Evidence from Fetal blood sampling

TTTS. Evidence from Fetal blood sampling.

The neonatal criterion of a difference in 5 g/dl of hemoglobin has shown to be unsuitable in utero, because of its lack of correlation with the ultrasonographic criteria and because neonatal cases select those TTTS cases with better outcome. Bruner and Rosemond18 found a difference of more than 5 g/dl by cordocentesis in only 1 of 6 cases with TTTS. 

This study aimed to demonstrate donor–recipient passage of blood by a positive Kleihauer–Betke test in the recipient after in-utero tranfusion of the donor with adult O Rh? red cells. In 6 cases in which the procedure could be performed, 

Kleihauer–Betke was positive in 4 recipients 5–19 minutes following transfusion in the donor. The conclusion of the authors was that 4/6 of TTTS diagnosed by ultrasound had a real donor to recipient transfusion (1–17%), and that perhaps the ultrasonographic criteria should be reviewed since in 2 out of 6 cases no transfusion could be demonstrated. 

The major criticism of that study is that perhaps 5 minutes is not enough time for the donor to replace 1% of the recipient’s volemia. Therefore this method may be insensitive for the diagnosis of feto–fetal transfusion. In a later report from Detroit,21 cordocentesis was performed in 8 cases of TTTS. Hemoglobin values were significantly lower in donors vs recipients, but were over 5 g/dl in only 3 cases. It was suggested that the tranfusion syndrome did not exist in 5 cases because the hemoglobin level was normal. An interesting study was performed to assess the difference in erythropoietin in fetuses with TTTS.22 In 15 TTTS pregnancies, erythropoietin was similar between donors and recipients, despite an important difference in fetal hemoglobin. In 6 monochorionic–diamniotic pregnancies used as controls, erythropoietin was found to be similar between the twins, but lower than in TTTS. 

The study was completed with immunohistology, in which the kidneys of donors and recipients stained similarly for erythropoietin antibodies, supporting the idea that both fetuses are synthethizing the hormone and that the similar concentration is not by the passage from the donor to the recipient. Ferritin and iron was studied by the same authors.23 A higher concentration of ferritin was found in the recipient, although it was well below that found in cases of iron overload. Ferritin was similar between donors and controls (non-TTTS monochorionic–diamniotic fetuses) and iron was similar in all groups. 

After these two studies, the authors conclude that anemia/ polycythemia is not a constant characteristic of TTTS, because erythropoiesis is similar in both fetuses and no signs of iron overload have been confirmed in the recipient, despite some differences in fetal hemoglobins. The study on fetal hormones and differences between donors and recipients in TTTS has contributed to the understanding of the pathophysiology. Although vascular anastomoses may equilibrate hormone concentrations on both sides, some substances have been found to have similar concentrations in both fetuses but others do not. 

Differences in the half-life of the hormones may also explain the results found. Cordocentesis was performed in 14 TTTS and 6 normal monochorionic–diamniotic pregnancies. Atrial natriuretic peptide and brain natriuretic peptides were higher in recipients than donors, and donors had similar concentrations with non-TTTS monochorionic twins.24 Vasopressin was measured in 44 non-TTTS monochorionic twins, 17 TTTS twins, and their mothers. Vasopressin was found to be three times higher in the donors than in recipients with TTTS. The normal fetuses had concentrations lower than that in donors but higher than in recipients, and the mothers had similar concentrations, whereas the condition of their fetuses.25 This suggests that the vasoconstriction in the donor is an important factor in the development of TTTS.