Race as social determinant of growth and body composition among infants born very preterm.

OBJECTIVE: Racism leads to disparities in health outcomes. Our objective was to determine if black race was independently associated with differences in fat accretion at discharge in a large cohort of very preterm infants (32 weeks of gestation or less). METHODS: De-identified demographic, anthropometric and body composition data were collected from seven neonatal units around the United States. Weight, length, and head circumference z-scores at birth and at the time of body composition assessment or hospital discharge were calculated. RESULTS: The median gestational age and birthweight for this cohort (n = 888) were 29 weeks [IQR, 27-30] and 1167 g [SD, 354], respectively. The study population included 53% black preterm infants. Birthweight was lower in black preterm infants compared with white infants (1112 ± 334 g vs. 1228 ± 366 g; p < 0.0001). After adjusting for birthweight, gestational age, and birthweight-for-age z-score, black preterm infants had more weight gain (adjusted mean difference: 0.5 g/kg/day; p = 0.03) but not higher BF% z-scores at hospital discharge (adjusted mean: 1.2 vs. 1.3; p = 0.14) than white infants. CONCLUSIONS: After adjusting for covariates, black race was associated with higher weight gain velocity but not higher BF% z-scores. IMPACT: This study presents findings from a large-scale multicenter cohort. Racial differences were observed in birth weight and the rate of weight gain; however, these differences were not associated with dissimilarities in body composition outcomes. Understanding nutrition and growth outcomes across racial groups is necessary to combat racial disparities in the neonatal intensive care unit (NICU).

Racial differences in opioid withdrawal syndrome among neonates with intrauterine opioid exposure.

BACKGROUND: The aim of this study was to investigate the association between race and severe neonatal opioid withdrawal syndrome (NOWS) in infants exposed to intrauterine opioids. METHODS: This is a prospective observational study on intrauterine opioid-exposed term infants. Exposure to opioids was based on maternal disclosure, urine, or umbilical cord drug screening. Severe NOWS was defined based on modified Finnegan scoring and the need for pharmacological intervention. RESULTS: One hundred and fifty mother-infant pairs, 60 Black and 90 White with history of opioid exposure during pregnancy, were included. More White than Black infants developed NOWS that required pharmacological treatment, 70 vs. 40%: RR = 1.75 (1.25-2.45). In adjusted analysis, there was no significant association between race and the development of severe NOWS in mothers who attended opioid maintenance treatment program (OMTP). However, in mothers who did not attend OMTP, White race remained a significant factor associated with the development of severe NAS, RR = 1.69 (1.06, 2.69). CONCLUSIONS: Severe NOWS that required pharmacological intervention was significantly higher in White than in Black infants born to mothers who did not attend OMTP. Larger studies are needed to evaluate the association between social as well as genetic factors and the development of NOWS. IMPACT: There is a significant association between race and development of severe NOWS.

A Simple Intervention to Decrease Nutrient Losses in Continuous Feeds With Human Milk.

OBJECTIVES: Current evidence suggests that a significant amount of human milk fat is lost because of tubing adsorption. The objective was to evaluate the effect of reintroducing tubing leftover milk on the quality of macronutrient content of delivered milk. METHODS: This was an in vitro study. The standard method of preparing and delivering fortified human milk includes preparing a small extra volume that would be used for priming the connection tubes. At the end of the infusion, the tubes and any milk leftover would be discarded. This method was compared with a new method where by the exact milk volume was prepared and used to prime the connection tubes. Leftover tubing milk was pushed with air. RESULTS: The standard method was associated with significant losses in fat, protein, and calories of 16.7%, 3.4%, and 9.2% compared with the new method of 8.2%, 0%, and 3.3%, respectively. These losses in the standard method were predominantly explained by the significant gains in the left over milk contents of fat 6.3 ±â€Š1.1 g/dL, protein 3.5 ±â€Š0.4 g/dL, and calories 28 ±â€Š2.6 kcal/oz as compared with prepared milk of 4.8 ±â€Š0.3, 2.9 ±â€Š0.3 g/dL, and 24.0 ±â€Š0.8 kcal/oz respectively, P = 0.002. CONCLUSIONS: Traditional continuous delivery methods of human milk are associated with significant losses of fat and protein. By preparing the exact amount of ordered milk and then pushing through the residual milk left in the tubing with a small amount of air, this study offers a simple intervention that would significantly decrease these losses.

Does prolonged severe hypercapnia interfere with normal cerebrovascular function in piglets?

