Peripheral fractional oxygen extraction and other measures of tissue oxygenation to guide blood transfusions in preterm infants

The physiological effects of anemia in the preterm infant are complex and the indications for transfusions in preterm infants are controversial. A measure of the adequacy of tissue oxygenation may be a better guide to the need for transfusions than currently used criteria. This article considers 2 measures of tissue oxygenation of preterm infants: 1) The whole blood lactate concentration, and 2) Peripheral fractional oxygen extraction (FOE) by using near infrared spectroscopy. Several studies have shown falls in blood lactate concentration after blood transfusion, but it has been difficult to establish a convincing link between raised lactate concentrations and significant anemia because even anemic infants have lactate concentrations that are within or close to the normal range. Lactate concentrations may be affected by the haematocrit of the blood sample. Peripheral FOE can be measured by using near infrared spectroscopy with partial venous occlusion and has been studied in preterm infants with symptomatic and asymptomatic anaemia. Mean (SD) FOE was significantly higher in symptomatic [0.425 (0.06)] (P< .01) but not asymptomatic [0.334 (0.05)] compared to controls [0.352 (0.06)], (P = .22). After transfusion there was a significant fall in FOE in symptomatic infants to 0.367 (0.06) (P = .001) but there was no change in infants who were asymptomatic. FOE correlated with other measures known to reflect the adequacy of oxygen availability during anemia. These results suggest that peripheral FOE may be suitable as a guide to the need for blood transfusions. A pilot randomized controlled trial is currently being undertaken to test this hypothesis.     

Serum homocysteine levels after preterm premature rupture of the membranes

OBJECTIVE: Preterm premature rupture of the membranes (PPROM) is believed to be caused, in part, by abnormalities of collagen and increased levels of oxidative stress. Elevated homocysteine levels have been shown to induce these same pathophysiologic changes. We tested the hypothesis that serum homocysteine levels would be higher in women with PPROM when compared with matched control women. STUDY DESIGN: A secondary analysis derived from 2 previously completed studies performed in the National Institutes of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. We identified 99 study cases with PPROM (24 to 32 weeks' gestation) and matched them with 99 asymptomatic control women from an observational study of preterm birth prediction. Cases and control women were matched for race, gestational age at sampling, and MFMU Network center. Serum homocysteine levels were determined by immunoassay in batch fashion by personnel masked to study arm and clinical outcomes. Serum homocysteine levels were compared between groups, as were the baseline characteristics of maternal age, cigarette smoking, nulliparity, infections during pregnancy, and body mass index (BMI) <19.8 kg/m 2. Serum homocysteine levels were dichotomized as >75th, 90th, and 95th %ile of control women, and the likelihood of elevated homocysteine levels was determined in women who smoked, had a BMI <19.8 kg/m 2, or who had PPROM. Statistical analyses included the Wilcoxon rank sum, chi-square, and Pearson correlation coefficient, where appropriate. Baseline characteristics were controlled with a logistic regression model. RESULTS: Serum homocysteine levels measured in patients with PPROM were not significantly different from matched control women: median and (25th to 75th %ile): 4.9 (3.5-6.2) vs 4.8 (3.9-6.2 micromol/L), P =.73. In our population, neither the number of cigarettes smoked ( r = -0.08, P =.57), nor BMI ( r = -0.08, P =.24) correlated with serum homocysteine levels. The strongest association was seen in women with PPROM having serum homocysteine levels >95th %ile of control women (odds ratio [OR] 2.7, P =.10). After adjusting for baseline characteristics, no correlation between serum homocysteine level and the presence of PPROM was seen, OR 1.0 (.9-1.1); P =.99. CONCLUSION: Women presenting with PPROM did not have significantly increased serum homocysteine levels when compared with control women.     

Serum ferritin level as a marker of preterm labor.

