Exchange blood transfusion in neonates with severe hyperbilirubinemia in a lower-middle-income country: can we minimise the incidence?

Our descriptive study examines the clinical profile of referred neonates who underwent exchange blood transfusion (EBT) and identifies possible interventions at peripheral hospitals to decrease their severe hyperbilirubinemia. Among the 38 neonates enrolled, the following were identified as potential clinical gaps in management: early discharge within 24 h of birth (57%); non-availability of ABORh blood grouping (43%); lack of anti-D immunoprophylaxis (75%); pathological weight loss because of inadequate breastfeeding (42%); and low usage of phototherapy. Because of late recognition, the mean age at admission was 5.4 ± 3.3 days, levels of total serum bilirubin (TSB) were 516.4 ± 123.1 µmol/L, and acute bilirubin encephalopathy (ABE) was seen in 45% of neonates. Rh iso-immunisation (39.5%), ABO iso-immunisation (21%) and sepsis (8%) were major risk factors for severe hyperbilirubinaemia. Quality prenatal screening identifying at-risk newborns, preventing early discharge after birth, a bilirubin nomogram risk assignment before discharge and assuring early recognition of hyperbiliubinaemia by parents may well minimise the incidence of EBT.

Prevalence and burden of illness of treated hemolytic neonatal hyperbilirubinemia in a privately insured population in the United States.

BACKGROUND: Prevalence of hemolytic neonatal hyperbilirubinemia (NHB) is not well characterized, and economic burden at the population level is poorly understood. This study evaluated the prevalence, clinical characteristics, and economic burden of hemolytic NHB newborns receiving treatment in U.S. real-world settings. METHODS: This cohort study used administrative claims from 01/01/2011 to 08/31/2017. The treated cohort had hemolytic NHB diagnosis and received phototherapy, intravenous immunoglobulin, and/or exchange transfusions. They were matched with non-NHB newborns who had neither NHB nor related treatments on the following: delivery hospital/area, gender, delivery route, estimated gestational age (GA), health plan eligibility, and closest date of birth within 5 years. Inferential statistics were reported. RESULTS: The annual NHB prevalence was 29.6 to 31.7%; hemolytic NHB, 1.8 to 2.4%; treated hemolytic NHB, 0.46 to 0.55%, between 2011 and 2016. The matched analysis included 1373 pairs ≥35 weeks GA. The treated hemolytic NHB cohort had significantly more birth trauma and hemorrhage (4.5% vs. 2.4%, p = 0.003), vacuum extractor affecting newborn (1.9% vs. 0.8%, p = 0.014), and polycythemia neonatorum (0.8% vs. 0%, p = 0.001) than the matched non-NHB cohort. The treated hemolytic NHB cohort also had significantly longer mean birth hospital stays (4.5 vs. 3.0 days, p < 0.001), higher level 2-4 neonatal intensive care admissions (15.7% vs. 2.4, 15.9% vs. 2.8 and 10.6% vs. 2.5%, respectively, all p < 0.001) and higher 30-day readmission (8.7% vs. 1.7%, p < 0.001). One-month and one-year average total costs of care were significantly higher for the treated hemolytic NHB cohort vs. the matched non-NHB cohort, $14,405 vs. $5527 (p < 0.001) and $21,556 vs. $12,986 (p < 0.001), respectively. The average costs for 30-day readmission among newborns who readmitted were $13,593 for the treated hemolytic NHB cohort and $3638 for the matched non-NHB cohort, p < 0.001. The authors extrapolated GA-adjusted prevalence of treated hemolytic NHB in the U.S. newborn population ≥ 35 weeks GA and estimated an incremental healthcare expenditure of $177.0 million during the first month after birth in 2016. CONCLUSIONS: The prevalence of treated hemolytic NHB was 4.6-5.5 patients per 1000 newborns. This high-risk hemolytic NHB imposed substantial burdens of healthcare resource utilization and incremental costs on newborns, their caregivers, and the healthcare system.