BACKGROUND: Hypercapnia causes cerebral vasodilation and increased cerebral blood flow (CBF). During prolonged hypercapnia it is unknown whether cerebral vasodilation persists and whether cerebrovascular function is preserved. We investigated the effects of prolonged severe hypercapnia on pial arteriolar diameters (PAD) and cerebrovascular reactivity to vasodilators and vasoconstrictors. METHODS: Piglets were anesthetized, intubated and ventilated. Closed cranial windows were implanted to measure PAD. Changes in PAD were documented during hypercapnia (PaCO2 75-80 mm Hg). Cerebrovascular reactivity was documented during normocapnia and at 30, 60, and 120 min of hypercapnia. RESULTS: Cerebral vasodilation to hypercapnia was sustained over 120 min. Cerebrovascular responses to vasodilators and vasoconstrictors were preserved during hypercapnia. During hypercapnia, vasodilatory responses to second vasodilators were similar to normocapnia, while exposure to vasoconstrictors caused significant vasoconstriction. CONCLUSIONS: Prolonged severe hypercapnia causes sustained vasodilation of pial arteriolar diameters indicative of hyperperfusion. During hypercapnia, cerebral vascular responses to vasodilators and vasoconstrictors were preserved, suggesting that cerebral vascular function remained intact. Of note, cerebral vessels during hypercapnia were capable of further dilation when exposed to additional cerebral vasodilators and, significant vasoconstriction when exposed to vasoconstrictors. Extrapolating these findings to infants, we suggest that severe hypercapnia should be avoided, because it could cause/increase cerebrovascular injury.

Trends in Medication Use in Very Low-Birth-Weight Infants in a Level 3 NICU over 2 Decades.

OBJECTIVE: This study aims to study the association between trends in medication utilization and survival in very low-birth-weight (VLBW) infants over a 22-year period. STUDY DESIGN: Medications received by VLBW infants were extracted retrospectively for the four periods 1990 to 1994, 1995 to 2000, 2001 to 2005, and 2006 to 2011 from our perinatal database and stratified by two birth weight groups: ≤ 1,000 g and 1,001 to 1,500 g. RESULT: A total of 5,529 VLBW infants were reviewed. The majority of them were African American (78%), with an increasing proportion over time. The median number of medications per patient in all VLBW infants remained similar over time, 9 (5, 15). A cardiovascular group of medications was most commonly used, with a significant increase in the use of dobutamine and indomethacin. A significant trend toward an increasing number of infants without any antibiotic exposure was also noted. Survival steadily and significantly increased from 83 to 87%. CONCLUSION: The trends of overall medication use remained the same in our neonatal intensive care unit (NICU) over the past 22 years. There was no association between medication utilization and survival. VLBW infants continue to receive a high number of medications in the NICU, including a variety of antibiotics.

Preterm Infants Can Mount Appropriate C-Reactive Protein Responses to Early Onset Sepsis.

OBJECTIVE: This study aims to evaluate whether infants born at ≤ 32 weeks' gestational age (GA) can mount C-reactive protein (CRP) responses during early onset bacterial sepsis that are comparable to infants born at > 32 weeks' GA. METHODS: Retrospectively (2003-2012) infants with a positive bacterial culture during the first 72 hours of life were identified and grouped into two categories based on their GA: ≤ 32 weeks (group A) and > 32 weeks (group B). RESULTS: Group A included 25 and group B included 122 infants. Both groups responded similarly to sepsis with an increase in CRP (p = 0.59). Each group had a significant change in intragroup CRP levels over time (p < 0.0001). However, in both groups, the degree of this change was at the same rate over time (p = 0.74). CONCLUSION: CRP responses to bacterial sepsis during the first 72 hours of life in infants born at ≤ 32 weeks' GA are comparable to infants born at > 32 weeks' GA.

Changes in premature infant mercury and lead blood levels after blood transfusions.

OBJECTIVE: To describe the blood level changes of mercury and lead after packed red blood cell (PRBC) transfusions in ≤ 750 g birth weight infants. STUDY DESIGN: Heavy metal blood levels were measured in infants in PRBC units on 1st, 4th, 5th, and 7th days (D1, D4, D5, and D7) of life and in urine on D1, D4, and D7. RESULTS: A total of 10 infants were enrolled with a mean birth weight of 632 ± 72 g. Out of which nine infants received one or more PRBC transfusions, with an average of 2.9 ± 2.5 transfusions per infant. Heavy metals were detected in all the transfusions. The average mercury level was 1.33 µg/L on D1 and 1.66 µg/L on D7, p > 0.05. The average lead level was 0.32 µg/dL on D1 and 0.56 µg/dL on D7, p > 0.05. Urinary mercury excretion increased in infants with no bowel movements. Urinary excretion of lead decreased over time as blood levels increased. CONCLUSIONS: After receiving blood transfusions, the blood levels of mercury and lead were maintained at the end of the 1st week of life. As there is no evidence of a proportionate increase in excretory amounts of these heavy metals, there is a concern that they are retained and potentially exert toxic effects.

