Retrospective analysis of reference intervals for dried blood spot based ms/ms newborn screening programs in Chinese preterm neonates: a nationwide study.

OBJECTIVES: Although recent discoveries regarding the biomarkers of newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) highlight the critical need to establish reference intervals (RIs) specifically for preterm infants, no such RIs has been formally published yet. This study addressed the gap by offering a comprehensive set of reference intervals (RIs) for preterm neonates, and illustrating the dynamic changes of each biomarker with age. DESIGN AND METHODS: The NBS data of 199,693 preterm newborns (< 37 weeks of gestation) who met the inclusion and exclusion criteria from the NNSCP database were included in study analysis. The birth weight stratified dynamic trend of each biomarker were captured by their concentrations over age. Reference partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated using a non-parametric rank approach. RESULTS: Increasing birth weight is associated with an elevation in the levels of arginine, citrulline, glycine, leucine and isobarics, methionine, ornithine, phenylalanine, and valine, whereas the levels of alanine, proline and tyrosine decrease. Additionally, two short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and isovalerylcarnitine + methylbutyrylcarnitine) and a median-chain acylcarnitine (octenoylcarnitine) decrease, while four long-chain acylcarnitines (tetradecanoylcarnitine, palmitoylcarnitine, palmitoleylcarnitine and oleoylcarnitine) increase with increasing birth weight. Age impacts the levels of all MS/MS NBS biomarkers, while sex only affects the level of malonylcarnitine + 3-hydroxybutyrylcarnitine (C3-DC + C4-OH) in very low birth weight preterm neonates. CONCLUSION: The current study developed reference intervals (RIs) specific to birth weight, age, and/or sex for 35 MS/MS biomarkers, which can help in the timely evaluation of the health and disease of preterm neonates.

Sex differences in the association of pretransfusion haemoglobin and cognition in preterm infants.

OBJECTIVES: To assess sex-specific differences in the association between pre-transfusion haemoglobin values and early neurodevelopmental function. DESIGN: Observational follow-up of infants with birth weights <1000 g and gestational ages 22-28 weeks who were enrolled in the NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial at 19 U.S. sites, 2012-2017. MAIN OUTCOME MEASURES: Pretransfusion haemoglobin values were obtained longitudinally through 36 weeks' postmenstrual age. The infant's mean pretransfusion haemoglobin was used as a marker of degree of anaemia (n=1655 measures). Measures of brain function were obtained at 22-26 months' corrected age using the Bayley Scales of Infant & Toddler Development, third edition (BSID-III) (n=1290 BSID-III scores). Sex-specific estimates for the linear relation between pretransfusion haemoglobin and BSID-III scores were obtained from repeated-measures regression analysis, adjusted for gestational age, birth weight, study site, clinical characteristics, and demographic covariates. RESULTS: The relation of pretransfusion haemoglobin with 24-month BSID-III scores showed significant, independent interactions with both (1) sex (p=0.046) and (2) retinopathy of prematurity (ROP; p=0.004). In 614 males, BSID-III scores were higher by 1.07 points per g/dL (95% CI 1.58 to 4.33; p=0.008), not differing significantly among the three subscales (cognitive, language and motor; p=0.94). In 247 infants with ROP, BSID-III scores were higher by 2.95 points per g/dL (95% CI 0.28 to 1.87; p<0.0001), uniformly across subscales (p=0.73). These associations were non-significant in 676 females (p=0.96) and 1043 infants without ROP (p=0.81). CONCLUSIONS: This study demonstrates sex-specific associations between mean pretransfusion haemoglobin (a marker of the severity of anaemia throughout the neonatal intensive care unit [NICU] hospitalisation) and early neurodevelopmental function at 22-26 months' corrected age.

Effect of Enteral Zinc Supplementation on the Anthropometric Measurements of Preterm Infants at Discharge from the Neonatal Intensive Care Unit and Evaluation of Copper Deficiency.

Enteral zinc supplementation in preterm infants has been reported to improve short-term weight and height gain. This study aims to evaluate whether early enteral zinc supplementation in preterm infants admitted to the neonatal intensive care unit (NICU) affects their physical measurements at discharge, and to periodically test serum copper levels. Of the 221 patients admitted to the NICU, 102 were in the zinc group and 119 were in the no-zinc group. The zinc group was administered 3 mg/kg/day of zinc. Body weight, height, and head circumference at discharge (or on the expected delivery date) were evaluated, and the factors affecting these parameters were examined. Serum zinc and copper levels were also evaluated on admission and monthly thereafter. Multivariate analysis was performed and showed that the weeks of gestational age and small for gestational age (SGA) status affected the height and weight at discharge. SGA also affected the head circumference. Serum copper levels were within the reference range for all patients at 3 months of age. Enteral zinc supplementation of 3 mg/kg/day in preterm infants did not affect the weight, height, or head circumference at discharge, but was shown to be relatively safe.

