Erythropoietin as treatment for late hyporegenerative anemia in neonates with Rh hemolytic disease after in utero exchange transfusion.

We report the effects of recombinant human erythropoietin (rHuEPO) in the treatment of late hyporegenerative anemia in 2 neonates with Rh hemolytic disease who had received several in utero exchange transfusions. In both cases anemia occurred at 6 weeks of age and we started therapy at approximately 70 days of age. We used rHuEPO at 250 U/kg three times a week. We also used high-dose intravenous immunoglobulin therapy. One week after initiation of erythropoietin treatment, an increase in reticulocyte count and Hb level was noted in our 2 patients. They did not require further erythrocyte transfusions but they already had received two transfusions after birth. There were no side effects attributable to rHuEPO treatment.     

Fetal hematocrit decrease after repeated intravascular transfusions in alloimmunized pregnancies

Background The aim of this study is to evaluate the fetal hematocrit (Hct) decrease along repeated intravascular intrauterine fetal transfusions (IUTs) and test the hypothesis that, after consecutive IUTs, there is a lower Hct drop off. Methods From July 1996 to June 2006, pregnancies submitted to IUT for fetal hemolytic anemia treatment had their data assessed. The daily rate of decrease in fetal Hct was calculated by dividing the difference between the posttransfusion Hct of the previous IUT and the pretransfusion Hct of the current IUT, by the number of days between the transfusions. Fetuses with other abnormalities or submitted to intraperitoneal transfusions were excluded. Results Eighty-one women were submitted to IUT during the alluded period, ensuing 296 intrauterine transfusions. The perinatal survival was 89.9% (n = 80), with 92.0% (n = 69) of nonhydropic fetuses survival. Hydropic fetuses showed higher hematocrit drop off than nonhydropic ones (P < 0.01). Compared to the interval between the first and second IUT, the daily fetal Hct decline was lower after the third one (P < 0.05). Stratifying by the presence of hydrops, nonhydropic fetuses showed a smaller decrease at the third and fourth intervals (P < 0.01 and P < 0.05, respectively). Among hydropic fetuses, there is a trend of smaller Hct decrease along successive IUTs (interval 3, P = 0.08; interval 4, P = 0.07; and interval 5, P = 0.10). Conclusions Following some IUTs, fetal hematocrit decrease is lower and larger intervals between the transfusions could be accomplished. Multicenter studies should investigate an algorithm for timing subsequent IUTs, considering Doppler values, estimated fetal hematocrit decline and other parameters.     

Neonatal outcome of fetuses receiving intrauterine transfusion for severe hydrops complicated by Rhesus hemolytic disease

ObjectiveTo evaluate neonatal outcomes among a homogeneous group of fetuses with severe hydrops treated with intrauterine transfusion (IUT).MethodsIn a prospective study at Dokuz Eylul University School of Medicine, Izmir, Turkey, outcomes were compared for 35 IUTs carried out between 2005 and 2010 in 19 pregnancies that were complicated by Rhesus D hemolytic disease with severely hydropic fetuses.ResultsThere was no correlation between the number of IUTs and the duration of phototherapy or number of exchange transfusions. After delivery, 36% (7/19) of neonates tested positive in a direct Coombs test and their requirement for exchange transfusion was higher than that of neonates who tested negative. The neonatal survival rate was 73.7%. Admission to the neonatal intensive care unit was 78%, and the median duration of neonatal unit stay was 4 days (range, 1–77 days). Only 1 newborn had hearing impairment.ConclusionIUT is a unique, gold standard treatment for severely hydropic fetuses. When treated optimally with IUT, fetuses with severe hydrops showed no increased risk of neurodevelopmental abnormalities. Factors affecting the survival of hydropic fetuses after IUT, and whether the number of IUTs performed affects the number of exchange transfusions required remain unclear.     

Late hyporegenerative anemia in neonates with rhesus hemolytic disease.

