Identifying Foods That Optimize Intake of Key Micronutrients During Pregnancy.

BACKGROUND: Most pregnant women in the United States are at risk of inadequate intake of vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids from foods alone. Very few United States dietary supplements provide sufficient doses of all 6 nutrients without inducing excess intake. OBJECTIVE: We aimed to identify energy-efficient foods that provide sufficient doses of these nutrients and could be consumed in lieu of dietary supplements to achieve the recommended intake in pregnancy. METHODS: In a previous analysis of 2,450 pregnant women, we calculated the range of additional intake needed to shift 90% of participants to intake above the estimated average requirement and keep 90% below the tolerable upper level for these 6 nutrients. Here, we identified foods and beverages from the 2019 to 2020 Food and Nutrient Database for Dietary Studies that provide target levels of these nutrients without exceeding the additional energy intake recommended for pregnancy beginning in the second trimester (340 kilocalories). RESULTS: We identified 2358 candidate foods meeting the target intake range for at least one nutrient. No candidate foods provided target amounts of all 6 nutrients. Seaweed (raw or cooked without fat) provided sufficient vitamin A, folate, calcium, iron, and omega-3s (5 of 6 nutrients) but would require an intake of >5 cups/d. Twenty-one other foods/beverages (mainly fish, vegetables, and beverages) provided target amounts of 4 of the 6 nutrients. Few foods met targets for vitamin D (n = 54) or iron (n = 93). CONCLUSIONS: Results highlight the difficulty in meeting nutritional requirements from diet alone and imply that dietary supplements are likely necessary to meet vitamin D and iron targets in pregnancy, as well as omega-3 fatty acid targets for individuals who do not consume fish products. Other foods could be added in limited amounts to help meet intake targets without exceeding caloric recommendations or nutrient safety limits.

Comparative safety profile of chloral hydrate versus other sedatives for procedural sedation in hospitalized infants.

BACKGROUND: Given the limited available evidence on chloral hydrate safety in neonatal populations and the discrepancy in chloral hydrate acceptance between the US and other countries, we sought to clarify the safety profile of chloral hydrate compared to other sedatives in hospitalized infants. METHODS: We included all infants <120 days of life who underwent a minor procedure and were administered chloral hydrate, clonidine, clonazepam, dexmedetomidine, diazepam, ketamine, lorazepam, midazolam, propofol, or pentobarbital on the day of the procedure. We characterized the distribution of infant characteristics and evaluated the relationship between drug administration and any adverse event. We performed propensity score matching, regression adjustment (RA), and inverse probability weighting (IPW) to ensure comparison of similar infants and to account for confounding by indication and residual bias. Results were assessed for robustness to analytical technique by reanalyzing the main outcomes with multivariate logistic regression, a doubly robust IPW with RA model, and a doubly robust augmented IPW model with bias-correction. RESULTS: Of 650 infants, 497 (76%) received chloral hydrate, 79 (12%) received midazolam, 54 (8%) received lorazepam, and 15 (2%) received pentobarbital. Adverse events occurred in 41 (6%) infants. Using propensity score matching, chloral hydrate was associated with a decreased risk of an adverse event compared to other sedatives, risk difference (95% confidence interval) of -12.79 (-18.61, -6.98), p <  0.001. All other statistical methods resulted in similar findings. CONCLUSION: Administration of chloral hydrate to hospitalized infants undergoing minor procedures is associated with a lower risk for adverse events compared to other sedatives.

Intranasal midazolam and fentanyl for procedural sedation and analgesia in infants in the neonatal intensive care unit.

