Human Milk Fortifier After Neonatal Intensive Care Unit Discharge Improves Human Milk Usage Rates for Preterm Infants.

BACKGROUND: A common neonatal intensive care unit (NICU) discharge feeding strategy for preterm infants with growth failure who are fed exclusively expressed human milk (EHM) has been to enrich mother's own milk with formula powder or supplement 2-3 feeds per day with formula. However, this strategy displaces human milk from the diet. Our NICU recently adopted the standard practice of adding commercial human milk fortifier (HMF) to human milk feedings after discharge. OBJECTIVES: We aimed to compare breastfeeding rates and growth using the aforementioned 2 strategies. METHODS: Preterm infants (<34 wk of gestation at birth) exclusively feeding EHM fortified with HMF at 2 weeks before discharge were included in this retrospective study. The HMF group (n = 92) continued fortifying with HMF at home, whereas the historical comparison group (n = 35) received our previous guidance to enrich or supplement using postdischarge formula. RESULTS: Rates of human milk exclusivity after discharge decreased significantly less in the HMF group than those in the historical comparison group (to 83% compared with 39% at the first outpatient visit and 27% compared with 6%, respectively, at the second outpatient visit). Rates of any EHM feedings were also significantly higher in the HMF group. Fenton z-scores for weight, length, and head circumference were not significantly different between the groups. CONCLUSIONS: Continuing EHM fortification with HMF after NICU discharge, rather than enriching or supplementing with postdischarge infant formula, increases rates of feeding EHM for ≥3 mo but does not affect growth.

Efficacy of continuous monitoring of maternal temperature during labor using wireless axillary sensors.

Neonatal early onset sepsis (EOS) occurs in 0.5-0.8/1000 live births and is a major cause of morbidity and mortality. Its presenting signs in newborns are non-specific, so risk assessment before birth is essential. Maternal fever during labor is the strongest predictor of EOS, but the current standard is for infrequent manual determinations of temperature. We aimed to determine whether continuous measurement of temperature during labor is feasible, accurate, and more effective than manual measurements for detecting fever. Women were recruited on admission in labor at > 35 weeks gestational age, with < 6 cm cervical dilation. Sensors were affixed in the axilla, which transmitted every 4 minutes by Bluetooth to a dedicated tablet. Conventional temperature measurements were taken every 3-6 hours per routine. Of 336 subjects recruited, 155 had both > 4 hours of continuous data and > 2 manual temperature measurements and were included for analysis. Continuous recordings were feasible and correlated well with manual measurements independent of mean temperature. Of 15 episodes of fever > 38 °C detected by both methods, 13 were detected earlier by continuous (9 of those more than 1 hour earlier). Manual measurements missed 32 fevers > 38 °C and 13 fevers > 38.5 °C that were identified by continuous. Continuous measurement of maternal temperature for the duration of labor is practical and accurate. It may be more sensitive for identifying infants at risk for EOS than the current practice, enabling earlier and more effective targeted treatment of affected infants.

Ultrasound Assessment of Gastric Emptying in Premature Infants Treated With Non-Invasive Ventilatory Support.