[Investigation of influencing factors and reference ranges for thyroid function in hospitalized preterm infants at the age of 7 days]. / 7æ—¥é¾„ä½é™¢æ—©äº§å„¿ç”²çŠ¶è ºåŠŸèƒ½å½±å“å› ç´ åŠå‚è€ƒå€¼èŒƒå›´æŽ¢è®¨.

OBJECTIVES: To investigate the influencing factors and reference ranges for thyroid function in preterm infants at the age of 7 days, with the aim of avoiding unnecessary clinical reexamination and intervention. METHODS: A retrospective analysis was performed for the data of 685 preterm infants from January 2020 to January 2023. According to gestational age and birth weight, they were divided into a high-risk group (gestational age <34 weeks or birth weight<2 000 g; 228 infants) and a low-risk group (gestational age ≥34 weeks and birth weight ≥2 000 g;457 infants). The influencing factors for thyroid function were analyzed, and 95% reference range was calculated. RESULTS: Gestational age, birth weight, birth season, sex, and assisted reproduction were the influencing factors for thyroid function (P<0.05). For the preterm infants in the high-risk group, the reference ranges of free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH) were 2.79-5.40 pmol/L, 8.80-25.64 pmol/L, 0.80-2.15 nmol/L, 50.06-165.09 nmol/L, and 0.80-18.57 µIU/mL, respectively. For those in the low-risk group, the reference ranges of these indicators were 3.08-5.93 pmol/L, 11.17-26.24 pmol/L, 1.02-2.27 nmol/L, 62.90-168.95 nmol/L, and 0.69-13.70 µIU/mL, respectively. FT3, FT4, TT3, and TT4 were positively correlated with gestational age (P<0.05); FT3, FT4, TT3, and TT4 were positively correlated with birth weight (P<0.05); TSH was negatively correlated with birth weight (P<0.05). CONCLUSIONS: Thyroid function in preterm infants at the age of 7 days is affected by the factors such as gestational age and birth weight, and the reference ranges of thyroid function in preterm infants at the age of 7 days should be established based on gestational age and birth weight.

Serum Ferritin Levels in Very Preterm Infants Receiving Erythrocyte Transfusions: A Retrospective Study.

Very preterm infants often need red blood cell transfusions (RBCT) during intensive care and are at risk of iron overload. This study reviewed the records of 65 very preterm neonates who required at least one RBCT to ascertain the iron status using serum ferritin levels at 4-6 weeks age before oral iron was commenced. High serum ferritin level was found in 52.3% (n = 34) neonates. Need for > 1RBCT was significantly and independently associated with iron excess (P < 0.001). Increased ferritin noted following transfusions in neonatal period can have implications for determining the appropriate time for starting iron supplementation in this subgroup of neonates.

Aryl hydrocarbon receptor (AhR) is regulated by hyperoxia in premature infants.

OBJECTIVE: To investigate whether aryl hydrocarbon receptor (AhR) is involved in hyperoxia-mediated oxidative stress by observing the relationship between AhR and reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) after oxygen exposure in premature infants. METHODS: After 48 h of oxygen inhalation at different concentrations, discarded peripheral blood was collected to separate PBMCs and plasma. ROS were labeled with MitoSOXTM Red and detected by fluorescence microscopy in PBMCs. The level of MDA in plasma was detected by thiobarbituric acid colorimetry, the level of MCP-1 in plasma was detected by enzyme-linked immunosorbent assay (ELISA), the localization of AhR was detected by immunofluorescence, and the level of AhR expression in PBMCs was detected by Western blotting. RESULTS: As the volume fraction of inspired oxygen increased, compared with those in the air control group, the levels of ROS, MDA in plasma, and MCP-1 in plasma increased gradually in the low concentration oxygen group, medium concentration oxygen group and high concentration oxygen group. The cytoplasm-nuclear translocation rate of AhR gradually increased, and the expression level of AhR gradually decreased. The levels of ROS in PBMCs, MDA in the plasma and MCP-1 in the plasma of premature infants were positively correlated with the cytoplasm-nuclear translocation rate of AhR but negatively correlated with the level of AhR expression. CONCLUSION: Aryl hydrocarbon receptor (AhR) is regulated by hyperoxia in premature infants.