BACKGROUND: The intranasal route is a minimally invasive method for rapidly delivering midazolam and fentanyl to provide short-term analgesia and sedation in infants. However, intranasal use of midazolam and fentanyl is not labeled for infants and safety data are sparse. The objective of this study is to evaluate the safety of intranasal midazolam and intranasal fentanyl in infants admitted to the Neonatal Intensive Care Unit (NICU). METHODS: We retrospectively identified all infants receiving intranasal midazolam or fentanyl in the NICU from 2009 to 2015. We recorded indication for use and vital signs and determined the proportion of infants experiencing the following adverse events: death within 24 hours, hypotension, bradycardia, worsening respiratory status, and chest wall rigidity. Vital signs 4 hours before and after each dose were compared using the Wilcoxon signed-rank test. RESULTS: We identified 17 infants (gestational ages 23- 41 weeks) receiving 25 intranasal doses. None of the infants died or developed hypotension, bradycardia, or chest wall rigidity. Intranasal delivery was most commonly used for sedation during magnetic resonance imaging studies. Other indications include analgesia or sedation for retinopathy of prematurity surgery, intubation, and peripherally inserted central catheter placement. One infant receiving intranasal midazolam experienced worsening respiratory status. Vital signs before and after dosing were not significantly different. CONCLUSIONS: Intranasal midazolam and fentanyl use in term and preterm infants appeared safe and well-tolerated in this small cohort of infants. Larger, prospective studies evaluating the safety and efficacy of intranasal midazolam and fentanyl use in infants are warranted.

The association of lipophilic phospholipids with native bovine casein micelles in skim milk: Effect of lactation stage and casein micelle size.

A known biological role of casein micelles is to transport calcium from mother to young and provide amino acids for growth and development. Previous reports demonstrated that modified casein micelles can be used to transport and deliver hydrophobic probes. In this study, the distribution of lipid-soluble phospholipids, including sphingomyelins (SM) and phosphatidylcholines (PC), was quantified in whole raw milk, skim raw milk, and casein micelles of various sizes during early, mid, and late lactation stages. Low-pressure size exclusion chromatography was used to separate casein micelles by size, followed by hydrophobic extraction and liquid chromatography-mass spectrometry for the quantification of PC and SM. Results showed that the SM d18:1/23:0, d18:1/22:0, d18:1/16:0, d16:1/22:0, d16:1/23:0, and d18:1/24:0 and the PC 16:0/18:1, 18:0/18:2, and 16:0/16:0 were dominating candidates appearing in maximum concentration in whole raw milk obtained from late lactation, with 21 to 50% of total SM and 16 to 35% of total PC appearing in skim milk. Of the total SM and PC found in skim milk, 35 to 46% of SM and 22 to 29% of PC were associated with the casein micelle fraction. The highest concentrations of SM d18:1/22:0 (341 ± 17 µg/g of casein protein) and PC 16:0/18:1 (180 ± 20 µg/g of casein protein) were found to be associated with the largest casein micelles (diameter = 149 nm) isolated in milk from late lactation, followed by a decrease in concentration as the casein micelle size decreased.

Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

OBJECTIVE: Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS. STUDY DESIGN: This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded. RESULTS: Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001). CONCLUSION: Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.

In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To characterize in-hospital outcomes of premature infants diagnosed with severe bronchopulmonary dysplasia (BPD). STUDY DESIGN: Retrospective cohort study including premature infants with severe BPD discharged from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2015. RESULTS: There were 10 752 infants with severe BPD, and 549/10 752 (5%) died before discharge. Infants who died were more likely to be male, small for gestational age, have received more medical interventions and more frequently diagnosed with surgical necrotizing enterocolitis, culture-proven sepsis and pulmonary hypertension following 36 weeks of postmenstrual age compared with survivors. Approximately 70% of infants with severe BPD were discharged by 44 weeks of postmenstrual age, and 86% were discharged by 48 weeks of postmenstrual age. CONCLUSIONS: A majority of infants diagnosed with severe BPD were discharged home by 44 weeks of postmenstrual age. These results may inform discussions with families regarding the expected hospital course of infants diagnosed with severe BPD.

A case of infant delirium in the neonatal intensive care unit.

Infant delirium is an under-recognized clinical entity in neonatal intensive care, and earlier identification and treatment could minimize morbidities associated with this condition. We describe a case of a 6-month-old former 32 weeks gestation infant undergoing a prolonged mechanical ventilation course diagnosed with delirium related to the combination of his underlying illness and the use of multiple sedative and analgesic medications. Initiation of the atypical antipsychotic risperidone allowed for weaning from continuous infusions of benzodiazepines and opiods, and lower dosages of bolus-dosed sedation and analgesics. The patient experienced no adverse side effects from use of this neuroleptic.