Effectiveness of universal hyperbilirubinemia screening on newborn health: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to assess the effectiveness of the universal hyperbilirubinemia screening program on common newborn health outcomes.Specifically, the review will assess: the incidence of severe hyperbilirubinemia/kernicterus/exchange transfusion, rate of readmission due to jaundice, length of hospital stay on birth admission, rate and utilization of phototherapy during birth hospitalization, and jaundice related emergency visits.

Fluid supplementation for neonatal unconjugated hyperbilirubinaemia.

BACKGROUND: Neonatal hyperbilirubinaemia is a common problem which carries a risk of neurotoxicity. Certain infants who have hyperbilirubinaemia develop bilirubin encephalopathy and kernicterus which may lead to long-term disability. Phototherapy is currently the mainstay of treatment for neonatal hyperbilirubinaemia. Among the adjunctive measures to compliment the effects of phototherapy, fluid supplementation has been proposed to reduce serum bilirubin levels. The mechanism of action proposed includes direct dilutional effects of intravenous (IV) fluids, or enhancement of peristalsis to reduce enterohepatic circulation by oral fluid supplementation. OBJECTIVES: To assess the risks and benefits of fluid supplementation compared to standard fluid management in term and preterm newborn infants with unconjugated hyperbilirubinaemia who require phototherapy. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to 7 June 2017), Embase (1980 to 7 June 2017), and CINAHL (1982 to 7 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We included randomised controlled trials that compared fluid supplementation against no fluid supplementation, or one form of fluid supplementation against another. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group using the Covidence platform. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), risk difference (RD), and risk ratio (RR) with 95% confidence intervals (CIs). MAIN RESULTS: Out of 1449 articles screened, seven studies were included. Three articles were awaiting classification, among them, two completed trials identified from the trial registry appeared to be unpublished so far.There were two major comparisons: IV fluid supplementation versus no fluid supplementation (six studies) and IV fluid supplementation versus oral fluid supplementation (one study). A total of 494 term, healthy newborn infants with unconjugated hyperbilirubinaemia were evaluated. All studies were at high risk of bias for blinding of care personnel, five studies had unclear risk of bias for blinding of outcome assessors, and most studies had unclear risk of bias in allocation concealment. There was low- to moderate-quality evidence for all major outcomes.In the comparison between IV fluid supplementation and no supplementation, no infant in either group developed bilirubin encephalopathy in the one study that reported this outcome. Serum bilirubin was lower at four hours postintervention for infants who received IV fluid supplementation (MD -34.00 µmol/L (-1.99 mg/dL), 95% CI -52.29 (3.06) to -15.71 (0.92); participants = 67, study = 1) (low quality of evidence, downgraded one level for indirectness and one level for suspected publication bias). Beyond eight hours postintervention, serum bilirubin was similar between the two groups. Duration of phototherapy was significantly shorter for fluid-supplemented infants, but the estimate was affected by heterogeneity which was not clearly explained (MD -10.70 hours, 95% CI -15.55 to -5.85; participants = 218; studies = 3; I² = 67%). Fluid-supplemented infants were less likely to require exchange transfusion (RR 0.39, 95% CI 0.21 to 0.71; RD -0.01, 95% CI -0.04 to 0.02; participants = 462; studies = 6; I² = 72%) (low quality of evidence, downgraded one level due to inconsistency, and another level due to suspected publication bias), and the estimate was similarly affected by unexplained heterogeneity. The frequencies of breastfeeding were similar between the fluid-supplemented and non-supplemented infants in days one to three based on one study (estimate on day three: MD 0.90 feeds, 95% CI -0.40 to 2.20; participants = 60) (moderate quality of evidence, downgraded one level for imprecision).One study contributed to all outcome data in the comparison of IV versus oral fluid supplementation. In this comparison, no infant in either group developed abnormal neurological signs. Serum bilirubin, as well as the rate of change of serum bilirubin, were similar between the two groups at four hours after phototherapy (serum bilirubin: MD 11.00 µmol/L (0.64 mg/dL), 95% CI -21.58 (-1.26) to 43.58 (2.55); rate of change of serum bilirubin: MD 0.80 µmol/L/hour (0.05 mg/dL/hour), 95% CI -2.55 (-0.15) to 4.15 (0.24); participants = 54 in both outcomes) (moderate quality of evidence for both outcomes, downgraded one level for indirectness). The number of infants who required exchange transfusion was similar between the two groups (RR 1.60, 95% CI 0.60 to 4.27; RD 0.11, 95% CI -0.12 to 0.34; participants = 54). No infant in either group developed adverse effects including vomiting or abdominal distension. AUTHORS' CONCLUSIONS: There is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy, kernicterus, or cerebral palsy in healthy, term newborn infants with unconjugated hyperbilirubinaemia requiring phototherapy. In this review, no infant developed these bilirubin-associated clinical complications. Low- to moderate-quality evidence shows that there are differences in total serum bilirubin levels between fluid-supplemented and control groups at some time points but not at others, the clinical significance of which is uncertain. There is no evidence of a difference between the effectiveness of IV and oral fluid supplementations in reducing serum bilirubin. Similarly, no infant developed adverse events or complications from fluid supplementation such as vomiting or abdominal distension. This suggests a need for future research to focus on different population groups with possibly higher baseline risks of bilirubin-related neurological complications, such as preterm or low birthweight infants, infants with haemolytic hyperbilirubinaemia, as well as infants with dehydration for comparison of different fluid supplementation regimen.

