Avoidance of red blood cell transfusion in an extremely preterm infant given recombinant human erythropoietin therapy

To avoid red blood cell (RBC) transfusions, recombinant human erythropoietin (rHuEPO) was given to an infant born at a gestation of 26 weeks and a birthweight of 830 g to parents who were Jehovah's Witnesses. The infant had hyaline membrane disease and required 52 days of assisted ventilation and 19 days of oxygen therapy. He received theophylline therapy for 61 days for recurrent apnoea and bradycardia. He developed bilateral intraventricular haemorrhage (IVH) and left-sided periventricular leucomalacia (PVL). Intravenous rHuEPO was started on day 1 at 200 U/kg per day for 1 month followed by subcutaneous rHuEPO 400 U/kg three times a week for 6 more weeks, supplemented with Vitamin E, folic acid and iron. Blood sampling was kept to a minimum and non-invasive blood-gas monitoring was used consistently. Consequently, the estimated cumulative volume of blood loss from sampling was only 21 mL during his hospital stay. His haemoglobin (Hb) was 150 g / L at birth and this fell to below 100 g / L from day 25 onwards. His lowest leucocyte count was 3.6x10⁹/L. He was discharged on day 83 with a Hb of 95 g/L, Hct of 29%, reticulocyte count of 2.8% and weight of 2400 g. At a postnatal age of 3 months, he had a Hb of 113 g/L. At 6 months, investigations showed: Hb 121 g/L, haematocrit 33%, reticulocyte 1% and a weight of 4.4 kg. He was readmitted to hospital once for an episode of vomiting and follow up to date showed developmental delay. Concerns remained whether the withholding of RBC transfusion in the infant was related to his IVH, PVL, prolonged recurrent apnoea and bradycardia and poor weight gain. Although rHuEPO therapy shows promise in reducing the need for RBC transfusions, its overall efficacy and safety remain to be proven and its routine use in preterm infants has to be weighed up against the potential benefits and risks of RBC transfusions.     

Enteral erythropoietin increases plasma erythropoietin level in preterm infants: a randomized controlled trial

OBJECTIVE: To evaluate the effects of enteral administration of recombinant human erythropoietin (rhEPO) on serum level of erythropoietin and erythropoiesis in preterm infants. STUDY DESIGN: Randomized controlled trial. SETTING: Level III NICU. SUBJECTS: 16 preterm infants less than 34 wk with birth weight less than 1800 g. INTERVENTION: Enteral rhEPO 400 U/kg, three times/week, plus FeSO4,3-6 mg/Kg/day ( Study group, n = 7) or FeSO4 only (Control group, n = 9). OUTCOME MEASURES: Hemoglobin, serum erythropoietin (EPO), reticulocyte count, and serum ferritin levels, measured at baseline, after 10 days and at discharge. RESULTS: Mean birth weight and gestational age for the Study and the Control groups were 1328.5 +/- 267.4 vs. 1392.8 +/- 196.7 g and 30.7 +/- 2.5 vs. 30.2 +/- 0.9 weeks, respectively. At discharge, there was no difference in hemoglobin or hematocrit but the reticulocyte counts were significantly higher in the Study group (1.4 +/- 0.7 vs. 0.7 +/- 0.4, P = 0.03). Serum erythropoietin level was significantly higher in the Study group (18 +/- 11 vs. 8.6 +/- 3.9 mU/mL, P = 0.006). Conversely, serum ferritin level was lower in the study group but did not achieve statistical significance. CONCLUSIONS: Enteral administration of rhEPO in preterm infants resulted in increase in serum erythropoietin and reticulocyte counts at the time of discharge without significantly affecting hemoglobin or hematocrit.     