Association of in utero magnesium exposure and spontaneous intestinal perforations in extremely low birth weight infants.

OBJECTIVE: The objective of this study is to determine whether antenatal exposure to magnesium is associated with spontaneous intestinal perforation (SIP) in extremely low birth weight (ELBW) infants (⩽1000 g). STUDY DESIGN: We identified all ELBW infants admitted to 1 of 323 neonatal intensive care units from 2007 to 2013. We used multivariable conditional logistic regression to compare outcomes in the first 21 days after birth between infants exposed and unexposed to magnesium in utero. RESULTS: Of the 28 035 infants, 11 789 (42%) were exposed to antenatal magnesium (AM). There was no difference in the risk of SIP, odds ratio=1.08 (95% confidence interval; 0.91 to 1.29), between infants exposed and unexposed to AM. Mortality in the first 21 days after birth was lower in the magnesium-exposed infants, odds ratio=0.76 (0.70 to 0.83). CONCLUSION: AM exposure in ELBW infants was not associated with increased risk of SIP.

Risk factors for group B streptococcal disease in neonates of mothers with negative antenatal testing.

OBJECTIVE: The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening. STUDY DESIGN: We performed a retrospective cohort study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS. RESULTS: EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)). CONCLUSION: Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.

Sildenafil and retinopathy of prematurity risk in very low birth weight infants.

OBJECTIVE: To examine the effect of sildenafil therapy on development of severe retinopathy of prematurity (ROP) requiring surgical intervention in premature infants. STUDY DESIGN: We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care units from 2003 to 2012 and who received an ophthalmologic exam. We matched each infant exposed to sildenafil before first eye exam to three nonexposed infants using propensity scoring to control for differences in baseline infant characteristics. We evaluated the association between sildenafil exposure and development of severe ROP using conditional logistic regression. RESULT: Of the 57 815 infants meeting inclusion criteria, 88 were exposed to sildenafil. We matched 81/88 (92%) sildenafil-exposed with 243 nonexposed infants. There was no difference in the proportion of infants who developed severe ROP in the sildenafil-exposed vs nonexposed groups (17/81 (21%) vs 38/243 (16%), P=0.27). On adjusted analysis, there was no difference in severe ROP in the sildenafil-exposed vs nonexposed infants (odds ratio=1.46, 95% confidence interval=0.76 to 2.82, P=0.26). CONCLUSION: We did not observe an association between risk of severe ROP and sildenafil exposure before first eye exam in this cohort of premature infants.

Impact of a palliative care program on end-of-life care in a neonatal intensive care unit.

OBJECTIVE: Evaluate changes in end-of-life care following initiation of a palliative care program in a neonatal intensive care unit. STUDY DESIGN: Retrospective study comparing infant deaths before and after implementation of a Palliative Care Program comprised of medication guidelines, an individualized order set, a nursing care plan and staff education. RESULT: Eighty-two infants died before (Era 1) and 68 infants died after implementation of the program (Era 2). Morphine use was similar (88% vs 81%; P =0.17), whereas benzodiazepines use increased in Era 2 (26% vs 43%; P=0.03). Withdrawal of life support (73% vs 63%; P=0.17) and do-not-resuscitate orders (46% vs 53%; P=0.42) were similar. Do-not-resuscitate orders and family meetings were more frequent among Era 2 infants with activated palliative care orders (n=21) compared with infants without activated orders (n=47). CONCLUSION: End-of-life family meetings and benzodiazepine use increased following implementation of our program, likely reflecting adherence to guidelines and improved communication.

Intestinal fatty-acid binding protein and metronidazole response in premature infants.

OBJECTIVES: In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection. STUDY DESIGN: We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates. RESULTS: Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p = 0.006). CONCLUSION: While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants.

