Etiology and Pathophysiology

Proposed Twin–Twin Transfusion Syndrome Etiology and Pathophysiology

The etiology of TTTS was proposed to be a consequence of the normal development of the placental anastomoses as compared to the natural growth of the fetuses. Here, because little is known about growth of anastomoses, we assumed that normal anastomotic development is that length and diameter of the anastomoses increase proportional to gestational age.

We hypothesized that anastomoses develop similarly as chorionic and umbilical vessels and available data of serial measurements show that the diameter of AA anastomoses umbilical veins as well as the length of umbilical veins and chorionic vessels – the latter considered proportional to the diameter of singleton placentas – all grow approximately proportional to gestational age (Figure 6.1). Implication is that anastomotic resistances decrease significantly during gestation, i.e. according to eqn (2) as inversely proportional to gestational age to the 3rd power.


Furthermore, the donor’s arterial minus recipient’s venous pressure, the driving pressure gradient of AVDR transfusion, increases approximately linearly with gestational age, based on fetal lamb experiments.4 Consequently, AVDR transfusion is proportional to gestational age to the 4th power. This assumption has been confirmed by published placental blood flow measurements,17 supposing it is proportional to cotyledonic blood flow (Figure 6.2). In contrast, natural growth of fetuses (and their blood volumes) is approximately proportional to gestational age to the 2nd power,4 which is a slower increasing function than AVDR flow.

Thus: AV-FetofetalTransf ? (Gestational Age)4 (3) NaturalBloodVolGrowth ? (Gestational Age)2 (4) where symbol ? denotes ‘proportional to’. These different growth rates cause donor twins to effectively lose blood volume through the AVDR and recipients to effectively gain this blood volume. Because of this mechanism, the natural fetal growth of each twin loses the competition with this continuous exogenous change in its blood volume.

Obviously, if only unidirectional AVDR anastomoses are present, the well-known deleterious effects of TTTS develop with increasing severity without the possibility of recovery. On the other hand, if other anastomoses (AVRD, AA, VV) are also present, part of the AVDR transfusion will be returned back to the donor, eqn (1). Under these circumstances, TTTS either will not develop, or it will have a reduced severity compared to TTTS caused by the single AVDR. Consequently, whether TTTS develops or not, and TTTS severity, is determined by the capacity (length and diameter) of AVDR anastomoses compared to the combined capacity of AVRD, AA, and VV anastomoses (recipient to donor).

This mechanism explains why some but not all monochorionic twin placentas with anastomoses develop TTTS. Thus far, quantifying unidirectional AV fetofetal transfusion throughout gestation has been impossible, although assessment of individual AV anastomotic flow at one gestational age was published very recently. First, Quintero’s group used intra-amniotic ultrasound,18 and, secondly, our group related AVDR flow with decreasing hemoglobin concentrations between the moment of an intrauterine blood transfusion and birth.