The pathophysiology

Feto–fetal transfusion syndrome. The pathophysiology

The pathophysiology of FFTS is still poorly understood. The shunting of blood from donor to recipient is a simplistic summary of the consequences of this syndrome. The donor and the recipient compensate this imbalance with oliguria and polyuria, respectively, that initiate the amniotic fluid disparity sequence. This theory is supported by higher ferritin concentrations in recipient fetuses but the same authors have challenged this latter hypothesis. They demonstrated the absence of iron overload in the recipient and depletion in the donor twins, and also that the total stainable liver iron was identical between twins pairs with and without FFTS.

In utero and at birth, hematological analyses of 36 fetuses complicated by FFTS revealed that 75% of them do not show hemoglobin discordance ≥5 g/dl, with a mean hemoglobin difference of 3.6 g/dl

Bromley and co-workers16 have usefully described the natural history of 12 monochorionic pregnancies complicated with the oligohydramnios/polyhydramnios sequence. Despite confusions in the definition, they have shown fluctuations in amniotic fluid and suggested that this phenomenon is a dynamic one.


This hemodynamic imbalance results in a net transfer of blood flow across placental vascular anastomoses from the donor to the recipient. It was described as mainly chronical and unidirectional, which could become acute and inverted Sebire and co-workers correlated this dynamic process to a random asymmetric reduction in the number of placental anastomoses. FFTS will occur when the random loss of these anastomoses ends up in an asymmetric flow resistance to interplacental transfusion. According to probabilistic calculations, they suggested that the chance for placental vascular circulation to become asymmetric will be greater in cases starting with several asymmetric connections.

An initially asymmetric pattern may become symmetric, and an initially symmetric pattern may become asymmetric. This theory may explain why not all fetuses with discordant increased nuchal translucency will develop FFTS, and why some fetuses with initially normal nuchal translucency measurements will develop FFTS.

Another hypothesis supported the fact that FFTS may develop as a consequence of a primary uteroplacental insufficiency affecting the donor side. In this situation, the subsequent increase in peripheral resistance could trigger shunting of blood to the recipent. In 1993, Fries and co-workers highlighted the role of a velamentous cord insertion in the genesis of FFTS. Velamentous cord insertions are more common in twins than in singletons, particularly in twins complicated by FFTS (63.6%), owing to the competition for uterine space by vascular placental territory. Velamentous cord insertion can easily be compressed, reducing the blood flow to its twin. It may contribute to the development of vascular imbalance and amniotic fluid discrepancy. Whether there is a pressure gradient between donors’ and recipients’ cavities or not has been debated. In 2000, Hartung and co-workers and Quintero et al demonstrated that intra-amniotic pressure was high in FFTS but equal in both cavities.

Because fetal urine is hypo-osmotic, a vicious cycle of hypervolemia–polyuria–hyperosmolality is established, leading to polyhydramnios and high-output cardiac failure in the recipient. Cardiac overload and ventricular dilatation in the recipient promote high atriopeptin (ANP) secretion by dilated atria. In addition, Mahieu-Caputo and co-workers speculated, supported by morphological studies, that fetal hypertension in the recipient might be partly mediated by the transfer of circulating renin originating from the donor through the placental vascular connections.

The secretion of renin caused by hypovolemia in the donor may negatively affect both fetuses by worsening hypoperfusion in the donor and increasing blood pressure and cardiac afterload in the recipient. Other metabolic pathways were suggested using fetal erythropoietin (Epo) and leptin
concentration measurements. First, fetal Epo concentrations were higher in the FFTS group than
in the non-FFTS group but comparable between donors and recipients. Secondly, the leptin levels
in the recipients were higher than in their siblings. Despite these provocative findings, no convincing explanation was given for these underlying mechanisms. These findings may therefore only reflect the consequences of FFTS rather than a trigger mechanism.