A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common cause of pulmonary morbidity in premature infants and is associated with life-long morbidities. Developing drugs for the prevention of BPD would improve public health. We sought to determine characteristics of favorable randomized controlled trials (RCTs) of drugs for BPD prevention. STUDY DESIGN: We searched MEDLINE and EMBASE from 1992 to 2014 using the MeSH terms 'BPD' and 'respiratory distress syndrome, newborn'. We included a Cochrane Library search to ensure inclusion of all available RCTs. We identified RCTs with BPD as a primary or secondary outcome and determined the definition of BPD used by the study. We determined whether a phase I or phase II study-to determine drug safety, efficacy or optimal dose-was performed before the RCT. Finally, we searched the Cochrane Library for meta-analyses for each drug and used the results of available meta-analyses to define a favorable versus unfavorable RCT. RESULT: We identified 2026 articles; 47 RCTs met our inclusion criteria encompassing 21 drugs; 5 of the drugs reduced the incidence of BPD. We found data from phase I or II studies for 16 of the drugs, but only 1 demonstrated a reduction of BPD. CONCLUSION: The majority of the drugs studied in RCTs failed to reduce the incidence of BPD. Performing early-phase studies before phase III trials might provide necessary information on drugs and drug doses capable of preventing BPD, thus informing the development of future RCTs.

Risk of necrotizing enterocolitis in very-low-birth-weight infants with isolated atrial and ventricular septal defects.

OBJECTIVE: Necrotizing enterocolitis (NEC) is associated with a significant morbidity and mortality in premature infants. We sought to identify the frequency of NEC in very-low-birth-weight infants with isolated ventricular septal defects (VSDs) or atrial septal defects (ASDs) using a large multicenter database. STUDY DESIGN: We identified a cohort of infants with birth weight <1500 g cared for in 312 neonatal intensive care units (NICUs) managed by the Pediatrix Medical Group between 1997 and 2010. We examined the association between the presence of an ASD or a VSD with development of NEC using logistic regression to control for small-for-gestational age status, antenatal steroid use, antenatal antibiotic use, gestational age, sex, race, Apgar score at 5 min and method of delivery. RESULT: Of the 98 523 infants who met inclusion criteria, 1904 (1.9%) had an ASD, 1943 (2.0%) had a VSD and 146 (0.1%) had both. The incidence of NEC was 6.2% in infants without septal defects, 9.3% in those with an ASD, 7.8% in those with a VSD, and 10.3% in infants with both an ASD and a VSD. Compared with infants without septal defects, the adjusted odds ratios for developing NEC for each group-ASD alone, VSD alone and ASD with VSD-were 1.26 (95% confidence interval 1.07 to 1.49), 1.27 (1.07 to 1.51) and 1.79 (1.03 to 3.12), respectively. CONCLUSION: The presence of an ASD or a VSD was associated with NEC in this cohort of premature infants.

Effects of low-dose dopamine on urine output in normotensive very low birth weight neonates.

OBJECTIVE: To determine the effects of low-dose dopamine on urine output (UOP) in very low birth weight premature neonates. STUDY DESIGN: Retrospective cohort study of all low-dose (3-5 µg kg(-1) per min) dopamine infusions >24-h duration in neonates 1500 g and 32 weeks gestation from August 2009 through September 2011. Linear regression was used to estimate the impact of covariates on UOP. RESULT: We identified 91 episodes of low-dose dopamine use in 65 neonates. Increased UOP occurred in 64% of episodes. Low-dose dopamine use was associated with a 0.6 ml kg(-1) h(-1) increase in UOP (P<0.001) and a 1.3 ml kg(-1)h(-1) increase when baseline UOP was <1.5 ml kg(-1) h(-1) (P<0.001). The improvement remained statistically significant after controlling for medications (diuretics and hydrocortisone) and fluid intake. CONCLUSION: Low-dose dopamine use was associated with increased UOP in very low birth weight neonates.

Urinary tract infection concordance with positive blood and cerebrospinal fluid cultures in the neonatal intensive care unit.

