An error in Rh testing in pregnancy.

Anti-D (anti-Rho) in the blood of two Rh-negative pregnant women was believed to be due to active immunization. In the first case, however, antibodies were no longer detectable 2 weeks later. In the second case they disappeared by the end of 31 weeks. It was discovered that both women had been given immune globulin (human) because of exposure to rubella. The globulin given to the first woman probably contained about 0.1 mug of anti-D per ml; that given to the second probably contained about 0.6 mug of anti-D per ml. Both babies were O Rh-positive. Both women were given Rh immune globulin after delivery. Both have completed a further pregnancy and no anti-D has been found on many tests. In tests carried out in 1971 all samples of immune globulin (human) examined contained anti-D, but usually in inconsequential trace amounts.     

Association between Foeto-maternal Bleeding and Hypertension in Pregnancy

A blind prospective survey of foeto-maternal bleeding in 200 primiparous pregnancies was carried out in an investigation of a possible association between foeto-maternal bleeding and hypertension in pregnancy. Evidence of foeto-maternal bleeding was found in 61% of 36 hypertensive pregnancies, and in 51% of 160 normotensive pregnancies, a difference which is not statistically significant.Significant differences between the hypertensive and the normotensive groups were found when foeto-maternal bleeding was related to gestation. In pregnancies that became hypertensive more foetal cells were found in the maternal circulation before week 36 than in normotensive pregnancies. In patients with oedema of the abdominal wall during pregnancy the incidence of foeto-maternal bleeding was significantly increased.These findings seem to explain why pre-eclamptic toxaemia is a significant predisposing factor in women who later develop Rh antibodies. It is recommended that anti-D gammaglobulin should be offered to all Rh-negative women with Rh-positive infants following a hypertensive pregnancy. Consideration should also be given to the question of administering anti-D gammaglobulin during Rh-negative hypertensive pregnancies if this procedure is proved to be both safe to mother and foetus and effective.The results provide contributory evidence that the placental vascular changes in toxaemic pregnancies precede the clinical signs and are not the result of hypertension.     

Incidence of Maternal Rh Immunization by ABO Compatible and Incompatible Pregnancies

The incidence of maternal Rh immunization in Rh-negative women following a single ABO compatible Rh-positive pregnancy is about 17%. This incidence was determined by following Rh-negative women through two Rh-incompatible pregnancies and analysing their sera for anti-Rh at the time of delivery of their second observed pregnancy. Maternal Rh immunization occurs almost exclusively after delivery; however, antibodies may not be detectable in the absence of further antigenic stimulation.The incidence of maternal Rh immunization when maternal-foetal ABO incompatibility is also present is 9–13% and 17% for group O and non-group O women respectively. This study emphasizes the need to offer Rh-immune prophylaxis to Rh-negative women having Rh-positive infants whether or not ABO incompatibility exists between the mother and infant.     

Rh-immunization by Pregnancy: Results of a Survey and Their Relevance to Prophylactic Therapy

A series of Rh-negative primiparae has been studied in order to gain further insight into the process of immunization by pregnancy. The distribution of foetal cell counts in blood samples taken after delivery was determined for 2,029 mothers giving birth to ABO-compatible babies and for 417 mothers with ABO-incompatible babies.A total of 760 mothers were tested for the development of Rh antibodies six months after the delivery of an ABO-compatible Rh-positive baby and 236 were further followed up through a second Rh-positive pregnancy. The incidence of anti-D six months after delivery is estimated to be 8.5%, and there is evidence of a direct relation between the count of foetal cells after delivery and the risk of developing antibodies. A further 8.5% of mothers were estimated to develop anti-D by the end of the second pregnancy, and it is postulated that these individuals had been primed by the first pregnancy. There is some evidence that the larger stimuli of Rh-positive blood in the first pregnancy are more likely to result in overt antibody formation, while the smaller stimuli are more likely to prime, antibodies not being detected until a second stimulus occurs during the second pregnancy.These findings are relevant to the programme for preventing Rh-immunization by injecting anti-D gammaglobulin.     

