B. Valenzuela-Alcaraz

Assisted Reproductive Technologies Are Associated With Cardiovascular Remodeling In Utero That Persists Postnatally

Background— Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies. Methods and Results— This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies. ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.5 mm [interquartile range, 6.1–7.1 mm]; tricuspid ring displacement in ART: 5.5 mm [interquartile range, 5.1–6.1]; P<0.001), impaired relaxation, and dilated atria (atrial area in controls, 1.46 cm2 [interquartile range, 1.2–1.5 cm2]; atrial area in ART, 1.6 cm2 [interquartile range, 1.3–1.8 cm2]; P<0.001). Additionally, ART infants showed persistence of most cardiac changes and a significant increase in blood pressure and aortic intima-media thickness (systolic blood pressure in controls, 74 mm Hg [interquartile range, 67–83 mm Hg]; systolic blood pressure in ART, 83 mm Hg [interquartile range, 75–94 mm Hg]; P<0.001; aortic intima-media thickness in controls, 0.52 mm [interquartile range, 0.45–0.56 mm]; aortic intima-media thickness in ART, 0.64 mm [interquartile range, 0.62–0.67]; P<0.001). We could not demonstrate that our findings were directly caused by ART because of their association with various confounding factors, including intrauterine growth restriction or factors related to the cause of infertility. Conclusions— Children conceived by ART manifest cardiac and vascular remodeling that is present in fetal life and persists in postnatal life, suggesting opportunities for early detection and potential intervention. The underlying mechanisms and the effect of potential confounders such as growth restriction or prematurity remain to be elucidated.

Value of annular M-mode displacement vs tissue Doppler velocities to assess cardiac function in intrauterine growth restriction

To compare the ability of two different methods for longitudinal annular motion measurement, M‐mode and tissue Doppler imaging (TDI), to demonstrate cardiac dysfunction in intrauterine‐growth‐restricted (IUGR) fetuses.

Patterns of maternal vascular remodeling and responsiveness in early- versus late-onset preeclampsia.

OBJECTIVE We sought to assess vascular structure and function in early- and late-onset preeclampsia (PE) at the time of diagnosis. STUDY DESIGN We evaluated 100 PE cases subdivided into 50 early- and 50 late-onset cases according to gestational age at onset (34 weeks), and 100 controls paired by maternal age and gestational age at scan with cases. Carotid intima-media thickness (IMT), distensibility, and circumferential wall stress together with inferior vena cava (IVC) collapsibility were assessed by ultrasound. RESULTS Early PE was characterized by increased carotid IMT diameters, and arterial stiffness with no significant changes in IVC parameters as compared to normotensive pregnancies. Late PE was characterized by significantly increased carotid IMT and lumen diameters as compared to controls while arterial stiffness, as expressed by distensibility, did not provide pronounced changes. A significant decrease of IVC collapsibility index was also observed in late PE as compared to controls. CONCLUSION The current data suggest that distinct vascular adaptations in early and late PE could reflect different pathophysiologic mechanisms. Future studies are warranted to further assess the complex etiologies and clinical expressions of the 2 entities.

Fetal cardiovascular remodeling persists at 6 months in infants with intrauterine growth restriction

Intrauterine growth restriction is associated with increased cardiovascular risk later in life but the link between fetal disease and postnatal risk is not well‐documented. We evaluated longitudinally the association between cardiovascular remodeling in small‐for‐gestational‐age (SGA) fetuses and at 6 months of age.

Aortic and carotid intima–media thickness in term small‐for‐gestational‐age newborns and relationship with prenatal signs of severity

To assess carotid and aortic intima–media thickness (IMT) in term small‐for‐gestational‐age (SGA) newborns with and without prenatal signs of severity.

Influence of equipment and settings on myocardial performance index repeatability and definition of settings to achieve optimal reproducibility

To compare left myocardial performance index (MPI) values and reproducibility using different settings and ultrasound equipment in order to standardize optimal machine settings.