BACKGROUND: Nasal continuous positive airway pressure (CPAP) introduces positive pressure of air into both the trachea and stomach, which may affect gastric emptying. The rate of gastric emptying can be estimated by ultrasound (US) in neonates by two validated techniques: "antral cross-sectional area" (ACSA, two-dimensional estimate of the surface area at the gastric antrum), and "spheroid gastric volume" (spheroid, three-dimensional estimate of the stomach volume). OBJECTIVE: To compare gastric emptying rates in neonates on machine-derived nasal CPAP (MD-nCPAP, Avea and RAM cannula) with those on bubble CPAP (bCPAP, Fisher Paykel and Babi.Plus nasal prongs). METHODS: Ultrasound measurements of the amount of the milk in the stomach were performed before feeding and at 1, 2, and 3 hours after the start of feeding, using both the ACSA and spheroid methods. Rates of gastric emptying were calculated during the "early" (1-2 hours) and "late" (2-3 hours) phases after feeding. RESULTS: We recruited 32 infants (25-34 weeks gestational age, full enteral tube feedings, on nasal CPAP). Seventeen infants were treated with MD-nCPAP (median birth weight 1015 g [interquartile range (IQR): 870-1300], gestational age 28 weeks [IQR: 27-29], postnatal age 20 days [IQR: 14-28]), whereas 15 infants were treated with bCPAP (median birth weight 960 g [IQR: 855-1070], gestational age 27 weeks [IQR: 26-28], postnatal age 17 days [IQR: 15-25]). Gastric emptying rates (% emptied/min) were significantly faster in the "early" compared to the "late" phase for all infants. There were no significant differences in the rates of gastric emptying (either "early" or "late") or volumes of gastric residuals between infants receiving MD-nCPAP or bCPAP, measured by either method. Although no feeding intolerance was seen in either group, the volumes of residual gastric contents measured by both methods were higher than the volumes traditionally considered abnormal when obtained by gastric tube aspiration. CONCLUSIONS: Gastric emptying is faster during the "early" compared to the "late" phase. Gastric emptying rates are not different in infants receiving MD-nCPAP versus bCPAP. The presence of large residual gastric contents in infants who are tolerating feedings challenges the value of traditional gastric aspiration for the assessment of feeding tolerance in infants.

Unbound bilirubin levels in phototherapy-treated preterm infants receiving soy-based lipid emulsion.

BACKGROUND: Phototherapy is an effective treatment for neonatal jaundice. Treatment indication uses total serum bilirubin (TSB), although unbound bilirubin (Bf) more accurately predicts disability risk. The goals of this investigation were to examine the response of Bf and TSB to phototherapy in preterm infants, and we hypothesized that (i) TSB and Bf respond differently; (ii) the relationship between TSB and Bf is altered; and (iii) unexpected Bf elevations are found. METHODS: One hundred and seventeen preterm infants <2 kg at birth and receiving (IL) were enrolled; and measurements of TSB and Bf were obtained. TSB was measured by the diazo method and Bf with a fluorescent Bf sensor BL22P1B11-Rh. RESULTS: Initial mean (± SD) TSB and Bf levels (41.4 ± 6.9 h) were 8.0 ± 9.0 mg/dL and 16.9 ± 12.4 nmol/L (P < 0.05). The rates of rise (ROR) were 0.21 ± 0.10 mg/dL/h for TSB and 0.38 ± 0.33 nmol/L/h for Bf. Phototherapy reduced TSB from 8.0 ± 9.0 to 5.8 ± 9.4 mg/dL (P = 0.068) but Bf did not change (16.9 ± 12.4 to 14.1 ± 9.4 nmol/L P = n.s.). Bf levels were >11 nmol/L in 64, >17 nmol/L in 18, and >22 nmol/L in 7 infants. CONCLUSIONS: Bf and TSB responded differently. While TSB and Bf correlated well before phototherapy, they did not correlate during phototherapy. TSB showed a trend toward a reduction with treatment, Bf did not. While TSB ROR information is not helpful, ROR Bf data can be utilized to anticipate treatment. Potentially high Bf levels existed before and after phototherapy and the mean Bf level at phototherapy termination remained elevated in a significant proportion of infants.

Interindividual Regulation of the Breast Cancer Resistance Protein/ABCG2 Transporter in Term Human Placentas.

