Long-Term Follow-Up of Intrauterine Growth Restriction: Cardiovascular Disorders

Abstract

In the modern world, cardiovascular disorders are the leading cause of mortality in developed countries, which in most cases undergo a long subclinical phase that can last decades before the first clinical symptoms appear. Aside from the well-known risk factors related to lifestyle and genetics, there is growing evidence that in a proportion of cases, the predisposition to cardiovascular disease lies in prenatal life. Moreover, numerous historical cohort studies and animal models have shown a clear association between low birth weight and increased cardiovascular mortality in adulthood, including increased risk of hypertension, diabetes, dyslipidemia and coagulation disorders in children and adults. Besides premature birth, low birth weight in the majority of the cases is caused by intrauterine growth restriction (IUGR), which affects up to 10% of all births. Several clinical and experimental studies showed that IUGR fetuses present signs of cardiac dysfunction in utero that persist postnatally and may condition higher cardiovascular risk later in life. The present review discusses the importance of the long-term cardiovascular follow-up of the patients who suffered early or late IUGR in utero, particularly with regard to the long-term epidemiological studies in adults, prospective studies in children and the possible mechanisms that trigger IUGR and cardiovascular programming. Considering the high prevalence of IUGR and the progressing availability of intervention strategies, it is of the highest clinical relevance to detect cardiovascular risks as early as possible, to introduce timely preventive interventions and to adapt the lifestyle, in order to improve the long-term cardiovascular health outcome of IUGR cases.

Ehmt2/G9a controls placental vascular maturation by activating the Notch pathway

“…Defects in placental vascular development can cause embryonic death and abnormal organogenesis, can negatively affect fetal growth and can confer a higher risk of disease in the postnatal life (Barker et al, 1989). For example, defective patterning of the fetoplacental vasculature, also known as the labyrinth, results in abnormal heart development in mouse (Shaut et al, 2008) and human (Demicheva and Crispi, 2014), and causes intrauterine growth restriction (IUGR) (Barut et al, 2010). IUGR affects up to 32% of pregnancies in some developing countries (Ananth and Vintzileos, 2009), and can cause cardiovascular disease in utero and in adulthood (Demicheva and Crispi, 2014).…”

“…For example, defective patterning of the fetoplacental vasculature, also known as the labyrinth, results in abnormal heart development in mouse (Shaut et al, 2008) and human (Demicheva and Crispi, 2014), and causes intrauterine growth restriction (IUGR) (Barut et al, 2010). IUGR affects up to 32% of pregnancies in some developing countries (Ananth and Vintzileos, 2009), and can cause cardiovascular disease in utero and in adulthood (Demicheva and Crispi, 2014). Understanding the mechanisms controlling development of the placental vasculature is essential to uncover the developmental origins of disease.…”

Influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction

“…FGR fetuses present cardiovascular remodeling already in utero that persist into childhood (4,5). This effect is thought to contribute to their subsequent long-term cardiovascular risk (6). One of the most prominent signs of cardiac remodeling associated with FGR in fetal life and childhood is a more spherical heart measured by lower values on left ventricular sphericity index (LVSI) (5).…”

Comparison of Two Different Ultrasound Systems for the Evaluation of Tissue Doppler Velocities in Fetuses

“…This concept is particularly relevant when applying these measurements to clinical practice in the assessment of fetal cardiac function for different pathologies [10,16,17]. …”

“…This technique has also been shown to be feasible and reproducible in fetuses [3,4], and reference values for TDI annular peak velocities and ratios have been published [5,6,7,8]. Recent studies have also shown that in fetuses, TDI could be a more sensitive tool than the currently applied methods to detect fetal cardiac dysfunction, and the technique has been applied to various fetal pathologies, such as intrauterine growth restriction, hydrops or twin-to-twin transfusion syndrome [3,9,10,11]. …”