Intrauterine growth restriction results in persistent vascular mismatch in adulthood

Abstract

Key points: Intrauterine growth restriction (IUGR) increases offspring risk of chronic diseases later in life, including cardiovascular dysfunction. Our prior studies suggest biventricular cardiac dysfunction and vascular impairment in baboons who were IUGR at birth because of moderate maternal nutrient reduction. The current study reveals changes in artery sizes, distensibility, and blood flow pattern in young adult IUGR baboons, which may contribute to cardiac stress. The pattern of abnormality observed suggests that vascular redistribution seen with IUGR in fetal life may continue into adulthood.

Abstract: Maternal nutrient reduction induces intrauterine growth restriction (IUGR), increasing risks of chronic diseases later in life, including cardiovascular dysfunction. Using ultrasound, we determined regional blood flow, blood vessel sizes, and distensibility in IUGR baboons (8 males, 8 females, 8.8 years, similar to 35 human years) and controls (12 males, 12 females, 9.5 years). The measured blood vessels were larger in size in the males compared to females before but not after normalization to body surface area. Smaller IUGR normalized blood vessel sizes were observed in the femoral and external iliac arteries but not the brachial or common carotid arteries and not correlated significantly with birth weight. Mild decrease in distensibility in the IUGR group was seen in the iliac but not the carotid arteries without between-sex differences. In IUGR baboons there was increased carotid arterial blood flow velocity during late systole and diastole. Overall, our findings support the conclusion that region specific vascular and haemodynamic changes occur with IUGR, which may contribute to the occurrence of later life cardiac dysfunction. The pattern of alteration observed suggests vascular redistribution efforts in response to challenges in the perinatal period may persist into adulthood. Further studies are needed to determine the life course progression of these changes.

Keywords: arteries; baboon; blood flow; blood vessels; developmental programming; distensibility; intrauterine growth restriction (IUGR); maternal nutrient reduction; nonhuman primates.

Figure 1. Measurement of vessel luminal area

Measurements of the arterial lumen area were obtained using cine axial images with focus zone set at the level of the vessel and depth of 2 cm using the built‐in software. The arteries were differentiated from the adjacent veins by either the presence of visible pulsatile movement or arterial Doppler waveform evaluations. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2. Measurement and analysis of common carotid Doppler waveform

A, Doppler waveforms of the bilateral common carotid arteries were obtained with angle correction maintained at or below 60 deg and sampling size of 2 mm. B and C, the automatic tracing algorithm of the built‐in processing software then was applied on the obtained spectra (B) to generate intensity‐weighted mean frequency velocity tracings (C). The various velocities were measured from the tracings. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3. Common carotid artery measurements

No group‐sex interaction was detected by ANOVA. A, the peak systolic velocity of the common carotid artery was higher in the males compared to the females without group differences. B and C, increased end‐systolic velocity (B) and end‐diastolic velocity (C) were seen in the IUGR group compared to controls (CTL) without between‐sex differences. D, time‐average velocity was not significantly different between groups. E, the lumen area was not different between groups. F, a trend of increased normalized carotid blood flow was observed in IUGR without reaching significance. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4. Brachial, femoral, and iliac artery measurements

ANOVA detected no group‐sex interaction. A, the normalized brachial artery lumen area was not different between groups. B and C, decreased femoral (B) and iliac (C) artery lumen sizes are seen in the IUGR groups both before and after normalization to BSA. D, decreased distensibility of the iliac artery was seen in the IUGR group. [Color figure can be viewed at http://wileyonlinelibrary.com]