This study was conducted to determine the risk factors of the late hyporegenerative anemia in Rh-isoimmunized infants. Data on 36 infants with rhesus hemolytic disease were analyzed. The mean gestational age and birth weight were 36 +/- 1.3 weeks and 2837 +/- 403 grams respectively. Twenty-seven infants (75%) received between 2 and 8 intravascular intrauterine blood transfusions. Fourteen infants (39%) required simple packed red blood cell transfusions and 11 infants (31%) required exchange blood transfusion in the immediate postnatal period. Thirty infants (83%) developed late anemia and required blood transfusions at a mean postnatal age of 43.3 +/- 15.7 days. Sixty-four percent of infants who had exchange blood transfusions did not develop late anemia, while 92% of infants who did not require exchange blood transfusion developed late anemia, and the difference was statistically significant (P = 0.035). Serum erythropoietin levels were determined in 8 infants immediately before simple transfusion for late anemia. The media serum erythropoietin level was 21.2 mU/ml, ranging between less than 10 to 114.2 mU/ml. We conclude that late hyporegenerative anemia is common among Rh isoimmunized infants, regardless of the intravascular intrauterine transfusion. Exchange blood transfusion was associated with less occurrence of late anemia.     

Antenatal maternal administration of phenobarbital for the prevention of exchange transfusion in neonates with hemolytic disease of the fetus and newborn

OBJECTIVE: Hemolytic disease of the fetus and newborn infant (HDFN) can be associated with bilirubin encephalopathy, which is usually averted through neonatal exchange transfusions (EXT). However, EXT can be associated with significant procedure-related morbidity. We hypothesized that maternal oral administration of phenobarbital (PB) to women with HDFN would reduce the rate of EXT. STUDY DESIGN: Cases of HDFN from January 1985 to June 2003 were reviewed. All patients who underwent serial intrauterine transfusions (IUTs) for red cell alloimmunization were included. Patients were offered oral phenobarbital (30 mg 3 times a day) after their last IUT in an effort to enhance fetal hepatic maturity. Variables studied included gestational age and hemoglobin multiples of the median at first transfusion and delivery, peak neonatal bilirubin, need for exchange transfusion, and maternal PB administration. Multivariate regression analysis was applied to determine relative risks and 95% CIs. RESULTS: Seventy-one patients met study criteria; 29% of the neonates underwent EXT. The use of antenatal PB was associated with a decreased incidence of EXT, 9% versus 52% ( P < .01). After controlling for confounding variables, the relative risk for EXT after antenatal PB administration was 0.23 (95% CI: 0.06-0.76). CONCLUSION: Maternal administration of PB reduces the need for neonatal EXTs in HDFN.     

Reassuring fetal middle cerebral artery doppler velocimetry in alloimmunised pregnancies: neonatal outcomes without invasive procedures

OBJECTIVE: To assess the neonatal outcome in red blood cell alloimmunised pregnancies at increased risk of fetal anaemia where invasive testing was avoided based on reassuring middle cerebral artery (MCA) Doppler velocity results. METHODS: We included 28 alloimmunised pregnant women at significant risk of fetal or neonatal anaemia who did not have invasive testing because of reassuring MCA Doppler velocimetry. Women requiring invasive testing or intrauterine transfusion were excluded. Outcome measures were admission to neonatal intensive care unit, cord haemoglobin and bilirubin levels and neonatal therapy. RESULTS: Ten neonates (36%) were anaemic at birth while 18 (64%) had normal haemoglobin. Seven neonates (25%) did not require any form of neonatal therapy, 10 (36%) had phototherapy only, 7 (25%) required exchange transfusions and 4 (14%) top-up transfusions. There were no treatment-related complications. Mean cord haemoglobin was 13.9 g/dl (range 7-18.9) and mean bilirubin was 84.1 micromol/l (range 29-192). CONCLUSION: Avoiding invasive procedures in pregnancies at risk of fetal anaemia by relying on reassuring MCA Doppler velocimetry did not result in life-threatening fetal or neonatal morbidities. The extent of neonatal therapy was acceptable. The routine use of this test can lead to less unnecessary invasive procedures in at-risk fetuses.     