Effect of recombinant human erythropoietin on transfusion needs in preterm infants

OBJECTIVE: To study the efficacy, safety and cost effectiveness of recombinant human erythropoietin (r-HuEPO) in reducing erythrocyte transfusion needs in very low birthweight (VLBW) infants. METHODS: We conducted a non-blind randomized controlled trial and assigned 100 VLBW infants, less than 33 weeks gestation, to receive either r-HuEPO 750 U/kg per week subcutaneously from day 5 to day 40 or no erythropoietin (EPO). Infants received oral iron 3-6 mg/kg per day from day 10. Transfusion needs were analysed for all enrolled infants and in five weight subgroups: birthweight of less than 600 g, 600-799 g, 800-999 g, 1000-1199 g and infants more than 1200 g. RESULTS: VLBW infants on r-HuEPO attained higher reticulocyte counts and haematocrit than control infants but the mean number of transfusions and volume of erythrocyte transfused per infant were not statistically different. Of infants 800-999 g at birth, the mean number of transfusions per infant was 2.1 compared with 3.5 transfusions per control infant (P = 0.04). Volume of erythrocytes transfused was 34.9 +/- 32.1 mL/kg in r-HuEPO-treated infants and 56.6 +/- 25.8 mL/kg in control infants (P = 0.03). The cost per patient for transfusion and EPO was S$388 for r-HuEPO recipient and S$438 for control infant. Blood pressure, neutrophil count, platelet count and complications of prematurity were not significantly different in both groups of VLBW infants. CONCLUSION: r-HuEPO at 750 U/kg per week stimulates erythropoiesis in VLBW infants but significantly reduces the need for erythrocyte transfusion only in infants weighing 800-999 g at birth.     

Erythropoietin in very preterm infants

Three neonates (a male and two females of gestational ages 27, 27 and 29 weeks with birthweight 985,660 and 1130 g), born to parents who are Jehovah's Witnesses, were admitted to our neonatal intensive care unit over a 2 month period in 1992. Human recombinant erythropoietin (rHuEpo, 200 u/kg sc. on alternate days for 6-8 weeks) was started early in conjunction with strict control of blood sampling in an attempt to avoid the need for blood transfusion. The lowest haemoglobin recorded was 95 g/L at 35 days of age in the first infant. The amount of blood withdrawn for sampling was 21.4 mL, 20.7 mL and 5.5 mL, respectively. All were discharged near their expected birthdate, never having received a blood transfusion in the Nursery. It is possible to manage sick, very preterm, very low birthweight neonates in a neonatal intensive care setting without the use of blood transfusions by the early use of rHuEpo in conjunction with strict control of blood sampling.     

Recombinant human erythropoietin therapy in low-birthweight preterm infants: A prospective controlled study

BACKGROUND: This study aimed to detect the effectiveness of recombinant human erythropoietin therapy in preventing premature anemia in low-birthweight preterm infants. METHODS: A total of 292 premature infants who were born earlier than 33 gestational weeks and smaller than 1500 g birthweight were enrolled into the study. In addition to their conventional supportive therapy (medications), recombinant human erythropoietin 200 U/kg twice a week, subcutaneously, was given to randomly selected 142 premature infants for 6 weeks. The blood count variables and need for transfusions were compared with the remaining 150 premature infants during 6 months follow up. RESULTS: Serum erythropoietin levels were 11.3 +/- 6.1 mU/mL and 38.3 +/- 19.1 mU/mL in the erythropoietin group before and at the fourth week of the study, respectively (P < 0.001). Reticulocyte counts of the group treated with erythropoietin were 146 x 10(6) +/- 28 x 10(6)/mL and 122 x 10(6) +/- 27 x 10(6)/mL at the fourth and seventh week of the study, respectively, and these values were significantly higher when compared with the control group (P < 0.001 and P < 0.001). At the same period, hematocrit values were also found to be higher in the treatment group than the control group (P < 0.001). Serum ferritin levels were lower in the treatment group compared with the control group at the fourth week of the study. No side-effects related to erythropoietin usage were encountered. The need for packed cell transfusions were 47% in the group treated with erythropoietin and 62.6% in the control group. A statistically significant difference was found for transfusion needs between the control and treatment groups (P < 0.001). CONCLUSION: Recombinant erythropoietin is effective therapy for maintaining stable hematocrit levels in low-birthweight preterm infants and prevents the need for blood transfusions.     

