Isoimmune Hemolytic Disease Research Articles

Three or four doses of intravenous immunoglobulin G treatment for isoimmune hemolytic disease: A case series and literature review.

Neonates affected by isoimmune hemolytic disease (HDN) are at risk of developing severe hyperbilirubinemia. Studies show that increasing levels of bilirubin impact neonatal neurodevelopment. To avoid complications associated with exchange transfusion, intravenous immunoglobulin G (IVIG) is used to treat hyperbilirubinemia. We included all infants who received more than two doses of IVIG treatment for isoimmune hemolytic disease. We analyzed the incidence of side effects associated with IVIG treatment and the rate of exchange transfusion. A retrospective chart review performed between October 2011-October 2022 at East Carolina University Health identified neonates who received more than two doses IVIG for HDN. Neonates of postmenstrual age greater than 28 days old, receiving less than three doses of IVIG or received IVIG for other indications were excluded. The occurrences of adverse events, demographics and use of other medical therapies were reviewed. Eleven neonates were included in the case series. Most common cause of severe hyperbilirubinemia was attributed to ABO incompatibility. Six patients (54%) received three doses of IVIG, and five patients (45%) received four doses of IVIG with bilirubin levels decreasing below exchange transfusion. No treatment exceeding four doses of IVIG was reported, nor adverse events during treatment. In this cohort of neonates with HDN, bilirubin levels decreased after treatment with multiple doses of IVIG. Future research on recommendations of optimal total number doses of IVIG to reduce the risk for exchange transfusion.

Role of IVIg in Severe Neonatal Jaundice due to Isoimmunization A Retrospective Cohort Study

Aim To see the efficacy of intravenous immunoglobulin (IVIg) in reducing the need for exchange transfusion (ET) in neonates with isoimmune hemolytic disease with serum bilirubin at or above exchange level. Methods Retrospective cohort study conducted in neonatal intensive care unit of a tertiary care center from March 2015 to February 2020 included neonates with gestational age ≥35 weeks with positive Direct Coombs Test with serum bilirubin at or above exchange level according to American Academy of Pediatrics charts with no bilirubin encephalopathy at presentation. Study subjects were followed till discharge. Results ET was prevented in 8/41 (19.5%) cases who received IVIg initially vs. 2/51 cases (3.92%) who didn’t ( P = .02, relative risk: 1.98 with 95% confidence interval [1.32-2.98] with number needed to treat: 2.51). Total duration of phototherapy was significantly lesser in those receiving IVIg ( P < .0001). Conclusion Targeted use of IVIg in isoimmune hemolytic disease of newborn with serum bilirubin rising despite intensive phototherapy or within 2 to 3 mg/dL of the exchange level is more likely to benefit than harm and remain prudent.

Technical Report: Diagnosis and Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.

Severe hyperbilirubinemia is associated with kernicterus. Informed guidance on hyperbilirubinemia management, including preventive treatment thresholds, is essential to safely minimize neurodevelopmental risk. To update the evidence base necessary to develop the 2022 American Academy of Pediatrics clinical practice guideline for management of hyperbilirubinemia in the newborn infant ≥35 weeks' gestation. PubMed. English language randomized controlled trials and observational studies. Excluded: case reports or series, nonsystematic reviews, and investigations focused on <35-weeks' gestation infants. Topics addressed in the previous clinical practice guideline (2004) and follow-up commentary (2009) were updated with new evidence published through March 2022. Evidence reviews were conducted for previously unaddressed topics (phototherapy-associated adverse effects and effectiveness of intravenous immune globulin [IVIG] to prevent exchange transfusion). New evidence indicates that neurotoxicity does not occur until bilirubin concentrations are well above the 2004 exchange transfusion thresholds. Systematic review of phototherapy-associated adverse effects found limited and/or inconsistent evidence of late adverse effects, including cancer and epilepsy. IVIG has unclear benefit for preventing exchange transfusion in infants with isoimmune hemolytic disease, with a possible risk of harm due to necrotizing enterocolitis. The search was limited to 1 database and English language studies. Accumulated evidence justified narrowly raising phototherapy treatment thresholds in the updated clinical practice guideline. Limited evidence for effectiveness with some evidence of risk of harm support the revised recommendations to limit IVIG use.

