Effect of delayed cord clamping on red blood cell alloimmunization: a retrospective cohort study.

BACKGROUND: Although delayed cord clamping has well-known benefits for preterm and term neonates, it has been inadequately assessed in alloimmunized neonates. OBJECTIVE: This study aimed to evaluate the benefits and risks of delayed cord clamping in alloimmunized neonates. STUDY DESIGN: This was a retrospective comparative pre-post cohort study conducted from 2003 to 2018 in a tertiary care center in France. All living singleton neonates whose mothers were followed up for red blood cell alloimmunization during gestation and confirmed at birth (N=224) were included. Neonates were either exposed to immediate (n=125) or delayed cord clamping (n=99). Our main outcome was the time from birth to first exchange transfusions and/or transfusions. Secondary outcomes were hemoglobin level at birth, rate of exchange transfusion, number of postnatal transfusions, maximum bilirubin level, and number of phototherapy hours. RESULTS: Hemoglobin at birth was significantly higher in case of delayed cord clamping (mean difference, 1.7 g/dL; 95% confidence interval, 0.7-2.8). Among infants treated with exchange transfusion or transfusion, the time to initial treatment was higher in case of delayed cord clamping (median difference, 8 days; rate ratio, 1.51; 95% confidence interval, 1.09-2.10). There were no significant differences in the need for exchange transfusion, the number of transfusions, the maximum total bilirubin level, nor the number of phototherapy hours. In the subgroup analysis of neonates needing intrauterine transfusion during pregnancy (ie, severe alloimmunization), neonates had a lower rate of exchange transfusion in case of delayed cord clamping (odds ratio, 0.36; 95% confidence interval, 0.15-0.82). CONCLUSION: Our results indicate a benefit of delayed cord clamping in alloimmunization, regardless of pathology severity, without increased risk of jaundice.

Neonatal outcomes following intrauterine transfusion for hemolytic disease of the fetus and newborn: a twenty-year service review.

OBJECTIVE: The primary objective was to explore perinatal and neonatal outcomes amongst infants who received intrauterine transfusion (IUT) for the management of hemolytic disease of the fetus and newborn (HDFN). The secondary objective was to evaluate the role of key investigations in the fetus at risk of HDFN and assess the relationship with neonatal outcomes. We hypothesized that middle cerebral artery peak systolic velocity (MCA-PSV) and corresponding multiples of the median (MoM) would be predictive of neonatal course. METHODS: This was a retrospective observational study conducted at a tertiary center in the United Kingdom between January 2000 and August 2020. Trust approval was obtained to conduct this service review. Pregnancies requiring IUT for HDFN were identified using the fetal medicine department database. Inclusion criteria were infants who received IUT for HDFN. 67 pregnancies were eligible for inclusion in the study with 156 IUT events. Data were extracted using healthcare records. Statistical analysis was performed using SPSS version 28.0, data were assessed for normality and Spearman's correlation analysis was performed with p values < .05 considered significant. RESULTS: 67 pregnancies were included in the study which led to the live birth of 68 infants (one twin pregnancy). There were no fetal deaths following IUT. There was one neonatal death due to extreme prematurity following spontaneous vaginal delivery at 23 + 4 weeks gestation, occurring three days following IUT. 97% of infants required admission to the neonatal intensive care unit and 88% required phototherapy. 25% of infants required readmission for red blood cell transfusion due to anemia. There was a significant correlation between maternal anti-D antibody levels and length of neonatal admission r = 0.477, p = .014. MCA-PSV and MoM measured prior to the last IUT had a significant positive correlation with the duration of phototherapy: r = 0.527 (p < .001) and r = 0.313 (p < .05) respectively. Linear regression analysis demonstrated a significant positive relationship between MCA-PSV and corresponding MoM recorded prior to the last IUT with r2= 0.177 (p = .003) and r2= 0.101 (p = .029). CONCLUSION: HDFN is an important cause of fetal anemia associated with significant neonatal morbidity. MCA-PSV and MoM may be predictive of neonatal phototherapy requirements. The predictive value of MCA-PSV appears to be dependent on the timing of measurement during the antenatal period and more research is needed. Multicentre collaboration is required to generate a reliable large-scale database to further delineate the value of MCA-PSV and MoM and predict neonatal outcomes in cases of HDFN requiring IUT. This data would assist clinicians in antenatal planning and enable more informed counseling of parents in the antenatal period.

Fetomaternal hemorrhage: evaluation of recurrence within a large integrated healthcare system.

