Acute cerebral redistribution in response to invasive procedures in the human fetus.

OBJECTIVES: We sought to investigate the fetal hemodynamic response to the acute stress of invasive procedures. STUDY DESIGN: The middle cerebral artery pulsatility index was measured by Doppler ultrasonography before and after 136 invasive procedures (fetal blood sampling, transfusion, shunt insertion, tissue biopsy, and ovarian cyst aspiration). The response of fetuses submitted to invasive procedures involving transgression of the fetal body, such as intrahepatic vein blood sampling, was compared with that of control procedures at the placental cord insertion. RESULTS: The middle cerebral artery pulsatility index value fell with fetal blood sampling performed at the intrahepatic vein (median, -0.26; 95% confidence interval, -0.35 to -0.15) but not at the placental cord insertion (median, 0.05; 95% confidence interval, -0.04 to 0.19). With transfusions, the middle cerebral artery pulsatility index also fell with procedures at the intrahepatic vein (mean, -0.51; 95% confidence interval, -0.66 to -0.35) but not at the placental cord insertion (mean, -0.04; 95% confidence interval, -0.23 to 0.14). The magnitude of the response was greater with transfusions than with blood sampling alone. The middle cerebral artery pulsatility index value also fell with non-fetal blood sampling procedures involving transgression of the fetal body (mean, -0.32; 95% confidence interval, -0.56 to -0.09) but not with control non-fetal blood sampling procedures. The change in the middle cerebral artery pulsatility index was not related to gestational age, with the youngest fetus showing a fall in the middle cerebral artery pulsatility index value being at 16 weeks' gestation. Although the degree of response was weakly correlated with the duration of needling (y = -0.21 - 0.00014x; R (2) = 0.08; P =.02), multiple logistic regression demonstrated that this was instead a function of the type of the procedure. A response was seen within 70 seconds of fetal puncture. The fetal heart rate did not change significantly with procedures in any of the above-mentioned groups. CONCLUSIONS: The human fetus mounts a cerebral hemodynamic response to invasive procedures involving transgression of the fetal body, which is consistent with the brain-sparing effect.     

The fetal intrahepatic umbilical vein as an alternative to cord needling for prenatal diagnosis and therapy

Seventy-one fetal blood samplings (FBS) were attempted from the intrahepatic portion of the umbilical vein (IHV) at 18-34 weeks; 54 were attempted primarily and 17 secondarily after a failed attempt at the placental cord insertion. Fetal blood was obtained in 89 per cent of the cases. Intravascular transfusion (IVT) was attempted on 31 occasions and successful in 24 (77 per cent). In all cases of failed sampling or transfusion via the IHV, prenatal diagnosis and/or therapy was accomplished using alternative procedures. On only one occasion was the procedure postponed. There were no losses or neonatal morbidity attributable to the procedure. FBS from the IHV may be considered as an alternative approach to sampling the placental cord insertion. It is recommended in cases where the approach to the placental cord insertion is difficult or hazardous.     

Two hundred intrauterine exchange transfusions in severe blood incompatibilities

Two hundred intrauterine exchange transfusions were performed under local anesthesia in 107 cases of blood incompatibilities (60 fetuses with severe anemia and 47 with hydrops). Under sonographic guidance, depending on fetal and placental position, an optimal puncturing site was selected along the umbilical vein: placental insertion, fetal insertion, or fetal intraabdominal segment. Tests were immediately performed to confirm fetal origin of blood obtained and estimate hemoglobin level. Blood used for exchange transfusion was compatible with maternal blood and had a hematocrit value of 75%. Exchange transfusion was continued until a hemoglobin level of 16 gm/dl was reached. This procedure was first associated with intraperitoneal transfusions and was subsequently used independently once a month to maintain an adequate hemoglobin level. In 4 fetuses with hydrops, antenatal regression of this sign was observed in 33 cases (70.2%). Overall outcome of 107 fetuses after exchanges was 84 living neonates (78.5%), 15 deaths in utero, and eight neonatal deaths. The survival rate was 91.6% for fetuses without hydrops and 61.7% for those with hydrops. The advantage of exchange transfusion appears to be rapid and efficient correction of anemia with elimination of incompatible fetal red blood cells.     