Adjusting for bias in C-reactive protein levels when using a vitros slide method in infants.

OBJECTIVE: Low total serum protein levels may cause a positive bias on C-reactive protein (CRP) detected by the Vitros 250 Chemistry System (Ortho-Clinical Diagnostics, Inc., Johnson & Johnson Co., Raritan, NJ). Low total serum protein levels are observed in some infants. Our objective was to define a cutoff value for normal levels of CRP measured on the Vitros System that is comparable to the cutoff value of 1.0 mg/dL measured by rate nephelometry on a Beckman Array System (Beckman Instruments Inc., Fullerton, CA). STUDY DESIGN: CRP was prospectively measured on the same serum sample on Vitros and Beckman systems. Using a result of ≥1.0 as the "gold standard" definition of an abnormal CRP, measures of association were calculated. RESULTS: CRP was measured in 981 blood samples that were collected from 361 infants. A cutoff CRP level using the Vitros system at 1.5 mg/dL had the highest sensitivity and negative predictive value comparable to 1.0 mg/dL measured by nephelometry. By regression analysis, each increase by 1 mg/dL by nephelometry caused an increase by 1.5 mg/dL on the Vitros system (R(2) = 0.94; p < 0.001; slope = 0.66; 95% confidence intervals, 0.65, 0.67). CONCLUSION: In infants, when measuring CRP levels by Vitros CRP slide system, a normal reference level of 1.5 mg/dL instead of 1 mg/dL should be used.

Lead content of blood transfusions for extremely low-birth-weight infants.

OBJECTIVE: Our objective was to evaluate the levels of lead in blood transfusions for extremely low-birth-weight (ELBW) infants and how they compare with lead levels suspected of causing neurotoxicity. STUDY DESIGN: This prospective cohort included infants with a birth weight ≤ 1000 g. The quantity of transfused lead was calculated based on transfused volume and packed red blood cell (PRBC) unit lead levels. The results were compared with the exposure reference. RESULTS: Thirty-seven infants (birth weight 736 ± 157 g, gestational age 25.5 ± 1.5 weeks) received 322 transfusions from 47 PRBC units with 6.5 ± 3.5 different units used to complete all transfusions per infant. Lead was detected in all units. The average lead level in a PRBC unit was 18.3 ± 10.4 µg/L. Of 322 transfusions, 139 (43%) had lead volumes that exceeded the exposure reference. All infants received at least one transfusion with a lead volume exceeding the daily reference dose equivalent, and four infants (11%) received several transfusions with a cumulative lead volume exceeding the weekly reference dose. CONCLUSION: Blood transfusions are a potential source of lead for ELBW infants with unknown safety implications in this critical time of brain development.

Detection of pepsinogen in the neonatal lung and stomach by immunohistochemistry.

OBJECTIVE: Evaluate the hypothesis that the same pepsinogen C molecule produced in the stomach is also produced by the lung. PATIENTS AND METHODS: Pulmonary and gastric tissues collected postmortem were immunohistochemically stained for pepsinogen C and pepsinogen A. RESULTS: Sixteen patients with diverse causes of death were evaluated. Gestational age at birth ranged between 21 and 37 weeks. Pepsinogen A was detected in 12 of the 13 stomach sections, mainly in the chief cells, but not in any lung sections. Pepsinogen C was detected in all stomach sections in chief and mucus cells and in 9 of the 16 lung sections, mainly in type II pneumocytes. Pepsinogen C was not detected in the 3 lung cases with a gestational age <23 weeks. CONCLUSIONS: The same pepsinogen C molecule is produced in the stomach and in the lung. These findings potentially affect previous study results that used an enzymatic pepsin detection assay to evaluate for and associate gastroesophageal reflux disease with other morbidities.

Changes in urinary kidney injury molecule-1 levels after blood transfusions in preterm infants.

