Fetal vascular programming: A twin study

Abstract

Background: Twin-twin transfusion syndrome (TTTS) occurring in monozygous twins is a useful model to investigate intrauterine programming independent of genetic influence. Both twins experience abnormal volume loading and increased placental resistance that may initiate vascular remodeling and permanently alter their physical properties. We examined whether twins surviving TTTS have altered arterial distensibility postnatally by comparing the pulse wave velocity (PWV ∝ 1/√distensibility) in the conduit arteries of twin pairs with and without TTTS and in a dichorionic control group. Methods Eighteen surviving twin pairs were studied; 6 pairs of monochorionic (MC) twins with TTTS, 7 pairs of MC twins without TTTS and 5 pairs of dichorionic twins. Fetal data on umbilical arterial pulsatility index, predictive factors for TTTS and duration of TTTS were collected prospectively. Brachio-radial arterial PWV was measured at a median corrected postnatal age of 9 (range 0.25 to 14) months using a photoplethysmographic technique and blood pressure measured. Results: MC twins with TTTS were more premature (p<0.01) and had the greatest co-twin birth weight difference. The mean PWV in donor twins was 98% higher (p=0.03) than that of their monozygous recipient co-twins. No co-twin difference in PWV was present in the other two groups, nor was any blood pressure difference identified in any of the three groups. Multiple regression analysis identified the donor status (β=2.50, p<0.01 ) and corrected postnatal age (β=0.32, p<0.01) as significant determinants of PWV. PWV discordance was significantly related to the duration of TTTS (r=0.94, p=0.005). Conclusions: Arterial distensibility in the brachio-radial artery was decreased in the donor twin in TTTS during infancy. These data suggest that vascular remodeling in utero, intended to be adaptive, may result in persistent functional vascular abnormalities that increase cardiac afterload and may prejudice later cardiovascular health.