Fetal blood sampling

Fetal blood sampling is now performed in many centres through different approaches (fetoscopy, placentacentesis, cardiac puncture, umbilical cord needling, intrahepatic vein puncture) for prenatal diagnosis of congenital defects, management of intrauterine growth retardation and fetal therapy. One hundred and thirty-nine fetal blood samples have been performed during a 10 month period at Queen Charlotte's Maternity Hospital, London, using an individualized approach. One failure to obtain fetal blood occurred and there were four fetal losses, three of which followed an intrauterine transfusion in very severely affected fetuses. Two of these losses were associated with peculiar circumstances (see above). The procedure-related risk is nowadays more difficult to evaluate than in the past, when most fetal blood samplings were carried out in the second trimester for prenatal diagnosis. Most case studies, and ours as well, are not homogeneous and high-risk patients such as those with Rhesus disease or intrauterine growth retardation are also included. It seems, however, that transabdominal needling of the cord, at either placental or fetal insertion, is a low-risk procedure although a larger number of cases should be collected to draw definite conclusions about sampling from the intrahepatic vein. Fetoscopy also has a low risk in experienced hands, but the training period is certainly longer and the application in the second half of the pregnancy has been limited to a few cases. It is likely to be used only very little in the future. A flexible approach to fetal blood sampling allows the best choice of technique and utilizes the advantages of each technique.     

Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia: platelet dynamics and perinatal outcome

OBJECTIVES: Our purpose was to describe the fetal loss rate and platelet dynamics in fetal alloimmune thrombocytopenia managed by serial platelet transfusions. METHODS: Retrospective analysis over 10 years of consecutive pregnancies affected by fetal alloimmune thrombocytopenia requiring in utero platelet transfusions. RESULTS: There were 2 perinatal losses in 12 pregnancies managed by 84 platelet transfusions. One was obviously procedure related from exsanguination despite platelet transfusion. The attributable procedure related fetal loss rate was 1.2% per procedure but 8.3% per pregnancy. The median rate of fall in fetal platelet count per day after transfusion was lower at the placental cord insertion (n = 54) 40.5 x 10(9)/L (range, 5.4-96.1 x 10(9)/L) compared with that at the intrahepatic vein (n = 30) 50.9 x 10(9)/L,(range, 29.5-91 x 10(9)/L) (P = .0009). CONCLUSION: Pooling our results with those previously published yields a cumulative risk of serial weekly transfusions of approximately 6% per pregnancy, indicating the need for development of less invasive approaches.     

Percutaneous umbilical transfusion in severe rhesus isoimmunization: resolution of fetal hydrops

The rhesus-sensitized fetus with the worst prognosis is one with early onset of hydropic changes. Percutaneous umbilical blood sampling now enables access to the fetal circulation and thereby allows more precise evaluation of fetal anemia and direct intravascular transfusion. A variation of this technique was used in three pregnancies complicated by fetal pericardial effusion, scalp edema, and abdominal ascites before 26 weeks' gestation. Twelve ultrasound-guided percutaneous transfusions of 30 to 85 ml packed red blood cells were administered into the umbilical cord at its placental insertion. In each fetus the hydropic changes completely resolved and pregnancy outcome was successful. Neither adjunctive therapy with digoxin or Lasix nor exchange transfusions were used. Percutaneous umbilical transfusions appear to have the potential to improve the prognosis for the severely isoimmunized fetus.     