Early versus late parenteral nutrition in term and late preterm infants: a randomised controlled trial.

BACKGROUND: There is limited evidence regarding the optimal time to commence parenteral nutrition (PN) in term and late preterm infants. DESIGN: Single-centre, non-blinded, exploratory randomised controlled trial. SETTING: A level-3 neonatal unit in a stand-alone paediatric hospital. PATIENTS: Infants born ≥34 weeks of gestation and ≤28 days, who needed PN. Eligible infants were randomised on day 1 or day 2 of admission. INTERVENTIONS: Early (day 1 or day 2 of admission, N=30) or late (day 6 of admission, N=30) PN. MAIN OUTCOME MEASURES: Plasma phenylalanine and F2-isoprostane levels on day 4 and day 8 of admission. Secondary outcomes were amino-acid and fatty-acid profiles on day 4 and day 8, and clinical outcomes. RESULTS: The postnatal age at randomisation was similar between the groups (2.3 (SD 0.8) vs 2.3 (0.7) days, p=0.90). On day 4, phenylalanine levels in early-PN infants were higher than in late-PN (mean (SD) 62.9 (26.7) vs 45.5 (15.3) µmol/L; baseline-adjusted percentage difference 25.8% (95% CI 11.6% to 39.9%), p<0.001). There was no significant difference in phenylalanine levels between the two groups on day 8. There was no significant difference between the groups for F2-isoprostane levels on day 4 (early-PN mean (SD) 389 (176) vs late-PN 419 (291) pg/mL; baseline-adjusted percentage difference: -4.4% (95% CI -21.5% to 12.8%) p=0.62) and day 8 (mean (SD) 305 (125) vs 354 (113) pg/mL; adjusted mean percentage difference -16.1 (95% CI -34.1 to 1.9) p=0.09).Postnatal growth restriction for weight was less severe in the early-PN group (change in weight z-score from baseline to discharge: -0.6 (0.6) vs -1.0 (0.6); p=0.02). The incidence of hyperglycaemia was greater in the early-PN group (20/30 (66.7%) vs 11/30 (36.7%), p=0.02). CONCLUSIONS: The timing of the commencement of PN did not seem to affect the degree of oxidative stress in critically ill term and late preterm infants. The effect of transiently high plasma phenylalanine with early PN on clinical outcomes requires further investigation. TRIAL REGISTRATION NUMBER: ACTRN12620000324910.

Timing of administration of antenatal magnesium sulphate and correlation with umbilical cord blood magnesium levels in preterm babies.

BACKGROUND: The effectiveness of MgSO4 for foetal neuroprotection is acknowledged, but the best time to provide it in relation to birth is a conundrum, and dose schedule is yet unknown. Understanding the determinants of the magnesium levels in cord blood aids in determining the appropriate timing and length of administration. AIM AND OBJECTIVE: To assess the cord blood magnesium concentration in relation to the timing of MgSO4 and delivery. To achieve ROC in relation to optimum level of cord blood magnesium concentration in relation to neonatal outcome variables. STUDY DESIGN: A prospective observational study conducted in a tertiary care hospital over 2 years in women having preterm delivery from 26 weeks to 33 + 6 weeks, who received Neuroprophylaxis. Cord blood was collected for magnesium level estimation. Baby followed 24 h after delivery. ROC analysis performed for predicting an optimal cut-off for a continuous predictor predicting binary outcome. RESULTS: 85 recruited cases divided into bolus group, bolus + infusion group. The mean cord blood magnesium (n = 85) was 3.8 mg/dl. The AUROC for Gestational Age at Administration predicting Baby Outcome: 0.699, It was statistically significant (p = 0.034). The AUROC for Cord Blood Mg predicting Baby Outcome: 0.606, It was not statistically significant (p = 0.262). CONCLUSION: Mean cord blood magnesium levels served as a tool to determine the timing and duration of Neuroprophylaxis. Mean cord blood magnesium of 3.8 mg/dl should be achieved to serve the purpose of Neuroprotection. To achieve this, Bolus followed by Infusion should be administered for at-least 6 h prior to delivery.

Endocan: A biomarker for endothelial dysfunction and inflammation, linking maternal obesity and pediatric obesity in a cohort of preterm neonates.