Readmission for neonatal hyperbilirubinemia in an area with a high prevalence of glucose-6-phosphate dehydrogenase deficiency: A hospital-based retrospective study.

BACKGROUND: Hyperbilirubinemia is one of the most common causes of neonatal readmission to hospital. AIMS: To assess risk factors for hyperbilirubinemia among neonates readmitted for this condition and the ratio of the mean corpuscular hemoglobin concentration (MCHC) to the mean corpuscular volume (MCV). METHODS: We retrospectively studied the clinical and laboratory findings, management and possible risk factors for hyperbilirubinemia in 301 neonates born at ≥35 weeks gestation and readmitted to hospital owing to hyperbilirubinemia over five years. RESULTS: No risk factors for hyperbilirubinemia were identified in 64 (21.3%) neonates, and one or more risk factors were found in 237 neonates (78.7%). The most prevalent risk factor (41.9%) was G6PD deficiency, which occurred in 11 of the 15 neonates with a serum bilirubin level ≥427 µmol/l. A double-volume exchange blood transfusion was performed in two neonate boys in whom G6PD deficiency was the single risk factor for hyperbilirubinemia. One of them developed kernicterus later. The MCHC/MCV ratio of neonates with idiopathic hyperbilirubinemia, unexplained hemolysis, or other risk factors overlapped. CONCLUSIONS: This study confirmed that in an area where G6PD deficiency is prevalent, it is the most common and most severe risk factor for hyperbilirubinemia. This finding supports routine neonatal screening for G6PD deficiency in such areas. The usefulness of determining the MCHC/MCV ratio in the management of hyperbilirubinemia is uncertain.

In utero treatment of severe fetal anemia resulting from fetomaternal red blood cell incompatibility: a comparison of simple transfusion and exchange transfusion.

OBJECTIVE: To compare in utero exchange transfusions (IUET) and in utero simple transfusions (IUST) for the treatment of fetal anemia resulting from red blood cell fetomaternal incompatibility. STUDY DESIGN: Retrospective comparative study from January 2006 through December 2011. The two techniques were compared for effectiveness, complications, and neonatal outcomes. RESULTS: 36 patients had 87 IUETs and 85 patients 241 IUSTs. Gestational age at the first transfusion was similar in both groups (IUET: 27±3.8 weeks; IUST: 27±4.7 weeks; NS) as was the initial fetal hemoglobin level (IUET: 6.4±2.8g/dL; IUST: 6.0±2.5g/dL; NS). No significant differences were noted for postprocedure complications or efficacy. The daily drop in hemoglobin level was similar in both groups (IUET: 0.41±0.23g/dL/day; IUST: 0.44±0.17g/dL/day; NS) as were the time intervals between two procedures. Gestational age at birth was earlier in the IUET group (34.4±1.3 weeks vs 35.5±1.8 weeks; p<0.001), but the postnatal transfusions or exchange transfusions rates and the duration of intensive phototherapy did not differ. No significant differences were noted for the overall survival rates (IUET: 100%; IUST: 96.4%; p>0.99). CONCLUSION: IUET does not appear to provide any benefits compared with IUST, neither to be associated with a higher complication rate. The choice of the technique depends on availability of packed blood cells with high hematocrit (70-80%).