Intraperitoneal fetal transfusion under direct ultrasound guidance

The outcomes of 77 fetal intraperitoneal transfusions in 35 pregnancies managed with direct ultrasound guidance and intensive perinatal management were reviewed. Patients were monitored with amniocentesis, and standard indications were used for timing of transfusions. The mean gestational age at first transfusion was 27.3 weeks (range 22-33). The overall mortality rate was 14% (five of 35). No immediate transfusion-related deaths occurred; all fetuses who were not hydropic at first transfusion survived (26 of 26). The mean gestational age at delivery was 33.6 weeks (range 25-36). One infant developed respiratory distress syndrome (RDS). Transfusion-related complications occurred in five cases (fetal colon infusions in two, fetal retroperitoneal infusion in two, and fetal abdominal wall hematoma in one). None of these infants required urgent delivery or suffered long-term sequelae. In nonhydropic fetuses, intraperitoneal transfusions under direct ultrasound guidance had a low incidence of morbidity and no mortality. These results should provide baseline data against which to compare new techniques, such as direct cord transfusion. With neonatal mortality rates of 10% and significant morbidity rates of 10-20% in infants delivered at 32 weeks who develop RDS, intraperitoneal transfusion should be considered in the 32- to 33-week fetus with marked pulmonary immaturity.     

Intravascular exchange and bolus transfusion in the severely isoimmunized fetus

Eight Rh-sensitized fetuses, between 21 weeks 2 days and 35 weeks of gestation, received 31 intravascular transfusions (13 exchange and 18 bolus) and one intraperitoneal transfusion under ultrasonographic guidance. The interval between transfusions was 13.4 +/- 4.7 days. Posttransfusion hematocrit dropped at a rate of 1.0% +/- 0.6% per day. Procedure time for the bolus transfusion was shorter than for the exchange transfusion (t test, p less than 0.001). Bleeding from the puncture site complicated 10 of the 31 intravascular transfusions, without apparent maternal or fetal consequences. Fetuses were delivered between 33 and 36 weeks of gestation, after lung maturity was achieved.     

An audit of outcome in intravascular transfusions using the intrahepatic portion of the fetal umbilical vein compared to cordocentesis

INTRODUCTION: Maternal red cell alloimmunization is a potential cause of perinatal morbidity and mortality. The outcome of severe disease has been transformed by the use of in-utero and particularly, fetal intravascular transfusion. In the majority of instances this is performed by cordocentesis. However, this cohort study represents the experience in a large tertiary referral centre in performing fetal intravascular transfusions via the intrahepatic vein (IHV). METHODS: Over an 8-year period, 1997-2004, 221 in-utero transfusions (IUT) were performed for rhesus disease in 66 pregnancies. 86% had severe fetal anaemia caused by anti-D, 10.6% by anti-Kell and 3.4% by anti-c. The median maternal age of the cohort was 31 years (range 19-43). The median gestation at initial IUT was 25 weeks (interquartile range (IQR) 23-29 weeks). RESULTS: A median number of three IUT were performed in each fetus (IQR 2-5) with a median haemoglobin at first fetal blood sampling of 7.3 g% (IQR 4.6-8.8 g%) (73% < or =5 SD and 27% < or =2 SD). Of the total intravascular transfusions, 170 were performed via the IHV (71.7%), 33 via cordocentesis (13.9%) and 1 by intracardiac puncture (0.5%). There were 'transient' bradycardias complicating 4.1% of all transfusions and amniorrhexis following 1.4%. 92% of babies were live born at a median gestation of 34 weeks (range 21-38) with a birth weight centile of 50 (range 3-90). There was no significant difference in intravascular transfusion complication rate when the procedure was performed via the IHV (7.6%) as compared to cord root puncture (3.0%) (Fisher's exact test, p < 0.47). CONCLUSION: IUT performed by fetal IHV puncture is safe and carries no excess morbidity when performed for severe rhesus disease.     

Is the sampling site along the umbilical artery significant?