Effect of recombinant erythropoietin on "late" transfusions in the neonatal intensive care unit: a meta-analysis.

OBJECTIVES: Using the approach of a meta-analysis, we sought to determine whether the administration of recombinant erythropoietin (rEpo) to very low birth weight (VLBW) infants, after the first week of life, results in fewer "late" transfusions. STUDY DESIGN AND METHODS: The guidelines set forth by the Cochrane Neonatal Review Group were used to identify all relevant studies. Medline was searched from January 1990 to November of 2000. Studies that used a randomized, placebo-controlled, and double-masked design were deemed acceptable. RESULTS: Eight studies meet the inclusion criteria. These involved 357 VLBW neonates: 183 rEpo and 174 placebo recipients. The neonates in the rEpo group received fewer erythrocyte transfusions during the study period than did those in the placebo group; the common odds ratio (OR)=0.33; 95% confidence interval (CI) 0.21-0.51. Furthermore, the rEpo effect size was a function of the dose of rEpo administered (p=0.0001). CONCLUSION: A meta-analysis of the most scientifically rigorous studies on this topic indicates that administration of rEpo to VLBW infants reduces "late" erythrocyte transfusions in a dose-dependent manner.     

G/A polymorphism at -258 of the hepatic glucokinase promoter is not associated with decreased birth weight in preterm neonates

BACKGROUND: A high percentage of preterm neonates are born small for gestational age (SGA). These children show a high morbidity and mortality after birth and often develop insulin resistance with ensuing impaired glucose metabolism in adulthood. Since insulin is important for intrauterine growth, fetal insulin resistance might also influence birth weight of preterm neonates. OBJECTIVES: A common polymorphism in the promoter region of the human hepatic glucokinase (-258) is associated with a decreased promoter activity, an enhanced insulin secretion, and hypertension and hepatic insulin resistance in adults. In this pilot study we wanted to investigate whether the G/A polymorphism at -258 of the hepatic glucokinase promoter has an effect on birth weight of preterm neonates and therefore might constitute a genotype leading to low birth weight and metabolic defects. METHODS: We enrolled 106 preterm neonates in our study. 44 of them were SGA and 62 AGA neonates. We extracted DNA from a buccal swab and identified the polymorphism by PCR-ARMS. RESULTS: We found no difference in the prevalence of the polymorphism in either groups. CONCLUSION: The polymorphism at -258 of the fetal hepatic glucokinase promoter is most probably not of a major relevance in the pathophysiology of low birth weight in preterm neonates.     

The results of prenatal treatment of fetal hemolytic disease in clinic material

Authors analysed results of prenatal treatment of 68 cases of fetal haemolytic disease in the Department of Obstetrics and Gynaecology in Bytom in the years 1994-1999. We evaluated a clinic value of umbilical vessels punctures and intrauterine intra-vessel transfusions as a basic methods of treatment of this disease. In the analysis we took into consideration frequency of complications, character of complications and condition of neonates. The most important in the treatment of fetal haemolytic disease are early diagnostics and treatment procedures performed in the appropriate prepared Centres.     

Hydrops fetalis and neonatal death from human parvovirus B19: an unusual complication

A case of prenatally diagnosed human parvovirus B19 (HPVB19) infection is reported. The neonate died after intrauterine therapy and premature delivery.The fetus was diagnosed with oedema, cardiomegaly, poor myocardial contractility and a pericardial effusion at 24/40 weeks' gestation. Ultrasound using colour flow Doppler showed a midcerebral artery peak systolic velocity (MCA PSV) raised at 45 cm/s, suggesting fetal anaemia. This was confirmed on fetal blood sampling, but recovery was suggested with a reticulocyte count of 16.8%. The fetal karyotype was normal, 46,XY. Fetal IgM was positive for Parvovirus. A week later, severe fetal anaemia was suspected and intrauterine transfusion carried out. Altogether three transfusions were given. At 31/40 weeks, the mother presented to her local hospital with suspected preterm labour, a caesarean section was carried out because of fetal compromise on cardiotocography. The baby was in poor condition at birth and resuscitation was stopped at 45 min of age. The post-mortem examination confirmed the hydrops and proved persistent Parvovirus infection, cardiac involvement and severe liver fibrosis.HPVB19 generally follows a benign course with intrauterine therapy; however, in this case, the fetus died despite successful transfusions. The reasons for this are discussed.     