Objective: To compare the serum ferritin levels in women with preterm labor (PTL) or preterm premature rupture of membranes with those in normal gravid women. Method: The study group consisted of 50 consecutive subjects with preterm labor and 49 subjects with preterm premature rupture of membranes (PROM). The control group consisted of 50 subjects matched with the study group for hemoglobin (Hb) and gestation who did not have PTL or preterm PROM. Serum ferritin levels were assayed in both the groups. Results: Mean serum ferritin levels in patients with preterm labor and preterm premature rupture of membranes were 23.24+/-12.13 ng/ml and 29.44+/-28.41 ng/ml, respectively. The mean serum ferritin in control subjects was 8.69+/-3.7 ng/ml. The difference was evaluated by Student's t-test and was found to be statistically significant. Conclusion: The serum ferritin level is significantly raised in pregnant women with preterm labor and preterm PROM.     

Serum ferritin and iron status in mothers and newborn infants

Iron status, including hemoglobin, S-ferritin, S-iron, S-transferrin, transferrin saturation and the erythrocyte zinc protoporphyrin/hemoglobin (ZPP:Hb) ratio, was evaluated in 85 healthy iron-supplemented mothers at parturition and in 74 of their term newborn infants. Of the mothers, 17% had a S-ferritin level less than 15 micrograms/l (i.e. depleted iron stores), 9.9% had S-ferritin less than 15 micrograms/l and transferrin saturation less than 15% (i.e. latent iron deficiency), and 2.4% had S-ferritin less than 15 micrograms/l, transferrin saturation less than 15% and Hb less than 120 g/l (i.e. iron deficiency anemia). Newborn infants had higher S-ferritin than mothers: median 128 micrograms/l versus 21 micrograms/l (p less than 0.0001), higher transferrin saturation: 48% vs. 21% (p less than 0.0001), and higher ZPP:Hb ratio: 74 mumol/mol Hb vs. 41 mumol/mol Hb (p less than 0.0001). During the first 5 post-natal days, median S-ferritin rose from 128 to 236 micrograms/l (p less than 0.0001). S-ferritin appeared to be the best single indicator of maternal iron status. Ferritin levels in newborn infants were correlated to levels in mothers (rs = 0.36, p less than 0.01), indicating that fetal iron reserves are dependent on maternal iron stores.     

Serum magnesium levels in pregnancy and preterm labor

Pregnancy is marked by a state of hypomagnesemia. The serum magnesium level shows no gestational dependence (mean, 1.79 +/- 0.44 mg/dl) until 33 weeks, at which point it continuously declines. Serum magnesium is not depressed further with the onset of labor at term. Patients in preterm labor have a significantly depressed serum magnesium level (mean, 1.60 +/- 0.46 mg/dl; 21 to 33 weeks; p less than 0.0005). This level was not dependent on whether the etiology for the preterm labor was premature rupture of the membranes (PROM), twin gestation, abruption, placenta previa with bleeding, or chorioamnionitis. With PROM, the serum magnesium level was not depressed prior to the initiation of preterm labor. However, observation of hypomagnesemia for this and other etiologies just prior to the initiation of preterm labor were not available. Possible mechanisms by which hypomagnesemia induces uterine irritability are explored, including inhibition of adenyl cyclase with resultant increase in cytoplasmic calcium levels. Patients with diabetes mellitus appeared to have slightly reduced serum magnesium levels, but the results were not statistically significant. Magnesium levels in patients with preeclampsia were not significantly different from controls. Hypomagnesemia (magnesium 1.4 mg/dl or less) may be a marker for true preterm labor.     

Variations in ferritin levels in blood during physiological pregnancy

Iron deficiency anemia is the most frequent haematological pathology in pregnancy. Serum ferritin levels represent the state of iron deposits. Low levels are a sure sign of iron deficiency. At the University of Turin we studied the variations of serum ferritin levels during physiological pregnancy and the sensitivity of routine blood tests with respect to serum ferritin levels. Routine haematological blood values along with ferritin levels were measured in 115 patients throughout pregnancy. The mean serum ferritin level was 56 ng/ml in the first trimester, 27.2 ng/ml in the second and 11.8 ng/ml in the third. The incidences of anemia per trimester was 6.6%, 4.8% and 49% respectively (p less than 0.05, chi squared). Our results show that it is important to evaluate iron deposits early in pregnancy by measuring serum ferritin levels in order to determine the need for iron therapy.     