Effect of holding on co-regulation in preterm infants: A randomized controlled trial

Objective

To determine whether kangaroo holding of healthy preterm infants over the first eight weeks of an infant's life facilitates co-regulation of salivary cortisol between mother and infant.

Study Design

Randomized control trial. Infants were assigned to receive 1 h of daily kangaroo (skin-to-skin contact on the chest of mother) or blanket holding (dressed and held in mother's arms). A registered nurse visited mothers weekly for eight weeks to encourage holding and provide information about infant development. A control group had no holding restrictions and received weekly brief social visits.

Subjects

The study included 79 preterm infants, born between 32 and 35 weeks gestational age and were a mean of 15 days (± 5.7) at enrollment.

Outcome Measures

Co-regulation was conceptualized as progressive reduction in the absolute difference between mother and infant cortisol levels across 60 min of holding at each holding session. Mother and infant cortisol levels were measured before holding and at 30 and 60 min after holding began during three holding sessions (baseline and at two and eight weeks after study initiation). Primary analyses were conducted using hierarchical linear models.

Results

There was much variability in cortisol levels. Levels of mother and infant cortisol decreased during holding. No significant co-regulation occurred in any group at any holding session or over time.

Conclusions

Decreasing level of cortisol in both mothers and infants suggests that holding promoted the expected decline in stress hormone levels. However, supported holding methods did not differentially affect co-regulation compared to controls. Holding is pleasurable and stress may need to be present in order for mothers and infants to demonstrate co-regulation in cortisol levels.     

脐带延迟结扎和脐带挤压输血对早产儿脑血流动力学的影响：一项随机双盲对照试验

目的 比较脐带延迟结扎（DCC）和脐带挤压（UCM）输血对早产儿脑血流的影响。方法 该试验是一项单中心、前瞻性、双盲、随机对照临床试验。纳入2018年11月2日至2019年11月15日遂宁市中心医院出生、胎龄30~33⁺⁶周早产儿46名,随机分为DCC组（23例）和UCM组（23例）。主要结局指标包括生后0.5~1 h、（24±1）h、（48±1）h、（72±1）h超声多普勒测得的脑血流动力学参数：收缩期峰值流速（PSV）、舒张期峰值流速（EDV）和阻力指数（RI）。次要结局指标包括生后第1天检测的红细胞压积、血红蛋白、红细胞计数和血清总胆红素水平及住院期间颅内出血的发生率。结果 DCC组和UCM组实际进入统计分析的早产儿分别为21例和23例。DCC组和UCM组两组患儿生后各观察时间点PSV、EDV、RI差异无统计学意义（P > 0.05）;两组生后第1天红细胞压积、血红蛋白、红细胞计数和总胆红素水平及住院期间颅内出血发生率的比较差异无统计学意义（P > 0.05）。结论 DCC和UCM对30~33⁺⁶周早产儿脑血流动力学的影响无明显不同。     

国产重组人类促红细胞生成素防治早产儿贫血的临床效果研究

为评价国产重组人类促红细胞生成素（rhEPO）防治早产儿贫血的效果和安全性，将40例胎龄≤34周的早产儿随机分为治疗组及对照组各20例。治疗组予国产rhEPO750IU／（kg.w），每周分3次皮下注射，用药6周；对照组未用rhEPO；两组早产儿均口服铁剂。结果显示治疗组用药后血清促工细胞生成素水平显著高于对照组（P＜0．01）；治疗组血红蛋白、红细胞压积比、网积红细胞显著高于对照组（P＜0．01）；血清铁蛋白水平在用药后治疗组明显低于对照组（P＜0．01）；治疗组输血率较对照组明显减少（P＜0．01）；治疗组体重增长指标高于对照组9P＜0．05）。研究提示，国产rhEPO能有效防治早产儿贫血，且用药安全，无明显副作用。     

Prediction of transfusions in extremely low-birthweight infants in the erythropoietin era