OBJECTIVE: Urinary tract infections (UTI) are common in the neonatal intensive care unit (NICU). Blood, urine and cerebrospinal fluid (CSF) cultures are frequently obtained to evaluate for infection. We sought to determine the concordance between positive urine cultures and blood or CSF cultures. STUDY DESIGN: Infants <121 days of age with a UTI admitted to 322 NICUs managed by the Pediatrix Medical Group from 1997 to 2010 were identified. UTIs were defined by isolation of a single pathogenic organism in a urine sample obtained by catheterization or suprapubic tap. The UTI was concordant if the same organism was identified in the blood or CSF within 3 days of the urine culture. RESULT: Of 5681 infants with a urine culture, 984 had 1162 UTIs. In total, 976 UTIs (84%) had a blood culture collected within 3 days, and 127 (13%) were concordant. Of the 1162 UTIs, 77 (7%) had a CSF culture collected within 3 days, and 2 (3%) were concordant. CONCLUSION: Collection of a urine culture in infants evaluated for late-onset sepsis is important. Concordance was observed in 13% of blood cultures and 3% of CSF cultures. These findings may be related to the initiation of empirical antimicrobial therapy before evaluation for disseminated infection or poor blood culture sensitivity.

Fluconazole pharmacokinetics and safety in premature infants.

Invasive candidiasis (IC) in the premature infant population is a common infection that results in substantial morbidity and mortality. For these patients, fluconazole is among the first line therapies to treat and prevent IC, and yet few prospective studies investigating its pharmacokinetics (PK) and safety have been performed in this vulnerable population. We review five phase I studies examining the PK of fluconazole in premature infants, which demonstrate markedly differing kinetics compared to adults. Based on these data, a treatment dose of 12 mg/kg/day, with the potential need of a loading dose of 25 mg/kg to achieve rapid steady state concentrations, achieves surrogate pharmacodynamic targets. Additionally, fluconazole appears to be safe to use in this population, with only minimal reversible hepatobiliary effects.

Neonatal fungal infections: when to treat?

Candida infections are a major cause of morbidity and mortality in neonatal intensive care units. Mortality following Candida bloodstream infections is as high as 40%, and neurodevelopmental impairment is common among survivors. Because invasive fungal infections are common and extremely difficult to diagnose, empirical treatment with antifungal therapy should be considered in high-risk, low-birth-weight infants who fail to quickly respond to empirical antibacterial treatment. Risk factors to consider when deciding to administer empirical antifungal therapy include: prior exposure to third-generation cephalosporins, extreme prematurity, and presence of central venous catheters.

Clinical characteristics and response to prophylactic fluconazole of preterm VLBW neonates with baseline and acquired fungal colonisation in NICU: data from a multicentre RCT.

BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them. RESULTS: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.

Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units.

BACKGROUND: Very-low-birth-weight (VLBW, <1500 g birth weight) infants are at high risk for both early- and late-onset sepsis. Prior studies have observed a predominance of Gram-negative organisms as a cause of early-onset sepsis and Gram-positive organisms as a cause of late-onset sepsis. These reports are limited to large, academic neonatal intensive care units (NICUs) and may not reflect findings in other units. The purpose of this study was to determine the risk factors for sepsis, the causative organisms, and mortality following infection in a large and diverse sample of NICUs. METHODS: We analysed the results of all cultures obtained from VLBW infants admitted to 313 NICUs from 1997 to 2010. RESULTS: Over 108,000 VLBW infants were admitted during the study period. Early-onset sepsis occurred in 1032 infants, and late-onset sepsis occurred in 12,204 infants. Gram-negative organisms were the most commonly isolated pathogens in early-onset sepsis, and Gram-positive organisms were most commonly isolated in late-onset sepsis. Early- and late-onset sepsis were associated with increased risk of death controlling for other confounders (odds ratio 1.45 [95% confidence interval [CI] 1.21,1.73], and OR 1.30 [95%CI 1.21, 1.40], respectively). CONCLUSIONS: This is the largest report of sepsis in VLBW infants to date. Incidence for early-onset sepsis and late-onset sepsis has changed little over this 14-year period, and overall mortality in VLBW infants with early- and late-onset sepsis is higher than in infants with negative cultures.