Anti-erythrocyte immunization in the pregnant woman. Apropos of the analysis of 761 cases of alloimmunized women delivered in the Paris area in 1978 and 1979

Through analysis of 760 cases of allo-immunized women delivered in the Paris area during 1978 and 1979, anti-erythrocyte immunization (ABO excluded) still appears to be a consequent perinatal risk, for the mother as for her fetus. During the considered period, general incidence in the parisian population has been of 3,78 for 1 000 livebirths, one out of four cases being a "non Rh D"immunization. Obviously, anti-D immunoglobulin prophylaxis has not proved to be as efficient as it promised to be, after more than ten years of application. Taking into account cases affecting "non ordinary" residents in the observed area, incidence of anti-D immunizations was of two out of a thousand. Anti-D immunoglobulin actual efficiency cannot be incriminated, for when correctly applied Rhesus immunization prophylaxis has demonstrated its ability to induce a twenty-fold reduction of immunization risk due to pregnancy. It must be pointed out, unfortunately, that most cases of undue immunizations are related to prophylatic omissions after delivery, miscarriage, abortion or fortuitous hetero-Rhesus blood transfusion. On another hand an important increase of "non Rh D" immunizations, which incidence, if one images that unknown cases are as frequent as known cases, could be two out of a thousand deliveries, is perhaps able to neutralize partially the decrease of Rh D immunizations. Though is underlined the absolute necessity to extend systematically anti-erythrocyte antibody screenings to all pregnant women, whatever the blood group is. A great variety of antibodies specificities can be found among "on Rh D" immunizations but anti-Kell and anti-c are by far the most frequently met. In most cases theses immunizations could easily be avoided, assessing that all female subjects aged less than 50 years are only given Kell negative and, if lacking c antigen, CC phenotyped blood.     

Incidence of rhesus immunisation after genetic amniocentesis.

Of 655 Rh negative women without anti-D antibody in their serum at genetic amniocentesis, 361 delivered a Rh positive infant. Prophylactic treatment with anti-D immunoglobulin was not given at amniocentesis. The women were followed prospectively, being given a screening test for antibody after amniocentesis, at delivery, and six months later. Five of these 361 women yielded a positive test result due to anti-D antibody. The immunisation rate after genetic amniocentesis was no higher than the spontaneous immunisation rate during pregnancy. Four women who had two amniocenteses in the same pregnancy and 34 women who had amniocentesis in two consecutive pregnancies with Rh positive fetuses were not immunised. Among six women with anti-D antibody in their serum before amniocentesis the titre of antibody increased in three. Amniocentesis may have worsened the outcome of these pregnancies. These results suggest that the risk of immunisation in Rh negative women is small.     

Prevention of Rh haemolytic disease.

Between 1970 and 1976 in the Yorkshire region the incidence of Rh antibodies in Rh-negative pregnant women fell by 70%. This decrease occurred in both old (long-standing) and new (first-affected) cases, which emphasised that the reduction in numbers was as much due to fewer pregnancies among Rh-negative mothers as to administration of anti-D immunoglobulin. Nevertheless, the incidence has begun to level out. The continued incidence of first-affected cases is caused by three main factors: failure of administration of anti-D immunoglobulin after normal deliveries and abortions; a steady incidence of antibodies in primigravidae; and cases in which administration of anti-D immunoglobulin had failed to protect. Administering anti-D antenatally might reduce the incidence of new cases among primigravidae who are sensitised before anti-D is normally given. Even without routine antenatal administration of anti-D, the incidence of severely affected Rh babies in the Yorkshire region could be reduced to one or two isolated cases a year in a population of three to four million by administering anti-D after all Rh-negative deliveries and after every abortion.     

COCCIDIOIDOMYCOSIS AS A COMPLICATION OF PREGNANCY

Records of 33 cases of coccidioidomycosis occurring during pregnancy were reviewed. In this group the incidence of dissemination of the disease was considerably greater than the reported incidence of dissemination in all cases of coccidioidomycosis.The incidence of dissemination was higher in the patients who contracted coccidioidomycosis late in pregnancy than it was in those in whom onset of the disease occurred earlier in gestation; but dissemination occurred in all Negro patients in the group, regardless of the time of onset during pregnancy.The chief complicating effect when onset was in the first trimester of pregnancy was a tendency to abortion. In cases in which onset was in the third trimester, the incidence of premature labor was extremely high.There was no evidence of congenital infection in any of the babies, but in one case invasion of the placenta by coccidioidal spherules was observed.     