Effect of multiple INSURE procedures in extremely preterm infants

Abstract

Objectives.?Our aim was to evaluate whether single and multiple intubation-surfactant-extubation (INSURE) procedures have similar effects on the need of mechanical ventilation (MV) and occurrence of bronchopulmonary dysplasia (BPD) in extremely preterm infants.

Methods.?We studied infants of <30 weeks of gestation with respiratory distress syndrome (RDS) who were treated with single (FiO₂?>?0.30 without need of MV) or multiple (FiO₂?>?0.40 without need of MV) INSURE procedures.

Results.?Seventy-five infants were studied: 53 (71%) received single INSURE and 22 (29%) received multiple INSURE procedures. Infants in the single and multiple groups had similar rates of need of MV (15 vs. 23%) and occurrence of BPD (9 vs. 9%), although the latter were more immature and affected by more severe RDS (higher FiO₂, lower a/ApO₂, and pO₂/FiO₂) than the former.

Conclusions.?Single and multiple INSURE procedures were followed by similar respiratory outcome in a cohort of extremely preterm infants. Further studies are warranted to evaluate whether the multiple INSURE strategy enhances the success rate of INSURE in preventing the need of MV and the occurrence of BPD.     

Serum netilmicin levels in premature AGA infants

Safe use of aminoglycosides requires close monitoring of serum concentrations. Limited information coupled with marked changes in fluid compartments and renal function during the first week of life in premature neonates makes interpretation of peak and trough levels very difficult. This study was designed to measure serum netilmicin levels following a 2.5 mg/kg IV push infusion. Blood samples were taken on the 5th day of therapy 1 hour before and 1, 6, and 11 hours after a dose. Fifteen premature infants weighing 1000-1500 gm at birth and 20 others whose weight ranged from 1501-2750 gm comprised the study population. All premature infants were appropriate for gestational age (AGA) and of them, only two were severely asphyxiated. At the time of the study, 10 neonates were still on respirators. Serum and urine sodium and creatinine, BUN, and urinalysis were obtained in 28 of these infants. No evidence of renal dysfunction was found. All infants received 100 mg/kg IV ampicillin every 12 hours, but none were being treated with diuretics. Serum netilmicin levels were measured by an enzymatic immunoassay, peak and trough were calculated by extrapolating the first order decay curve. Peak levels ranged from 3.4 to 14 micrograms/ml (means 6.1 +/- 2.5 micrograms/ml SD) and 90% of them were above 4 micrograms/ml. Half of the small premature infants (1000-1500 gm birthweight) presented trough values above 3 micrograms/ml. Pharmacokinetic analysis of our data predicts that a 2.5 mg/kg loading dose followed by 2 mg/kg given every 12 hours will decrease by one-half the number of small prematures exceeding the considered "safe" trough level (greater than 3 micrograms/ml).     

Plasma lactoferrin levels in newborn preterm infants with sepsis

Introduction: Lactoferrin (Lf) is one of the major proteins of all exocrine secretions with a role in the antinfective process. Our aim was to evaluate how plasma Fl levels may change in response to infection in newborn preterm infants.

Methods: A total of 15 (8 females, 7 males) newborn preterm infants with a postnatal age >72?h of life, underwent to blood culture and others markers of infection, for suspected sepsis, were enrolled in the study.

Results: We found that Lf serum concentration was significantly lowest in four neonates (26.7%) with confirmed sepsis than in 11 (73.3%) with clinical sepsis. The AUC was 0.90 (95%CI: 0.63–0.99). The optimal cutoff for Lf was?<1.2?μg/ml with a sensibility of 100% and a specificity of 81.8%. Lf serum concentration was positively correlated with WBC or neutrophil (Spearman rho = 0.69 and 0.49, respectively).

Conclusions: Serum Lf could prove a promising, sensitive and specific marker in the diagnostic approach to infants with suspected sepsis, thanks to its role in defense mechanisms and physiological functions of the immune system. Low levels of Lf in sepsis may suggest an immature response due to suboptimal leukocites activity in newborn preterm infants.     