Patient-specific estimates of vascular and placental properties in growth-restricted fetuses based on a model of the fetal circulation

INTRODUCTION Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood-flow redistribution in order to maintain perfusion to the brain. However, some hemodynamic parameters that might be more directly related to staging of the disease cannot be measured non-invasively in clinical practice. For this, we developed a patient-specific model of the fetal circulation to estimate vascular properties of each individual. METHODS A lumped model of the fetal circulation was developed and personalized using measured echographic data from 37 normal and IUGR fetuses to automatically estimate model-based parameters. A multivariate regression analysis was performed to evaluate the association between the Doppler pulsatility indices (PI) and the model-based parameters. The correlation between model-based parameters and the placental lesions was analyzed in a set of 13 IUGR placentas. A logistic regression analysis was done to assess the added value of the model-based parameters relative to Doppler indices, for the detection of fetuses with adverse perinatal outcome. RESULTS The estimated model-based placental and brain resistances were respectively increased and reduced in IUGR fetuses while placental compliance was increased in IUGR fetus. Umbilical and middle cerebral arteries PIs were most associated with both placental resistance and compliance, while uterine artery PI was more associated with the placental compliance. The logistic regression analysis showed that the model added significant information to the traditional analysis of Doppler waveforms for predicting adverse outcome in IUGR. DISCUSSION The proposed patient-specific computational model seems to be a good approach to assess hemodynamic parameters than cannot be measured clinically.

Differential effect of assisted reproductive technology and small‐for‐gestational age on fetal cardiac remodeling

Fetuses conceived by assisted reproductive technology (ART) and those that are small‐for‐gestational age (SGA) show cardiovascular remodeling in utero; however, these two conditions are often associated. We aimed to evaluate the differential effect of ART and SGA on fetal cardiac remodeling.

Zidovudine treatment in HIV-infected pregnant women is associated with fetal cardiac remodelling.

Objective:To evaluate the cardiac structure and function of the fetuses of pregnant women with HIV infection on combined antiretroviral treatment (cART) and the HIV-related and nonrelated determinants of abnormal findings. Design:A prospective cohort study including 42-noninfected fetuses from HIV pregnant women on cART and 84 fetuses from non-HIV-infected women. Methods:Fetal echocardiography was performed at 26–32 weeks of pregnancy to assess cardiac structure and function. The impact of maternal and perinatal factors on fetal cardiac remodelling was evaluated by multivariate regression analysis. Results:Fetuses from HIV pregnant women on cART presented larger hearts and pericardial effusion together with thicker myocardial septal walls (mean 3.56 mm (SD 0.88) vs non-HIV mean 2.75 mm (SD 0.77); P = 0.002) and smaller left ventricular cavities (10.81 mm (SD 2.28) vs 12.3 mm (SD 2.54); P = 0.033). Fetuses from HIV women also presented signs of systolic (mitral systolic annular peak velocity 5.85 cm/s (SD 0.77) vs non-HIV 6.25 cm/s (SD 0.97); P = 0.007) and diastolic (isovolumic relaxation time 52 ms (SD 8.91) vs non-HIV 45 ms (SD 7.98); P < 0.001) dysfunction. In the multivariate analysis, maternal treatment with zidovudine was the only factor significantly associated with fetal cardiac changes (P = 0.014). Conclusion:Fetuses from HIV-infected mothers on cART have cardiac remodelling and dysfunction, which might explain the cardiovascular changes described in childhood. Fetal cardiac remodelling was essentially associated with maternal treatment with zidovudine which challenges its use during pregnancy.

Differential effect of mode of conception and infertility treatment on fetal growth and prematurity

Abstract Objectives To examine perinatal outcomes in pregnancies conceived by different methods: fertile women with spontaneous pregnancies, infertile women who achieved pregnancy without treatment, pregnancies achieved by ovulation induction (OI) and in vitro fertilization or intra-cytoplasmic sperm injection (IVF/ICSI). Methods Retrospective single-center cohort study including 200 fertile and 748 infertile women stratified according to infertility treatment. The outcome measurements were preterm delivery (PTD), small-for-gestational-age (SGA), gestational diabetes, placenta previa or preeclampsia. Results The overall rate of pregnancy complications was significantly increased in all infertility groups regardless of the infertility treatment (adjusted odds ratio (OR): infertile without treatment 2.3 versus OI 2.2 versus IVF/ICSI 3.4). While PTD was mainly associated to IVF/ICSI (adjusted OR: infertile without treatment 1.3 versus OI 1.6 versus IVF/ICSI 3.3), SGA was significantly associated to both OI and IVF/ICSI (adjusted OR: infertile without treatment 1.9 versus OI 2.7 versus IVF/ICSI 2.6). All these associations remained statistically significant after adjusting by maternal age and twin pregnancy. Conclusions This study confirms the higher prevalence of pregnancy complications in infertile women irrespectively of receiving infertility treatment or not, and further describes a preferential association of prematurity with IVF/ICSI, and SGA with treated infertility (OI and IVF/ICSI).