Early Erythropoietin for Preventing Red Blood Cell Transfusion in Preterm and/or Low Birth Weight Infants

Background: Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anemia. Objectives: To assess the effectiveness and safety of early initiation of EPO in reducing red blood cell (RBC) transfusions in preterm and/or low birth weight infants. Search Methods: The Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published in Pediatric Research and reference lists of identified trials and reviews were searched through July 2009. Selection Criteria: Randomized or quasi-randomized controlled trials of early (<8 days of age) initiation of EPO treatment vs. placebo or no intervention in preterm and/or low birth weight neonates. Data Collection and Analysis: Data collection and analysis were accomplished using the methods of the Cochrane Neonatal Review Group. Main Results: Update includes 27 studies that enrolled 2,219 preterm infants. Early EPO reduced the risk of the 'use of one or more RBC transfusions' [typical RR; 0.80 (95% CI 0.75, 0.86); 16 studies, 1,825 infants] (fig. 1). Early EPO led to a significant reduction in the total volume (ml/kg) of blood transfused per infant and in the number of transfusions per infant. Two studies (n = 188) reported a significant reduction in the number of donors to whom the infant was exposed. There was a significant increase in the risk of stage ≥3 retinopathy of prematurity (ROP) in the early EPO group [typical RR; 1.65 (95% CI 1.12, 2.43); 8 studies, 984 infants] (fig. 2). The rates for mortality and other neonatal morbidities were not significantly changed by early EPO treatment nor were neurodevelopmental outcomes at 18-22 months in the small number of infants tested to date.     

Placental transfusion: umbilical cord clamping and preterm infants.

OBJECTIVE: To investigate the clinical effects of early versus late cord clamping in preterm infants. STUDY DESIGN: A total of 32 premature infants were prospectively randomized. The following parameters were measured: Initial spun hematocrit (Hct), hemoglobin (Hgb), red blood cell (RBC) counts, frequency of blood transfusions, peak serum bilirubin, mean blood pressure (MBP), oxygen index, intraventricular hemorrhage, and significant patent ductus arteriosus (PDA). RESULTS: Over the 4-week study period, the delayed cord clamping (DCC) group exhibited a decrease in the frequency of blood transfusion (p < 0.001) and also a decrease in albumin transfusions over the first 24 hours (p < 0.03). MBP in the first 4 hours was higher in the DCC group (p < 0.01), and there were statistically significant increases in Hct (21%), Hgb (23%), and RBC count (21%) compared with the early cord clamping group. The risks of patent ductus arteriosus, hyperbilirubinemia, or intraventricular hemorrhage were similar in both groups. Late clamping of the umbilical cord had little or no effect on the oxygen index. CONCLUSION: DCC significantly reduced the requirement for blood and albumin transfusion. It also increased the initial Hct, RBC count, Hgb levels, and MBP.     

Treatment of fetal anemia in Rh isoimmunized pregnancies with intrauterine fetal blood transfusion

Introduction

Despite the availability of prophylactic rhesus immune globulin, hemolytic disease of the newborn and fetal death (hydrops fetalis) due to rhesus alloimmunization, is still a major contributor to perinatal morbidity and mortality in India. Pregnancy outcome after fetal therapy with ultrasound guided intrauterine transfusion (IUT) for fetal anemia was studied.

Methods

A prospective cohort study of 99 Rh isoimmunized pregnancies, Indirect Coomb’s test Positive (ICT > 1:16) was conducted from July 2002 to June 2007. Intensive fetal monitoring by sériai ultrasound and middle cerebral artery peak systolic velocity using Color Doppler was performed to detect fetal anemia. When necessary, invasive testing with cordocentesis for Hb, PCV was per-formed if pregnancy was less than 32–34 weeks gestation. If PCV was <30, or there was fetal hydrops, Ultrasound guided intrauterine transfusion was carried out by the intravascular (IVT) or the intraperitoneal (IPT) routes. Primary outcome variables were fetal survival in relation to gestational age and procedure related factors.