BACKGROUND: Fetomaternal hemorrhage is associated with severe fetal morbidity and mortality. The recurrence risk of fetomaternal hemorrhage is unknown. OBJECTIVE: We sought to establish the recurrence rate of fetomaternal hemorrhage in a large integrated healthcare system over a 10-year period. STUDY DESIGN: In this retrospective study within the Kaiser Permanente Northern California medical system, cases of fetomaternal hemorrhage were defined by either an elevated fetal hemoglobin level as determined by flow cytometry for a concerning pregnancy outcome (preterm delivery, perinatal demise, neonatal anemia, or transfusion within the first 2 days of life) or by perinatal demise with autopsy findings suggestive of fetomaternal hemorrhage. The outcomes of subsequent pregnancies were reviewed for features of recurrence. RESULTS: Within the 2008 to 2018 birth cohort of 375,864 pregnancies, flow cytometry testing for fetal hemoglobin levels was performed in 20,582 pregnancies. We identified 340 cases of fetomaternal hemorrhage (approximately 1 in 1100 births). Within the cohort of 340 affected pregnancies, perinatal loss was recorded for 80 (23.5%) pregnancies and 50 (14.7%) pregnancies delivered neonates who required transfusion. The affected patients had 225 subsequent pregnancies of which 210 were included in the analysis. Of these, 174 (82.9%) advanced beyond the threshold of viability and were delivered within our healthcare system. There was 1 case of recurrent fetomaternal hemorrhage identified. The recurrent case involved a spontaneous preterm delivery of an infant who was noted to have an elevated reticulocyte count but was clinically well. CONCLUSION: Within our large integrated healthcare system, approximately 1 in 1100 pregnancies was affected by fetomaternal hemorrhage within a 10-year period, which is comparable with previous studies. We identified 1 case of recurrence, yielding a recurrence rate of 0.5%. This infant did not have features of clinically important fetomaternal hemorrhage. This information can inform counseling of patients with affected pregnancies.

Association of maternal hemoglobin and iron stores with neonatal hemoglobin and iron stores.

BACKGROUND: One of the commonest causes of anemia in pregnancy is iron deficiency. This study aims at understanding and exploring the association between fetal and maternal iron status. Predelivery maternal hemoglobin (Hb) and iron stores, serum iron, ferritin, and soluble transferrin receptor (sTfR), were assessed and compared to the cord blood Hb and iron stores with an attempt to identify the level of maternal Hb and ferritin at which the fetal iron stores reduce, helping to identify the neonates who will require earlier iron supplementation. METHOD: Four hundred eight participants were enrolled, and maternal and cord blood was collected at the time of delivery and tested for Hb and iron parameters. The results were statistically analyzed. RESULTS: Of all mothers, 27.2% mothers were anemic (Hb less than 11 g/dl). Of all newborns, 15.4% newborns had Hb less than 14 g/dl. There was a significant association between the maternal and cord blood iron, ferritin, sTfR and sTfR/log ferritin index. Eighty-five percent of the babies with cord blood Hb <14 g/dl had maternal serum ferritin (SF) <50 µg/L. Maternal SF <10 µg/l was associated with a significant number of babies with cord blood SF <75 µg/l (77.7%). One hundred sixty six neonates had sTfR 2 µg/ml or more. Of these, 80.7% had maternal SF <50 µg/l. Of the 115 newborns with a high sTfR/log ferritin index (>1.5), 56.5% had raised maternal sTfR (>2µg/ml). CONCLUSION: In view of a significant association between maternal and neonatal Hb and iron stores, newborns of mothers with iron deficiency anemia (IDA) during pregnancy should be monitored and followed up after birth for development of IDA and early iron supplementation.

Delayed clamping vs milking of umbilical cord in preterm infants: a randomized controlled trial.

BACKGROUND: It has been established that delayed umbilical cord clamping in preterm infants results in improvement in neonatal anemia, need for transfusion, incidence of necrotizing enterocolitis, and intraventricular hemorrhage by increasing neonatal circulating blood volume. However, the effects of umbilical cord milking as an alternative to delayed clamping in preterm infants are unclear. OBJECTIVE: The primary objective of this study was to compare the effect of delayed clamping vs milking of the umbilical cord on the initial hematocrit concentration in preterm births (23-34 weeks gestation). In addition, we sought to compare the effects of delayed clamping vs milking on the incidences of intraventricular hemorrhage, necrotizing enterocolitis, and need for transfusion (secondary objectives). STUDY DESIGN: The study was an unblinded randomized controlled trial of singleton preterm infants who were born 23 weeks 0 days to 34 weeks 6 days gestation and were assigned to 1 of 2 controlled study groups: delayed cord clamping for 60 seconds or milking of the cord towards the infant 4 times before clamping. Randomization occurred via block randomization with an allocation ratio of 1 to 1. The patients' third stage of delivery was standardized for route of delivery and randomization arm. All comparisons were preformed with an intent-to-treat analysis approach. The study was powered at 80% with a probability value of .05 for the primary outcome measure of a hematocrit difference of 3% between the 2 groups. RESULTS: Of the 204 randomized patients, 104 were assigned to the delayed subgroup, and 100 were assigned to the milking subgroup. There were no significant differences in baseline maternal characteristics noted between groups. Though there was not any statistically significant difference in neonatal outcomes between the cord clamping and milking groups, the occurrences of transfusion (15.5% vs 9.1%; P=.24), necrotizing enterocolitis (5.8% vs 3.0%; P=.49), and intraventricular hemorrhage (15.5% vs 10.1%; P=.35) were all lower in the milking group. The milking group had higher initial hematocrit concentration compared with the delayed clamping group, although this was not significant (51.8 [6.2%] vs 49.9 [7.7%]; P=.07]. Peak bilirubin levels and need for phototherapy were similar between groups. CONCLUSION: This study demonstrates that milking the umbilical cord may be an acceptable alternative to delayed cord clamping because there were similar effects on neonatal hematocrit concentrations and the need for neonatal transfusions and no increased risk for complications or neonatal morbidity. The present data support the concept that milking of the umbilical cord may offer an efficient and timely method of providing increased blood volume to the infant.