Impact of hypertensive disorders of pregnancy on offspring cardiovascular function. Study from fetal life to early childhood.

OBJECTIVE: Epidemiological studies suggest that children following in utero exposure to hypertensive disorders of pregnancy (HDP) may be at increased long term cardiovascular risk. However, data in early childhood are lacking. We aimed to investigate the independent influence of HDP on childhood heart after accounting for differences in childhood risk factor profile. METHODS: We performed detailed cardiovascular assessment in fetuses at mid-gestation and at a median of 2.3 years (IQR: 2.1, 2.4 years) postnatally in 71 cases where the mothers had HDP and 304 who did not have HDP. RESULTS: There were no differences in demographic characteristics between groups but in the HDP group delivery was earlier and birthweight was lower. In fetal life, there were no significant differences in cardiac function or structure between the HDP and non-HDP groups. In early childhood, in the HDP compared to the non-HDP group, there was greater relative wall thickness (0.7 SD 0.3 vs. 0.6 SD 0.3 mm, p=0.047) and increased left ventricular mass (80.9 SD 20.4 vs. 75.7 SD 16.5, p=0.024); however, these differences were abolished following multivariable analysis. Longitudinal analysis revealed that in HDP, compared to the non-HDP group, there was no difference in the change of cardiac functional indices from fetal life to early childhood. CONCLUSION: Epidemiological studies suggest that HDP have an adverse impact on offspring cardiovascular health, but such an effect is not apparent in fetal life or in early childhood. This article is protected by copyright. All rights reserved.

Long-term cardiovascular assessment of women who had a pregnancy complicated by a hypertensive disorder.

BACKGROUND: Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing hypertension and cardiovascular disease later in life. However, from studies so far, it is difficult to define whether this association reflects preexisting maternal cardiovascular risk or merely reflect a potentially causal relationship between HDP and later cardiovascular risk. OBJECTIVES: We performed detailed cardiovascular assessment in women at mid-gestation, prior to development of a HDP and at 2 years post-partum aiming to identify cardiovascular changes prior to development of HDP and to assess persistent cardiovascular alterations long after the HDP event. METHODS: This was a prospective observational study in which we performed detailed cardiovascular assessment at mid-gestation and at median of 2.3 years (interquartile range 2.1 to 2.4 years) post-partum. We examined 112 women who developed a HDP and 451 women whose pregnancy was not complicated by hypertension. We used conventional and more advanced echocardiographic techniques, i.e. speckle tracking, to accurately determine left ventricular systolic and diastolic function. We used M-mode measurements to determine left ventricular remodeling and estimate left ventricular mass. Maternal vascular status was assessed using ophthalmic artery Doppler and by calculating peak systolic velocity (PSV) ratio, as a marker of peripheral vascular resistance. RESULTS: At mid-gestation, women who subsequently developed HDP had increased ophthalmic artery PSV ratio. These women also had mild cardiac functional and morphological alterations which were mostly accounted for by maternal cardiovascular risk factors. At 2 years post-partum, women who experienced HDP, compared to those who did not, had cardiovascular abnormalities with reduction in left ventricular systolic and diastolic function which remained after multivariable analysis. Longitudinal analysis demonstrated that the evolution of cardiovascular changes in the HDP and non-HDP groups was similar. CONCLUSION: Mild cardiac functional and morphological alterations precede the development of HDP and such changes persist for at least 2 years postpartum. The cardiac changes are likely to be the consequence of preexisting maternal cardiovascular risk factors rather than an adverse consequence of HDP. This article is protected by copyright. All rights reserved.

Fetal cardiac function at midgestation and conception by in-vitro fertilization.

OBJECTIVE: To assess differences in cardiac morphology and function at midgestation in fetuses conceived by in-vitro fertilization (IVF), using fresh or frozen embryo transfer, compared with those conceived naturally. METHODS: This was a prospective study of 5801 women with a singleton pregnancy attending for a routine ultrasound examination at 19 + 0 to 23 + 6 weeks' gestation, including 343 that conceived by IVF. Conventional and more advanced echocardiographic modalities, including speckle-tracking analysis, were used to assess fetal cardiac function in the right and left ventricles. The morphology of the fetal heart was assessed by calculating the right and left sphericity index. Placental perfusion and function were assessed by measurement of uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF), respectively. RESULTS: Fetuses that were conceived by IVF, compared with those conceived spontaneously, had significantly lower right and left ventricular sphericity index, higher left ventricular global longitudinal strain and lower left ventricular ejection fraction. There were no significant differences in any of the cardiac indices within the IVF group between the fresh and frozen embryo transfers. In the IVF group, compared with spontaneously conceived pregnancies, UtA-PI was lower and PlGF was higher, suggesting better placental perfusion and function. CONCLUSIONS: Our study demonstrates that, in IVF pregnancies, compared with those conceived spontaneously, there is evidence of fetal cardiac remodeling at midgestation, which is not related to the use of fresh or frozen embryo transfer. In the IVF group, compared with naturally conceived pregnancies, fetal heart was globular and left ventricular systolic function was mildly reduced. Whether these cardiac changes are accentuated later in pregnancy and remain in the postnatal period remains to be established. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Competing-risks model for prediction of small-for-gestational-age neonate at 36 weeks' gestation.

OBJECTIVES: To develop further a competing-risks model for the prediction of a small-for-gestational-age (SGA) neonate by including sonographically estimated fetal weight (EFW) and biomarkers of impaired placentation at 36 weeks' gestation, and to compare the performance of the new model with that of the traditional EFW < 10th percentile cut-off. METHODS: This was a prospective observational study in 29 035 women with a singleton pregnancy undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. A competing-risks model for the prediction of a SGA neonate was used. The parameters included in the prior-history model were provided in previous studies. An interaction continuous model was used for the EFW likelihood. A folded plane regression model was fitted to describe likelihoods of biomarkers of impaired placentation. Stratification plans were also developed. The new model was evaluated and compared with EFW percentile cut-offs. RESULTS: The performance of the model was better for predicting SGA neonates delivered closer to the point of assessment. The prediction provided by maternal factors alone was improved significantly by the addition of EFW, uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF) but not by mean arterial pressure or soluble fms-like tyrosine kinase-1. At a 10% false-positive rate, maternal factors and EFW predicted 77.6% and 65.8% of SGA neonates < 10th percentile delivered before 38 and 42 weeks, respectively. The respective figures for SGA < 3rd percentile were 85.5% and 74.2%. Addition of UtA-PI and PlGF resulted in marginal improvement in prediction of SGA < 3rd percentile requiring imminent delivery. A competing-risks approach that combines maternal factors and EFW performed better when compared with fixed EFW percentile cut-offs at predicting a SGA neonate, especially with increasing time interval between assessment and delivery. The new model was well-calibrated. CONCLUSIONS: A competing-risks model provides effective risk stratification for a SGA neonate at 35 + 0 to 36 + 6 weeks' gestation and is superior to EFW percentile cut-offs. The use of biomarkers of impaired placentation in addition to maternal factors and fetal biometry results in small improvement of the predictive performance for a neonate with severe SGA. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.