The breast cancer resistance protein (BCRP/ABCG2) is a maternally-facing efflux transporter that regulates the placental disposition of chemicals. Transcription factors and gene variants are important regulatory factors that influence transporter expression. In this study, we sought to identify the genetic and transcriptional mechanisms underlying the interindividual expression of BCRP mRNA and protein across 137 term placentas from uncomplicated pregnancies. Placental expression of BCRP and regulatory transcription factor mRNAs was measured using multiplex-branched DNA analysis. BCRP expression and ABCG2 genotypes were determined using Western blot and Fluidigm Biomark genetic analysis, respectively. Placentas were obtained from a racially and ethnically diverse population, including Caucasian (33%), African American (14%), Asian (14%), Hispanic (15%), and mixed (16%) backgrounds, as well as unknown origins (7%). Between placentas, BCRP mRNA and protein varied up to 47-fold and 14-fold, respectively. In particular, BCRP mRNA correlated significantly with known transcription factor mRNAs, including nuclear factor erythroid 2-related factor 2 and aryl hydrocarbon receptor. Somewhat surprisingly, single-nucleotide polymorphisms (SNPs) in the ABCG2 noncoding regions were not associated with variation in placental BCRP mRNA or protein. Instead, the coding region polymorphism (C421A/Q141K) corresponded with 40%-50% lower BCRP protein in 421C/A and 421A/A placentas compared with wild types (421C/C). Although BCRP protein and mRNA expression weakly correlated (r = 0.25, P = 0.040), this relationship was absent in individuals expressing the C421A variant allele. Study results contribute to our understanding of the interindividual regulation of BCRP expression in term placentas and may help to identify infants at risk for increased fetal exposure to chemicals due to low expression of this efflux protein.

Effects of Soybean Lipid Infusion on Unbound Free Fatty Acids and Unbound Bilirubin in Preterm Infants.

OBJECTIVE: To assess the effects of a soybean lipid emulsion infusions on levels of unbound (free) bilirubin (Bf) and unbound free fatty acids (FFAu) as well as changes in Bf and total serum bilirubin (TSB) during phototherapy in infants born preterm. STUDY DESIGN: Ninety-seven infants born preterm (birth weight: 500-2000 g; gestational age: 23-34 weeks) were enrolled to investigate the effect of 0, 1, 2, and 3 g/kg/d of intralipid infusion on Bf and FFAu. Pre- and postphototherapy TSB, FFAu, and Bf also were analyzed in 91 infants to assess the effects of phototherapy. FFAu levels were measured with the fluorescent probe ADIFAB2 and Bf by the fluorescent Bf sensor BL22P1B11-Rh during intralipid infusion and at start and end of phototherapy. TSB and plasma albumin were measured by the diazo and bromcresol green techniques, respectively. Bilirubin-albumin dissociation constants were calculated based on Bf and plasma albumin. RESULTS: Bf and FFAu increased with increasing intralipid dosage across all gestational ages. TSB and Bf were correlated significantly when infants received 0 or 1 g/kg/d of intralipid but not at greater doses of intralipid (2 and 3 g/kg/d). Although phototherapy effectively reduced both TSB and Bf in the total phototherapy group (by 32% and 12%, respectively), it reduced TSB, but not Bf, in infants less than 28 weeks of gestation. CONCLUSIONS: Increasing intralipid doses result in increasing FFAu levels, which are associated with increased Bf independent of TSB. In infants born extremely preterm (<28 weeks of gestation), phototherapy effectively reduces TSB but not Bf.

Genetic and Dietary Regulation of Glyburide Efflux by the Human Placental Breast Cancer Resistance Protein Transporter.

Glyburide is frequently used to treat gestational diabetes owing to its low fetal accumulation resulting from placental efflux by the breast cancer resistance protein (BCRP)/ABCG2 transporter. Here we sought to determine how exposure to the dietary phytoestrogen genistein and expression of a loss-of-function polymorphism in the ABCG2 gene (C421A) impacted the transport of glyburide by BCRP using stably transfected human embryonic kidney 293 (HEK) cells, human placental choriocarcinoma BeWo cells, and human placental explants. Genistein competitively inhibited the BCRP-mediated transport of (3)H-glyburide in both wild-type (WT) and C421A-BCRP HEK-expressing cells, with greater accumulation of (3)H-glyburide in cells expressing the C421A variant. In BeWo cells, exposure to genistein for 60 minutes increased the accumulation of (3)H-glyburide 30%-70% at concentrations relevant to dietary exposure (IC50 ∼180 nM). Continuous exposure of BeWo cells to genistein for 48 hours reduced the expression of BCRP mRNA and protein by up to 40%, which impaired BCRP transport activity. Pharmacologic antagonism of the estrogen receptor attenuated the genistein-mediated downregulation of BCRP expression, suggesting that phytoestrogens may reduce BCRP levels through this hormone receptor pathway in BeWo cells. Interestingly, genistein treatment for 48 hours did not alter BCRP protein expression in explants dissected from healthy term placentas. These data suggest that whereas genistein can act as a competitive inhibitor of BCRP-mediated transport, its ability to downregulate placental BCRP expression may only occur in choriocarcinoma cells. Overall, this research provides important mechanistic data regarding how the environment (dietary genistein) and a frequent genetic variant (ABCG2, C421A) may alter the maternal-fetal disposition of glyburide.

