Barbara Ulm

Prenatal management of alloimmune thrombocytopenia of the fetus

Alloimmune thrombocytopenia of the fetus is a serious disease, which may cause intracranial haemorrhage leading to death or permanent neurological disability. The prenatal management of fetuses at risk is therefore very important. Ten years ago we published an International Forum on this subject. At that time there was no consensus of opinion among the experts on this important issue. It therefore seemed of interest to obtain information on current opinions. To achieve this, the following questions were sent to experts in the field: Question 1. If a fetus is at risk of alloimmune thrombocytopenia, do you routinely measure the fetal platelet count by fetal blood sampling (FBS)? If so, at what time and do you administer compatible platelets during the procedure? Question 2. If the fetus is found to be thrombocytopenic, what is your form of treatment: (a) Transfusions of compatible platelets and, if so, what is the transfusion trigger, the dose and the frequency? (b) Intravenous immunoglobulin (IVIG), with or without corticosteroids, to the mother? (c) Both (a) and (b)? (d) Other treatment? How do you evaluate the efficacy of the treatment? Question 3. If you do not routinely determine the platelet count of the fetus, how do you manage the case? Question 4. What are the requirements for transfusion of platelets to the fetus: ABO/RhD compatibility; cytomegalovirus (CMV) status of the donor; irradiation; if maternal platelets are used, how are they washed; must maternal platelets be compatible for human leucocyte antigen (HLA) class I antibodies detectable in the mother against an antigen for which the fetus is negative; recommended dose, volume and frequency? It is clear from the answers that the management of fetuses at risk of alloimmune thrombocytopenia is by no means standardized. Most experts are reluctant to perform FBS because of the danger of this procedure. However, in three centres it is still performed routinely in all cases in which HPA (human platelet antigen) antibodies are detected in the mother and the father is positive for the corresponding antigen. For the other experts, the decision to perform FBS depends on further, additional factors, such as a previously affected child, homozygozity of the father, strength of the HPA antibodies, etc. In one centre, regular fetal platelet counting is strongly recommended when the mother has anti-HPA-1a or -3a and there was a previously affected child (Kroll et al .). One expert even restricts FBS to cases in which a previous child had intracranial haemorrhage and the umbilical cord insertion is anterior (Kanhai). For details, see the responses, below, of the individual authors. Transfusions of compatible platelets are given at each FBS by some of the experts, but others find the danger (such as prolonged bradycardia) of such transfusions to be too great. If the platelet count has been determined, therapy – either IVIG or corticosteroids alone, or both – depends on this count. Platelet transfusions are given by some if the above therapy is inadequate, but the transfusion trigger varies considerably, i.e. from < 30 × 10 9 /l to < 100 × 10 9 /l, or when bleeding is suspected or ‘seen’ on ultrasound. In the experience of Kroll et al ., the response of the mother to treatment with IVIG was found to often be poor and sometimes intracranial haemorrhage occurred during this treatment. Therefore, this group prefer to administer repeated platelet transfusions to the fetus. The effect of therapy is usually checked by FBS at monthly intervals. If the platelet count is not determined routinely, the mother is treated with IVIG from ± 20 weeks of gestation and the effect is checked at monthly intervals or only once, at 30 weeks, by FBS or ultrasound. FBS is usually carried out at the end of pregnancy to decide on the mode of delivery and further treatment. In order to fully appreciate the various policies of management, it is essential to read the answers from the individual groups, as stated below. The requirements for transfusion of platelets to the fetus are fairly standardized. However, only some experts take into account maternal HLA antibodies against an antigen that is absent in the fetus. The CMV status of the donor is not always considered if leucocyte-reduced platelet concentrates are used. In conclusion, the management of this serious condition of the fetus is by no means standardized. In fact, there seems to be less consensus of opinion concerning this management than 10 years ago when we published the first International Forum on this subject.

Male fetuses are particularly affected by maternal alloimmunization to D antigen.

BACKGROUND: It is hypothesized that male fetuses are more severely affected by fetomaternal alloimmunization to D antigen than female fetuses.

Three-dimensional ultrasonographic imaging of fetal tooth buds for characterization of facial clefts

The purpose of this prospective study was to investigate whether the antenatal characterization of fetal facial clefts can be improved by three-dimensional ultrasonographic visualization of fetal tooth buds. Between January 1996 and June 1998, seventeen consecutive fetuses with facial clefts were examined for fetal maxillary tooth buds in the cleft area using three-dimensional multiplanar reconstruction. It was possible in all cases to classify the clefts either as cleft lip alone or unilateral cleft lip and palate or bilateral cleft lip and palate. Three-dimensional computed tomography and histological jaw sections of three stillborn infants were produced in order to examine the correlation between the sonographic, radiographical and histological findings. The prenatal characterization of the facial clefts by means of a visualization of the tooth buds showed to be accurate postnatally in all cases. The sonographic proof of tooth buds might gain increasing importance as this technique seems to facilitate and improve the prenatal classification of suspected facial clefts.