Benefits of Delayed Cord Clamping in Red Blood Cell Alloimmunization.

BACKGROUND AND OBJECTIVE: Several studies have shown the benefits of delayed cord clamping (DCC) in preterm and in healthy newborns at short and long term. Our objective was to evaluate the potentials benefits and risks of DCC in red cell alloimmunization. METHODS: This was a comparative before/after study of all living born neonates followed after fetal anemia requiring in utero transfusion. DCC was defined as cord clamping 30 seconds after birth. RESULTS: We included a continuous series of 72 neonates: 36 without DDC (group 1) and 36 with DDC (group 2). Hemoglobin at birth was lower in group 1 (10.2 vs 13.4 g/dL, P = .0003); 7 (25%) neonates in group 1 vs 24 (70.6%) in group 2 had no anemia at birth (P = .004). The rate of transfusion was similar between the 2 groups. Postnatal exchange transfusions were more likely performed in the group without DCC than in the group with DCC (47.2% vs 19.4%, P = .0124). Delay between birth and first transfusion was higher in group 2 (0 [0-13] vs 1 [0-21], P = .0274). The maximum level of bilirubin, the rate of intensive phototherapy, and the total duration of phototherapy were similar in the 2 groups. CONCLUSIONS: This study highlights a significant benefit of DCC in anemia secondary to red blood cell alloimmunization with a resulting decreased postnatal exchange transfusion needs, an improvement in the hemoglobin level at birth and longer delay between birth and first transfusion with no severe hyperbilirubinemia.

Evaluation of a simple intervention to reduce exchange transfusion rates among inborn and outborn neonates in Myanmar, comparing pre- and post-intervention rates.

BACKGROUND: In Myanmar, approximately half of all neonatal hospital admissions are for hyperbilirubinaemia, and tertiary facilities report high rates of Exchange Transfusion (ET). The aim of this study was to evaluate the effectiveness of the pilot program in reducing ET, separately of inborn and outborn neonates. METHODS: The study was conducted in the Neonatal Care Units of four national tertiary hospitals: two exclusively treating inborn neonates, and two solely for outborn neonates. Prior to intervention, no high intensity phototherapy was available in these units. Intervention in late November 2011 comprised, for each hospital, provision of two high intensity LED phototherapy machines, a photo radiometer, and training of personnel. Hospital-specific data were assessed as Relative Risk (RR) ratios comparing ET rates pre- and post-intervention, and individual hospital results were pooled when appropriate. RESULTS: In 2011, there were 118 ETs among inborn neonates and 140 ETs among outborn neonates. The ET rate was unchanged at Inborn Hospital A (RR = 1.07; 95 % CI: 0.80-1.43; p = 0.67), and reduced by 69 % at Inborn Hospital B (RR = 0.31; 95 % CI: 0.17-0.57; p < 0.0001). For outborn neonates, the pooled estimate indicated that ET rates reduced by 33 % post-intervention (RRMH = 0.67; 95 % CI: 0.52-0.87; p = 0.002); heterogeneity was not a problem. CONCLUSION: Together with a photoradiometer and education, intensive phototherapy can significantly reduce the ET rate. Inborn Hospital A had four times as many admissions for jaundice as Inborn Hospital B, and did not reduce ET until it received additional high intensity machines. The results highlight the importance of providing enough intensive phototherapy units to treat all neonates requiring high intensity treatment for a full course. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615001171505 , 2 November 2015.

Care practices and traditional beliefs related to neonatal jaundice in northern Vietnam: a population-based, cross-sectional descriptive study.