Result

Of 99 pregnancies, 43 cases (25 — hydropic, 18-nonhydropic fetuses) required 135 intrauterine blood transfusions. The rest 56 pregnancies were managed conservatively and did not need IUT. IUTs were performed when indicated starting from 16 weeks (IPT) and 21 weeks (IVT) of gestation by the intraperitoneal / intravascular routes respectively. Pre-transfusion Hb ranged from 3g% to 8g%. The amount of blood transfused varied from 10 ml to > 110 ml depending on the period of gestation and degree of fetal anemia. The number of transfusions per pregnancy was 1–7, at intervals of 1–4 weeks, till delivery at 28 to 36 weeks of gestation. Survival of hydropic babies (88%) was almost similar to those without hydrops (83.3%) Prognosis was slightly better in Rh isoimmunized pregnancies not requiring IUT (94%) compared to fetuses receiving transfusions (85.6%)

Conclusion

Intrauterine fetal blood transfusion was found to be the only life saving therapy, and very effective in the management of preterm Rh isoimmunized pregnancies. Results are comparable with the best centers in the world, hence early referral to specialized centers with expertise of specialized intensive fetal monitoring for early diagnosis of fetal anemia, and of intrauterine fetal blood transfusion are important for optimal perinatal outcome.     

Neonatal necrotizing enterocolitis following intrauterine transfusions: is there an association?

The case of a neonate with necrotizing enterocolitis (NEC) following intrauterine transfusions (IUTs) for Rhesus hemolytic disease (RHD) prompted us to undertake a retrospective study (1995-2002) to determine whether there is an association between IUT and NEC. Maternal and neonatal demographics, and details concerning IUT and definite (> or =Stage II) NEC, were collected. Chi2 tests of association were performed. In our population 281/38,200 (0.73%) pregnancies were complicated by RHD. Fetal anemia necessitated IUT in 25/281 pregnancies. Definite NEC occurred in 59/11,814 (very low birth weight=1874) neonatal admissions. Except for the index case, no other neonate developed NEC following IUT. No significant association was found between IUT and NEC.     

Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death

To assess the role of fetal blood sampling and intrauterine transfusion in monochorionic (MC) multiple pregnancy complicated by single intrauterine death (IUD), we reviewed ten cases over a 4-year period in a tertiary referral centre which underwent fetal blood sampling within 24 h of death of its MC co-twin. Intrauterine rescue transfusion was performed in all seven anaemic fetuses (hematocrit; Hct < 30%) to raise the fetal Hct to > or = 40%. The rationale was to prevent death and/or brain injury. Two fetuses, which were severely acidaemic at blood sampling, died in utero within 24 h of the procedure. In two cases, the surviving twins manifested abnormal sonographic findings of the fetal brain 2-5 weeks later and underwent late termination. In two cases, the pregnancies continued uneventfully until delivery at 35 and 40 weeks' gestation with good neonatal outcome. In one case the co-twin delivered 1 week later at 29 weeks but died within 12 h. Fetuses without anaemia were not transfused and had normal clinical outcomes. We suggest that intrauterine rescue transfusion before the development of severe acidaemia in anaemic surviving MC co-twins may prevent fetal death, but does not necessarily prevent brain injury. Until its role becomes clearer, we recommend that its use be restricted to situations in which the parents and the local jurisdiction allow late termination as an option if brain injury subsequently manifests on ultrasound.     