Optimal Evaluation for DAT-Positive Newborns Remains Elusive

Source: Papacostas MF, Robertson DW, McLean MD, et al. Sixth-hour transcutaneous bilirubin and need for phototherapy in DAT positive newborns. Pediatrics. 2022;149(3):e2021054071; doi:10.1542/peds.2021-054071Investigators from Naval Medical Center Portsmouth (NMCP), Portsmouth, VA, and the University of Pittsburgh School of Medicine, Pittsburgh, PA, conducted a retrospective study to assess the utility of a transcutaneous bilirubin (TcB) measurement at 6 hours of age in predicting the need for phototherapy at ≤24 hours of age in newborns with ABO incompatibility. Data on neonates born at NMCP between May 2013 and March 2017 who were ≥35 weeks’ gestation were reviewed. Infants were classified as having ABO incompatibility if born to mothers with type O blood and negative antibody screens and themselves had type A or B blood with positive direct antiglobulin tests (DAT).At NMCP, blood is obtained from newborns with ABO incompatibility at 6 hours of age for total serum bilirubin (TSB), hemoglobin, hematocrit, and reticulocyte counts; providers are encouraged to also obtain a TcB measurement. Infants with paired blood test and TcB results were included in study analyses; demographic and clinical data were abstracted from the medical records of these newborns. The primary study outcome was need for phototherapy at ≤24 hours of age, as determined by the attending pediatrician. Demographic and clinical characteristics associated with this outcome in univariate analyses were included in 2 logistic models; 1 with blood test results and no TcB levels, and the other with TcB results and no blood test data. Receiver operator characteristic (ROC) curves were constructed and the area under the curve (AUC) calculated. The positive and negative predictive values (PPV and NPV, respectively) of different TcB cutoff values in predicting the need for phototherapy at ≤24 hours also were determined.Among 10,942 newborns born at ≥35 weeks’ gestation, 5,167 (47.2%) were born to mothers with type O blood, DAT was positive in 829 (7.6%), and 772 (7.1%) infants met criteria for ABO incompatibility. A total of 346 newborns had paired blood test and TcB results, 21% of whom were treated with phototherapy at ≤24 hours of age. In univariate analyses, birth weight, type B blood, TSB level, reticulocyte count, and TcB were significantly associated with the need for phototherapy at ≤24 hours. In the multivariate model that excluded TcB results, only TSB and reticulocyte counts were independently associated with the outcome (odds ratio [OR], 12.6; 95% CI, 6.1, 25.6; and OR, 1.5; 95% CI, 1.0, 2.1, respectively). In the other model, TcB was significantly associated with the need for phototherapy at ≤24 hours of age (OR, 3.1; 95% CI, 2.4, 4.0). The ROC AUCs were similar for the 2 models (0.96 and 0.90, respectively). A TcB value of ≤3.0 mg/dL yielded a NPV of 98%, a value of ≥5.3 mg/dL, and a PPV of 85% for predicting the need for phototherapy at ≤24 hours of age.The authors conclude that a 6-hour TcB level was predictive of the need for phototherapy at ≤24 hours of life in newborns with ABO incompatibility.Dr Von Kohorn has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The most recent (although outdated) AAP clinical practice guidance advises universal pre-discharge assessment of bilirubin level in newborns, with treatment based on risk stratification combining bilirubin level and risk factors.1,2 Isoimmune hemolytic disease is a risk factor both for severe hyperbilirubinemia and neurotoxicity.2 Although recent evidence about the risks of phototherapy has called universal screening into question, close monitoring of infants with risk factors remains a priority.3,4The current investigators demonstrate that 6-hour blood and TcB tests predict the need for phototherapy at or before 24 hours of life. The investigators do not describe the trend in phototherapy use. They suggest using TcB values that correspond to 98% NPV and 85% PPV to guide clinical practice at 6 hours of life. Importantly, the study does not indicate whether 6-hour testing or the proposed TcB values reduce key outcomes such as severe hyperbilirubinemia, bilirubin encephalopathy, hospital readmission, or cost. The authors report that significantly more infants who received TcB measurements were admitted to the NICU compared to those who received only blood tests, but they do not comment on the explanations for this finding that implies possible overtreatment. In a web comment on the original article by Papacostas, Mazar astutely states that phototherapy should be started at currently recommended thresholds, regardless of projected risk.5 The authors’ reply states “it would be beneficial to identify [infants projected to need phototherapy] and start treatment earlier.” Evidence for such benefit is not presented.Six-hour bilirubin testing predicts phototherapy at ≤24 hours of life, with TcB performing nearly as well as TSB plus reticulocyte count. The relationship of 6-hour testing to clinical outcomes remains unknown.