BACKGROUND: The National Hospital of Pediatrics in Vietnam performed >200 exchange transfusions annually (2006-08), often on infants presenting encephalopathic from lower-level hospitals. As factors delaying care-seeking are not known, we sought to study care practices and traditional beliefs relating to neonatal jaundice in northern Vietnam. METHODS: We conducted a prospective, cross-sectional, population-based, descriptive study from November 2008 through February 2010. We prospectively identified mothers of newborns through an on-going regional cohort study. Trained research assistants administered a 78-item questionnaire to mothers during home visits 14-28 days after birth except those we could not contact or whose babies remained hospitalized at 28 days. RESULTS: We enrolled 979 mothers; 99% delivered at a health facility. Infants were discharged at a median age of 1.35 days. Only 11% received jaundice education; only 27% thought jaundice could be harmful. During the first week, 77% of newborns were kept in dark rooms. Only 2.5% had routine follow-up before 14 days. Among 118 mothers who were worried by their infant's jaundice but did not seek care, 40% held non-medical beliefs about its cause or used traditional therapies instead of seeking care. Phototherapy was uncommon: 6 (0.6%) were treated before discharge and 3 (0.3%) on readmission. However, there were no exchange transfusions, kernicterus cases, or deaths. CONCLUSIONS: Early discharge without follow-up, low maternal knowledge, cultural practices, and use of traditional treatments may limit or delay detection or care-seeking for jaundice. However, in spite of the high prevalence of these practices and the low frequency of treatment, no bad outcomes were seen in this study of nearly 1,000 newborns.

The efficacy of the use of intravenous human immunoglobulin in Brazilian newborns with rhesus hemolytic disease: a randomized double-blind trial.

BACKGROUND: The purpose of this study was to evaluate the efficacy of intravenous human immunoglobulin (IVIG) in the presence of high-intensity phototherapy in decreasing the need for exchange transfusion in newborns with rhesus hemolytic disease. STUDY DESIGN AND METHODS: We performed a randomized, double-blind, placebo-controlled trial. The trial included D+ newborns born at 32 weeks of gestational age or later with a positive direct antiglobulin test and whose mothers were Rh-alloimmunized and did or did not receive intrauterine transfusion. The newborns were randomly assigned to receive either IVIG at a dose of 500 mg/kg or placebo (saline solution, 10 mL/kg) during the first 6 hours of life. The primary outcome was the need for exchange transfusion. The criteria for exchange transfusion were total serum bilirubin (TSB) level at or above 340 µmol/L (20 mg/dL) or increasing by 8.5 µmol/L/hr (0.5 mg/dL/hr) despite intensive phototherapy. RESULTS: The trial included 92 newborns. There was no difference in the rate of exchange transfusion between groups: 6 of 46 (13%) in the IVIG group versus 7 of 46 (15.2%) in the placebo group (p = 0.765). There were no significant differences between groups with respect to their need for exchange transfusion, phototherapy time, peak bilirubin, or length of hospital stay. There were no adverse events related to the drug or the form of administration. CONCLUSION: Nonspecific human immunoglobulin was not effective in preventing the need for exchange transfusion in neonates with rhesus hemolytic disease.

The use of intensive phototherapy in severe neonatal hyperbilirubinemia.

Phototherapy has been the therapy of choice for the newborn with indirect hyperbilirubinemia. Intensive phototherapy requires a spectral irradiance of 30 microw/ cm2/nm, delivered over as much of the body surface as possible and is nowadays recommended for cases of neonatal hyperbilirubinemia with elevated total serum bilirubin (TSB) levels according to the guidelines. This study was conducted on neonates presenting to the out-born Neonatal Intensive Care Unit (NICU) of Cairo University Hospital with severe and extreme neonatal unconjugated hyperbilirubinemia during a 6 month period from August 2011 to January 2012. A total of 212 neonates presented with TSB > or = 20 mg/dl and were admitted for intensive phototherapy. The mean TSB on admission for all the cases was 26.8 +/- 6.2 mg/dl, ranging from 20 to 44 mg/dl. The mean duration of intensive phototherapy use was 14 hr. The mean rate of TSB declined during stay in the bilisphere was 1.019 mg/dl/hr. Exchange blood transfusion was indicated in 13 cases with extreme hyperbilirubinemia. 31 cases (14.62%) had rebound hyperbilirubinemia after phototherapy removal.

