Tomas Gottvall

Alloimmunization in pregnancy during the years 1992–2005 in the central west region of Sweden

Objectives. To study the incidence of red cell immunization and to evaluate the use of low‐risk invasive procedures in the management of alloimmunized during pregnancy. Design. A 14‐year retrospective study of all immunized mothers and their newborns. Population. All reported alloimmunizations between the years 1992 and 2005 in our catchment area were examined. Methods. Background factors, maternal antibody classification, antibody titers, anti‐D quantitation, procedures and maternal treatments instituted during pregnancy, fetal outcome and treatment of the newborn were evaluated. Results. There were 78,145 deliveries in the region. Alloimmunization during pregnancy was detected in 0.4% of all pregnancies, excluding ABO immunizations. A significant alloimmunization (titer level ≥8) was detected in 0.16%. Anti‐D immunizations were responsible for 60% of significant immunizations followed by anti‐Fya in 10%, anti‐c in 7% and anti‐K in 4%. Maternal plasma exchange and high‐dose intravenous immunoglobulin were used as low‐risk invasive treatments in 12 cases. Delivery was in ≥38 weeks in 93% of cases. Twenty‐nine newborns were treated with exchange transfusions (ETs) after delivery, whereof 21/29 were due to anti‐D, seven due to anti‐c and anti‐E and in one case anti‐Fya. No deaths occurred due to severe alloimmunization. Conclusion. Anti‐D still accounts for the most severe immunizations and for most of the cases where ET was necessary. Low‐risk invasive techniques to evaluate and treat pregnancies complicated by alloimmunization seem possible and accurate, avoiding invasive procedures that may exacerbate the immunization during pregnancy.

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 ≤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.

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.

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 ≥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 μg/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 ≥64, anti‐D concentration is ≥0,7 μg/mL and data indicate an aggravation of the immunization.

Maternal obesity and risk of Down syndrome in the offspring.

The objective of this article is to determine if maternal obesity is associated with an increased risk of Down syndrome in the offspring and whether the risk estimates for trisomy 21 based on combined screening is affected by maternal body mass index (BMI).

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?

Plasma exchange and intravenous immunoglobulin treatment of the mother to diminish fetal rhesus hemolytic disease

Abstract Three pregnant women with a previous history of and laboratory findings consistent with severe rhesus immunization were treated with high-dose intravenous immunoglobulin (IVIG) after a mean reduction of the antibody concentration of 64% by plasma exchange. Two of the cases were successful as judged by the clinical condition of the newborns, the slow increase in serum anti-D concentrations, and the decrease in amniotic fluid bilirubin levels after the combined treatment. The effect was less pronounced in the third case treated with a different preparation of IVIG. The maternal antibody production rate seems to be decreased by IVIG treatment and the placental transfer of IgG antibodies may also be affected. However, as anti-D antibodies were found at a high concentration in the blood of the newborns, we suggest that a major effect of the treatment is decreased fetal hemolysis, which may be caused by blockade of the fetal reticuloendothelial system.

Routine assessment of amniotic fluid alpha-Fetoprotein in early second-trimester amniocentesis is no longer justified

Background. Open fetal neural tube defects are often followed by an increase in alpha‐Fetoprotein concentration in amniotic fluid. For over 25 years there has been a routine to measure amniotic fluid alpha‐Fetoprotein in conjunction with early genetic amniocentesis. The efficacy of such a screening test in a low‐risk population has been questioned but never evaluated in a Swedish population. Methods. Data were reviewed retrospectively from all consecutive early second‐trimester genetic amniocenteses from two hospitals during the years 1993–2003. Indications for the genetic amniocenteses were maternal age ≥35 years, maternal anxiety or a history of fetal aneuploidy. A questionnaire was sent to all obstetric clinics in Sweden regarding current common policy and experience of routine amniotic fluid alpha‐Fetoprotein measurements, in the detection of open fetal neural tube defects. Results. A total of 1,813 samples were included. In eight cases (0.4%) the amniotic fluid alpha‐Fetoprotein concentrations were ≥3 multiples of median, but five of them were false positive (63%). Out of the three true positive cases, one had clinical relevance. In the other two cases the detection of open fetal neural tube defects was of subordinate importance. In Sweden, during 2004, 91% of the obstetric clinics performed routine assessment of amniotic fluid alpha‐Fetoprotein at second‐trimester genetic amniocentesis, but only 9% regarded the analysis useful in clinical practice. Conclusions. According to our results, routine measurement of amniotic fluid alpha‐Fetoprotein in early second‐trimester genetic amniocentesis, to rule out a risk of open fetal neural tube defects, does not seem justified. The clinical usefulness seems to be limited.

External cephalic version of non‐cephalic presentation; is it worthwhile?

A retrospective study of 186 consecutive external cephalic versions (ECV) late in the third trimester was done. Logistic regression analysis of background factors leading to a successful ECV showed that multiparity, a larger amount of amniotic fluid, measured as amniotic fluid index, and a transverse fetal position were each significantly correlated with a successful version. The total success rate was 62%, and after a successful ECV 84% of the fetuses were delivered vaginally. No severe complications were registered during the ECVs, and all babies had normal Apgar scores at delivery. Attempting ECV at least once or even twice seems to be appropriate because a successful ECV can decrease the rate of cesarean section in this group of patients and by so doing may also decrease the risk of cesarean section in future pregnancies.

Maternal obesity and detection rate of fetal structural anomalies.

Objective: To estimate the effects of maternal body mass index (BMI) on the sensitivity of detecting fetal anomalies by a routine ultrasound performed either in the first or in the second trimester. Methods: Unselected pregnant women (n = 19,140) were divided into four BMI groups: underweight (<18.5), normal weight (18.5-24.9, reference group), overweight (25.0-29.9), and obese (≥30.0). Fetal anomaly diagnoses were grouped according to their likely clinical consequences as suggested by the Royal College of Obstetricians and Gynaecologists. Minor anomalies were excluded. The detection rate of fetal anomalies in each BMI group was calculated and compared. Results: The prevalence of infants with structural anomalies in the study population was 4% and the prevalence of material obesity was 10%. The detection rates of fetal structural anomalies were 26% for normal-weight, 29% for overweight (odds ratio (OR) 1.15, 95% confidence interval (CI) 0.68-1.95), and 19% for obese women (OR 0.67, 95% CI 0.29-1.52). The detection rate of anomalies with long-term handicap was lower in the obese group (27.3%; OR 0.44, 95% CI 0.11-1.79) compared to normal-weight women (46.3%). Conclusion: The detection rate of fetal anomalies seems to be lower for obese women, but these findings need to be further investigated.