Late-onset hyporegenerative anemia in an infant with rhesus isoimmunization

Late-onset anemia is a complication of hemolytic disease of fetus and newborn. It includes late hemolytic anemia and late hyporegenerative anemia. This case report is to discuss an Rh isoimmunized infant who presented with late-onset hyporegenerative anemia. The infant had low reticulocyte count, negative direct antiglobulin test, high erythropoietin, and high ferritin levels. She was treated with repeated blood transfusions and improved after 4 months of age. The follow-up of infants with Rh isoimmune hemolytic disease is needed for identification of late-onset anemia.

Intravenous Immunoglobulins as Adjunct Treatment to Phototherapy in Isoimmune Hemolytic Disease of the Newborn: A Retrospective Case-Control Study.

BackgroundIsoimmune hemolytic disease is a major cause of neonatal severe indirect hyperbilirubinemia that requires phototherapy or exchange transfusion which is an invasive procedure to avoid brain injury. Administration of intravenous immunoglobulin (IVIG) is used as an adjunct treatment to phototherapy in order to decrease the rate of exchange transfusion.MethodsThis retrospective case-control study aimed to describe the safety and efficacy of IVIG therapy in newborns with isoimmune hemolytic disease and to compare their clinical outcomes to those of a control group who were treated only with phototherapy. Criteria for IVIG treatment were variable; when phototherapy threshold was reached or when exchange transfusion level was approached, using either indication is based on the attending discretion.ResultsNinety-four infants were included in the IVIG group, compared to 108 infants in the control group. Most of the included infants were term infants and most common cause was ABO incompatibility. There were no side effects documented in all the included infants. The IVIG group had more severe hemolysis with average highest bilirubin of 14.6 ± 3.7 mg/dL in the IVIG group versus 12.6 ± 3 in the control group (P = 0.0001). Complication of hemolysis was seen more in the IVIG group with higher rate of rebound hyperbilirubinemia, blood transfusion and exchange transfusion.ConclusionsIVIG use as an adjunct treatment to phototherapy in isoimmune hemolytic disease of the newborns is safe. The favorable results of the phototherapy only group were supportive of using selective criteria for administration of IVIG in neonates with isoimmune hemolytic disease.

Cord Serum Bilirubin Level in Predicting the Development of Significant Hyperbilirubinemia in Newborns with ABO Incompatibility