Exchange transfusions and top-up transfusions in neonates with Kell haemolytic disease compared to Rh D haemolytic disease.

OBJECTIVE: To evaluate neonatal outcome in Kell haemolytic disease compared to Rh D haemolytic disease. STUDY DESIGN: Retrospective study of all (near)-term neonates with Kell (n=34) and Rh D haemolytic disease (n=157) admitted to our centre between January 2000 and December 2008. We recorded the need for exchange transfusion and top-up transfusions up to 3 months of age. RESULTS: Neonates in the Kell group required less days of phototherapy than neonates in the Rh D group [2.4 vs. 4.1 days, respectively (P<0.01)]. The percentage of neonates requiring an exchange transfusion was lower in the Kell group than in the Rh D group [6% (2/34) and 62% (98/157), respectively (P<0.01)]. The percentage of neonates in the Kell group and Rh D group requiring a top-up transfusion was 62% (21/34) and 72% (113/157), respectively (P=0.20). The median number of top-up transfusions per neonate in the Kell group and Rh D group was 1 [interquartile range (IQR) 0-2] and 2(IQR 0-2), respectively (P=0.07). CONCLUSION: Neonates with Kell haemolytic disease require less phototherapy and less exchange transfusions compared to neonates with Rh D haemolytic disease, but an equal number of top-up transfusions.

Why we are still doing so many exchange blood transfusion for neonatal jaundice in Nigeria.

BACKGROUND: Since exchange blood transfusion (EBT) is associated with serious complications, phototherapy has been made more powerful to reduce the need for EBT in the developed world. This study was undertaken to determine the indications for EBT in neonatal jaundice (NNJ) at our unit and what proportion of EBTs was possibly avoidable. METHODS: All the babies who had EBT for hyperbilirubinemia over a three-year period were included. Age, sex, weight, place of delivery, blood group of baby and mother, other investigations, management, and the outcome of the babies were recorded. RESULTS: Of the 1686 babies admitted to the neonatal unit, 90 (5.3%) had EBT. Fourteen (15.6%) were inborn while 76 (84.4%) were out-born babies. Fifty-six (62.2%) babies were admitted primarily for NNJ while 34 (37.8%) developed NNJ during admission. Thirty-six (40.0%) of the babies had phototherapy for more than 24 hours prior to EBT either because they were of very low birthweight or NNJ was detected very early and therapy was so commenced. Sixty-eight (75.6%) babies had single EBT while the remaining 22 (24.4%) had two sessions of EBT. Factors associated with severe NNJ in babies requiring EBT included low birthweight (<2500 g, 44.4%), ABO incompatibility (30.0%), glucose-6-phosphate dehydrogenase deficiency (34.4%) and septicemia (26.1%). Twenty-seven (30.0%) of the neonates developed features of kernicterus: 26 before admission while 1 during admission; all except one were delivered outside the hospital. CONCLUSIONS: The EBT rate in our center was high. With more effective phototherapy, EBT could be avoided in most of the babies who initially had phototherapy for more than 24 hours before EBT and repeated EBT sessions. Health education of the population at risk, especially pregnant women, and early referral at the primary health care level will reduce the burden of severe NNJ.

Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated. STUDY DESIGN AND METHODS: Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified. RESULTS: The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1. CONCLUSION: First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.

Management of neonatal hyperbilirubinemia: pediatricians' practices and educational needs.