Mustard vesicant-induced lung injury: Advances in therapy.

Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant.

Inherited disorders of bilirubin clearance.

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.

SARS-CoV-2 neutralizing antibody titers in maternal blood, umbilical cord blood, and breast milk.

OBJECTIVE: We quantified neutralizing SARS-CoV-2 antibody against spike protein (nAb) levels after vaccination and SARS-CoV-2 infection in maternal serum, cord blood, and breast milk and determined whether they correlate with levels of spike protein binding antibody. STUDY DESIGN: Women (n = 100) were enrolled on admission for delivery. Previous SARS-CoV-2 infection was defined by anti-nucleocapsid antibodies. Levels of nAb and binding antibodies against spike receptor binding domain were measured in maternal blood, cord blood, and milk. RESULTS: Maternal nAb levels were higher after vaccine and infection than vaccine alone but waned rapidly. Levels of nAb in cord blood and milk correlated with maternal levels and were higher in cord blood than maternal. Spike protein binding antibody levels correlated with nAb. CONCLUSION: SARS-CoV-2 vaccination near delivery may boost antibody-mediated immunity in the peripartum period. Neutralizing antibodies are passed transplacentally and into milk. Spike protein binding antibody may be a feasible proxy for nAb.

Breast Milk Production Variability Among Mothers of Preterm Infants.

Introduction: Mothers of preterm infants are at risk for inadequate milk production. Pumping logs are often used to both encourage lactation in the first week and track its efficacy. Our objectives were to determine whether mothers of preterm infants who keep pumping logs are demographically different from those who do not and to determine whether this practice affects the amount of mother's own milk (MOM) fed to their infants. We also aimed at determining whether there is a correlation between: (1) time to first breast milk expression, (2) cumulative frequency of expression in the first week, and (3) milk volume on day 7 with subsequent milk volumes and percent of infant diet consisting of MOM. Methods: Mothers of infants born ≤32 weeks and ≤1,500 g were enrolled within 48 hours of birth and encouraged to keep a pumping log. Data were collected on maternal characteristics, patterns of milk expression, and milk volumes on days 7, 14, 21, and 28 after delivery. Infant data were collected via chart review. Results: Mothers who kept pumping logs provided their own milk for a greater percentage of their infant's feeds at the time of achieving full feeds (p = 0.017). The total number of expressions in the first week was correlated with milk volume on day 21 (p = 0.016) and the provision of a higher percentage of MOM feeds at discharge (p = 0.03). Milk volume on day 7 correlated with volumes obtained at days 14, 21, and 28 (p < 0.001). Conclusions: Pumping logs may affect the availability of MOM for preterm infants. Frequency of pumping in the first week and milk volume on day 7 may impact long-term lactation success for these women.

Prediction of intrapartum fever using continuously monitored vital signs and heart rate variability.

Objectives: Neonatal early onset sepsis (EOS), bacterial infection during the first seven days of life, is difficult to diagnose because presenting signs are non-specific, but early diagnosis before birth can direct life-saving treatment for mother and baby. Specifically, maternal fever during labor from placental infection is the strongest predictor of EOS. Alterations in maternal heart rate variability (HRV) may precede development of intrapartum fever, enabling incipient EOS detection. The objective of this work was to build a predictive model for intrapartum fever. Methods: Continuously measured temperature, heart rate, and beat-to-beat RR intervals were obtained from wireless sensors on women (n = 141) in labor; traditional manual vital signs were taken every 3-6 hours. Validated measures of HRV were calculated in moving 5-minute windows of RR intervals: standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD) between normal heartbeats. Results: Fever (>38.0 °C) was detected by manual or continuous measurements in 48 women. Compared to afebrile mothers, average SDNN and RMSSD in febrile mothers decreased significantly (p < 0.001) at 2 and 3 hours before fever onset, respectively. This observed HRV divergence and raw recorded vitals were applied to a logistic regression model at various time horizons, up to 4-5 hours before fever onset. Model performance increased with decreasing time horizons, and a model built using continuous vital signs as input variables consistently outperformed a model built from episodic vital signs. Conclusions: HRV-based predictive models could identify mothers at risk for fever and infants at risk for EOS, guiding maternal antibiotic prophylaxis and neonatal monitoring.