Measurement of human corticosteroid binding globulin by enzyme-linked immunoassay

Thirteen monoclonal antibodies have been raised against corticosteroid binding globulin (CBG). From four of those with highest affinity for the antigen, two were selected for development of a sandwich enzyme-linked immunoassay (ELISA). The sensitivity of the assay was such that 0.7 fmol CBG could be detected. Levels of the binding protein in men (740 +/- 67 nmol/l) and women (690 +/- 103 nmol/l) were not significantly different, while those found during the third trimester of pregnancy (1500 +/- 423 nmol/l) were approximately twice these levels. CBG denatured by heating to 60 degrees C could not be detected by the ELISA.     

Haemolytic Disease of the Newborn Caused by Anti-Lan Antibody

The first recorded example of anti-Lan associated with haemolytic disease of the newborn is reported. This emphasizes the importance of screening for atypical antibodies early in pregnancy, even though prophylactic use of anti-D immunoglobulin will eventually reduce the incidence of haemolytic disease due to anti-D antibody.     

WinRho: Rh immune globulin prepared by ion exchange for intravenous use.

An Rh immune globulin [Rh IgG] for intravenous use, WinRho, has been prepared by the Winnipeg Rh Institute by a modification of the ion-exchange column method of Hoppe and colleagues. When administered to Rh-negative male and nonpregnant female volunteers WinRho was found to be nonpyrogenic, nontoxic, safe and protective against Rh alloimmunization. In a clinical trial with 240 microgram given at about 28 weeks'' gestation and 120 microgram given after delivery to Rh-negative women at risk of Rh immunization WinRho was effective in preventing Rh immunization. Of the 870 women carrying Rh-positive fetuses who were treated with WinRho during pregnancy and were not tested several months after delivery 14 would have shown evidence of Rh immunization by the time of delivery if WinRho had been ineffective; none showed such evidence. Of the 1122 women carrying Rh-positive fetuses who were retested 4 to 6 months after delivery 83 would have shown evidence of Rh immunization at that time if WinRho had been ineffective; only 1 showed such evidence. The efficiency of yield of anti-D with the modified method of production, the fct that it can be given intravenously (a route that causes the patient less discomfort and immediately results in high anti-D levels) and the lower levels of contaminating IgA and IgM make WinRho the preparation of choice for preventing Rh immunization.     

Targeted Routine Antenatal Anti-D Prophylaxis in the Prevention of RhD Immunisation - Outcome of a New Antenatal Screening and Prevention Program

Objective

To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP).

Materials and Methods

We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy.

Results

During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500.

Conclusions

Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.     

Bile acid and cholesterol excretion in the pregnant guinea pig: Studies on the hypercholesterolemia of pregnancy

The relationship of bile acid and cholesterol excretion to changes in plasma cholesterol during pregnancy were studied in guinea pigs. Plasma cholesterol level increased in the first trimester of pregnancy, reached to a peak during the second trimester and decreased in the third trimester reaching the lowest level at one week prior to parturition. Cholesterol level returned to the control level after parturition. Plasma triglyceride level followed a similar trend attaining peak values at second trimester and gradually returned to the control level at the third trimester of pregnancy. Bile acid and total sterol excretion were significantly higher in guinea pigs during the last phase of pregnancy while they remained unchanged during early stage of pregnancy.     

Immunohistological localization of human pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), a glycosylated beta-lactoglobulin homologue, in the decidua and placenta during pregnancy

Monoclonal and polyclonal antibodies to pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), a glycosylated human beta-lactoglobulin homologue, were used in an immunohistological technique to determine the cellular localization of this protein in the decidua and placental tissues during pregnancy. During the first trimester the protein was principally localized to the glandular epithelium of the decidua spongiosa region of the endometrium with only weak staining associated with glands of the decidualized decidua compacta region. No significant cellular staining was detected in the decidua capsularis. At term in the decidua of the amniochorion and the placental bed weak staining for alpha 2-PEG was only associated with the epithelium of attenuated glands. No significant staining was detected in the placenta during pregnancy. These results suggest that the epithelium of glands associated with non-decidualized stroma represents the primary source of alpha 2-PEG during the first trimester and that a function of the decidua spongiosa in early pregnancy may be related to production of alpha 2-PEG. The decline in production of alpha 2-PEG during pregnancy is suggested to result from involution of the decidua spongiosa and at term the attenuated glands of the decidua represents the source of alpha 2-PEG.     