OBJECTIVES: Numerous animal and epidemiologic studies have demonstrated a positive association between maternal obesity in pregnancy and obesity in offspring. The biologic mechanisms of this association remain under investigation. One proposed mechanism includes fetoplacental endothelial dysfunction secondary to inflammation. Endocan is a relatively new biomarker for endothelial dysfunction and inflammation. Our objectives were to examine (1) the association between maternal obesity and neonatal serum endocan at birth, and (2) the association between neonatal serum endocan at birth and pediatric obesity at 24-36 months of age. STUDY DESIGN: This was a secondary analysis of a prospective cohort of neonates born < 33 weeks gestation. Serum endocan was collected within 48 hours of birth. Serum endocan levels were compared in neonates born to obese mothers vs. those born to non-obese mothers. BMI data were retrospectively collected from cohort neonates between 24 and 36 months of age. RESULTS: The analysis included 120 mother/neonate dyads. Neonates born to obese mothers had higher median serum endocan at birth compared to neonates born to non-obese mothers (299 ng/L [205-586] vs. 251 ng/L [164-339], p = 0.045). In a linear regression modeled on neonatal serum endocan level, maternal obesity had a statistically significant positive association (p = 0.021). Higher mean serum endocan level at birth was associated with pediatric obesity between 24 and 36 months (obese vs. non-obese offspring; 574 ng/L (222) vs. 321 ng/L (166), p = 0.005). CONCLUSIONS: In our cohort of preterm neonates, elevated serum endocan at birth was associated with both maternal obesity and downstream pediatric obesity. More research is needed to understand intergenerational transmission of obesity. A large focus has been on epigenetic modification. Endothelial dysfunction and inflammation may play important roles in these pathways. Effective biomarkers, including endocan, may also serve as intermediate outcomes in future pregnancy research.

Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.

Reference intervals for thyroid function from the fifth to seventh day of life in twin-pregnancy preterm neonates: an 8-year retrospective study.

PURPOSE: The immature and developing hypothalamic-pituitary-thyroid axis leads to different levels of thyroid function in twin neonates, including free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) levels. No reference intervals for twins have been established until now. To compensate for this lack, we collected data and established this standard across different gestational ages (GAs) and sexes. METHODS: A total of 273 pairs of neonates admitted to the NICU in Southeast China from 2015 to 2022 were included. Each pair was divided into Neonate A (relatively heavy birth weight (BW)) and Neonate B (relatively light BW). Their thyroid functions were analyzed to establish reference intervals and comparisons were made stratified by GA and sex. RESULTS: The FT3, FT4, and TSH reference intervals in twin neonates with a GA of 26-36 weeks were as follows: Neonate A and B: 3.59 ± 0.99 and 3.57 ± 1.00 pmol/L; Neonate A and B: 17.03 ± 5.16 and 16.77 ± 5.29 pmol/L; and Neonate A and B: 4.097 ± 3.688 and 4.674 ± 4.850 mlU/L, respectively. There were significant differences between serum FT3 and FT4 reference intervals and GA (p < 0.05). The serum FT3 and FT4 reference intervals for male neonates were lower than those for female neonates in the 29-32-week group (p < 0.05). CONCLUSION: This was the first study, to our knowledge, to establish reference intervals for thyroid function in twin neonates from the fifth to seventh day of life, which will be beneficial for the diagnosis and management of congenital hypothyroidism.

Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Pneumoprotein CC16 in the Umbilical Cord Blood of Preterm Neonates.

OBJECTIVE: We examined the impact of perinatal factors on cord serum club cell protein (CC16) and the association of CC16 with mechanical ventilation and bronchopulmonary dysplasia (BPD) in preterm neonates. STUDY DESIGN: A retrospective cohort study including 60 neonates born with gestational age (GA) < 34 weeks. The impact of categorical perinatal factors on cord blood levels of CC16 was examined with univariate and multivariate regression analyses. RESULTS: In neonates with GA < 32 weeks, cord blood CC16 concentrations were significantly lower compared to neonates with GA between 320/7 and 336/7 weeks (5.4 ± 2.5 compared to 7.6 ± 2.9 ng/mL, p = 0.039). Neonates with prolonged rupture of membranes had significantly lower CC16 compared to those without prolonged rupture of membranes (4.0 ± 1.9 compared to 7.2 ± 2.2, p < 0.001). Finally, neonates with BPD had significantly lower CC16, compared to neonates without BPD (4.2 ± 2.1 compared to 7.0 ± 2.2 ng/mL, p = 0.004).Prolonged rupture of membranes was significantly negatively associated with CC16 (b = -2.67, 95% confidence interval [CI] -0.49 to -4.85, p = 0.017), after adjusting for GA (b = 0.23, 95% CI 0.03-0.42, p = 0.022), mode of conception, and mode of delivery. Finally, higher CC16 levels were significantly inversely associated with BPD (odds ratio = 0.33, 95% CI 0.12-0.88, p = 0.028), after adjusting for GA (b = 0.27, 95% CI 0.09-0.78, p = 0.015), and birth weight. CONCLUSION: Prolonged rupture of membranes was significantly negatively associated with cord serum CC16, after adjusting for GA, conception, and delivery mode, and CC16 was significantly inversely associated with BPD, after adjusting for GA and birth weight. KEY POINTS: · Neonates with prolonged rupture of membranes had lower CC16 levels.. · CC16 was significantly negatively associated with BPD.. · CC16 could be a biomarker of lung injury and BPD..

