Fetal hemoglobin accumulation in vitro. Effect of adherent mononuclear cells

In clonal cultures of erythroid burst-forming units (BFU-E) obtained from blood, the accumulation of fetal and adult hemoglobins (Hb F and Hb A) was measured by radioligand immunoassay. Inclusion of adherent mononuclear cells in the culture promoted a striking increase in the relative amount of Hb F in each of 44 experiments with 14 donors. In two-thirds of the instances, this was accounted for by a selective increase in the absolute amount of Hb F. The differential effect on Hb F and Hb A accumulation was achieved without altering the maturity of the erythroid cells, their mean hemoglobin content, or the asynchrony of the production of the two hemoglobins. Virtually all bursts produced Hb F, and the population of BFU-E as a whole, rather than a selected subset, appeared to be the target of adherent cell action. When the adherent cells were excluded from the culture input, the base-line value of Hb F was reproducible for each donor over a period of several months, and correlated with the number of in vivo circulating F cells.     

Fetal hemoglobin of transfused neonates and spectrophotometric measurements of oxyhemoglobin and carboxyhemoglobin

The records of 32 neonates in an intensive care unit were examined retrospectively to determine if fetal hemoglobin concentrations could be predicted on the basis of gestational or postnatal age, or on the volume of red blood cell transfusions. In nontransfused neonates, the correlation between measured concentrations of fetal hemoglobin and postnatal age wasr=0.53 with a 17.2 standard error of prediction. In these same neonates, the correlation between measured fetal hemoglobin divided by birth weight and gestational age wasr=0.70, with a 9.6 standard error of prediction. A three-variable regression equation (the latter two variables plus calculated fetal hemoglobin) was found to have a high correlation with data for measured fetal hemoglobin (r=0.97) and a relatively low 8.4 standard error of prediction. In transfused neonates, however, measured hemoglobin concentrations divided by birth weight correlated poorly with gestational age (r=0.30 and a 12.4 standard error of prediction). In addition, the transfused neonates had low correlations when fetal hemoglobin concentrations alone were compared with the total volume of red blood cell transfusions (r=0.35) and with postnatal age (r=0.18) and the standard errors of prediction were all approximately 17. The correlations found between concentrations of fetal hemoglobin and age in transfused neonates were poorer than those reported in earlier nontransfused infant studies. Previous studies have also shown that neonatal blood containing fetal hemoglobin interferes with the spectrophotometric measurements of carboxyhemoglobin and oxyhemoglobin. Because of the imprecision in the predictions of fetal hemoglobin using age, weight, or the volume of transfusion, we conclude that fetal hemoglobin should be measured if accurate spectrophotometric determinations of carboxyhemoglobin and oxyhemoglobin are desired. Supported by National Institutes of Health grant HD14426, the Mead Johnson Nutritional Division, and the Christopher Taylor Harrison Fund. The authors thank Natalie Malachowski for efforts in retrieving the patient chart data.     

Fetal hemoglobin of transfused neonates and spectrophotometric measurements of oxyhemoglobin and carboxyhemoglobin

The records of 32 neonates in an intensive care unit were examined retrospectively to determine if fetal hemoglobin concentrations could be predicted on the basis of gestational or postnatal age, or on the volume of red blood cell transfusions. In nontransfused neonates, the correlation between measured concentrations of fetal hemoglobin and postnatal age wasr=0.53 with a 17.2 standard error of prediction. In these same neonates, the correlation between measured fetal hemoglobin divided by birth weight and gestational age wasr=0.70, with a 9.6 standard error of prediction. A three-variable regression equation (the latter two variables plus calculated fetal hemoglobin) was found to have a high correlation with data for measured fetal hemoglobin (r=0.97) and a relatively low 8.4 standard error of prediction. In transfused neonates, however, measured hemoglobin concentrations divided by birth weight correlated poorly with gestational age (r=0.30 and a 12.4 standard error of prediction). In addition, the transfused neonates had low correlations when fetal hemoglobin concentrations alone were compared with the total volume of red blood cell transfusions (r=0.35) and with postnatal age (r=0.18) and the standard errors of prediction were all approximately 17. The correlations found between concentrations of fetal hemoglobin and age in transfused neonates were poorer than those reported in earlier nontransfused infant studies. Previous studies have also shown that neonatal blood containing fetal hemoglobin interferes with the spectrophotometric measurements of carboxyhemoglobin and oxyhemoglobin. Because of the imprecision in the predictions of fetal hemoglobin using age, weight, or the volume of transfusion, we conclude that fetal hemoglobin should be measured if accurate spectrophotometric determinations of carboxyhemoglobin and oxyhemoglobin are desired.Supported by National Institutes of Health grant HD14426, the Mead Johnson Nutritional Division, and the Christopher Taylor Harrison Fund.The authors thank Natalie Malachowski for efforts in retrieving the patient chart data.     

Low proportions of glycosylated hemoglobin associated with hemoglobin S and hemoglobin C.

Using a cation-exchange chromatographic method, we found normal or subnormal values for glycosylated hemoglobin in a few diabetic patients with persistent hyperglycemia. Subsequent investigations revealed that these unexpected results had originated from black patients with diabetes. In view of common occurrence of abnormal hemoglobins in the Negro population, we subjected blood preparations to electrophoresis on cellulose acetate and acrylamide gel. The results have shown the presence of hemoglobin S or hemoglobin C in each patient. When allowance was made for the percentage of the abnormal hemoglobin, the "corrected values" of glycosylated hemoglobin increased to the diabetic range. Furthermore, the corrected values agreed well with the "expected values" calculated from a regression line correlating fasting blood glucose concentrations and proportions of glycosylated hemoglobin in more than 300 diabetics with no evidence of hemoglobinopathy. We conclude that in diabetic patients presenting with hemoglobin S or hemoglobin C, there is a considerable decrease in the values for glycosylated hemoglobin as measured by cation-exchange chromatographic methods, and that this decrease is proportional to the percentage of the abnormal hemoglobin.     

