The iron status at birth of neonates with risk factors for developing iron deficiency: a pilot study.

OBJECTIVE: Small-for-gestational-age (SGA) neonates, infants of diabetic mothers (IDM) and very-low-birth weight premature neonates (VLBW) are reported to have increased risk for developing iron deficiency and possibly associated neurocognitive delays. STUDY DESIGN: We conducted a pilot study to assess iron status at birth in at-risk neonates by measuring iron parameters in umbilical cord blood from SGA, IDM, VLBW and comparison neonates. RESULTS: Six of the 50 infants studied had biochemical evidence of iron deficiency at birth. Laboratory findings consistent with iron deficiency were found in one SGA, one IDM, three VLBW, and one comparison infant. None of the infants had evidence of iron deficiency anemia. CONCLUSIONS: Evidence of biochemical iron deficiency at birth was found in 17% of screened neonates. Studies are needed to determine whether these infants are at risk for developing iron-limited erythropoiesis, iron deficiency anemia or iron-deficient neurocognitive delay.

Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with activated neutrophils extruding neutrophil extracellular traps.

OBJECTIVE: Neonates with necrotizing enterocolitis (NEC) have higher calprotectin levels in stool than do healthy neonates. However, it is not known whether high stool calprotectin at the onset of bowel symptoms identifies neonates who truly have NEC vs other bowel disorders. STUDY DESIGN: Neonates were eligible for this study when an x-ray was ordered to 'rule-out NEC'. Stool calprotectin was quantified at that time and in a follow-up stool. Each episode was later categorized as NEC or not NEC. The location of calprotectin in the bowel was determined by immunohistochemistry. RESULTS: Neonates with NEC had higher initial and follow-up stool calprotectin levels than did neonates without NEC. Calprotectin in bowel from neonates with NEC was within neutrophil extracellular traps (NETs). CONCLUSION: At the onset of signs concerning for NEC, fecal calprotectin is likely to be higher in neonates with NEC. Calprotectin in their stools is exported from neutrophils via NETs.

Why do four NICUs using identical RBC transfusion guidelines have different gestational age-adjusted RBC transfusion rates?

OBJECTIVE: To compare neonatal red blood cell (RBC) transfusion rates in four large Intermountain Healthcare NICUs, all of which adhere to the same RBC transfusion guidelines. STUDY DESIGN: This retrospective analysis was part of a transfusion-management quality-improvement project. De-identified data included RBC transfusions, clinical and laboratory findings, the anemia-prevention strategies in place in each NICU, and specific costs and outcomes. RESULT: Of 2389 NICU RBC transfusions given during the 4-year period studied, 98.9 ± 2.1% (mean ± S.D.) were compliant with our transfusion guidelines, with no difference in compliance between any of the four NICUs. However, RBC transfusion rates varied widely between the four, with averages ranging from 4.6 transfusions/1000 NICU days to 21.7/1000 NICU days (P < 0.00001). Gestational age-adjusted transfusion rates were correspondingly discordant (P < 0.00001). The lower-transfusing NICUs had written anemia-preventing guidelines, such as umbilical cord milking at very low birth weight delivery, use of cord blood for admission laboratory studies, and darbepoetin dosing for selected neonates. Rates of Bell stage ⩾ 2 necrotizing enterocolitis and grade ⩾ 3 intraventricular hemorrhage were lowest in the two lower-transfusing NICUs (P < 0.0002 and P < 0.0016). Average pharmacy costs for darbepoetin were $84/dose, with an average pharmacy cost of $269 per transfusion averted. With a cost of $900/RBC transfusion, the anemia-preventing strategies resulted in an estimated cost savings to Intermountain Healthcare of about $6970 per 1000 NICU days, or about $282,300 annually. CONCLUSION: Using transfusion guidelines has been shown previously to reduce practice variability, lower transfusion rates and diminish transfusion costs. Based on our present findings, we maintain that even when transfusion guidelines are in place and adhered to rigorously, RBC transfusion rates are reduced further if anemia-preventing strategies are also in place.

Whole-blood viscosity in the neonate: effects of gestational age, hematocrit, mean corpuscular volume and umbilical cord milking.