Complications of intrauterine intravascular transfusion for fetal anemia due to maternal red-cell alloimmunization

OBJECTIVE: The purpose of this study was to establish the true procedure-related complication rate of intrauterine transfusion therapy. STUDY DESIGN: A cohort study of 254 fetuses treated with 740 intrauterine blood transfusions for red-cell alloimmunization in a single center in the years 1988 to 2001. Our database was searched for perinatal deaths, emergency deliveries, infections, and preterm rupture of membranes associated with intrauterine blood transfusion. Complications were categorized by two independent obstetricians as procedure-related (PR) or not procedure-related (NPR). Logistic regression analysis was used to identify risk factors for complications. RESULTS: Overall survival was 225/254 (89%). Fetal death occurred in 19 cases (7 PR) and neonatal death in 10 cases (5 PR). There were two cases of intrauterine infection with Escherichia coli (both PR) and two other cases of preterm premature rupture of membranes (1 PR) within a week of a procedure. Emergency delivery after a transfusion was performed in 18 pregnancies (15 PR). The total PR complication rate was 3.1%, resulting in an overall PR loss rate of 1.6% per procedure. Arterial puncture, transamniotic cord puncture, refraining from fetal paralysis, and advancing gestational age were associated with the occurrence of PR complications. CONCLUSION: Our study shows that intrauterine transfusion is a safe procedure, with a relatively low PR perinatal loss rate. Arterial puncture and transamniotic cord needling carry a high risk for serious complications, whereas fetal paralysis improves the safety of the procedure. This information on risks of intrauterine transfusion therapy may help to further improve the safety of intrauterine transfusions. Data on complication rates of intrauterine transfusions are essential in counseling patients.     

Prevention of neonatal anemia with recombinant human erythropoietin: a cost-benefit analysis

A few years ago recombinant human erythropoietin (rh-EPO) has been introduced for the prophylaxis of anaemia of prematurity. Aim of this controlled study was a cost-effectiveness analysis of the prophylaxis with rh-EPO versus sole transfusion with packed red blood cells. In the study group 33 infants (gestational age 30 +/- 2 weeks, birthweight 1217 g +/- 244 g) were treated with rh-EPO beginning on the fifth day of life for a six week period. They received 750 IE rh-EPO/kg/week and transfusion with packed red blood cells when indicated. In the historic control group 33 infants (gestational age 29.2 +/- 1.9 weeks, birthweight 1181 g +/- 205 g) did not receive rh-EPO, patients were only transfused. Indication and guidelines for transfusion were identical for both groups. The number of transfusions was registered after 2 and 4 weeks of life and by the time of hospital discharge. The cost analysis was carried out by using current prices for packed red blood cells including material and processing and prices for rh-EPO (Neo-Recormon, Boehringer Mannheim). Infants in the study group received 1.39 +/- 1.94 transfusions per patient while patients in the control group needed 2.7 +/- 1.93 transfusions per patient (p < 0.05). Cost for treatment was slightly increased in the study group (DM 536,- vs. DM 459,-). Prophylaxis of anaemia of prematurity with recombinant human erythropoietin proved to be effective. Compared with sole blood transfusion treatment, expenses for the prophylaxis with rh-EPO were only little higher.     

Risk of cesarean section in singleton pregnancies after assisted reproductive techniques

OBJECTIVE: To evaluate the perinatal outcome of singleton pregnancies after assisted reproductive techniques in comparison with that in matched controls from spontaneous pregnancies. STUDY DESIGN: A total of 11,776 deliveries from January 1, 1995, to May 31, 2001, were subjected to retrospective analysis. Data on 259 neonates from singleton pregnancies after ovulation induction (n = 85, 32.8%), intrauterine insemination (n = 17, 6.6%) or in vitro fertilization (n = 157, 60.6%) were evaluated. The pregnancy outcome was compared with that for controls (n = 518) matched for age, gravidity and parity after spontaneous pregnancies. RESULTS: Cesarean section was significantly more frequent in the study group than in the control group (42.1% vs. 27.6%, P < .001, odds ratio [OR] 1.91, 95% confidence interval [CI] 1.39-2.61). The prevalence of preterm deliveries was not significantly higher (P = .40, OR 1.23, 95% CI .78-1.95) in the study group as compared with the controls (12.7% vs. 10.6%). There was no significant difference in intrauterine growth retardation between the two groups (9.3% vs. 6.2%, P = .14, OR 1.55, 95% CI .89-2.69). CONCLUSION: Singleton pregnancies after assisted reproductive techniques are associated with an increased rate of cesarean section, whereas neonatal outcome is not influenced.     