Evaluation of Fetal Growth and Fetal Well-Being

This article reviews the actual knowledge and future developments of ultrasound techniques for the evaluation of fetal growth and well-being. Sonography allows the visualization of the fetus in utero and is utilized worldwide for the evaluation of fetal growth and well-being. Fetal biometry assessment is performed in the second half of pregnancy when deviations of fetal growth can be best recognized through alterations of fetal abdominal circumference growth. Doppler velocimetry of utero-placental vessels identifies alterations of placental perfusion and is valuable in the assessment of fetal brain, heart, and liver perfusion, thus being utilized in the timing of delivery. Recently, three-dimensional ultrasound evaluation of fetal organs and placenta is being developed.     

Interference of fetal hemoglobin and labile glycosylated hemoglobin with measurements of glycosylated hemoglobin

We examined the effect of fetal hemoglobin and labile glycosylated hemoglobin on a number of diverse methods used to measure glycosylated hemoglobin. Samples were supplemented with various amounts of cord blood to give proportions of fetal hemoglobin ranging from 1 to 20% of total hemoglobin concentration. Procedures in which the separation of hemoglobin A1 from the major hemoglobin A fraction is based on differences in ionic properties (cation-exchange chromatography and electrophoresis) are subject to interference by fetal hemoglobin, whereas procedures that base the quantitation on other properties (colorimetry and affinity column chromatography) are not. The same procedures that are affected by the presence of fetal hemoglobin are also subject to interference by labile glycosylated hemoglobin. We conclude that the affinity chromatographic and colorimetric methods may give a more nearly accurate determination of glycosylated hemoglobin.     

Fetal Monitoring

The severe risk situations characterized by fetal growth retardation are outlined. The small fetus, whether growth retarded or severely premature, is best delivered where both fetal monitoring and newborn resuscitation are available. The moderate risk fetus can be monitored at home base with clinical skills described in this article.     

Fetal Surgery

As prenatal diagnosis has become increasingly sophisticated and as technological advances have enhanced the range of diagnostic capabilities, invasive therapies have developed from our expanded understanding of the natural history and pathophysiology of structural anomalies. This article presents a comprehensive review of the treatment options currently available for the entire spectrum of fetal diagnoses that are potentially surgically correctable. The current indications, contraindications, and outcomes for shunting procedures, open fetal surgery, and fetoscopic surgeries are reviewed.     

Fetal imaging

Presently, MRI is an adjunct to prenatal sonography. It provides information that can aid in the diagnosis of fetal anomalies, affect prenatal counseling and management of the pregnancy, and guide prenatal intervention and delivery planning. With further advances in technology, particularly shorter scan times and better image resolution, the applications for fetal imaging are likely to increase.     

Fetal Megacystis

The purpose of our retrospective observational series was to determine whether the sonographic characteristics of fetal megacystic bladders can be used to reliably establish the most likely diagnosis in fetuses with this condition. The sonographic records of pregnant patients referred to our institutions over a 10‐year period who were found on initial 2‐dimensional sonography to be carrying fetuses with megacystis were examined for evidence of a keyhole sign, bladder thickness, amniotic fluid index, and fetal sex. When available, 3‐/4‐dimensional sonography, Doppler angiography, tomographic ultrasound imaging, virtual organ computer‐aided analysis, and automatic volume calculation were used as part of the detailed fetal anatomic survey. Twenty fetuses with megacystis were identified. Seventeen were male; 2 were female; and 1 had ambiguous genitalia. All male fetuses with megacystis originally had a diagnosis of prune belly syndrome. The diagnosis for 10 male fetuses with a keyhole sign was changed to megacystis secondary to posterior urethral valves. The fetus with ambiguous genitalia had prune belly syndrome. One of the female fetuses had a diagnosis of urethral atresia, and the diagnosis for the other female fetus was megacystis‐microcolon‐intestinal hypoperistalsis syndrome. In conclusion, in fetuses with megacystic bladders, it is possible to distinguish between cases with prune belly syndrome, posterior urethral valves, urethral atresia, and megacystis‐microcolon‐intestinal hypoperistalsis syndrome by a detailed anatomic survey using 2‐ and 3‐/4‐dimensioinal sonographic techniques.     

Fetal surgery

Fetal surgery has emerged from the realm of medical curiosity into an exciting, multidisciplinary specialty now capable of improving patient outcomes for a wide variety of diseases. Recent advances allow prenatal providers to both accurately diagnose and treat many fetal anomalies while maintaining maternal safety. As the initial postnatal health care providers to the majority of these newborns, neonatologists need to be familiar with some of the more recent state-of-the-art procedures currently being used. In this review, the authors discuss the prenatal evaluation process and various operative approaches (ie, open hysterotomy, fetoscopy, and percutaneous) to conduct fetal surgery. They then analyze the effectiveness of some of the more established and experimental prenatal therapies that are being performed for a number of fetal anomalies, including twin-twin transfusion syndrome, thoracic malformations, airway obstruction, congenital diaphragmatic hernia, myelomeningocele, and aortic valve stenosis.     

Fetal Imaging

Given that practice variation exists in the frequency and performance of ultrasound and magnetic resonance imaging (MRI) in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development hosted a workshop to address indications for ultrasound and MRI in pregnancy, to discuss when and how often these studies should be performed, to consider recommendations for optimizing yield and cost effectiveness, and to identify research opportunities. This article is the executive summary of the workshop.