Cord blood presepsin as a predictor of early-onset neonatal sepsis in term and preterm newborns.

BACKGROUND: To date, no studies on presepsin values in cord blood of term infants with risk factors for early-onset sepsis (EOS) are available, whereas only one study reported presepsin values in cord blood of preterm infants at risk. In this study, we investigated the presepsin values in cord blood of term and preterm infants with documented risk factors for EOS. METHODS: In this single-center prospective pilot study, we enrolled neonates presenting with documented risk factors for EOS. P-SEP levels were assessed in a blood sample collected from the clamped umbilical cord after the delivery in 93 neonates, using a point-of-care device. The primary outcome of our study was to evaluate the role of cord blood P-SEP in predicting clinical EOS in term and preterm infants. RESULTS: During the study period, we enrolled 93 neonates with risk factors for EOS with a gestational age ranging between 24.6 and 41.6 weeks (median 38.0). The median P-SEP value in all infants was 491 pg/ml (IQR 377 - 729). Median cord P-SEP values were significantly higher in infants with clinical sepsis (909 pg/ml, IQR 586 - 1307) rather than in infants without (467 pg/ml, IQR 369 - 635) (p = 0.010). We found a statistically significant correlation between cord P-SEP value at birth and the later diagnosis of clinical sepsis (Kendall's τ coefficient 0.222, p = 0.002). We identified the maximum Youden's Index (best cut-off point) at 579 pg/ml, corresponding to a sensitivity of 87.5% and a specificity of 71.8% in predicting clinical sepsis. CONCLUSIONS: Maximum Youden's index was 579 pg/ml for clinical EOS using cord P-SEP values. This could be the starting point to realize multicenter studies, confirming the feasibility of dosing P-SEP in cord blood of infants with risk factors of EOS to discriminate those who could develop clinical sepsis and spare the inappropriate use of antibiotics.

cfDNA and DNases: New Biomarkers of Sepsis in Preterm Neonates-A Pilot Study.

INTRODUCTION: An early and accurate diagnosis of early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) is essential to improve the outcome of this devastating conditions. Especially, preterm infants are at risk. Reliable biomarkers are rare, clinical decision-making depends on clinical appearance and multiple laboratory findings. Markers of NET formation and NET turnover might improve diagnostic precision. Aim of this study was to evaluate the diagnostic value of NETs in sepsis diagnosis in neonatal preterm infants. METHODS: Plasma samples of neonatal preterm infants with suspected sepsis were collected. Blood samples were assayed for markers of NET formation and NET turnover: cfDNA, DNase1, nucleosome, NE, and H3Cit. All clinical findings, values of laboratory markers, and epidemiological characteristics were collected retrospectively. Two subpopulations were created to divide EONS from LONS. EMA sepsis criteria for neonatal sepsis were used to generate a sepsis group (EMA positive) and a control group (EMA negative). RESULTS: A total of 31 preterm neonates with suspected sepsis were included. Out of these, nine patients met the criteria for sepsis according to EMA. Regarding early onset neonatal sepsis (3 EONS vs. 10 controls), cfDNA, DNase I, nucleosome, and CRP were elevated significantly. H3Cit and NE did not show any significant elevations. In the late onset sepsis collective (6 LONS vs. 12 controls), cfDNA, DNase I, and CRP differed significantly compared to control group.

A hydrophilic interaction liquid chromatography - Tandem mass spectrometry method for the determination of phenylephrine in dried blood spots from preterm infants.

