Discordance in maximum velocities in the middle cerebral arteries of monochorionic twins: beyond twin anemia-polycythemia sequence.

Abstract

In monochorionic pregnancies, elevated middle cerebral artery peak systolic velocity in 1 twin is a key marker of fetal anemia, notably in twin anemia-polycythemia sequence, but may also occur spontaneously in selective intrauterine growth restriction, owing to brain-sparing mechanisms or in the context of twin-to-twin transfusion syndrome, particularly following laser therapy. Distinguishing between these etiologies remains challenging, complicating clinical management and counseling. In addition, current middle cerebral artery peak systolic velocity charts are primarily derived from singleton pregnancies, with limited data on monochorionic twins, especially before 18 weeks of gestation. The aim of this study was two-fold: first, to establish a dedicated middle cerebral artery peak systolic velocity chart for monochorionic twins, and second, to propose a new hemodynamic index (middle cerebral artery peak systolic velocity/umbilical artery pulsatility index ratio) for differentiating middle cerebral artery peak systolic velocity changes due to hemodynamic adaptation from fetal anemia. All consecutive monochorionic twin pregnancies referred to our tertiary reference center between January 2019 and December 2023, either for standard follow-up or for a specific complication, were included. This study was conducted in 2 phases: first, the development of gestational age-specific charts for middle cerebral artery peak systolic velocity and the middle cerebral artery peak systolic velocity/umbilical artery pulsatility index ratio using data from uncomplicated pregnancies; second, the evaluation of the hemodynamic index in pathological conditions associated with elevated middle cerebral artery peak systolic velocity values (selective intrauterine growth restriction, spontaneous twin anemia-polycythemia sequence, and postlaser follow-up). A z score of 2.32 (corresponding to the 99th percentile) was used as the threshold for pathological values. Overall, 810 monochorionic twin pregnancies were included; 389 patients with uncomplicated pregnancies were used to generate gestational age-specific charts for both middle cerebral artery peak systolic velocity and middle cerebral artery peak systolic velocity/umbilical artery pulsatility index ratio. With a total of 4021 observations of middle cerebral artery peak systolic velocity, including 640 observations between 14 and 18 weeks of gestation, the estimated mean middle cerebral artery peak systolic velocity before 18 weeks differed from both singleton and twin charts. Differences between the observed and smoothed mean middle cerebral artery peak systolic velocity were small (0.49 cm/s, standard deviation±0.34). We investigated pathological conditions associated with elevated middle cerebral artery velocity. Among 67 severe selective intrauterine growth restriction cases, 40% presented elevated middle cerebral artery velocity. Their middle cerebral artery peak systolic velocity/umbilical artery pulsatility index ratio was significantly different from spontaneous twin anemia-polycythemia sequence (mean middle cerebral artery peak systolic velocity/umbilical artery pulsatility index ratio Z-score of 0.60 vs 4.16 for selective intrauterine growth restriction and twin anemia-polycythemia sequence, respectively, P<.001): The ratio Z-score was within the normal range for 93% of selective intrauterine growth restriction cases and for none of the spontaneous twin anemia-polycythemia sequence. Postlaser follow-up showed middle cerebral artery peak systolic velocity elevation in 15/281 twin-to-twin transfusion syndrome cases (5%), with 9/15 diagnosed as postlaser twin anemia-polycythemia sequence. No clear correlation was found between Doppler indices and postlaser twin anemia-polycythemia sequence. This study provides a new gestational age-specific middle cerebral artery peak systolic velocity chart and introduces a novel hemodynamic index (middle cerebral artery peak systolic velocity/umbilical artery pulsatility index ratio) that may help differentiate spontaneous anemia from hemodynamic changes and thus, refine both diagnosis and prognosis of complicated monochorionic pregnancies, especially in early gestational ages.