European Journal of Obstetrics & Gynecology and Reproductive Biology
Left ventricular isovolumic relaxation and renin-angiotensin system in the growth restricted fetus
Introduction
Fetal growth restriction (FGR) complicates 10%–15% of all pregnancies [1]. The cause of FGR is multifactorial. Pregnancy induced hypertension (PIH), preeclampsia and maternal nutritional deficiencies are among the most common causes of FGR [1], [2]. Although perinatal complications of FGR are well documented, it is only recently that researchers are focused on the long-term morbidity which is associated with this phenomenon. Numerous epidemiological studies have described the relationship between low birth weight and high blood pressure in adult life. It was proposed that factors associated with FGR could program the development of the cardiovascular system and act as a risk for essential hypertension, hyperlipidemia and death from cardiovascular disease in later life [3], [4], [5]. However, there is no information about the mechanisms of this programming. Whether these mechanisms start during intrauterine life or factors of intrauterine life could serve as a background for the early development of hypertension in adults and adolescents is still unknown.
Current management of FGR fetuses consists of serial ultrasound examinations to assess growth as well as Doppler velocimetry in the umbilical artery and several other vessels [6], [7], [8]. FGR is usually characterized by an elevated umbilico-placental vascular resistance which may also affect the afterload of the fetal heart [7]. The specific sequence of Doppler changes and hemodynamic modifications in FGR fetuses has been shown, including a change in peripheral arterial impedance resulting in redistribution of blood flow to the vital organs (heart and brain) which is followed by progressive impairment of cardiac function and abnormal venous flow patterns [6], [8].
The effects of experimental restriction of placental function and fetal growth on fetal arterial blood pressure regulation during late gestation have been investigated in fetal sheep [9]. A special role of endogenous renin-angiotensin system in the maintenance of blood pressure in growth restricted fetus was determined by captopril infusion [9].
Earlier we have shown the increase in left ventricular isovolumic relaxation time (LV IRT) in FGR fetuses [10]. It is well known that the main determinant of IRT is ventricular afterload [11]. Direct measurements of intraventricular pressure and time course of isovolumic relaxation demonstrated a strong correlation between LV IRT and end-systolic LV pressure (afterload) in sheep [12]. A higher end-systolic pressure value means longer period of isovolumic relaxation. During this time intraventricular pressure should decay from end-systolic pressure (systolic blood pressure) to the value about zero mmHg, which is essential for the initiation of ventricular filling.
We speculated that LV IRT could serve as a noninvasive index of human fetal cardiac afterload. To test this hypothesis we studied the changes of fetal left ventricular isovolumic relaxation time in normally growing and growth restricted fetuses and measured the activity of the renin-angiotensin system which could be involved in the maintenance of arterial blood pressure in the normal sized and growth restricted newborn.
Section snippets
Patients and methods
A total 171 consecutive singleton pregnancies was enrolled in the study which was approved by the local Ethics Review Board of the Mother and Child Care Institute. All women consented to participate. The gestational age at enrolment ranged between 22 and 26 weeks of gestation. Gestational age was determined from the patient's last menstrual period and was confirmed by a first-trimester fetal crown-rump length or early second-trimester fetal biparietal diameter measurement. Fetal biometry and
Results
Table 1 presents the clinical data concerning the normal and growth restricted fetuses. Pregnancy was uneventful in 124 of 171 women. Fetal abdominal circumference was always situated between 10th and 90th percentile [14]. There were no structural abnormalities in this subset.
Fetal growth restriction, as expressed by an abdominal circumference below the 10th percentile during all serial measurements [14], was diagnosed in the remaining 47 pregnancies. Pregnancy-induced hypertension (PIH),
Discussion
The present study shows that in the growth restricted fetus an increase in LV IRT occurs well before changes in the umbilical artery PI. We suggest that Doppler measurement of LV IRT could serve as an early indicator of increase in fetal cardiac afterload. It is known that, in the mammalian myocardium the main determinant of isovolumic relaxation is afterload (systolic blood pressure) [12]. Therefore, we speculate that elevated afterload could be considered the main cause of LV IRT increase in
References (23)
- et al.
Fetal nutrition and adult disease
Am J Clin Nutr
(2000) - et al.
Assessment of fetal left cardiac isovolumic relaxation time in appropriate and small-for-gestational-age fetuses
Ultrasound Med Biol
(1995) - et al.
New birthweight and head circumference centiles for gestational ages 24–42 weeks
Early Hum Dev
(1987) - et al.
Placental transport rather than maternal concentration of amino acids regulates fetal growth in monochorionic twins: Implications for fetal origins hypothesis
Am J Obstet Gynecol
(2001) - et al.
Intrauterine growth restriction is accompanied by decreased renal volume in the human fetus
Am J Obstet Gynecol
(2003) - et al.
Intrauterine growth retardation: definition, classification, and etiology
Clin Obstet Gynecol
(1992) - et al.
Z-velocity in screening for intrauterine growth restriction
Ultrasound Obstet Gynecol
(2005) Consequences of fetal growth restriction
Curr Opin Obstet Gynecol
(1998)- et al.
Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease
BMJ
(1989) - et al.
Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth restricted fetus
Ultrasound Obstet Gynecol
(2002)
Changes of pulsatility index from fetal vessels preceding the onset of late decelerations in growth retarded fetuses
Obstet Gynecol
Cited by (17)
Investigating myocardial performance in normal and sick fetuses by abdominal Doppler signal derived indices
2021, Current Research in PhysiologyCitation Excerpt :Isovolumic relaxation time (IRT: aortic valve closure until mitral valve opening) measures ventricular relaxation which also correlates with invasive indices (Myreng and Smiseth, 1990). Prolongation of the IRT accurately categorized fetuses with FGR and abnormal placental function up to 8 weeks prior to abnormalities detected by conventional Doppler hemodynamic indices (Tsyvian et al., 2008). Fetuses with Hb Bart's disease were reported to have reduced ventricular filling time (VFT) (Chao et al., 2009).
Biomarkers of cardiovascular disease risk in the neonatal population
2023, Journal of Developmental Origins of Health and DiseaseInfluence of accelerated arterial aging in growth-restricted cohorts on adult-onset cardiovascular diseases
2023, American Journal of Physiology - Heart and Circulatory PhysiologyOntogenetic Principles of Accelerated Aging and the Prospects for Its Prevention and Treatment
2022, Advances in GerontologyOn systemic pathophysiology of preeclampsia: The role of maternal venous hemodynamic disorders and renal dysfunction
2021, Akusherstvo i Ginekologiya (Russian Federation)Foetal haemodynamic response to anaemia
2020, ESC Heart Failure