Intervention during pregnancy to reduce excessive gestational weight gain­a randomised controlled trial.

OBJECTIVE: To evaluate if a feasible, low-cost intervention could decrease the percentage of women gaining weight above the Institute of Medicine (IOM) recommendations on gestational weight gain (GWG) compared with standard maternity care. DESIGN: A randomised controlled interventional design. SETTING: Antenatal clinics (n = 14) in Örebro county, Sweden, participated. POPULATION: Healthy women with a body mass index (BMI) ≥19 kg/m(2), age ≥18 years and adequate knowledge of Swedish language who signed in for maternity care at ≤16 weeks of gestation. METHODS: Standard care was compared with a composite intervention consisting of education on recommended GWG according to IOM, application of personalised weight graph, formalised prescription of exercise and regular monitoring of GWG at every antenatal visit. OUTCOME: The proportion of women gaining weight above IOM guidelines (1990) and mean GWG (kg) was compared between groups. RESULTS: In all, 445 women were randomised and 374 women remained for analysis after delivery. A majority of the women analysed were normal weight (72%). The intervention reduced the proportion of women who exceeded the IOM guidelines (41.1% versus 50.0%). The reduction was, however, not statistically significant (P = 0.086). Mean GWG was significantly lower among women receiving the intervention, 14.2 kg (SD 4.4) versus 15.3 kg (SD 5.4) in the standard care group (P = 0.029). CONCLUSIONS: The low-cost intervention programme tested did significantly reduce the mean GWG but the proportion of women who exceeded the IOM recommendations for GWG was not significantly lower. ClinicalTrials.gov Id NCT00451425 http://clinicaltrials.gov.

Consumption of anti-D in the erythroblastotic fetus.

BACKGROUND: Maternal serum anti-D is actively transported across the placenta into the fetal blood where it adheres to D-positive erythrocytes. The anti-D coated red cells attach to Fc-receptors on fetal reticuloendothelial cells and are subsequently phagocytosed and hemolysed. It is not known if anti-D is consumed or recirculated in this process. MAIN QUESTION: Is anti-D in the fetus consumed in the hemolytic process in the erythroblastotic fetus and can the consumption be modulated by high-dose immunoglobulins (i.v.IG) given to the mother? METHODS: Fetal/maternal serum anti-D concentration ratios were calculated for simultaneously taken blood samples from three groups of Rh(D) immunized pregnant women; six women with fetuses who were of Rh(D) negative phenotype, 19 women with fetuses who were Rh(D) positive and received no treatment and, seven women who were treated with i.v.IG because they bore anemic, Rh(D) positive fetuses. RESULTS: Fetuses with a Rh(D) negative phenotype expressed an increase in fetal/maternal anti-D concentration ratios from 10 to 55% between 25 and 31 gestational weeks, while Rh(D) positive fetuses without i.v.IG treatment had stable values at the 10% level between 24 and 35 gestational weeks. During i.v.IG-treatment of the mothers, Rh(D) positive fetuses showed an increase in ratio from 10 to 30% between 26 and 34 gestational weeks. There was a statistically significant (p<0.001) difference between regression results of the three groups. CONCLUSIONS: Fetal anti-D is consumed in the hemolytic process and the consumption can be modulated by i.v.IG given to the mother.

Placental transport of maternal immunoglobulin G in pregnancies at risk of Rh (D) hemolytic disease of the newborn.

