We postulated that there may be sex-specific differences in the activity of the RAS in early gestation in pregnancies later complicated by preterm birth (PTB) or delivery of small for gestational age (SGA) babies. Women in the Adelaide SCOPE cohort had blood collected at 15 weeks gestation, uterine and umbilical Doppler sonography performed at 20 weeks and placenta and birth weights recorded at birth. Maternal angiotensin (Ang) II, Ang 1-7, prorenin and angiotensin-converting enzyme (ACE) concentrations were measured in 50 PTB women (males: 27; females: 23); 50 women with SGA babies (males: 32; females: 18) and 100 BMI-matched women with normal pregnancy outcomes.
Women who had PTB females had lower Ang II (P = 0.026) but higher Ang 1-7 concentrations (P = 0.006) at 15 weeks gestation, with higher uterine artery resistance indices (P = 0.048) at 20 weeks gestation.
Women who delivered SGA babies had higher uterine artery resistance indices (P = 0.002) at 20 weeks gestation than controls. Women who delivered female SGA babies also had higher circulating Ang 1-7 (P = 0.051) and ACE concentrations (P = 0.009) at 15 weeks gestation. No differences were seen in the RAS of women who delivered male SGA babies even though maternal arterial pressures (P = 0.010) and umbilical artery resistance indices were higher (P = 0.019) than controls.
In summary, in early gestation, there were no differences in the circulating maternal RAS in PTB or SGA women who later delivered a male baby. Conversely, women delivering a PTB or SGA female baby had higher Ang 1-7 concentrations at 15 weeks gestation. Since Ang 1-7 is a peripheral vasodilator we postulate that higher levels of Ang 1-7 in women carrying female fetuses may divert blood from the uteroplacental circulation compromising fetal growth and/or increasing the probability of PTB.