Serum ferritin levels and their significance in normal full-term pregnant women

Serum ferritin levels were determined by radioimmunoassay (RIA) method and then analysed in 240 normal full-term pregnant women. Their hemoglobin concentrations were found to be normal in the first trimester. None of them had received any hematonic during their whole pregnancy period. Their mean age was 27.7 years and the mean pregnancy duration was 39.5 weeks. Mean hemoglobin concentration in these normal pregnant women was 12.6 g%. Mean serum ferritin was 23.1 ng/ml. It was significantly lower than the mean value of the normal non-pregnant women of the same age. In this study, we found that even normal pregnant women, 15.42% (37 out of the 240) had subclinical iron deficiency and 12.92% (31 out of the 240) of the previously normal pregnant women had clinical anemia during their term of pregnancy. Multiparity was found to be a factor in the prevalence of iron deficiency but age and gravida number played no role in the occurrence of iron deficiency anemia.     

Correlation between plasma and urinary caffeine levels in preterm infants

BACKGROUND: We hypothesize that urine levels might be reliable to assess the therapeutic range of caffeine. OBJECTIVES: We correlated plasma and urinary levels of caffeine in preterm infants treated with this drug for apnea of prematurity. METHODS: Infants (n=56) were given a loading dose of caffeine citrate (10 mg/kg, per os) and 24 h later a maintenance dose (2 mg/kg, per os, once a day). Plasma and urinary levels of caffeine were determined 24 h after the loading dose (before administration of the maintenance dose) and then weekly. RESULTS: Plasma and urinary levels correlate at all examined ages: 29 weeks (r=0.92, P<0.001), 30 weeks (r=0.97, P<0.001), 31 weeks (r=0.82, P<0.001), 32 weeks (r=0.92, P<0.001), 33 weeks (r=0.87, P<0.001), 34 weeks (r=0.81, P<0.001). CONCLUSION: Urinary levels of caffeine might be a useful means to assess therapeutic ranges.     

Serum tobramycin levels in low- and very low-birthweight infants

This study was designed to evaluate the serum concentration of tobramycin sulfate following a 2.5-mg/kg intravenous infusion in 43 premature infants on days 1, 3, and 5 of age (therapy). Twenty premature infants weighing 1500 gm or less at birth and 23 others whose birthweights ranged from 1501 to 2500 gm made up the study population. Serum tobramycin levels were measured by an enzymatic immunoassay (EMIT) at one, four to six, and 12 hours after injection. Peak serum levels increased from day 1 (means, 5.2 +/- 2.2 mcg/ml) to day 3 (means, 6.1 +/- 2.6 mg/ml) and then remained unchanged at day 5 (means, 6.1 +/- 2.4 mg/ml). Approximately 40% of the study population presented trough levels above 2 mcg/ml on day 1 and over 70% on days 3 and 5. No evidence of renal toxicity or auditory dysfunction was observed. In light of the high trough levels observed during the first week of life in premature infants, it may be judicious to monitor serum tobramycin concentration and to decrease the dosage or to prolong the dose interval in order to maintain trough concentrations below 2 mcg/ml.     

Early postnatal growth in preterm infants and cord blood leptin.

Although circulating leptin and insulin concentration is linked to intrauterine growth, fetal development and birth weight in full-term infants, there has been no enquiry into the influence of cord blood insulin and leptin for catch-up growth in preterm infants. The study evaluated the association of cord blood leptin with growth and weight gain of 96 premature babies during 6 months (corrected age). The temporal changes of anthropometric indexes over this period were calculated by repeated random regression (PROC MIXED) using SAS. Cord blood leptin was negatively associated with the rate of change in BMI (p=0.01) and length (p<0.001), from birth until 64 postnatal weeks. Insulin was positively associated with the change rate in BMI (p=0.03); however, this disappeared when adjusted for birth weight. For the first time, the association between lower leptin levels with greater catch up growth is shown for both BMI and length among preterm children. In conclusion, leptin levels at birth, but not insulin levels, predict growth rates.     