PROBLEM: The following questions were addressed: Is the placental transport of immunoglobulin (Ig)G, IgG1, and IgG3 diminished in pregnancies at risk of hemolytic disease of the newborn? Is the placental transport of IgG, IgG1, and IgG3 correlated with the hemoglobin concentration in the fetus and AutoAnalyzer (AA) quantitations of maternal anti-D? METHOD OF STUDY: IgG concentrations were determined retrospectively in 41 paired fetal/maternal (f/m) samples in 31 Rh (D) alloimmunized pregnancies. IgG1 and IgG3 concentrations were determined in those 23 cases in which the results of fetal hemoglobin concentration and quantitations of maternal anti-D were available. The results were compared with values found in normal pregnancy and correlated with maternal anti-D AA quantitations and fetal hemoglobin concentrations. RESULTS: Fetal IgG, IgG1, and IgG3 concentrations, and the corresponding fetomaternal ratios in Rh (D) alloimmunized pregnancies, increased with gestational age according to the following formulas (obtained by simple regression): Fetal IgG = -8.846 + 0.491.gestational age (GA), (R2 = 0.544); fetal IgG = 10.021 + 0.46.GA (R2 = 0.463); fetal IgG3 = -0.865 + 0.039.GA, (R2 = 0.327); f/m IgG = -1.006 + 0.054.GA, (R2 = 0.557); f/m IgG1 = -1.876 + 0.085.GA, (R2 = 0.654); f/m IgG3 = -0.199 + 0.026.GA, (R2 = 0.146). CONCLUSIONS: The placental transport of IgG, IgG1, and IgG3 in women with Rh (D) immunizations is not diminished compared with normal pregnancy. However, AA quantitations of anti-D are inversely correlated with f/m IgG ratio, f/m IgG1 ratio, and fetal IgG and IgG1 concentrations (P = 0.002, P = 0.004, P = 0.02, and P = 0.02 respectively). The placental transport of IgG3 is significantly higher in pregnancies at risk of hemolytic disease of the newborn compared with IgG3 concentrations in normal pregnancy.

Concentration of anti-D antibodies in Rh(D) alloimmunized pregnant women, as a predictor of anemia and/or hyperbilirubinemia in their newborn infants.

OBJECTIVES: To define a simple, safe and reliable program for the monitoring of anti-D alloimmunized pregnancies by analysis of the covariation between antenatal values of the titer and the concentration of anti-D antibodies in maternal serum, the deltaOD(450 nm) in amniotic fluid samples, and the levels of B-hemoglobin and S-bilirubin in the newborns at birth. SUBJECTS: Ninety-three Rh(D) negative women with anti-D antibody titers > or = 16 who, after the completed 34th gestational week, gave birth to Rh(D) positive babies with a positive direct antiglobulin test. METHODS: The titers and the concentrations of anti-D antibodies in maternal serum were determined by standard procedures every second week from the 25th week of gestation. In 47 of the 93 women, deltaOD(450 nm) in amniotic fluid was determined at least once. All antenatal values used in the study were determined within 14 days before delivery. RESULTS AND CONCLUSION: Maternal serum antibody titers < or = 32 or > or = 1000 could in themselves well predict unaffected and affected newborns. Antibody titers between 64 and 512 could not accurately predict newborns with or without hemolytic disease. As a complementary monitoring test, determination of the deltaOD(450 nm) was found to be less accurate when compared to determination of the concentration of anti-D antibodies. In order to monitor Rh(D) alloimmunized pregnancies, determination of the concentration of anti-D antibodies may possibly replace determination of deltaOD(450 nm).

Alloimmunization during pregnancy treated with high dose intravenous immunoglobulin. Effects on fetal hemoglobin concentration and anti-D concentrations in the mother and fetus.

BACKGROUND: High dose intravenous immunoglobulin has been reported to be advantageous in the treatment of alloimmunization during pregnancy. The mode of action is unknown. METHOD: High dose intravenous immunoglobulin was used as the sole prenatal treatment in six severely rhesus(D) sensitized pregnant women. Maternal and fetal anti-D concentrations as well as fetal hemoglobin concentrations were studied. Seven pregnancies in rhesus(D) sensitized women served as controls. They received no treatment because they had milder forms of erythroblastosis fetalis or, in one case, a rhesus(D) negative fetus. RESULT: No obvious inhibitory effect of the treatment on maternal anti-D production and transplacental anti-D passage to the fetus was found. The fetal hemoglobin concentrations remained stable at about 80 g/L (hematocrit 27%) in five of six treated patients while there was a significant decrease in the control group. CONCLUSION: High dose intravenous immunoglobulin treatment seems to act mainly on fetal red cell destruction rate, possibly by blocking Fc receptor mediated macrophage phagocytosis. We claim that the treatment can successfully be used to prevent further deterioration of fetal anemia in rhesus(D) immunizations if started before severe fetal anemia (hemoglobin concentration < 70 g/L, hematocrit < 23%) and imminent hydrops fetalis arises.