The purpose of umbilical blood sampling is to obtain accurate reflection of fetal acid-base status at birth. The site along the umbilical artery from which blood should be sampled postpartum was not specified. We evaluated if blood gases and pH values from three sampling sites along the umbilical artery are different. After defining the range of intraobserver (method) variability, blood pO(2), pCO(2), and pH were directly determined. The data showed consistent and significant increases in arterial pH and pCO(2) values and decreases in pO(2) values from near the fetal cord insertion to the placenta. The largest difference was noted between the fetal site and the placental plate and the smallest between the site near the placental cord insertion and the placental plate. We conclude that the site of cord blood sampling should be standardized and the umbilical artery should be sampled at a site nearest to the neonate.     

Fetomaternal transfusion and pregnancy outcome after cordocentesis

OBJECTIVE: To study the extent of fetomaternal transfusion and the outcome of pregnancy after cordocentesis. MATERIAL AND METHODS: 268 women underwent percutaneous fetal umbilical cord blood sampling for fetal karyotyping between 15 and 26 gestations of weeks. Complete follow-up was available in 221 (82.5%) of the cases. Cordocentesis was performed under continuous real-time ultrasound guidance. The duration of the procedure and the post-procedural bleeding time was counted in seconds. Fetomaternal transfusion was calculated by using the measurements of the maternal serum levels of alpha-fetoprotein before and after the procedure. The data were analyzed by Student's t and multiple regression tests. RESULTS: The maximum and mean amounts of fetomaternal transfusion were 1.067 and 0.061 ml, respectively. Twenty percent or more alpha-fetoprotein elevation was in 35.4% of the cases. Positive correlation was found between bleeding time after cordocentesis and fetomaternal transfusion (r = 0.174, p < 0.0129) as well as between the duration of the procedure (r = 0.165, p < 0.0171) and the amount of fetomaternal transfusion. Comparing the cordocentesis at the placental insertion site and at the free cord loop, a smaller amount of fetomaternal transfusion was observed (p < 0.0123) in the latter. Transplacental passage was associated with a higher amount of fetomaternal transfusion (p < 0.0067). No association was found between the extent of fetomaternal transfusion and the outcome of pregnancy. The fetal loss related to the cordocentesis was 0.50%. CONCLUSIONS: The extent of fetomaternal transfusion was influenced by the subsequent four parameters: procedural time, bleeding time, puncture site and transplacental penetration. The lack of the association between the degree of fetomaternal transfusion and the outcome of pregnancy, along with the low (0.50%) post-procedural fetal loss rate, suggest that cordocentesis is clinically a safe procedure.     

Management of anti-Rhesus-D antibodies in pregnancy: a review from 1994 to 1998

OBJECTIVE: To review our management of anti-Rhesus-D antibodies in pregnancy over a 5-year period in order to assess possible changes in the management or prognosis which may have developed with time. METHOD: Retrospective analysis of prospectively collected data from 31 pregnancies with maternal anti-D levels >4 IU/ml and in which the fetus was Rhesus positive. RESULTS: There were a total of 30 amniocenteses, 8 cordocenteses, and 54 fetal blood transfusions performed. When undertaken as the first procedure, the mean gestational age at amniocentesis was 30 weeks as compared with 25 weeks for fetal blood sampling/transfusion (p < 0.05). The median anti-D level at the first procedure was 24 IU/ml for amniocentesis and 64 IU/ml for fetal blood sampling. Of the 54 blood transfusions, 43 were intravascular, 4 were intraperitoneal, and 7 transfusions were both intravascular and intraperitoneal. CONCLUSIONS: Intravascular as opposed to intraperitoneal transfusions were found to be the main method of transfusion in the later years in this study, a finding which was expected with improved sonographic equipment. Apart from this, management and prognosis of anti-D red cell isoimmunisation in pregnancy have remained relatively stable since the 1980s. Amniocentesis was useful in the management of such pregnancies, especially as an initial procedure in the cases with a lower initial anti-D level. In this series 90% of the fetuses requiring blood transfusion, but were without hydrops, survived, whereas this was about 70%, if they had become hydropic (this latter figure was reduced by 2 hydropic deaths before 20 weeks' gestation in the same very severely affected woman).     