BACKGROUND: The purpose of the present paper was to detect the clinical factors most predictive of red blood cell (RBC) transfusion in extremely low-birthweight (ELBW) infants in the recombinant human erythropoietin era. METHODS: Between 1995 and 2000, 66 ELBW infants were admitted to a level III neonatal intensive care unit. Fifty-four of 66 infants were eligible for enrollment in the present study. Infants were treated with erythropoietin 200 IU/kg per dose s.c. twice a week with 4-6 mg/kg per day iron supplement. RESULTS: The mean gestational age and birthweight were 26.5 +/- 2.1 weeks and 776 +/- 134 g, respectively. Ten of 54 ELBW infants (18.5%) died during the first 21 days. Eight of 10 dead infants (80.0%) and 27 of 44 surviving infants (61.4%) received one or more RBC transfusions. The overall requirement for RBC transfusions in the surviving infants was 3.0 +/- 3.2 per infant/hospital course (range: 0-9) . There were significant differences in gestational weeks, birthweight, initial hemoglobin value, 5 min Apgar score, phlebotomy loss, phlebotomy loss/birthweight, duration of mechanical ventilation, duration of oxygen supplement, and incidence of both intraventricular hemorrhage and chronic lung disease between the transfused and non-transfused group. The predictive variables, initial hemoglobin level (odds ratio [OR] 2.61; 1 g/dL), birthweight (OR 3.00; 100 g), and gestational week (OR 1.89; 1 week), were found to be most predictive for transfusion on logistic regression analysis. CONCLUSION: ELBW infants are still the population at greatest risk for repeated blood transfusions after introduction of erythropoietin treatment. If labor develops, it is often impossible to extend the pregnancy period, therefore efforts should be made to increase hemoglobin level at birth.     

乳糖酶添加剂对早产儿乳糖不耐受有效性和安全性的前瞻性随机对照研究

目的 探讨乳糖酶添加剂对改善早产儿乳糖不耐受的有效性和安全性.方法 选取上海交通大学医学院附属新华医院2018年1月至2019年12月收治的有乳糖不耐受症状的早产儿60例纳入研究,随机分为乳糖酶治疗组和对照组,每组30例.乳糖酶治疗组给予乳糖酶添加剂4滴(180 mg)加入早产儿配方奶或母乳中;对照组给予安慰剂,同时予...     

不同维持剂量枸橼酸咖啡因对极早产儿呼吸窘迫综合征撤机影响：前瞻性随机对照研究

目的 分析不同维持剂量枸橼酸咖啡因对胎龄≤32周极早产儿呼吸窘迫综合征（respiratory distress syndrome,RDS）撤机成功率的影响。 方法 前瞻性选取2016年1月至2018年12月该院收治的胎龄≤32周、需有创机械通气的162例RDS早产儿为研究对象,随机分为咖啡因高剂量组和低剂量组,每组81例。两组患儿生后6 h内均给予负荷量咖啡因20 mg/kg治疗,24 h后高、低剂量组分别给予每日10 mg/kg和5 mg/kg的咖啡因维持剂量治疗。比较两组患儿撤机后48 h内的重新插管率、总通气时间、氧疗时间、肠内喂养及体重增长情况、住院期间并发症和不良反应的发生率。 结果 高剂量组撤机后48 h内再插管率低于低剂量组（P<0.05）,两组主要撤机失败原因均为频繁呼吸暂停。高剂量组总机械通气时间及氧疗时间均短于低剂量组（P<0.05）。两组患儿达完全肠内喂养时间、平均每天体重增长量、出院时体重及住院期间并发症（支气管肺发育不良、早产儿视网膜病、坏死性小肠结肠炎、颅内出血）和不良反应（心动过速、高血压、喂养不耐受）发生率比较差异均无统计学意义（P>0.05）。 结论 高维持剂量咖啡因可安全有效降低胎龄≤32周早产儿RDS撤机后呼吸暂停发生率和撤机失败率,值得临床推广应用。 引用格式:     

口腔运动干预改善早产儿脑功能发育的随机对照研究

目的 探讨口腔运动干预(oral motor intervention,OMI)对早产儿脑功能发育的影响.方法 采用分层随机分组方法,将112例早产儿按胎龄分为小胎龄(30～31+6周)及大胎龄(32～33+6周)两层,再随机分为对照组(分别23、22例)和干预组(分别24、23例).对照组予以常规治疗,干预组在此基础...     