Severe Rh(D) immunization: anti-D quantitation and treatment possibilities during pregnancy and after birth.

An extremely aggressive Rh(D), (C) and Kell alloimmunization during pregnancy is reported. Exceptionally high concentrations of anti-D were observed in the mother, in the fetus and in the amniotic fluid, indicating an active transport across the placenta and a passive excretion into the amniotic fluid. Treatment during pregnancy included maternal plasmapheresis and high-dose intravenous immunoglobulin. Intravascular transfusions were given to the fetus. Postpartum the newborn was given immunoglobulin, one exchange transfusion and four top-up transfusions. In the newborn the elimination rate of anti-D could be followed. Not until almost 4 months postpartum did the anti-D concentration drop below the level of detection. This coincided with an elevated reticulocyte production and appearance of the child's true blood group in parallel with ceasing need for blood transfusions. Elimination rate and absolute anti-D values can be used as a prognostic tool to predict the need of blood transfusions. Immunoglobulin treatment can also be considered as an optional form of treatment in newborns affected by alloimmunization.

HLA phenotypes and severe Rh(D) immunization.

Blood samples from 24 Rh(D) immunized women were analyzed for antibody titers and quantification of anti-D. The HLA-DR and -DQ polymorphisms were identified as RFLP. In 11 women with titers 16-256 the HLA-DQB1 allele *0201 was found in 18%, i e as in a reference population. In 13 women with titers > or = 512 the HLA-DQB1 allele *0201 was found in 85% indicating a correlation between severe Rh(D) immunization with high titers/quantification values and the DQB1 allele *0201. In this group the fetus was severely affected by the immunization and treatment during pregnancy was frequently needed. HLA phenotyping of women known to have anti-D antibodies early in pregnancy seems to be an effective way to assess the probability of severe hemolytic disease of the newborn.

Evaluation of standard parameters to predict exchange transfusions in the erythroblastotic newborn.

During the time period 1983-90, 91,300 consecutive pregnancies were monitored for red cell alloimmunization. Once revealed, the immunizations were followed by means of repeated maternal antibody titers, maternal anti-D quantitation in D-immunized women, amniotic fluid bilirubin levels and fetal hemoglobin concentrations. High dose intravenous immunoglobulin and/or intrauterine intravascular transfusion was given to prevent or treat fetal anemia. Delivery was induced for all before term when antibody titers were > or = 16. Nevertheless, exchange transfusions were performed in 41 newborns with mothers alloimmunized to Rh(D), Rh(c), Rh(E) and Kell antigens. Eight of the mothers were Rh(D) positive. Phototherapy alone was given to 35 newborns. Both maternal antibody titers and amniotic fluid bilirubin levels were found to be unreliable to predict the need of exchange transfusions in the newborns. Quantitation of maternal anti-D concentration was found to be significantly better predicting 62% at a cut-off level of 0.7 microgram/mL. Analysis of fetal hemoglobin concentration by cordocentesis is the only direct method to evaluate the degree of fetal affection, and should probably be performed when maternal antibody titers are > or = 64, anti-D concentration is > or = 0.7 microgram/mL and data indicate an aggravation of the immunization.

Evaluation of a new Swedish protocol for alloimmunization screening during pregnancy.

Screening protocols for alloimmunization during pregnancy usually make a difference between primi- and multigravidae as well as between Rh(D) negative and Rh(D) positive pregnant women. We have evaluated a new screening program including antibody tests at 25 and 35 gestational weeks only, for all, and regardless of Rh(D) group. During the time period 1983-89, 78,300 consecutive pregnancies were tested. Red cell antibody immunizations were detected in 287 (0.37%) pregnancies subdivided into fourteen different red cell IgG antibody specificities. Significant antibody titers (defined as IAT or enzyme titers > or = 8) were observed in 225 pregnancies, where 127 (56%) were previously unknown. A majority (63%) of the new immunizations occurred among the Rh(D) positive pregnant women. All newborns that needed phototherapy or exchange transfusion due to alloimmunization were recognized at the time of delivery. We conclude that antibody screening tests at 25 and 35 gestational weeks for both Rh(D) negative and positive pregnant women is sufficient, effective and a safe procedure for the fetus as well as for the mother.