A sensitive and accurate hydrophilic interaction liquid chromatography - tandem mass spectrometry method (HILIC-MS/MS) was developed and validated for the determination of phenylephrine concentration in Dried Blood Spot (DBS) samples from preterm infants, after ocular administration of an ophthalmic solution with phenylephrine. Sample preparation involved the extraction of the analyte from an 85 µL DBS sample with methanol - acetonitrile (50:50, v/v). Chromatographic separation was achieved on an ACQUITY UPLC BEH AMIDE column, under isocratic conditions within a 5 min run. Detection was achieved with a triple quadrupole MS applying electrospray ionization in positive mode. The method was fully validated and proved precise and accurate with in a linear range of 0.59-3.53 ng/ml in blood. The method was developed to provide insights on the level of exposure of infant population to phenylephrine after ocular administration.

Continuous Glucose Monitoring in the Management of Neonates With Persistent Hypoglycemia and Congenital Hyperinsulinism.

BACKGROUND: Persistent hypoglycemia is common in the newborn and is associated with poor neurodevelopmental outcome. Adequate monitoring is critical in prevention, but is dependent on frequent, often hourly blood sampling. Continuous glucose monitoring (CGM) is increasingly being used in children with type 1 diabetes mellitus, but use in neonatology remains limited. We aimed to introduce real-time CGM to provide insights into patterns of dysglycemia and to support the management of persistent neonatal hypoglycemia. METHODS: This is a single-center retrospective study of real-time CGM use over a 4-year period in babies with persistent hypoglycemia. RESULTS: CGMs were inserted in 14 babies: 8 term and 6 preterm infants, 9 with evidence of congenital hyperinsulinism (CHI). A total of 224 days of data was collected demonstrating marked fluctuations in glucose levels in babies with CHI, with a higher sensor glucose SD (1.52 ±â€…0.79 mmol/L vs 0.77 ±â€…0.22 mmol/L) in infants with CHI compared with preterm infants. A total of 1254 paired glucose values (CGM and blood) were compared and gave a mean absolute relative difference of 11%. CONCLUSION: CGM highlighted the challenges of preventing hypoglycemia in these babies when using intermittent blood glucose levels alone, and the potential application of CGM as an adjunct to clinical care.

Effects of Umbilical Cord Milking on Anemia in Preterm Infants: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to investigate whether umbilical cord milking (UCM) prevents and controls anemia in preterm infants, as compared with immediate cord clamping (ICC). STUDY DESIGN: Pregnant women delivering at <34 weeks' gestation in four hospitals were randomly assigned to undergo UCM or ICC from July 2017 to June 2019. Hematological parameters and iron status were collected and analyzed as primary outcomes at 24 hours, 1 week, 2 weeks, and 6 months after delivery. RESULTS: Neonates receiving UCM had significant higher levels of hemoglobin (Hb), hematocrit, and serum iron (p < 0.05). Lower prevalence of anemia and lower need for transfusions were noted in UCM group. Although UCM was associated with prolonged duration of phototherapy, the maximum levels of bilirubin were similar between two groups (p > 0.05). CONCLUSION: UCM is an effective intervention to help preterm infants experience less anemia with the potential to increase blood volume, as seen by higher Hb levels and more enhanced iron stores.

Association between blood carboxyhemoglobin level and bronchopulmonary dysplasia in extremely low birthweight infants.

Carboxyhemoglobin (CO-Hb) can be endogenously formed in the presence of oxidative stress and may be elevated in inflammatory lung disease. There is lack of evidence of its relationship with the development of bronchopulmonary dysplasia (BPD) in extremely low birthweight (ELBW) infants. The objective of the study is to evaluate the relationship between blood CO-Hb levels in the first 14 days of life (DOL) in ELBW infants and the development of BPD at 36 weeks postmenstrual age (PMA). This is a retrospective cohort study of 58 ELBW infants born at LAC-USC Medical Center between June 2015 and and June 2019 who survived to 36 weeks PMA. CO-Hb values were collected daily from DOL 1 to DOL 14. BPD definition using the recent 2019 NICHD criteria was used. Multivariate logistic regression was performed to determine the association between blood CO-Hb levels and BPD. Receiver operator curve was used to evaluate the ability of the median fraction of inspired oxygen (FiO2) level used at DOL 11-14 in discriminating absent to mild BPD versus moderate to severe BPD. 58 ELBW infants were included in the study. 24 (41%) were diagnosed with moderate to severe BPD, while 34 (59%) were diagnosed with no to mild BPD. Severity of BPD was fairly discriminated by FiO2 at DOL 11-14, but not with CO-Hb levels at any point within the first 14 DOL. The role and mechanism of CO-Hb production in this population need to be further studied.