BACKGROUND: Early detection and treatment of neonatal hyperbilirubinemia is important in the prevention of bilirubin-induced encephalopathy. In this study, we evaluated the New Jersey pediatricians' practices and beliefs regarding the management of neonatal hyperbilirubinemia and their compliance with the recommendations made by the American Academy of Pediatrics (AAP) in 1994. METHODS: A survey questionnaire was mailed to a random sample of 800 pediatricians selected from a list of 1623 New Jersey Fellows of the AAP initially in October 2003 and then in February 2004 for the non-respondents. In addition to the physicians' demographic characteristics, the questionnaire addressed various aspects of neonatal hyperbilirubinemia management including the diagnosis, treatment, and follow up as well as the pediatricians' beliefs regarding the significance of risk factors in the development of severe hyperbilirubinemia. RESULTS: The adjusted response rate of 49.1% (n = 356) was calculated from the 725 eligible respondents. Overall, the practicing pediatricians reported high utilization (77.9%) of the cephalocaudal progression of jaundice and low utilization (16.1%) of transcutaneous bilirubinometry for the quantification of the severity of jaundice. Most of the respondents (87.4%) identified jaundice as an indicator for serum bilirubin (TSB) testing prior to the neonate's discharge from hospital, whereas post-discharge, only 57.7% felt that a TSB was indicated (P < 0.01). If the neonate's age was under 72 hours, less than one-third of the respondents reported initiation of phototherapy at TSB levels lower than the treatment parameters recommended by the AAP in 1994, whereas if the infant was more than 72 hours old, almost 60% were initiating phototherapy at TSB lower than the 1994 AAP guidelines. Most respondents did not regard neonatal jaundice noted after discharge and gestational ages 37-38 weeks as being significant in the development of severe hyperbilirubinemia. However, the majority did recognize the importance of jaundice presenting within the first 24 hours and Rh/ABO incompatibility. CONCLUSION: The pediatricians' practices regarding the low utilization of laboratory diagnosis for the quantification of jaundice after discharge and underestimation of risk factors that contribute to the development of severe hyperbilirubinemia are associated with initiation of phototherapy at lower than AAP recommended treatment parameters and recognition of neonatal hyperbilirubinemia as an important public health concern.

Intravenous immunoglobulin G (IVIG) therapy for significant hyperbilirubinemia in ABO hemolytic disease of the newborn.

BACKGROUND: Although intravenous immunoglobulin G (IVIG) therapy has been reported in hyperbilirubinemia of Rh hemolytic disease, its use in ABO hemolytic disease has been reported in only a few studies. In our institute we have observed that almost 30% of babies with hyperbilirubinemia due to ABO hemolytic disease required exchange transfusion. OBJECTIVE: To determine whether administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease would reduce the need for exchange transfusion as a primary goal in these babies. DESIGN: This was a prospective study involving all newborns with significant hyperbilirubinemia due to direct Coombs-positive ABO hemolytic disease. METHODS: All healthy term babies with ABO hemolytic disease with positive direct Coombs test in the period between 2000 and 2002 were identified. Significant hyperbilirubinemia was defined as hyperbilirubinemia requiring phototherapy and/or rising by 8.5 micromol/l per h (0.5 mg/dl per h) or more to require exchange transfusion. Babies were randomly assigned into two groups: group 1 (study group) received phototherapy plus IVIG (500 mg/kg); and group 2 (control group) received phototherapy alone. Exchange transfusion was carried out in any group if at any time the bilirubin level reached 340 micromol/l (20 mg/dl) or more, or rose by 8.5 micromol/l per h (0.5 mg/dl per h) in group 2. RESULTS: A total of 112 babies were enrolled over 2 years, 56 in each group. Exchange transfusion was carried out in four babies in the study group, while 16 babies in the control group required exchange. Late anemia was not of concern in either group. No adverse effects related to IVIG administration were recorded. CONCLUSION: Administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease with positive direct Coomb's test reduces the need for exchange transfusion without producing immediate adverse effects.

Effect of publication of the "Practice Parameter for the management of hyperbilirubinemia" on treatment of neonatal jaundice.

UNLABELLED: The aim of this study was to evaluate the change in the treatment of neonatal jaundice following introduction of the "American Academy of Pediatrics' Practice Parameter for the management of hyperbilirubinemia in the healthy term newborn". In a historical control observation cohort study, we examined the rate of phototherapy and exchange transfusions among full-term (> or = 37 wk gestation) and near-term (gestational age between 35 and 37 wk and birthweight > 2000 g) infants in two community hospitals. The study included all consecutive infants born during two 15-mo study periods immediately before and after the introduction of the new guidelines. Data were prospectively recorded in a computerized database. The rate of phototherapy significantly decreased in the second study period from 7.9% (514/6499) to 2.9% (251/8650) (p < 0.0001) among full-term infants, and from 20.9% (102/489) to 9.4% (47/502) (p < 0.0001) in near-term infants. The use of exchange transfusion was significantly higher (p < 0.001) in the first compared to the second period: 0.2% (15/6499) vs 0.03% (3/8650). A significant decrease was found when the data from each hospital were analyzed separately. CONCLUSION: A significant decrease in the use of phototherapy and exchange transfusion occurred after the publication of the new practice parameters. This trend was observed for both term and preterm newborns, although the new guidelines were not intended for infants born before term.