Effect of beginning recombinant erythropoietin treatment within the first week of life, among very-low-birth-weight neonates, on "early" and "late" erythrocyte transfusions: a meta-analysis.

OBJECTIVES: Erythrocyte transfusions to neonates can be categorized as "early" if given during the first 3 weeks of life and "late" if given thereafter. We used a meta-analysis to determine whether recombinant erythropoietin (rEpo) administration to very-low-birth-weight (VLBW, <1500 g) neonates, beginning in the first week of life, reduces either "early" or "late" transfusions. STUDY DESIGN AND METHODS: Studies that used a randomized, placebo-controlled, double-masked design were deemed acceptable. We identified 12 acceptable, relevant, clinical trials. Additional data not provided in the publications were obtained from two of the authors. RESULTS: The acceptable studies involved an aggregate of 561 rEpo and 529 placebo recipients. If rEpo was begun in the first week of life, the summary odds ratio (OR) for receiving any transfusion ("early" or "late") was 0.52, 95% confidence interval (CI): 0.34 to 0.79 (p=0.001). The OR for receiving an "early" transfusion was 0.54 (95% CI: 0.25 to 1.15; p=0.055), and the OR for receiving a "late" transfusion was 0.56 (95% CI: 0.37 to 0.83; p=0.036). Heterogeneity among studies was too great to estimate the effect of rEpo on the number of transfusions received or the volume of blood transfused (p<0.001 for the Q-test statistic). Subgroup analysis suggested that when rEpo is begun in the first week of life, neonates 1000 to 1500 g and >29 weeks are more likely to completely avoid transfusion than are extremely low-birth-weight (ELBW, <1000 g) neonates. No dose-response relationship was apparent between rEpo dose or iron dose and transfusion. No difference was apparent depending on whether the rEpo was given subcutaneously vs intravenously. CONCLUSION: If rEpo is begun in the first week of life, a moderate reduction can be expected (p=0.001) in the proportion of VLBW neonates transfused. Reduction is less significant in "early" transfusion (p=0.055) than in "late" transfusion (p=0.036). Such treatment is not likely to eliminate transfusions among ELBW neonates completely.     

Interleukin-6 in preterm premature rupture of membranes as an indicator of neonatal outcome

BACKGROUND: The aim of this study was to investigate whether the levels of interleukin-6 (IL-6) can be used as markers of adverse outcome in preterm neonates born after preterm premature rupture of membranes (PPROM). METHODS: This study involved 109 preterm neonates and their mothers. The PPROM group consisted of 58 neonates who were born after PPROM, and the control group consisted of 51 neonates. IL-6 levels were measured in umbilical cord blood, maternal blood sampled during delivery and in neonatal blood taken on the fourth day of life. RESULTS: In the PPROM group, IL-6 concentrations in maternal blood, cord blood, and neonatal blood were significantly higher in neonates with sepsis, compared with those without sepsis (P < 0.001). Choosing 108.5 pg/ml as a cut-off concentration of IL-6 in umbilical cord blood for neonatal sepsis resulted in sensitivity 95%, specificity 100%, positive predictive value 100%, and negative predictive value 97.4%. Concerning IL-6 in maternal blood, a cut-off concentration of 81 pg/ml showed sensitivity 90%, specificity 97.4%, positive predictive value 94.7%, and negative predictive value 94.9%. Eighteen of 20 neonates with early sepsis and seven of nine neonates, who died in the PPROM group, were born of mothers with IL-6 levels above the cut-off concentration in their blood during delivery. CONCLUSIONS: IL-6 in umbilical cord blood was the most significant variable for predicting early onset sepsis in preterm neonates. IL-6 in maternal blood was indicative of intrauterine environmental threats and might be used to identify pregnancies where intervention would be appropriate.