Introduction
In recent years, there has been a significant rise in twin pregnancies due to the advancements in assisted reproductive technologies. However, these pregnancies are more susceptible to complications such as fetal growth restriction (FGR), premature birth, and perinatal loss. Twin pregnancies can also experience selective fetal growth restriction (sFGR), where one twin is compromised while the other grows normally. This condition puts the affected twins at a higher risk of perinatal mortality and morbidity[1]. Additionally, compared to non-sFGR pregnancies, those with sFGR tend to have earlier deliveries and higher rates of neonatal unit admission[2].
It is estimated that 10-20% of twin pregnancies are affected by sFGR. Monochorionic twins have a higher incidence rate of 19.7% compared to dichorionic twins at 10.5%[3]. According to the latest guidelines from the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), sFGR is characterized by an estimated fetal weight (EFW) below the 10th percentile in one twin and an inter-twin EFW discordance of over 25%. Additionally, a discordance threshold of 20% may be used to identify pregnancies with a higher likelihood of negative outcomes[4]. Detecting pregnancies at risk of sFGR or birth weight discordance in the early stages can enhance counseling, intervention timing, and potentially enable preventive treatment trials. Various parameters identified during early pregnancy have been linked to the development of sFGR later in pregnancy. Although abnormal cord insertion is associated with sFGR in twins, it is present in more than 55% of all twin pregnancies[5]. A particularly isolated screening test is urgently needed in clinical practice.
Placental pathology often correlates with the onset and prognosis of sFGR. In cases of MC twins, sFGR is believed to be the result of an unequal distribution of blood through placental anastomoses due to uneven sharing of the placenta[6], whereas in DC twins, from placental insufficiency in one of the placentas[7]. Throughout gestation, the villous trophoblast in the placenta experiences ongoing turnover, which leads to the release of apoptotic debris and cell-free DNA (cfDNA) into the maternal bloodstream. Research suggests that levels of cfDNA may also indicate placental issues. The amount of cfDNA specifically from the fetus is known as fetal fraction, and it has been associated with negative perinatal outcomes, including FGR in single pregnancies[8, 9]. Here, we testing the hypothesis that the fetal fraction in twin pregnancy would reflect birthweight discrepancy.