OBJECTIVE: The American College of Obstetrics and Gynecology Committee on Obstetric Practice recently endorsed delayed cord clamping at preterm delivery. However, the committee report expressed the concern by some practitioners that delayed clamping or cord milking might induce hyperviscosity in preterm neonates. To address this issue we: (1) established reference ranges for whole-blood viscosity among preterm neonates (viscosity reference ranges had previously been reported only in term neonates) and (2) determined the effect of umbilical cord milking at deliveries <32 weeks gestation on subsequent blood viscosity measurements. STUDY DESIGN: This was a prospective study in two Neonatal Intensive Care Units. Blood viscosity was measured using a cone and plate viscometer. Associations were sought with gestation, hematocrit/hemoglobin and mean corpuscular volume. Reference ranges were determined for preterm infants <32 weeks gestation. Then, after umbilical cord milking at deliveries <32 weeks, viscosity was measured at birth and again during the 12 h after birth. In neonates with viscosities >95th % range, we sought signs of hyperviscosity (plethora, hypotonia, hypoglycemia, hyperbilirubinemia, thrombocytopenia). RESULT: Viscosity at higher and lower sheer rates were linearly related (n=32, r=0.971). Within the range of hematocrits measured (29-63%) viscosity correlated with hematocrit (r=0.877) and hemoglobin (r=0.853) but not with erythrocyte size (r=0.179). Viscosity was related to gestational age (n=58), primarily due to the lower hematocrits at lower gestational ages. In the 12 h after cord milking viscosity ranged from 3.1 to 9.5 centipoise. Three of twenty preterm, neonates had viscosities >95th % reference range. However, all values were well below those where hyperviscosity is defined in term neonates and all lacked features of hyperviscosity. CONCLUSION: Cord blood viscosity is directly proportional to hematocrit/hemoglobin, lower at early gestation and not associated with erythrocyte size. Cord milking at preterm delivery is associated with a low risk of clinical hyperviscosity. Practioners should not refrain from cord milking at preterm delivery because of a concern that it will commonly cause neonatal hyperviscosity.

Evaluating neonatal hyperbilirubinemia in late preterm Hispanic twins led to the diagnosis of hereditary spherocytosis in them, and in their sibling and in their mother.

We identified four cases of hereditary spherocytosis (HS) in one Utah family, originally from Southwestern Mexico. The index cases were twin girls born at 35 weeks gestation, in whom the combination of hyperbilirubinemia, reticulocytosis and elevated mean corpuscular hemoglobin concentration (MCHC) led to studies that confirmed the diagnosis of HS. Scleral icterus in their 4-year-old sibling and in their mother led to the diagnosis of HS in them as well. Although much less commonly reported in Hispanic neonates than in those of Northern European ancestry, HS does occur among Hispanic neonates and can contribute to significant neonatal hyperbilirubinemia. These cases are consistent with our earlier report, which identified an MCHC cutoff of >36 as suggestive of further evaluation for HS.

Effect of ampicillin on bleeding time in very low birth-weight neonates during the first week after birth.

OBJECTIVE: On the day of birth, the bleeding time of very low birth-weight (VLBW, <1500 g) neonates is generally prolonged, compared with term neonates. However, their bleeding time generally improves (shortens) over the next 7 to 10 days. Ampicillin can prolong the bleeding times of term and late preterm neonates, but its effect on VLBW neonates, who already have a somewhat prolonged bleeding time initially, is not known. STUDY DESIGN: This was a prospective, single-centered, paired, before vs after test of the effect of ampicillin on template bleeding time and PFA-100 time (platelet function analyzer). Ampicillin was dosed at every 12 h intravenously, but decisions about discontinuation were made by the responsible clinician, independent of this study. RESULT: A total of 20 VLBW neonates were studied. They ranged from 23- to 30-weeks gestation at birth and weighed 500 t 1410 g. Initial bleeding times averaged 166 s (95% CI, 138 to 194) and initial PFA-100 times averaged 119 s (95% CI, 90 to 148). In all, 10 had ampicillin dosing stopped after a shorter course (4 to 7 doses) and 10 had it continued for a longer course (10 to 15 doses). Blood cultures were sterile in all 20, and no differences in laboratory or clinical features were found between those treated with a shorter vs longer course. After stopping the ampicillin following a short course the bleeding times and PFA-100 times were similar to the initial values. However, after a longer course the bleeding times were prolonged by an average of 2 min, to 284 s (95% CI, 242 to 326; P=0.001 vs initial). The PFA-100 times also trended longer by an average of 44 s (P=0.07). The number of doses of ampicillin received in the first week correlated with the degree of prolongation in bleeding time (r=0.68). CONCLUSION: Over the first week of life, a period when the bleeding time of VLBW neonates normally shortens, the opposite occurred (the bleeding time lengthened) if ≥ 10 doses of ampicillin were administered.

Effect of ampicillin on the bleeding time of neonatal intensive care unit patients.