BiliBlanket phototherapy system versus conventional phototherapy: A randomized controlled trial in preterm infants

Objective: This study compares the use of standard overhead fluorescent phototherapy units with the BiliBlanket a woven fibreoptic pad which delivers high intensity light with no ultraviolet or infrared irradiation in the treatment of jaundice in preterm infants.
Methodology: We chose to study infants between 800 and 2500 g, with strict criteria for commencing and ceasing phototherapy. Serum bilirubin levels were followed at 12–24 h intervals until 24 h after cessation of phototherapy. Infants were allocated at random to receive either conventional phototherapy or the BiliBlanket.
Results: There were 24 infants in the conventional group and 20 in the BiliBlanket group. Mean duration of phototherapy was compared and was 44 h for the conventional group versus 42 h for the BiliBlanket group.
Conclusions: We have shown that the BiliBlanket is as effective as conventional phototherapy and was well accepted by nursing staff and parents.     

Acquired cytomegalovirus infection and blood transfusion in preterm infants

The urinary excretion of cytomegalovirus (CMV) DNA, amplified by polymerase chain reaction using two pairs of primers for late antigen (LA) and major immediate-early antigen (MIE), and serum CMV IgM were examined in 85 pre-term infants (birth-weight less than 2000 g) on admission and monthly until 6 months after birth. Of these 85 infants, 27 had blood exchange transfusions (BET) and 28 had bolus blood transfusions two to nine times. Fifteen of 27 infants underwent BET with blood that had been filtered through Pall RC100 leukocyte removal filter; the other 12 with unfiltered blood. Neither urinary CMV DNA nor serum CMV-specific IgM was detected at birth in any of the 85 pre-term infants; during the first 6 months after birth urinary CMV DNA, for both MIE and LA, appeared in 22 of the 85 infants (25.9%) and CMV IgM was positive in 14 of the 85 (16.5%). Nine of the 12 (75%) infants who received BET of unfiltered blood showed a significantly higher prevalence of urinary CMV DNA compared to the infants in the other three groups (i.e., those who received no blood transfusion, those who had bolus blood transfusions, or those who received BET of filtered blood; P < 0.01 in each instance). In a logistic regression model, CMV, DNA urinary excretion was significantly associated with the mode of blood transfusion (unfiltered BET), and the Odds ratio was 38.9 (95% confidence interval, 9.4–160). There was no significant association with other independent variables such as gender, mother's seropositivity, gestational age, birth-weight or delivery mode. In addition breast milk feeding was not likely to have influence on the high incidence of CMV infection among the infants who received the BET with unfiltered blood. In regions where the incidence of CMV seropositivity is high, as it is in the Japanese population, reduction of white blood cell and cellular blood components, such as platelets, through filtration is a convenient and effective way to successfully reduce the occurrence of acquired CMV infection in high-risk neonates.     

早产儿代谢性骨病4例

早产儿出生后由于消化道功能极不成熟,发生坏死性小肠结肠炎的风险很高,常常不能顺利地开始胃肠道喂养,而需要较长时间的胃肠外营养支持。胃肠外营养虽然给早产儿提供必要的营养素使其得以存活,但是也可以导致一系列的代谢并发症,给早产儿的脏器功能和生长发育带来严重影响。早产儿代谢性骨病（Metabolic bone disease of prematurity）便是其中之一,该疾病不仅影响婴儿期的生长,而且可以影响成年后的骨骼健康。虽然该疾病并非罕见,但在我国一直未得到重视,国内几乎没有相关报道。随着早产儿胃肠外营养技术在各地的推广,我们认为很有必要对该疾病进行报道,以引起广大新生儿科医师的关注。