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

OBJECTIVE: To 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 syndrome (RDS) receiving non-invasive ventilatory support. SETTING: Two large neonatal intensive care units (NICUs) at Northwell Health (New Hyde Park, New York, USA). STUDY POPULATION: Infants with RDS receiving continuous positive airway pressure in the NICU and eligible for surfactant administration. RESULTS: LISA was initiated in our NICUs in January 2021, after extensive guideline development, education programmes, hands-on training and provider credentialing. Our Specific, Measurable, Achievable, Relevant and Timely aim was to deliver surfactant by LISA for 65% of total doses by 31 December 2021. This goal was achieved within 1 month of go-live. In total, 115 infants received at least one dose of surfactant during the year. Of those, 79 (69%) received it via LISA and 36 (31%) via INSURE. Two Plan-Do-Study-Act cycles contributed to improved adherence to guidelines on timely surfactant administration and both written and video documentation. CONCLUSIONS: Safe and effective introduction of LISA with the use of video laryngoscopy is achievable with careful planning, clear clinical guidelines, adequate hands-on training and comprehensive safety and quality control.

Newborn screening for Duchenne muscular dystrophy: A two-year pilot study.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis. METHODS: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first-tier screen measured creatine kinase-MM (CK-MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK-MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next-generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene. RESULTS: In the two-year pilot study, 36,781 newborns were screened with CK-MM. Forty-two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified. INTERPRETATION: This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Lipid peroxidation products as predictors of oxidant-mediated disease in preterm infants.

BACKGROUND: Preterm infants are susceptible to "oxygen radical diseases" (ORD). 8-isoprostane (8-IP) is a bioactive eicosanoid generated by reactive oxygen species-catalyzed peroxidation of arachidonic acid. Malondialdehyde (MDA) is generated by the decomposition of oxidant-induced lipid hydroperoxides. We hypothesize that the development of ORD is associated with elevated plasma 8-IP on day 0-1, and increasing urine levels of MDA in the first month. METHODS: Preterm (<32 weeks, n = 39) and term (n = 39) infants were recruited at birth. Plasma 8-IP was quantified by ELISA on day 0-1, and urine MDA by colorimetric assay of thiobarbituric acid reactive substances (TBARS) on days 0-1, 7, 14, 21, and 28. ORD was defined as retinopathy of prematurity ≥ stage 1, pneumatosis, or oxygen requirement at 36 weeks corrected gestational age. RESULTS: Plasma 8-IP was higher on day 0-1 in preterm infants who developed ORD compared to term infants. Urine TBARS levels increased in preterm infants from day 0-1 to day 28 but were not different in infants with or without ORD. Preterm infants who developed ORD demonstrated a significant rise in urine TBARS levels from day 1 to 14. CONCLUSIONS: Elevated plasma 8-IP on day 1 is associated with ORD in preterm infants. If validated as a biomarker for ORD, it may be useful in directing antioxidant therapies to the most susceptible infants. Urine TBARS during the first month are not significantly different in term infants, preterm infants with ORD, and preterm infants without ORD, but rapid rise of TBARS in the first 2 weeks may be associated with ORD.

