Interpretation
GHD, particularly PE and CH, is a significant risk factor for intertwin
birthweight discordance. Though the reason for the existence of this
association remains unclear and may be in connection with the
multifactorial aspect of GHD, there are some possible explanations for
this association. Findings such as
retroplacental hematomas, thrombotic lesions, fibrin deposition and more
velamentous cord insertions were observed in the placentas of discordant
twins.36,37
In discordant twins complicated with PE, the placental mass hypothesis
might further explain the histological findings observed in the
placentas. In twin pregnancies, an increased release of some
antiangiogenic molecules may be related to lager placental
mass.
Soluble fms-like tyrosine kinase-1
(sFlt-1) turned out to play a crucial part in the pathogenesis of
PE,38,39 which possibly causes placental
ischemia/hypoxia, supposing the placentas contract diseases, the smaller
one in the twins might fail to achieve the growth potential because of
the placental vascular dysfunction.40,41
Moreover, the genetic incompatibility and/or increased immunologic
response theory maybe another explanation. Some studies revealed higher
levels of syncytiotrophoblast
microparticles and fetal nucleic acids in the maternal blood in twin
pregnancies complicated by PE.42-44 Other studies
showed that the interactions between paternal antigens of leukocytes and
maternal natural killer cell, and cytotoxic T-cell response to those
antigens were mechanisms contributing to the development of
PE.45 Exposed to increased levels of placental
microparticles or fetal antigens which can trigger in appropriate immune
responses, women will possibly deliver twins with birthweight
discordance.
Additionally, as common umbilical cord abnormalities,
velamentous cord insertions are risk
factors for PE.46 It was found that velamentous cord
insertion is a crucial indicator of intertwin birthweight
discordance.47 It was speculated that the high
incidence of velamentous insertions in twin pregnancies complicated with
PE leads to an increased risk of birthweight discordance.
When it comes to twin pregnancies complicated with CH, Sparks et
al.22 pointed out that the chronic hypertension
environment may further impose much more stress on twins with
pre-existing differences regarding growth potential. However, whether
related to potential genetic differences or not, abnormal placentation
itself might lead to the development of fetal growth abnormalities.
Therefore, the mechanism of the correlation between CH and intertwin
birthweight discordance deserves further investigation.
However, GH might play an unknown beneficial role in MC pregnancies
according to the stratified analysis, which was reflected by
Ferrazzani S et
al.18 that GH could be a paraphysiological phenomenon
in twin pregnancies ensuring a better placental perfusion. More studies
are necessary to explain the pathogenesis of this finding.
According to the subgroup and stratified analyses, the risk of intertwin
birthweight discordance differed based on chorionicity. DC twins are
mostly fraternal twin pregnancies, either due to two separate placentas
or pre-existing genetic differences between twins in growth
potential.40 The potential genetic differences between
the twins might probably interact with hypertensive environments,
leading to discordant uteroplacental blood flow, placental changes, and
growth in DC group. The placental anatomy is unique in MC twin
pregnancies, and the fetal circulations were conjoined in a single
placenta. Among MC twins, birthweight discordance is related to
placental territory discordance
between the fetuses, velamentous cord insertions, and the type and
number of vascular anastomoses.48-50
So as to why birthweight seemed to be less affected by GHD in MC twin
pregnancies. It could be attributed to an earlier gestational age at
delivery and before the occurrence of PE in MC twin
pregnancies,51 otherwise the true risk of birthweight
discordance in MC twin pregnancies with PE might actually be higher. In
addition, compared to DC ones, the circulating blood volume is lower in
MC twin pregnancies, which brings about better cardiovascular adaptation
to pregnancy.52
However, the findings of our study should be elucidated carefully due to
small number and sample size of selected studies,
more fundamental and clinical
studies are warranted to focus on the effect of GHD on intertwin
birthweight discordance.