OBJECTIVE: Studies in adults indicate that ampicillin, in a dose-dependent manner, impairs platelet function and moderately prolongs the bleeding time (generally by 60 to 90 s). Unlike aspirin, the inhibition induced by ampicillin involves both reversible and irreversible mechanisms and is not observed immediately after initial dosing (generally requiring approximately 24 h). Ampicillin is administered commonly to neonatal intensive care unit (NICU) patients, but its effect on bleeding time in this population has not been reported earlier. STUDY DESIGN: We performed neonatal template bleeding times and platelet function analyzer (PFA)-100 tests on 15 NICU patients before and at various intervals after intravenous ampicillin dosing. RESULT: Neonates were only studied if no beta-lactam antibiotics were administered to their mother during labor, and if they had ampicillin ordered by the clinician at a dose of 50 to 100 mg kg(-1) every 12 h. Subjects ranged from 33 to 41 weeks gestation and weighed 1760 to 3835 g. Bleeding times before the first ampicillin dose (n=15) averaged 134 s (95% confidence interval (CI), 120 to 148 s) and PFA-100 times averaged 123 s (95% CI, 96 to 149 s). After the first dose of ampicillin (n=5), bleeding times and PFA-100 times did not increase, but after the third (n=5) and fourth doses (n=4) bleeding times lengthened by an average of 60 s (95% CI, 37 to 83 s, P<0.001) and PFA-100 times lengthened by an average of 20 s (95% CI, -20 to 60 s, P=0.15). CONCLUSION: Ampicillin administered intravenously to NICU patients prolongs the bleeding time, with a magnitude-of-effect and time-to-effect similar to that shown earlier in adults.

Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements.

OBJECTIVE: Ibuprofen might have advantages over indomethacin, when used to effectuate closure of a neonate's patent ductus arteriosus (PDA). Several previous studies indicate that platelet plug formation is impaired after administration of indomethacin, but it is not clear whether a similar impairment occurs following ibuprofen dosing. STUDY DESIGN: We performed template bleeding times and PFA-100 tests (platelet function analyzer) on 20 neonates who had a PDA, before and again at various preset intervals following ibuprofen dosing. RESULT: Patients ranged from 23 to 40 weeks gestation and weighed 511 to 2566 g. Their first dose of ibuprofen was administered at 72 h (18 to 363 h) after birth (median, range). None of the subjects had clinical bleeding problems noted during the days they received ibuprofen dosing. The template bleeding times before dosing ranged from 135 to 450 s. Repeat tests were performed in groups of four, at 2 h, 4 to 6 h, 12 to 18 h, 24 h after the first dose, and at 2 h after the third dose of ibuprofen. No changes in bleeding times were detected. (P=0.299) A PFA-100 time was performed on all 20 patients before and again after the ibuprofen administration. However, 3 of the 40 tests were unsuccessful, because of microclots in the blood sample (n=1) or failure of the analyzer for an unspecified reason (n=2). Before the dosing the PFA-100 time ranged from 52 to 300 s. A paired t-test showed a slight but statistically significant lengthening in PFA-100 time after the ibuprofen administration (P=0.019). The correlation between the bleeding time and the PFA-100 was poor (R(2)=0.212, P=0.576). CONCLUSION: On the basis of our present studies, we speculate that ibuprofen lysine administration to neonates with a PDA, when used according to the manufacturer's recommendations, has little adverse effect on platelet plug formation. This information might be a factor to consider when deciding whether to select indomethacin or ibuprofen for PDA closure.

Enhancement of Agkistrodon piscivorus piscivorus venom phospholipase A2 activity toward phosphatidylcholine vesicles by lysolecithin and palmitic acid: studies with fluorescent probes of membrane structure.

The activity of phospholipase A2 from snake venom to hydrolyze bilayers of phosphatidylcholines is greatly enhanced by the presence of the hydrolysis products, lysolecithin and fatty acid, in the bilayer. The fluorescence of several probes of membrane structure was used to monitor changes in bilayer physical properties during vesicle hydrolysis. These changes were compared to emission spectra and fluorescence polarization results occurring upon direct addition of lysolecithin and/or fatty acid to the bilayer. The excimer to monomer ratio of 1,3-bis(1-pyrene)propane was insensitive to vesicle hydrolysis, suggesting that changes in the order of the phospholipid chains were not relevant to the effect of the hydrolysis products on phospholipase activity. The fluorescence of 6-propionyl-2-(dimethylamino)-naphthalene (Prodan) suggested that the polarity of the bilayer in the region of the phospholipid head groups increases as the hydrolysis products accumulate in the bilayer. The fluorescence of 6-dodecanoyl-2-(dimethylamino)naphthalene (Laurdan) confirmed that such effects were restricted to the bilayer surface. Furthermore, the lysolecithin appeared to be the product most responsible for these changes. These results suggested that lysolecithin increases the activity of phospholipase A2 during vesicle hydrolysis by disrupting the bilayer surface, making the phospholipid molecules more accessible to the enzyme active site.