Lung ultrasound assessment of pulmonary edema in neonates with chronic lung disease before and after diuretic therapy.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is characterized by lung injury with varying degrees of disrupted alveolarization, vascular remodeling, inflammatory cell proliferation, and pulmonary edema. Diuretics are often used to ameliorate the symptoms or progression of BPD. Our primary objective was to use lung ultrasound (LUS) to determine if diuretics decrease pulmonary edema in infants with BPD. The secondary objective was to assess changes in respiratory support during the first week after initiation of diuretics. METHODS: Premature infants requiring noninvasive respiratory support and starting diuretic therapy for evolving BPD were compared with a similar group of infants not receiving diuretics (control). For the diuretic group, LUS exams were performed before and on Days 1, 3, and 6 after initiation of treatment. For the control group, LUS was performed at equivalent time points. A composite pulmonary edema severity (PES) score of 0-5 was calculated based on the total number of B-lines in six scanned areas. Respiratory support parameters (FiO2 , nasal cannula flow, or CPAP) were also recorded. RESULTS: Infants in the diuretic (n = 28) and control (n = 23) groups were recruited at median corrected gestational ages of 34.2 (33.3-35.9) and 34.0 (33.4-36.3) weeks, respectively (p = 0.82). PES scores, FiO2 , and respiratory flow support decreased significantly from Days 0 to 6 (p < 0.0001, p = 0.001, and p = 0.01, respectively) in the diuretic group, but not in the control group. CONCLUSION: Diuretic use is associated with decreased pulmonary edema and improved oxygenation in infants with BPD during the first week of treatment.

Effects of lipid emulsions on unbound bilirubin and response to phototherapy in preterm infants.

OBJECTIVE: Bilirubin-induced neurotoxicity is mediated by the fraction of total serum bilirubin (TSB) not bound to albumin (Bf). Unbound free fatty acids (FFAu) generated from lipid emulsions compete with bilirubin for albumin binding, increasing Bf. Soy-based (IL) and soy-MCT-olive-fish oil-based (SMOF) lipid emulsions contain different fatty acids with distinct albumin binding affinities. IL increases Bf in preterm infants, but the effects of SMOF on Bf are not known. Our objective was to compare changes in TSB, Bf, FFAu, and response to phototherapy in preterm infants receiving SMOF and IL. We hypothesized that SMOF would be associated with lower Bf and better response to phototherapy than IL. METHODS: Very preterm and low birth weight infants (<1500 g, <32 weeks) were infused with IL (n = 20) or SMOF (n = 20) as prescribed by providers. Phototherapy was prescribed using the standard care practice. FFAu profiles and levels, TSB, and Bf were measured on 0, 1, 2, and 3 g/kg/day of lipid infusion and at the initiation and termination of phototherapy. TSB was analyzed in the clinical laboratory using the diazo technique. FFAu and Bf were measured using fluorescent probes. RESULTS: Escalating doses of IL and SMOF increased FFAu levels and Bf, but not TSB. Phototherapy did not significantly decrease Bf for infants receiving either lipid. IL-treated infants had higher levels of unbound linoleic acid, and SMOF-treated infants had higher unbound arachidonic, oleic, and docosahexaenoic acids. CONCLUSIONS: IL and SMOF both increase Bf similarly, and phototherapy does not significantly affect Bf for infants receiving them.

Suppression of Bile Acid Synthesis in a Preterm Infant Receiving Prolonged Parenteral Nutrition.

Bile acid metabolism is altered in neonates on parenteral nutrition (PN), predisposing them to parenteral nutrition-associated liver disease. Cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the bile acid synthesis pathway, is repressed by fibroblast growth factor 19 (FGF19) and phytosterols (PS). We describe a case of a preterm infant who developed necrotizing enterocolitis (NEC) and received exclusive PN for over 2 months. Our objective was to serially assess CYP7A1 activity and plasma FGF19 and PS concentrations in this infant case compared to five healthy preterm infants. We found that CYP7A1 activity increased during the first 2 weeks of life in control infants but was undetectable in the infant case. FGF19 concentrations were high at birth in all infants and subsequently declined and did not differ between the case and control infants. As expected, PS concentrations were elevated in the infant case and continued to increase despite lipid minimization. In conclusion, CYP7A1 activity was gradually upregulated in healthy preterm infants but remained suppressed in the infant requiring prolonged PN. Preterm infants also had elevated FGF19 concentrations at birth, which decreased with advancing postnatal age.