Introduction: Neonatal hyperbilirubinaemia is common problem which is benign in majority of neonates. Rh iso immune hemolytic disease as a cause of hyperbilirubinemia is becoming nearly nonexistent due to the use of prophylactic anti D. Hence Isoimmune hemolytic disease due to ABO incompatibility assumes significance as a cause of significant hyperbilirubinaemia. This study was conducted to determine the incidence of ABO incompatibility, ABO iso immune disease in new born, to determine critical cord serum bilirubin level to predict subsequent significant hyperbilirubinemia.Material and Methods: The study was done in neonatal ICU of a tertiary care hospital where 100 full term healthy newborns with B.W≥2500gm and gestational age ≥37 wk with blood group A, B, AB, born to mothers with O blood group without simultaneous Rh incompatibility at SGRDIMSR were included. Serum bilirubin was measured approximately at 12-24hrs, 36-48hrs, 60-72hrs. Results: Out 100 ABO incompatible newborns 33(33%) developed ABO isoimmune disease manifesting as significant hyperbilirubinaemia with any of the four total serum bilirubin levels exceeding threshold levels defined for phototherapy. TSB of ≥ 2.16mg/d1 from cord blood has a sensitivity of 100% specificity of 89.55%, NPV 100% and PPV of 82.50% to predict significant hyperbilirubinaemia. Conclusion: A critical cord S.bilirubin between 2.16 mg/d1 and 4.09mg/d1 will predict all newborns who will have significant hyperbilirubinaemia and can be used as a safe demarcator to decide time of discharge. Any therapeutic intervention if necessary can be started as early as possible.J Nepal Paediatr Soc 2015; 35(3): 231-236

Necrotizing enterocolitis following intensive phototherapy in full-term newborns – is there a possible association?

Abstract Background: Necrotizing enterocolitis is rare in full-term infants, and is currently not considered a known complication of phototherapy. Highlights: Three cases of necrotizing enterocolitis in full-term babies possibly associated to intensive phototherapy for treatment of early neonatal hyperbilirubinemia due to isoimmune hemolytic disease of the newborn. Conclusions: Although rare, the association between occurrences of necrotizing enterocolitis in full-term newborn infants and intensive phototherapy merits caution and clinical awareness to such possible complication. Presumptive explanation is that intensive phototherapy causes marked vasodilataion in the skin that may result in decreased perfusion of the intestine leading to ischemia and necrotizing enterocolitis. This calls for further studies to investigate the effects of phototherapy on the vascular bed in the gut and other vital organs that could have clinical implications.

Phenobarbital and Phototherapy Combination Enhances Decline of Total Serum Bilirubin and May Decrease the Need for Blood Exchange Transfusion in Newborns with Isoimmune Hemolytic Disease.

OBJECTIVEThe objective of this study was to evaluate the effect of phenobarbital and phototherapy combination on the total serum bilirubin of the newborn infants with isoimmune hemolytic disease (IHD) and its impact on blood exchange transfusion rates.PATIENTS AND METHODThis single-blinded, prospective, randomized, controlled trial was conducted between March 2013 and December 2014 at the pediatric ward of two Military Hospitals in Jordan. A total of 200 full-term neonates with IHD were divided randomly into two groups: (1) the phenobarbital plus phototherapy group (n = 103), and (2) the phototherapy-only group (n = 97). Infants in group 1 received an oral dose of 2.5 mg/kg phenobarbital every 12 hours for 3 days in addition to phototherapy. The total serum bilirubin was observed.RESULTSOf the total 200 included newborn infants, 186 infants completed the study: 97 infants were included in group 1 and 89 infants in group 2. The difference between the mean total serum bilirubin levels at 24, 48, and 72 hours after starting the trial was clinically and statistically significant at P < 0.05. The differences between the two groups were also statistically significant at P < 0.05. Of the total 186 who completed the study, only 22 underwent blood exchange transfusion [7 from group 1, and 15 from group 2 (P = 0.0478)].CONCLUSIONIn a limited-resources setting, phenobarbital in combination with phototherapy may be helpful to newborn infants with IHD, as it results in a faster decline in total serum bilirubin, thus decreasing the need for blood exchange transfusion than phototherapy alone.

Should intravenous immunoglobulin be used in infants with isoimmune haemolytic disease due to ABO incompatibility?

The use of intravenous immunoglobulin in isoimmune haemolytic disease due to ABO incompatibility is recommended by the American Academy of Pediatrics and the National Blood Authority, Australia. However, the evidence these recommendations are based on appears limited and, in some instances, outdated. In our article, we review the current available literature to help answer the question, 'In infants with isoimmune haemolytic disease due to ABO incompatibility [P], does use of intravenous immunoglobulin and intensive phototherapy [I] compared with intensive phototherapy alone [C] provide any clinically important benefits [O]?'

