A carregar...
Publicação
Role of liver hemodynamics in fetal development in twin pregnancies
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 11.11 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
In recent years there has been an increased in twin births, mainly due to the readily access to
assisted reproduction and increased maternal age. The rise in twin births have a deep impact to
all health systems as multiple pregnancies carries an increased risk of maternal and fetal
complication. Although twins can be classified as mono or dizygotic in relation to their embryo
origin, it is their classification according to the chorionicity that plays a more significant role
in daily clinical practice. Based on this criterion, twins can either be mono or dichorionic. Both
are at increased risk of complications, but monochorionic twins carries an even higher risk of
adverse outcomes. Monochorionic twins are monozygotic, therefore genetically similar. They
can be in in separated amniotic sac if the twinning process occurs between 3 to 8 days after
fertilization or have a single amniotic sac if the splitting occurs between 9 to 12 days; in this
manuscript we will focus in the first type, also called monochorionic diamniotic (MCDA)
twins. The single placental mass of monochorionic twins enables a shared feto-placenta
circulation, meaning that co-twins share their blood through a complex network of vascular
anastomosis. These vascular connections can be bidirectional or unidirectional and their
arrangement seems crucial to a less complicated pregnancy. Nevertheless, this organisation is
extremely fragile and unfortunately, often unbalanced.
In about 10% of MCDA pregnancies, the circulation favours one twin over the other, giving
rise to a disease called twin-to-twin transfusion syndrome. Despite not existing a typical TTTS
vascular tree, this condition involves the existence of unidirectional anastomosis, usually
arterio-venous, that are not compensated by bidirectional anastomosis. The presence of
unidirectional connections allows for a transference of significant blood volume, leaving both
fetuses affected. One fetus becomes the donor and suffers with hypovolemia while the other
turns into a recipient that experience the effects of hypervolemia.
In about 15% of the monochorionic diamniotic twins the placental mass is unequally shared
and, if the difference is significant, it will lead to a selective fetal growth restriction. This is an
intriguing disease, mainly because the literature failed for a long time to agree upon a definition
to this condition. Only recently a panel of international experts reached an agreement and
define an objective diagnostic criteria, consequently, even less is known about sFGR compared
to TTTS. Contrary to what happens in TTTS, in selective growth restriction the vascular
anastomosis may be beneficial if favours the affected fetus. Apart from the placenta characteristics of the main complications in MCDA, very little is
known about the pathophysiology and natural history of TTTS and sFGR, leading to numerous
unanswered questions. It's reasonable to assume that in events as serious as those, the affected
fetuses experience significant burden. These disorders likely affect multiple systems and will
require an array of compensatory mechanisms to sustain the fetus during the course of the
disease and following successful treatment. One of the systems that can be involved is the
Hepatic Arterial Buffer Response (HABR).
The Hepatic Arterial Buffer Response is an important liver defence mechanism that focus on
preserve hepatic perfusion. Adenosine works as a vasodilator of the hepatic artery (HA) and is
produced at constant rate near the final branches of this vessel. Its concentration depends on a
washout effect derived from the circulating blood in the space of Mall. If there is a reduction
in hepatic blood flow, the concentration of adenosine increases producing vasodilation of HA
therefore improving hepatic prefusion. It has been described that in some fetal diseases such
mechanism could be active yet, in the context of complicated MCDA it is unknow. It is possible
that in TTTS donors, that deals with hypovolemia, HABR could be activated. Similarly, in
sFGR, the affected fetus could experience reduction in hepatic perfusion leading to the
activation of this liver defence mechanism even though, through a different pathway. Our main
goal in this project was to find out if the HABR is active in MCDA twins affected by TTTS
and sFGR.
To answer this question, three prospective studies were developed with a population of 247
monochorionic twin pregnancies. In the first study we created a ratio between the hepatic artery
peak systolic velocities of both co-twins, called HAV-ratio. A ratio between co-twins
accentuates subtle variations in HA peak systolic velocities (PSV). This is particularly relevant
if the underlying hypothesis posits divergent effects between the co-twins or no effect in one.
Such approach highlights the relationship between small variations rendering it particularly
advantageous for initial studies. We demonstrated that HAV-ratio is significantly lower in
MCDA pregnancies with TTTS when compared to normal MCDA (p<0.001, 95% CI 0.443,
0.643). In TTTS the mean HAV-ratio is 0.47 (±0.035) while in normal pregnancies it is 1.014
(±0.021).
The second study was built up on the first and analysed the HA PSV of each affected fetus
independently and compared to normal fetuses. Additionally, we analysed the variation in HA
PSV in donors before and after fetoscopic laser ablation of vascular anastomosis (FLAVA). We found a significant difference in HA PSV z-scores (HAV-Z) between donor and normal
fetuses (β=2.429, 95 % CI 1.887, 2.971; p<0.001). In donors this measurement was 2.4 z-scores
higher compared to normal fetuses. This measurement reduces significantly after FLAVA
(β=−1.829, 95 % CI −2.593, −1.064; p<0.001). The observed data supports the hypothesis of
the activation of hepatic arterial buffer as a direct adaptive response to TTTS in donor twins.
The third study focus on the activation of HABR in sFGR. To assess this effect, we used the
HAV-ratio between pregnancies affected by sFGR and normal twins and found a significant
difference between these two groups. For normal pregnancies the mean HAV-ratio was 1.01
(±0.20) while for sFGR was 0.77 (±0.25). Our findings demonstrate that, in pregnancies
affected with selective fetal growth restriction, HAV-ratio is significantly lower than in normal
MCDA pregnancies, nevertheless the effect appears less intense than in TTTS. This
observation appoints to the activation of HABR in the restricted fetus.
This project results in the description of a novel physiologic adaptation in monochorionic twins
complicated by either TTTS or sFGR. Improving our knowledge of the pathophysiological
processes involved in any medical condition will invariably steer to better understanding of the
disease and, in time, will push us to a better care providing safer, more reliable and specific
treatments that will improve outcomes of such complicated disorders.
Descrição
Palavras-chave
liver hemodynamics fetal development twin pregnancies