Ultrasound evaluation of fetal spine length between 14 and 24 weeks of gestation

The objective of our study was to establish a nomogram of fetal spine length in the second trimester of pregnancy by using two and three‐dimensional ultrasound. Fetal spine length was measured prospectively by means of transabdominal ultrasonography in 114 normal singleton pregnancies between 14 and 24 weeks of gestation. Regression analyses were performed on spine length, gestational age, biparietal diameter and femur length. Supplementary three‐dimensional ultrasound to assess fetal spine length was performed in 75 cases. Fetal spine length, as a function of gestational age, was expressed by the following regression equation: spine length (mm)=−47.2+7.16×gestational age (weeks), with a Pearson correlation coefficient of R2=0.956. The results of the measurements revealed no difference between two and three‐dimensional ultrasound. Our study defines the normal limits of fetal spinal length in the second trimester of pregnancy and demonstrates a high correlation between spinal length, gestational age, biparietal diameter and femur length. However, there are still too few prenatal research data to say whether and to what extent an assessment of fetal spine length at this stage of pregnancy can be used for prenatal diagnosis of congenital syndromes, which, among other manifestations, are marked by fetal spine lengthening or shortening. Copyright

Fetal bradycardia following cordocentesis

Several clinical investigations on the course and outcome of pregnancies following cordocentesis have mentioned the occurrence of fetal bradycardia at the time of umbilical cord puncture. The prognostic impact of this common complication has remained controversial. Our purpose was to investigate the prevalence and the short‐term and long‐term consequences of fetal bradycardia associated with cordocentesis. This study included all 339 cordocenteses performed in 290 fetuses at the Division of Prenatal Diagnosis and Therapy, University of Vienna, between 1991 and 1994. Clinically significant bradycardia was defined as a drop in the heart rate to less than 100 beats/min for a period of ≥60 s. Bradycardia during or immediately after cordocentesis was observed in 13 cases (3.8 per cent). The fetal/neonatal loss rate per procedure was 61.5 per cent (8/13) in cases with bradycardia and 3.1 per cent (10/326) in those without bradycardia (P<0. 001). Early gestational age and hydrops fetalis correlated significantly with the development of bradycardia at cordocentesis. The other risk groups, including fetuses with intrauterine growth retardation, the puncture site, and the number of puncture attempts did not correlate with fetal bradycardia. Our results indicate that prolonged fetal bradycardia during or after cordocentesis is characteristic of a group of fetuses with an especially unfavourable prognosis.

Twenty-Four Cordocenteses in One Woman

We report on 2 consecutive pregnancies in a woman with a history of neonatal death secondary to Rhesus alloimmunization. Her first subsequent pregnancy was complicated by fetal hydrops at 20 weeks of gestation. The fetus received a total of 11 intrauterine transfusions, and was delivered at 38 weeks. In the patient’s next pregnancy, the fetus developed hydrops at 18 weeks of gestation. Thirteen intrauterine transfusions were given to correct fetal anemia, and a healthy baby was delivered at 38 weeks of gestational age. Continuation of intravascular transfusion therapy may represent a reasonable alternative to selective premature delivery even in cases with highly aggressive maternal Rhesus alloimmunization.

Immunoglobulin administration to fetuses with anemia due to alloimmunization to D

BACKGROUND: The purpose of this study was to examine fetal tolerance of high‐dose intravenous immunoglobulin (IVIG), given directly at the time of intravascular transfusion, and its effects on fetal hemolysis and pregnancy outcome in the setting of alloimmunization to D.

An undetected reason for severe fetal growth retardation.

In a severely growth-retarded fetus, repeated Doppler ultrasound examinations from the 23rd week of gestation on, showed normal and highly pathological blood flow velocities in the umbilical artery. A caesarean section performed in the 39th week of gestation revealed two true umbilical cord knots. Sonographic screening for umbilical cord knots may be valuable in similar cases. The use of color Doppler could help to visualize the entire course of the umbilical cord.

Spontaneous rise of fetal platelet counts despite increasing anti-HPA-5b antibodies.

Background and objectives: Maternal anti‐HPA alloantibodies are a rare cause of severe fetal thrombocytopenia. So far there have been no reports on the dynamics of maternal anti‐HPA‐5 during gestation and its effect on the fetus. Materials and methods: We monitored maternal anti‐HPA‐5b antibody titers and fetal platelet counts during gestation in a woman with known anti‐HPA‐5b alloimmunization. The patient was a 32‐year‐old woman in her third pregnancy. The 1st pregnancy and delivery of a healthy child had been uneventful. At delivery, anti‐HPA‐5b was detectable in the maternal serum. A 2nd pregnancy ended in early miscarriage. Results: A steady rise in the alloantibody titer was recorded throughout the 3rd pregnancy. Therefore, cordocentesis was performed at 28 weeks of gestation (platelet count 76×109/l). Serial platelet transfusions were administered to the fetus at 28, 32, and 37 weeks of gestation. The platelet counts rose spontaneously thereafter and were 220×109/l at delivery, despite an increase in the anti‐HPA‐5b antibody titer. The child developed normally during the first year of life. Conclusions: This case illustrates the spontaneous recovery of fetal platelet counts in late pregnancy despite a rise in maternal alloantibody titer.

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