A Case of Hemolytic Disease of a Newborn by an Anti-DiaAntibody Treated with Intravenous Immunoglobulin

aantibody rarely occurs. The anti-Di a antibody was observed in the serum and red-cell eluate of an infant, and in the serum of his mother. The frequency of the appearance of the Di a antigen in the Korean population is estimated to be 6.4-14.5%. This paper reports a case of hemolytic disease in a newborn associated with the anti-Di a antibody. A full-term male infant was transferred to the authors’ hospital due to hyperbilirubinemia the day after his birth. The laboratory data indicated a hemoglobin value of 11.6 g/dL, a reticulocyte count of 10.6%, a total bilirubin count of 14.4 mg/dL, a direct bilirubin count of 0.6 mg/dL, and a positive result in the direct Coombs’ test. Due to the identification of an irregular antibody from the maternal serum, an anti-Di a antibody was detected, which was also found in the eluate made from the infant’s blood. The infant had been treated with phototherapy and intravenous immunoglobulin since the second day after his birth and was discharged due to an improved condition without exchange transfusion. Therefore, in cases of iso-immune hemolytic disease in a newborn within 24 hours from birth who had a negative result in an antibody screening test, the conduct of an anti-Di a antibody identification test is recommended due to the suspicion of an anti-Di a antigen, followed by early administration of intravenous immunoglobulin.

A Case of Neonatal Isoimmune Hemolytic Disease due to Anti-MiaAntibody with Massive Fetomaternal Hemorrhage

Authors experienced a newborn treated with severe anemia transferred to our hospital due to pulselessness and apnea shortly after birth. Laboratory analysis of the blood on admission revealed hemoglobin 3.1 g/dL, reticulocyte 11.0%. Kleihauer-Betke test for fetal hemoglobin from maternal blood was seen Hgb F 7%, then we suggested almost 180 ml fetomaternal hemorrhage. But, anemia was not improved despite repeated packed RBC transfusion. So, we evaluated the other cause of intractable anemia. The results were as follows; the Coombs' test was positive. The antibody identification test using mother's serum revealed anti-Mia antibody. The patient improved with supportive treatment, but got hypoxic brain injury due to massive fetomaternal hemorrhage. At day 29, the infant was doing well and was discharged. We report a case of neonatal isoimmune hemolytic disease due to anti-Mia with massive fetomaternal hemorrhage with a brief review of the related literatures.

Intervention Guidelines for Neonatal Hyperbilirubinemia: An Evidence Based Quagmire

The American Academy of Pediatrics has proposed guidelines for treating term/near term infants with hyperbilirubinemia based primarily on maintaining the total serum bilirubin concentration (TSB) below a "critical" level of 25 mg/dL (426 micromol/L). We estimated the sensitivity and specificity of this critical TSB using patient data from published reports. A TSB >25 mg/dL is recorded in about 92% of term/near term infants with kernicterus. When TSB is adjusted lower for risk factors of prematurity, sepsis, and isoimmune hemolytic disease, the guidelines have nearly a 98% sensitivity. The specificity of the critical TSB, however, is very poor; false positive rates exceed 90% if all cases of acute bilirubin toxicity are included, and about 94-96% if the endpoint is mild or severe residual brain injury. Clinically measurable confounders that might explain the large variance in critical TSB include the plasma unbound "free" bilirubin concentration (Bf) and, possibly, the concentration of bilirubin photoisomers. Limited clinical experience supports the proposition that Bf is superior to TSB in identifying patients at risk. Specificity of Bf and TSB was compared in small cohort of babies with acute and permanent bilirubin encephalopathy. The false positive rate for TSB (at 100% sensitivity) was 94%, compared with only 55% for Bf. A more comprehensive comparison of TSB and Bf, controlled for clinical confounders and photoiomers, is needed to formulate intervention guidelines with improved specificity that will reduce hospital admissions for unnecessary treatment.

Immunoglobulin infusion for isoimmune haemolytic jaundice in neonates.

Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Exchange transfusion is not without risk and intravenous immunoglobulin has been suggested as an alternative therapy for isoimmune haemolytic jaundice to reduce the need for exchange transfusion. To assess whether the use of intravenous immunoglobulin, in newborn infants with isoimmune haemolytic jaundice, is effective in reducing the need for exchange transfusion. The search strategy of the Cochrane Neonatal Review group was used. Searches were made of MEDLINE 1966-2002, EMBASE Drugs and Pharmacology 1990-2002, Cochrane Controlled Trials Register, The Cochrane Library, Issue 1, 2002, expert informants, review articles, cross references, and hand searching of abstracts and conference proceedings of the annual meetings of The Society for Pediatric Research 1990-2001 and The European Society for Paediatric Research 1990-2001. All randomised and quasi-randomised controlled trials of the use of intravenous immunoglobulin in the treatment of isoimmune haemolytic disease were considered. The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Studies were assessed for inclusion and quality by two reviewers working independently, with the second reviewer blinded to trial author, institution and journal of publication. Data were extracted independently by the two reviewers. Any differences of opinion were discussed and a consensus reached. Investigators were contacted for additional or missing information. For categorical outcomes, the relative risk (RR), risk difference (RD) and the number needed to treat (NNT) were calculated. For continuous variables, the weighted mean difference (WMD) was calculated. Seven studies were identified. Three of these fulfilled the inclusion criteria and included a total of 189 infants. Term and preterm infants and infants with rhesus and ABO incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.28, 95% CI 0.17, 0.47; typical RD -0.37, 95% CI -0.49, -0.26; NNT 2.7). The mean number of exchange transfusions per infant was also significantly lower in the immunoglobulin treated group (WMD -0.52, 95% CI -0.70, -0.35). None of the studies assessed long term outcomes. Although the results show a significant reduction in the need for exchange transfusion in those treated with intravenous immunoglobulin, the applicability of the results is limited. The number of studies and infants included is small and none of the three included studies was of high quality. The protocols of two of the studies mandated the use of early exchange transfusion, limiting the generalizability of the results. Further well designed studies are needed before routine use of intravenous immunoglobulin can be recommended for the treatment of isoimmune haemolytic jaundice.

Rhesus isoimmunization: increased hemolysis during early infancy.

The objective of the present study was to determine whether whole blood carboxyhemoglobin (COHb) and plasma bilirubin, two indicators of hemolysis, are elevated in infants with severe Rh isoimmune hemolytic disease during the first months of life. Beginning at 2 wk of age and continuing monthly for 3 mo, serial blood samples were obtained for COHb, plasma bilirubin, Hb, reticulocyte count, plasma erythropoietin, plasma enzymes, and plasma iron. Because control infants (n = 13) and infants with ABO hemolytic disease (n = 5) did not differ from one another in any of the study parameters, these two groups were combined and compared with infants with the Rh isoimmunization. Infants with severe Rh isoimmune hemolytic disease (n = 13) were found to have significantly lower Hb and significantly higher bilirubin, the COHb fraction divided by the Hb concentration (COHb/Hb), and plasma erythropoietin levels at 2 and 6 wk of age, and reticulocyte counts at 6 wk. The remaining parameters were not different between the control-ABO group and Rh-isoimmune group at any of the study intervals. The study's two primary indicators of hemolysis, plasma bilirubin and COHb/Hb, were significantly correlated with one another in the Rh-immunized group (r = 0.66, p < 0.0001), but not in the combined control-ABO group. Serial Rh antibody concentrations measured in the serum of four neonates with Rh isoimmunization demonstrated a mean half-life of 14.3 d. We speculate that, among infants with severe Rh isoimmune hemolytic disease, elevated total bilirubin levels and COHb/Hb ratios identified in the early weeks of life indicate continuing hemolysis due to persistence of maternal Rh antibodies.

