Vincent J. Freda

Successful Prevention of Experimental Rh Sensitization in Man with an Anti-Rh Gamma2-Globulin Antibody Preparation: A Preliminary Report

An anti‐Rh gamma2‐globulin antibody preparation has been developed which can be administered intramuscularly and appears to be both safe and effective in the prevention of experimental Rh sensitization. Nine unsensitized Rh‐negative male volunteers were challenged once a month for five successive months with intravenous injections of 2 ml. of Rh‐positive blood. Four of these nine volunteers were passively protected each month with intramuscular injections of 5 ml. of this antibody preparation, administered 24 hours prior to the antigenic challenge. Three months after the last injection the passively acquired Rh antibodies were no longer demonstrable (by either the saline or indirect antiglobulin technics) in any of the four protected subjects and there was no sign of active antibody production six months after the last injection, whereas four of the five controls were all strongly sensitized.

The Rh problem in obstetrics and a new concept of its management using amniocentesis and spectrophotometric scanning of amniotic fluid

Abstract 1. Amniocentesis has been performed on more than 900 occasions in a group of over 300 Rh-immunized pregnant women without a major mishap to either the fetus or the mother. A detailed account of the antepartum management of these cases and the clinical outcome in 245 completed pregnancies is presented. The total perinatal loss (stillbirths and neonatal deaths) due to hemolytic disease was 8 per cent of the total 245 immunized pregnancies, and 9 per cent of the total number of affected Rh-positive infants (211 pregnancies). The previous perinatal mortality rate from hemolytic disease at this hospital was 30 per cent of the total number of affected Rh-positive infants. In addition, only one first affected baby was lost in this study as a result of hemolytic disease, and no unnecessary inductions of premature labor nor cesarean sections were performed to deliver unaffected infants. 2. In the antepartum management of a Rh-immunized pregnancy, the spectrophotometric scanning of the amniotic fluid appears to be the most clinically useful procedure. However, it is suggested that the true value of this procedure can only be realized by repeating the test at biweekly intervals (or sometimes at weekly intervals); in order to minimize the risk of amniocentesis, the placenta should be localized by both the radioisotope and thermograph methods. 3. The physical characteristics and the clinical interpretation of the spectrophotometric tracings has been discussed in detail. 4. There appears to be a better correlation between the spectrophotometric tracings within 10 days of delivery and the clinical condition of the infant at birth, as assessed by the Apgar score and the presence or absence of circulatory failure, than with the level of cord hemoglobin and cord bilirubin, etc. It is suggested that the standard evaluation of the severity of hemolytic disease of the newborn should be revised to include the general condition (as assessed by recent amniotic fluid analysis) of the infant. 5. The principal value of amniocentesis and spectrophotometry is to determine the fetal outcome (survival or death) and not the level of hemoglobin at birth.

Rh Factor: Prevention of Isoimmunization and Clinical Trial on Mothers

The results on the use of γG-immunoglobulin to Rh factor for the prevention of active immunization of Rh-negative mothers at risk appear most promising. One hundred and seven mothers in the clinical trial have been followed for periods of about 6 months to 1�12 years after delivery. Of these, 48 were treated mothers who received 5 ml γG-immunoglobulin to Rh, and 59 were untreated mothers. Of the 48 treated mothers none are actively immunized; seven of the 59 control mothers have become actively immunized to Rh.

Results of Clinical Trials of RhoGAM in Women

Intramuscularly administered RhoGAM, Rh0 (D) Immune Globulin (Human) has been evaluated for its capacity to prevent the primary Rh immunization of Rh negative women giving birth to ABO compatible Rh positive infants. Since March 1964, over 3,000 women have been admitted to clinical studies in 43 centers ranging geographically from Argentina to Ganada and from Australia to Scotland. RhoGAM prepared at the Ortho Research Foundation used throughout these studies is derived from plasma of persons previously immunized to the Rh0 (D) antigen, and the antibody content of the final preparation is determined by a modification of the radioimmune assay of Hughes-Jones.8

A-B-O(H) blood group substances in the human maternal-fetal barrier and amniotic fluid☆

Abstract The placenta, membranes, and amniotic fluid obtained from 20 full-term human pregnancies were studied for the presence of A, B, O(H) blood group substances and this in turn was related to the blood group and secretor status of the mother and infant. 1. 1. In cases of maternal-fetal heterospecificity, only when the mother was a secretor could her blood group substance be found in the amniotic fluid and fetal membranes as well as in the decidua basalis and decidua vera. The concentration of the maternal antigen was greater in the amniotic fluid than it was in the maternal serum. Also the maternal antigen was not found in the fetal circulation (cord serum) or in the fetal secretions. 2. 2. In cases of maternal-fetal heterospecificity, only when the fetus was a secretor could the fetal antigen be found in the decidua vera and decidua basalis as well as in the amniotic fluid, membranes, and occasionally the placental villi. The concentration of fetal antigen was greater in the decidua vera than it was in the fetal serum. These and other findings suggest that the blood group substances A, B, and O(H), despite their large molecular weight, do traverse the membranes directly from the uterine wall to the amniotic fluid and vice versa. It is also suggested that when the mother is a secretor the source of antigen is the uterine glands. The clinical implications of these findings have been discussed.

Suppression of the primary Rh immune response with passive Rh IgG immunoglobulin.

THAT passive immunity can block active immunity is an established concept dating from as early as 1909.1 The precise mechanism of the immunosuppressive action, however, is still not clearly underst...

THE RELATION OF FLUORESCENCE POLARIZATION VALUES TO LECITHIN SPHINGOMYELIN RATIOS |[lpar]|L|[sol]|S|[rpar]| IN AMNIOTIC FLUID |[lpar]|AF|[rpar]|

Fluorescence polarization (FP) measures the microviscosity of phospholipid micelles. The technique has been evaluated in both artificial solutions and in AF and its usefulness in determining gestational age and lung maturity examined.We have shown that in lipid dispersions of known composition and in amniotic fluid the FP value correlates directly with the L/S ratio. Gestational age was studied in 97 serial samples from 19 isoimmunized pregnancies. There was a significant change in slope of FP values vs. gestational age occurring between 29 to 35 weeks (mean = 31.5 wks). In single samples from 120 pregnancies a significant correlation was also found between FP and L/SThus FP values correlate well with both gestational age and lung maturity.The determination of fluorescent polarization is precise with a coefficient variation of 0.48%. It can be performed rapidly (45 min)and is technically easy. This physical method therefore offers a great advantage over the currently available chemical methods. (Supported by NHLI HL-14218)