The management of severe rhesus isoimmunization by fetoscopic intravascular transfusions

Twenty-five severely rhesus-isoimmunized fetuses, including 15 with hydrops fetalis, underwent a total of 77 intrauterine transfusions between 19 and 32 weeks' gestation. Fifty-eight of the procedures were fetoscopically directed intravascular transfusions, nine were ultrasound-guided intraperitoneal transfusions, and 10 were a combination of intravascular transfusion, fetal paracentesis, and intraperitoneal transfusion. The average number of antenatal procedures per patient was three (range, one to five). The survival rate for the 19 fetuses that received their initial intrauterine transfusion at or before 25 weeks' gestation was 84%; 11 of the 13 hydropic fetuses and five of the six fetuses without antenatal evidence of hydrops survived. In six cases hydrops fetalis was reversed in utero. The outcome in patients referred after 25 weeks' gestation was poor; neither of the two hydropic fetuses and only two of the four nonhydropic ones survived, which suggests the importance of early referral to a team experienced in the management of this problem. However, most of these fetal losses occurred early in the series. Seven of the 20 neonates were hydropic, and nine had severe thrombocytopenia (platelet count, <50,000 × 10⁶/L). The mean cord blood hematocrit and bilirubin of the neonates were 25.1% and 82 μmol/L, respectively. The babies required a total of 69 exchange transfusions (range, 0 to 9) and 68 simple transfusions (range, 0 to 25). One newborn infant who had had ultrasound evidence of hydrops fetalis at 22 weeks' gestation did not require any exchange transfusions. Nine patients required intermittent positive pressure ventilation (eight had respiratory distress syndrome and one had apnea) for a range of 1 to 86 days. The neonatal survival rate was 90% ($\text{18}\text{20}$).     

Percutaneous ultrasound-guided fetal blood sampling in the management of nonimmune hydrops fetalis

Nonimmune hydrops fetalis can be caused by fetal chromosomal, hematologic, cardiac, or infectious conditions. A fetal blood sample obtained from percutaneous ultrasound-guided fetal blood sampling can offer vital information about the underlying cause of nonimmune hydrops fetalis, and perinatal management can be planned accordingly. Ten cases of nonimmune hydrops fetalis were investigated with percutaneous ultrasound-guided fetal blood sampling and subsequent fetal blood analysis. Nine were proved to be Bart's hemoglobin hydrops fetalis, with 78.2% to 99% of Bart's hemoglobin in the fetal blood. Terminations of pregnancy were undertaken immediately, resulting in a lowered maternal morbidity rate. Free cord loops or an intra-abdominal portion of the dilated umbilical vein can be used for percutaneous fetal blood sampling in nonimmune hydrops fetalis when the placental cord insertion is difficult to visualize. Percutaneous ultrasound-guided fetal blood sampling and subsequent fetal blood analysis will eventually play a key role in the management of the puzzling nonimmune hydrops fetalis if the safety of ultrasound-guided fetal blood sampling can be verified by further clinical studies.     

Perinatal outcome following intravascular transfusion in severely isoimmunized fetuses.

Twenty-six severely isoimmunized pregnancies managed exclusively with ultrasonographically guided intravascular fetal transfusions are reported. The mean gestational age plus and minus one standard deviation (+/- SD) was 26.3 +/- 3.6 weeks and the mean hematocrit (+/- SD) prior to initial transfusion was 20.6 +/- 6.7%. Four of seven hydropic fetuses and 9 of 19 without hydrops were less than or equal to 26 weeks gestation at the first transfusion. Overall survival was 85% (22/26). Survival was similar whether or not fetal hydrops was present (6/7 vs. 16/19) and whether or not the first transfusion was administered at less than or equal to 26 weeks gestation (10/13 vs. 12/13).     