High‐Dose Intravenous Gammaglobulin Therapy for Neonatal Immune Haemolytic Jaundice due to Blood Group Incompatibility

Three newborn infants who developed hyperbilirubinemia due to blood group incompatibility were treated with high-dose gammaglobulin. Hyperbilirubinemia was caused by Rhesus (Rh) incompatibility (anti-E + anti-c) in Infant 1 and ABO incompatibility (anti-B) in Infants 2 and 3. Hyperbilirubinemia was refractory to conventional phototherapy but responded well to intravenous gammaglobulin (IVGG) at a dose of 1 g/kg in all infants. No adverse effects were observed. These findings suggest that high-dose IVGG may be useful in the treatment of hyperbilirubinemia due to isoimmune haemolytic disease resistant to phototherapy.

Neonatal ABO Incompatibility

The authors present two infants with isoimmune hemolytic disease due to ABO incompatibility complicated by massive hemoglobinuria and secondary acute renal failure. This represents an incidence of 0.36% of all neonates with ABO hemolytic disease in the author's newborn population. Only two patients have been reported previously to have similar complications. Analysis of data of these four infants revealed the clinical characteristics of this complication of ABO incompatibility: 1) very low frequency; 2) early onset of hemoglobinuria (first voided urine) and of acute renal failure (first 2 days of life); 3) lack of correlation between the clinical presentation of hemolytic disease and appearance and severity of renal failure; 4) complete recovery of renal functions following intravenous fluid administration; and 5) normal renal radiologic investigations.

Neonatal bilirubin production estimated from "end-tidal" carbon monoxide concentration.

The relationship between the pulmonary excretion rate of carbon monoxide (VECO) and the concentration of CO, in a sample of breath, drawn through a nasopharyngeal catheter at end-expiration, was assessed in 25 studies of nine preterm and 14 term infants. The VECO and this approximate end-tidal sample of CO (ETCO) correlated significantly over a wide range of CO elimination rates: VECO = 10.45 ETCO + 2.25 (n = 25, r = 0.95). The ETCO correctly predicted elevations in VECO greater than 2 SD of the mean VECO for normal infants (13.9 +/- 3.5 microliter/kg/h), with 90% sensitivity and 73% specificity (p less than 0.01). Three subjects with Rh isoimmune hemolytic disease were easily identified by the ETCO as well as the VECO. The ETCO is a simple, noninvasive measurement for rapidly identifying infants with significant hemolytic disease.

Neonatal Bilirubin Production Estimated from “End‐Tidal” Carbon Monoxide Concentration

SummaryThe relationship between the pulmonary excretion rate of carbon monoxide (VECO) and the concentration of CO, in a sample of breath, drawn through a nasopharyngeal catheter at end‐expiration, was assessed in 25 studies of nine preterm and 14 term infants. The VECO and this approximate end‐tidal sample of CO (ETCO) correlated significantly over a wide range of CO elimination rates: VECO = 10.45 ETCO + 2.25 (n = 25, r = 0.95). The ETCO correctly predicted elevations in VECO &gt; 2 SD of the mean VECO for normal infants (13.9 ± 3.5 μl/kg/h), with 90% sensitivity and 73% specificity (p &lt; 0.01). Three subjects with Rh isoimmune hemolytic disease were easily identified by the ETCO as well as the VECO. The ETco is a simple, noninvasive measurement for rapidly identifying infants with significant hemolytic disease.

Indications for early exchange transfusion in patients with erythroblastosis fetalis

The postnatal rate of rise of the undirect bilirubin concentration was compared with cord hematocrit and bilirubin values in 44 newborn infants with Rh isoimmune hemolytic disease. Cord blood values failed to predict the severity of hyperbilirubinemia with sufficient accuracy to warrant their use as therapeutic guidelines. A statistically significant positive correlation was found between the cord serum indirect bilirubin concentration and its subsequent rise in 19 infants who had received antenatal phenobarbital therapy, but this relationship was not observed in untreated infants. The phenobarbital-treated infants had a slower postnatal rise of indirect bilirubin than did nontreated controls. There was no reliable indicator of the severity of hyperbilirubinemia other than careful monitoring of the serum bilirubin concentration during the early hours of life.