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.