The effects of hemodilution with polyethylene glycol bovine hemoglobin (PEG-Hb) in a conscious porcine model.

BACKGROUND: Severe hemodilution in large mammals has been used rigorously for the safety and efficacy testing of hemoglobin-based red blood cell substitutes. The effects of hemodilution with polyethylene glycol-modified bovine hemoglobin (PEG-Hb) were investigated in an unanesthetized porcine model. METHODS: Immature Yorkshire cross barrow pigs were subjected to exchange transfusion with PEG-Hb (n = 6) or dextran 70 (n = 4) until an 80% reduction in hematocrit was achieved. RESULTS: All six (100%) PEG-Hb-infused pigs and only one (25%) dextran 70 control pig survived the resultant reduction in erythrocytes. Heart rates and mean arterial pressure were not significantly affected by PEG-Hb infusion. Pigs infused with PEG-Hb maintained normal levels of blood pH, PO2, and PCO2 while dextran 70 controls showed low PvO2, PaCO2, and the development of acidosis. Histological evaluation revealed that the surviving dextran 70 control animal exhibited possible anoxia-induced hepatic centrilobular necrosis. PEG-Hb-treated pigs demonstrated the presence of renal tubular cell cytoplasmic vacuoles and vacuolated macrophages in spleens. CONCLUSIONS: The results indicate that PEG-Hb effectively supports life close to lethal levels of anemia.

Therapeutic approaches to neonatal jaundice: an international survey.

Jaundice is one of the most common clinical phenomena in the neonatal period and a frequent indication for treatment with phototherapy, exchange transfusion, or drugs. The present study documents the variability in approaches to the treatment of this condition. A mail questionnaire was sent to neonatal units worldwide. One hundred and eight answers (49% response rate) were received from Europe (n = 72), North America (n = 28), Africa (n = 7), and Asia (n = 1). The neonatal intensive care units represented by the respondents had 31 +/- 18 beds [mean +/- SD], and 638 +/- 519 admissions per year. All units offered phototherapy, 106/108 performed exchange transfusion, while 44/108 used some form of drug therapy. There was considerable variability among the units in their approaches to the jaundiced neonate. This applied to all aspects of care, including type of phototherapy lights used, practical implementation of phototherapy, use of fluid supplementation, and use of prophylactic phototherapy. The majority used written protocols for investigation and treatment of neonatal jaundice and would let their decision on whether to treat be influenced by the infant's clinical state. There was great variability between units in the level of serum bilirubin that would trigger therapy. This applied across weight groups and to phototherapy as well as exchange transfusion. The significant heterogeneity in our approach to the treatment of jaundiced neonates suggests that our understanding of the biology of neonatal jaundice is inadequate and that further research will be necessary in order to provide a more solid biological foundation for therapy.

The impact of phototherapy in the management of neonatal hyperbilirubinemia: comparison of historical cohorts.

To quantitatively assess the impact of phototherapy (PT) in the prevention of kernicterus we calculated the rate of exchange transfusion (ET) in two large historical cohorts of Greek neonates (birthweight > or = 2.5 kg), one before (period I: 1957-61) and one after (period II: 1980-92) the introduction of PT. Overall, the introduction of PT was associated with a reduction of the rate of ET from 0.43% in period I to 0.05% in period II. The reduction was observed in all etiological categories but was more marked in the ABO-incompatible group. With an estimated rate of kernicterus without treatment of 0.085% (excluding rhesus hemolytic disease of the newborn and prematurity) we estimated that 4.2 and 0.36 infants were treated by ET for each spared kernicterus in periods I and II, respectively. Finally, in period II 185 infants were treated with PT or PT and ET for each spared kernicterus.