氨茶碱对早产儿脑血流的影响

目的　研究不同胎龄早产儿脑血流(cerebral blood flow,CBF)特点及氨茶碱对早产儿CBF的影响. 方法　 46例早产儿分为早产Ⅰ组和早产Ⅱ组.早产Ⅰ组胎龄≤32周,24例;早产Ⅱ组32周<胎龄<36周,22例.使用彩色多普勒超声诊断仪动态监测早产儿(出生3 d内)在输注氨茶碱前0.5 h,输注完后1、2和6 h双侧大脑前动脉(anterior cerebal artery,ACA)及大脑中动脉(media cerebal artery,MCA)的三项脑血流速度(cerebral blood flow velocity,CBFV)参数即收缩期峰值流速(peak-systolic velocity,PSV)、舒张期末峰值流速(end-diastolic velocity,EDV)和时间平均血流速度(time-mean flow velocity,TMFV)及搏动指数(pulsatility index,PI)、阻力指数(resistance index,RI).同时测量肱动脉平均动脉压(mean arterial blood pressure,MABP)变化.并与20例正常足月儿(对照组)的脑血流参数进行比较. 结果 左侧ACA(L-ACA)、MCA(L-MAC)和右侧ACA(R-ACA)、MCA(R-MAC)的PSV、EDV、TMFV在早产Ⅰ组低于早产Ⅱ组,这两组又分别低于对照组,差异均有统计学意义(P<0.05);而PI和RI在三组间差异无统计学意义(P＞0.05);三组中同侧MCA的CBFV高于ACA,差异有统计学意义(P<0.05),但三组左右两侧MCA和ACA的差异无统计学意义(P＞0.05).静脉输注完氨茶碱后1和2 h,早产儿ACA和MCA的CBFV均显著下降,与用药前比较差异有统计学意义(P<0.05),输注完后6 h CBFV回升至用药前水平,用药前后ACA和MCA的PI或RI无明显改变(P＞0.05).输注完后1、2或6 h两组早产儿左侧ACA或MCA的CBFV分别与右侧ACA或MCA的CBFV比较,组内及组问差异均无统计学意义(P＞0.05).两组早产儿用药前后各时间点肱动脉MABP差异无统计学意义(P＞0.05),各组不同时间点的MABP与双侧ACA、MCA-TMFV之间均不存在直线相关关系(P＞0.05). 结论 早产儿CBFV明显低于正常足月儿,CBFV随胎龄增长而增加;早产儿双侧MCA的CBFV显著高于ACA;使用氨茶碱早期可能引起早产儿脑血流波动,临床上应合理用药,加强监护.     

Influence of maternal pre-eclampsia on VEGF/PlGF heterodimer levels in preterm infants

Objective: To measure VEGF/PlGF heterodimer levels in preterm infants born to mothers with preeclampsia.

Methods: Neonates with birth weight <2000?g and gestational age ≤34 weeks were divided into two groups: born to mothers with Preeclampsia (PE) and controls. Neonates transferred from outside after the 72nd hour of life, death before blood collection, major congenital malformations or inborn errors of metabolism, and mothers with multiple pregnancies, STORCH complex infections, HIV or autoimmune conditions were excluded. Blood was collected within 72?h of birth and again at 28 days. VEGF/PlGF heterodimer levels were measured by ELISA.

Results: We included 73 neonates (24 born to mothers with PE and 49 without PE). Mean gestational age was 30.32?±?2.88 weeks and mean birth weight was 1288.62?±?462.22?g. Median VEGF/PlGF levels were significantly higher in infants born to mothers with PE. VEGF/PlGF levels were inversely proportional to birth weight. There were no between-group differences in blood samples collected at age 28 days.

Conclusion: Higher VEGF/PlGF levels were higher in neonates exposed to PE, and there was a significant negative correlation between birth weight and VEGF/PlGF levels. Further studies to elucidate the role of this substance in the fetal and neonatal period are needed.