Abstract
BackgroundThere are sex differences in the risk of development of cardiovascular disease (CVD). According to the developmental origins of health and disease paradigm (DOHaD), CVD originates in fetal life. This study examines fetal sex differences in cardiovascular development in utero.MethodsIn 1028 pregnant women, we assessed fetal circulation using pulsed wave Doppler examinations between 28 and 34 weeks gestation. To test associations between fetal sex and fetal circulation measurements, linear regression models were used adjusting for fetal size, gestational age, and fetal heart rate.ResultsA higher pulsatility index in the ductus venosus was observed in male fetuses compared to female fetuses (difference 0.02, 95 % CI 0.01; 0.05) with a lower E/A ratio of the tricuspid (difference −0.01, 95 % CI −0.03; −0.00) and mitral (difference −0.02, 95 % CI −0.03; −0.01) valves. This was mainly determined by differences in the E wave of the tricuspid and mitral valves (differences −1.02, 95 % CI −1.81; −0.24 and −1.28, 95 % CI −2.11; −0.46, respectively). Also in males, a lower peak systolic velocity was seen in the pulmonary artery (difference −1.33, 95 % CI −2.63; −0.03) with a similar lower trend regarding peak systolic velocity in the ascending aorta.ConclusionsMale fetuses exhibit an increased preload and reduced afterload conditions compared to females. While it is difficult to relate these measurements to exact cardiac function, our findings strongly suggest that the known differences in cardiovascular performance between the sexes already start in utero.
Highlights
There are sex differences in the risk of development of cardiovascular disease (CVD)
All analyses were adjusted for gestational age and estimated fetal weight at the time of measurement PI pulsatility index, Venous pulsatility index (PIV) pulsatility index for veins, Peak systolic velocity (PSV) peak systolic velocity, Not significant (NS) not significant aCardiac measurements were adjusted for fetal heart rate male fetuses compared with female fetuses in the third trimester of pregnancy
A significant lower peak systolic velocity was observed in the pulmonary artery, with a similar, but not significant, trend towards a lower peak systolic velocity of the aorta ascendens
Summary
There are sex differences in the risk of development of cardiovascular disease (CVD). According to the developmental origins of health and disease paradigm (DOHaD), CVD originates in fetal life. This study examines fetal sex differences in cardiovascular development in utero. CVD develops over decades, but according to the theory of developmental plasticity, its cornerstone is already laid during fetal life [2]. Women are protected from most cardiovascular events compared to men until after menopause. Men are thought to be at risk of cardiovascular disease at earlier ages than women. Left ventricular hypertrophy is a strong and independent risk factor of cardiovascular morbidity and mortality in adulthood, and it has been shown that left ventricular mass tracks from fetal life through childhood into adulthood [4]. It has been reported that elevated blood pressure tracks from childhood into adulthood with eventual progression into essential hypertension [5]
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