The effect of intravascular transfusion for rhesus haemolytic disease on umbilical artery Doppler flow velocity waveforms

Summary. To test the hypothesis that an increase in fetal blood viscosity is associated with an increase in resistance to flow, the effect on Doppler flow velocity waveforms of percutaneous umbilical blood sampling and intravascular transfusion was studied in 20 patients undergoing a total of 35 procedures. All but four of the 22 transfusions were associated with a decrease in resistance to flow, as shown by a reduction in the umbilical artery systolic/diastolic ratio, and this also occurred on 10 of the 13 occasions when blood sampling only was performed. These findings suggest that acute changes in blood viscosity following intravascular transfusion arc not associated with an increase in resistance to flow as assessed by Doppler velocimetry. Umbilical blood sampling per se may be associated with a Immorally mediated reduction in placental vascular resistance to flow.     

The effect of intravascular transfusion for rhesus haemolytic disease on umbilical artery Doppler flow velocity waveforms

To test the hypothesis that an increase in fetal blood viscosity is associated with an increase in resistance to flow, the effect on Doppler flow velocity waveforms of percutaneous umbilical blood sampling and intravascular transfusion was studied in 20 patients undergoing a total of 35 procedures. All but four of the 22 transfusions were associated with a decrease in resistance to flow, as shown by a reduction in the umbilical artery systolic/diastolic ratio, and this also occurred on 10 of the 13 occasions when blood sampling only was performed. These findings suggest that acute changes in blood viscosity following intravascular transfusion are not associated with an increase in resistance to flow as assessed by Doppler velocimetry. Umbilical blood sampling per se may be associated with a humorally mediated reduction in placental vascular resistance to flow.     

Treatment of fetal anemia due to red-cell alloimmunization with intrauterine transfusions in the Netherlands, 1988-1999

OBJECTIVE: To assess pregnancy outcome after intrauterine transfusion (IUT) for fetal anemia due to red-cell alloimmunization in the Netherlands over 11 years, in order to improve care and counseling. METHODS: A retrospective cohort study was conducted from January 1, 1988, to January 1, 1999. Data were collected prospectively on all red-cell alloimmunized pregnancies requiring intrauterine blood transfusions. Primary outcome variables were fetal and neonatal survival in relation to the type of antibody, gestational age and presence or absence of hydrops. In addition, we studied short-term neonatal morbidity and procedure-related complications. RESULTS: A total of 210 fetuses from 208 pregnancies received 593 transfusions. Overall survival rate was 86%. Survival of hydropic fetuses (78%) was significantly different from those without hydrops (92%). Low survival rates were especially found in hydropic fetuses with the first transfusion at gestational ages of 20 weeks or less (55%) or between 28 and 32 weeks (59%). In maternal rhesus D [Rh(D)] immunization 89% of fetuses survived, whereas survival in the case of Kell immunization was 58%. All fetuses with anemia due to Rh(c) immunization survived. The overall fatal procedure-related complication rate was 1.7% per procedure, resulting in a fetal loss rate of 4.8%. CONCLUSIONS: Intrauterine intravascular transfusions are effective in the management of fetal alloimmune anemia. Fetal hydrops, mostly associated with late referral, decreases the chance of survival. To improve the outcome of red-cell alloimmunized pregnancies early diagnosis of fetal anemia and referral to a specialized center are important, enabling the start of treatment before hydrops develops.     

Diagnosis and treatment of fetal anemia due to isoimmunization

45 pregnant women affected by rhesus incompatibility were treated at the Department of Prenatal Diagnosis and Therapy, Vienna, between January 1992 and March 1993. 32 patients had a cordocentesis and on 21 fetuses, anemia requiring treatment was diagnosed. A total of 71 intravascular transfusions via the umbilical vein was given. The mean number of transfusions per fetus was 3.4 (range 1-11). Of the 7 fetuses who had already developed hydrops when therapy was started (hematocrit <13%), 5 (71%) survived. The survival rate of non-hydropic anemic fetuses was 93% (13/14). By using intravascular transfusion for treatment of severe fetal anemia, a success rate of 86% (18/21) was achieved. Received: 13 January 1994 / Accepted: 25 May 1994