Literature supports an association between transfusions and gut injury in preterm infants. We hypothesized that packed red blood (PRBC) transfusions are associated with kidney inflammation marked by a rise in urinary levels of Kidney Injury Molecule 1 (KIM-1). Prospectively, KIM-1 levels were measured before and then at 6, 12 and 24 h after a PRBC transfusion. Results are presented as mean (± SD) and median (IQR). Thirty-four infants, birth weight 865 (± 375) g, had higher pretransfusion KIM-1 levels of 2270 (830, 3250) pg/mg than what is normal for age. These were not associated with hematocrit levels. KIM-1 levels peaked between 6 and 12 h after the transfusion. Levels peaked to 3300 (1990, 6830) pg/mg; levels returned to pretransfusion levels of 2240 (1240, 3870) pg/mg by 24 h, p < 0.01. The 24-h post-transfusion KIM-1 levels were similar to pretransfusion levels, p = 0.63. PRBC transfusions in preterm infants are associated with an elevation in urinary KIM-1 levels. The mechanism of this association may be important in studying transfusion associated organ injury. KIM-1, as an inflammatory marker, may be helpful in assessing the effect of different transfusion volumes or in evaluating operational thresholds of anemia in premature infants.

Brain-derived circulating endothelial cells in peripheral blood of newborn infants with seizures: a potential biomarker for cerebrovascular injury.

Neonatal seizures have been associated with cerebrovascular endothelial injury and neurological disabilities. In a piglet model, the long-term loss of endothelial regulation of cerebral blood flow coincides with the surge of brain-derived circulating endothelial cells (BCECs) in blood. We hypothesized that BCECs could serve as a noninvasive biomarker of cerebrovascular injury in neonates with seizures. In a prospective pilot feasibility study, we enrolled newborn infants with confirmed diagnoses of perinatal asphyxia and intraventricular hemorrhage (IVH); both are commonly associated with seizures. Infants without clinical evidence of cerebrovascular injuries were representative of the control group. BCECs were detected in the CD45-negative fraction of peripheral blood mononuclear cells by coexpression of CD31 (common endothelial antigen) and GLUT1 (blood-brain barrier antigen) via automated flow cytometry method. In Infants with asphyxia (n = 12) and those with IVH grade III/IV (n = 5), the BCEC levels were 9.9 ± 0.9% and 19.0 ± 2.0%, respectively. These levels were significantly higher than the control group (n = 27), 0.9 ± 0.2%, P < 0.001. BCECs in infants with cerebrovascular insults with documented clinical seizures (n = 10; 16.8 ± 1.3%) were significantly higher than infants with cerebrovascular insults with subclinical or no seizures (n = 7; 9.5 ± 1.2%); P < 0.001. BCEC levels decreased with seizure control. BCECs levels were elevated in infants with seizures caused by severe IVH and perinatal asphyxia. We suggest that monitoring BCEC levels in peripheral blood can potentially offer a biological marker that reflects cerebrovascular insult and recovery. Further studies with a larger number of patients are required to support these findings.

Mercury content of blood transfusions for infants with extremely low birth weight.

OBJECTIVES: To assess whether blood transfusions for infants with birth weights of 1000 g or less are a source of mercury and whether any mercury delivered through the transfusion is above the currently set oral reference dose. PATIENTS AND METHODS: We studied an observational cohort. Inclusion criteria included birth weight 1000 g or less and receipt of 1 or more packed red blood cell transfusions. Packed red blood cell units were tested prospectively for mercury levels. The quantity of transfused mercury was calculated on the basis of transfused volume and packed red blood cell mercury level. The resulting mercury level was compared with the reference dose as set by the Agency for Toxic Substances and Disease Registry, the World Health Organization, and the US Environmental Protection Agency. RESULTS: Thirty-seven infants (birth weight: 736 ± 157 g; gestational age: 25.5 ± 1.5 weeks) met the inclusion criteria. A total of 325 transfusions from 49 packed red blood cell units were administered. Mercury was detected in 40 units. The average mercury level in a packed red blood cell unit was 1.9 ± 2.6 µg/L (median: 0.9 µg/L [interquartile range: 0.3-2.5]). None of the infants received any mercury above the reference dose set by the Agency for Toxic Substances and Disease Registry and the World Health Organization. Twelve infants received 1 transfusion, and 5 infants received 2 transfusions above the Environmental Protection Agency reference dose during their entire hospitalization. CONCLUSIONS: Packed red blood cells are a source of mercury for infants. However, the amount delivered is low compared with currently set safety levels. The episodes in which mercury intake exceeded the reference dose were rare. However, without long-term follow-up, no conclusions can be made about the cognitive implications of these episodes.