in the provision of nutritional support in infants with CHD. The review of evidence and recommendations focused on 6 predefined areas of clinical care for a target population of infants <6 months with CHD admitted to the ICU or inpatient ward. These areas include energy needs, nutrient requirements, enteral nutrition, feeding practice, parenteral nutrition, and outcomes. Future progress will be directed at quality improvement efforts to optimize perioperative nutrition management with an increasing emphasis on individualized care based on nutritional status, cardiorespiratory physiology, state of illness, and other vulnerabilities.
Subject(s)
Enteral Nutrition , Heart Defects, Congenital , Infant , Infant, Newborn , Humans , Parenteral Nutrition , Nutritional Requirements , Nutritional Support , Critical Illness/therapy , Nutritional StatusABSTRACT
OBJECTIVE: The objective of this multi-center study was to compare, in infants ≤1250 g birth weight (BW) with neurodevelopmental assessment at 18-22 months of corrected age (CA), whether their neurodevelopmental outcomes differed based on exposure to an exclusive human milk-based (HUM) or to a bovine milk-based fortifier and/or preterm formula (BOV). STUDY DESIGN: Retrospective multi-center cohort study of infants undergoing neurodevelopmental assessment as to whether HUM or BOV exposure related to differences in outcomes of infants at 18-22 months CA, using the Bayley Scales of Infant Development III (BSID-III). BSID-III cognitive, language, and motor scores were adjusted for BW, sex, study site, and necrotizing enterocolitis. RESULTS: 252 infants from 6 centers were included. BSID-III cognitive scores were higher in the HUM group (96.5 ± 15.1 vs 89.6 ± 14.1, adjusted p = 0.0001). Mean BSID-III language scores were 85.5 ± 15.0 in HUM and 82.2 ± 14.1 in BOV (adjusted p = 0.09). Mean BSID-III motor scores were 92.9 ± 11.7 in HUM and 91.4 ± 14.6 in BOV (adjusted p = 0.32). CONCLUSION: In this cohort of infants undergoing neurodevelopmental assessment, infants receiving HUM diet had significantly higher cognitive BSID-III scores at 18-22 months CA. Further investigation is needed of this potential for HUM to positively influence infant cognitive outcomes.
Subject(s)
Enterocolitis, Necrotizing , Milk, Human , Infant , Child , Infant, Newborn , Humans , Infant, Extremely Premature , Cohort Studies , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/epidemiology , Enterocolitis, Necrotizing/etiology , Birth Weight , Diet , Infant, Very Low Birth WeightABSTRACT
OBJECTIVE: To determine the relationship between number of attempts and adverse events during neonatal intubation. STUDY DESIGN: A retrospective study of prospectively collected data of intubations in the delivery room and NICU from the National Emergency Airway Registry for Neonates (NEAR4NEOS) in 17 academic centers from 1/2016 to 12/2019. We examined the association between tracheal intubation attempts [1, 2, and ≥3 (multiple attempts)] and clinical adverse outcomes (any tracheal intubation associated events (TIAE), severe TIAE, and severe oxygen desaturation). RESULTS: Of 7708 intubations, 1474 (22%) required ≥3 attempts. Patient, provider, and practice factors were associated with higher TI attempts. Increasing intubation attempts was independently associated with a higher risk for TIAE. The adjusted odds ratio for TIAE and severe oxygen desaturation were significantly higher in TIs with 2 and ≥3 attempts than with one attempt. CONCLUSION: The risk of adverse safety events during intubation increases with the number of intubation attempts.
Subject(s)
Intubation, Intratracheal , Oxygen , Humans , Infant, Newborn , Intubation, Intratracheal/adverse effects , Registries , Retrospective StudiesABSTRACT
Human milk is the optimal infant nutrition. However, although human-derived metabolites (such as lipids and oligosaccharides) in human milk are regularly reported, the presence of exogenous chemicals (such as drugs, food, and synthetic compounds) are often not addressed. To understand the types of exogenous compounds that might be present, human milk (n = 996) was analyzed by untargeted metabolomics. This analysis revealed that lifestyle molecules, such as medications and their metabolites, and industrial sources, such as plasticizers, cosmetics, and other personal care products, are found in human milk. We provide further evidence that some of these lifestyle molecules are also detectable in the newborn's stool. Thus, this study gives important insight into the types of exposures infants receiving human milk might ingest due to the lifestyle choices, exposure, or medical status of the lactating parent.
Subject(s)
Lactation , Milk, Human , Infant , Infant, Newborn , Female , Humans , Milk, Human/chemistry , MetabolomicsABSTRACT
The first week after birth is a critical time for the establishment of microbial communities for infants. Preterm infants face unique environmental impacts on their newly acquired microbiomes, including increased incidence of cesarean section delivery and exposure to antibiotics as well as delayed enteral feeding and reduced human interaction during their intensive care unit stay. Using contextualized paired metabolomics and 16S sequencing data, the development of the gut, skin, and oral microbiomes of infants is profiled daily for the first week after birth, and it is found that the skin microbiome appears robust to early life perturbation, while direct exposure of infants to antibiotics, rather than presumed maternal transmission, delays microbiome development and prevents the early differentiation based on body site regardless of delivery mode. Metabolomic analyses identify the development of all gut metabolomes of preterm infants toward full-term infant profiles, but a significant increase of primary bile acid metabolism only in the non-antibiotic treated vaginally birthed late preterm infants. This study provides a framework for future multi-omic, multibody site analyses on these high-risk preterm infant populations and suggests opportunities for monitoring and intervention, with infant antibiotic exposure as the primary driver of delays in microbiome development.