Intrauterine sensitization of ovalbumin in the third trimester increases the risk of food allergy in progeny

Intrauterine sensitization caused by food allergens plays an important role in the food allergy development in progeny. The aim of our study was to determine the critical period of intrauterine sensitization during pregnancy. Female mice were exposed to ovalbumin (OVA) during different trimesters of pregnancy. Lymphocytes from their offspring were isolated and cultured, and proliferation was evaluated by CCK-8 assay. The levels of IFN-γ and IL-4 in serum were measured using ELISA. In addition, the expressions of IFN-γ and IL-4 mRNAs and proteins were detected by real-time PCR and western blot. The mice were divided into the first trimester pregnancy (FTP1 and FTP2) group, the second trimester pregnancy (STP1 and STP2) group, and the third trimester pregnancy (TTP1 and TTP2) group based on the stages of pregnancy in which their mothers were exposed to OVA and their ages. The OVA-specific lymphocyte proliferation of the TTP1 group was statistically significantly greater that in the FTP1 and STP1 groups. The serum level of IFN-γ in the TTP1 group was significantly decreased, and the serum level of IL-4 in the TTP1 group was significantly increased compared with the levels in the FTP1 and STP1 groups. The mRNA and protein expression levels of IFN-γ in the TTP1 group were significantly decreased and the mRNA and protein expression levels of IL-4 in this group were significantly increased compared with the levels in the FTP1 and STP1 groups. Our results suggest that OVA-induced intrauterine sensitization in the third trimester may increase the risk of food allergy after birth.     

Rh isoimmunization during pregnancy: antenatal prophylaxis.

Of 3533 Rh-negative women who began a pregnancy without detectable Rh antibodies, 62 (1.8%) demonstrated evidence of Rh isoimmunization during pregnancy or within 3 days after delivery. All denied transfusions as well as abortions or previous pregnancies not followed by the administration of Rh immune globulin. Rh isoimmunization during pregnancy or within 3 days after delivery, which will not be prevented by the administration of Rh immune globulin after delivery, is the most important cause of residual Rh isoimmunization. A clinical trial of antenatal administration of Rh immune globulin, initially at 34 weeks''s and subsequently at 28 and 34 weeks'' gestation, in 1357 Rh-negative pregnant women who were delivered of Rh-positive babies, was effective in preventing the development of Rh isoimmunization during pregnancy or within 3 days after delivery. Antenatal prophylaxis with Rh immune globulin will be necessary if the incidence of Rh isoimmunization is to be reduced to its lowest possible level. Antenatal prophylaxis at 28 weeks'' gestation is now an insured service in Manitoba.     

Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin.

OBJECTIVE--To measure the safety and efficacy of antenatal treatment with anti-D immunoglobulin. DESIGN--Open study with historical controls. SETTING--Multicentre study in 17 hospitals in West Yorkshire. PATIENTS--1238 Rh negative women who delivered Rh positive infants after 34 weeks in their first pregnancy in 1980-1 (group 1) and 2000 similar primigravidas from 1978-9 (group 2). Obstetric data were collected for 616 women in group 1 who had a subsequent pregnancy, 536 similar women in group 2, and 410 Rh positive but otherwise similar primigravidas who delivered in the same hospitals in 1978-81 (group C). INTERVENTIONS--Anti-D immunoglobulin 100 micrograms intramuscularly was given at 28 and 34 weeks to the mothers in their first pregnancy who delivered in 1980-1. END POINTS--Detection of anti-D antibody in the first or any subsequent pregnancy in groups 1 and 2. For all three groups having subsequent pregnancies gestation at delivery, birth weight, fetal survival at one month, pre-eclampsia defined as blood pressure greater than 140/90 on two occasions more than 12 hours apart, and proteinuria greater than 0.25 milligram. MEASUREMENTS AND MAIN RESULTS--Antenatal immunisation to Rh(D) occurred in six mothers in group 1 and 32 group 2. Most immunisations occurred in the first or second pregnancy. The rates of abortion, gestation at delivery, birth weight, and fetal survival were not significantly different among the three groups. The incidence of pre-eclampsia was lower in mothers given antenatal anti-D immunoglobulin, but the difference was not significant. CONCLUSIONS--Antenatal prophylaxis with anti-D immunoglobulin is effective, and the effect of giving it in the first pregnancy persists into at least the second pregnancy. It seems to be safe for the fetus in the index and subsequent pregnancies.     

Dydrogesterone in threatened abortion: pregnancy outcome

OBJECTIVE: To determine whether therapy with dydrogesterone in threatened abortion during the first trimester of pregnancy will improve pregnancy outcome. DESIGN: Prospective open study. SUBJECTS: Pregnant women presenting to the obstetric and gynaecology clinic admitting center with vaginal bleeding before 13 weeks gestation were evaluated for entry into the study. Women were excluded if they had a history of recurrent miscarriage. METHOD: Eligible subjects were randomized to receive either dydrogesterone 40 mg stat dose followed by 10 mg twice a day for one week or conservative therapy. RESULTS: One hundred and 54 women were recruited. There was no statistically significant differences between the two groups with regard to pre-treatment status. The continuing pregnancy success rate was significantly (p=0.037) higher in women treated with dydrogesterone (95.9%) compared with women who received conservative treatment (86.3%). The odds ratio of the success rate between dydrogesterone treatment and non-treatment was 3.773 (95% confidence interval: 1.009-14.108). CONCLUSION: Corpus luteal support with dydrogesterone has been shown to reduce the incidence of pregnancy loss in threatened abortion during the first trimester in women without a history of recurrent abortion.     

Characteristics and analysis of uterine electromyographic activity in pregnant cows

The electromyographic activity of the cow uterus in the last trimester of pregnancy was investigated. The investigation was performed on 12 animals and the electrical activity was recorded in the last trimester of pregnancy during 11 different periods until the delivery. The duration of the action potential bursts (APB) recorded during the first 7 periods, was small. It did not exceed 2 seconds. A significant increase, however, was recorded at 7 to 9 days before the labor and it involved all the investigated areas in the uterus. The number of APB of the gravid horn was significantly higher than that recorded at other locations in the uterus with the exception of the day of delivery. A significant correlation was found between the number of APB and the level of magnesium in blood serum. The levels of 17-beta estradiol and progesterone were similar during all studied periods with the exception of the last week, in which a dramatic fall in estradiol level and a significant increase in the progesterone concentration were observed. The results showed that it is possible to distinguish three different phases of electric activity in the cow uterus during the last trimester of pregnancy. The features of these phases were discussed.     

Plasma copper concentrations in pathological pregnancies.

Copper is an essential element required for the formation of many enzymes with important roles in the human body. During pregnancy, the maternal serum copper concentration is increased due to the higher levels of ceruloplasmin that are the result of elevated oestrogen levels. The aim of this work was to investigate maternal plasma copper concentrations in relation to various pathological conditions during pregnancy. A total of 319 maternal plasma samples were analysed: 103 taken from women in the first trimester, 73 in the second trimester, 99 in the third trimester of pregnancy and 44 at delivery. The plasma concentration of copper during each trimester of normal pregnancy was taken as a reference value. Group comparisons performed by analysis of variance (ANOVA) followed by Dunnett test indicated substantially lower plasma concentrations of copper in pathological conditions diagnosed during the first trimester of pregnancy (spontaneous abortion, threatened abortion, missed abortion and blighted ovum). No significant differences in maternal plasma blood copper concentrations were found in pathological conditions (threatened abortion, threatened preterm delivery and pyelonephritis) diagnosed in the second trimester of pregnancy. Significant differences in plasma copper concentrations were found in the third trimester, for which finding the Dunnett test indicated the cholestasis group to be responsible. Except for twin pregnancy, a tendency to higher plasma copper concentrations, however not statistically significant, was observed in other pathological conditions during the third trimester (gestosis, intrauterine growth retardation, preterm labour).