Midgestation cardiovascular phenotype in women who develop gestational diabetes and hypertensive disorders of pregnancy: comparative study.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) and/or hypertensive disorders of pregnancy (HDP) are at increased long-term cardiovascular risk. Mild cardiac functional alterations have been detected in women with GDM or HDP in midgestation, prior to clinical onset of the disease, but these functional alterations have not been found to be useful as screening tools. In contrast, increased impedance to peripheral blood flow, measured by echocardiography or ophthalmic artery Doppler, has been shown to provide incremental value to maternal characteristics for the prediction of pre-eclampsia. However, it is unknown whether similar changes can be detected in women at risk of GDM. In this study, we performed detailed cardiovascular phenotyping in a large, unselected population of women in midgestation to identify similarities and differences in cardiovascular adaptation in women who are at risk of GDM and/or HDP. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries, echocardiography for assessment of maternal cardiovascular function and measurement of uterine artery pulsatility index and serum placental growth factor (PlGF) for assessment of placental perfusion and function. The measured indices were converted to either multiples of the median (MoM) values or deviation from the median (delta) after adjusting for maternal characteristics and elements of medical history. Biomarker delta or MoM values in the GDM and HDP groups were compared with those in the unaffected group using 95% CI and t-tests. RESULTS: The study population of 5214 pregnancies contained 4429 (84.9%) that were unaffected by GDM or HDP, 509 (9.8%) complicated by GDM without HDP, 41 (0.8%) with GDM and HDP, and 235 (4.5%) with HDP without GDM. In HDP cases, with or without GDM, there was evidence of impaired placentation, with a decrease in PlGF, and increased impedance to flow in the peripheral circulation, suggested by an increase in ophthalmic artery peak systolic velocity (PSV) ratio, peripheral vascular resistance assessed on echocardiography and mean arterial pressure. In the GDM group without HDP, there was no evidence of altered placental perfusion or function and ophthalmic artery PSV ratio was not significantly different from that in the unaffected group; peripheral vascular resistance and mean arterial pressure were increased but to a lesser degree than in the HDP group. In the HDP group, there was an increase in global longitudinal systolic strain and slight increase in isovolumic relaxation time, while in the GDM group, there was an increase in mitral valve E/e', myocardial performance index and global longitudinal systolic strain. CONCLUSIONS: In midgestation, women who subsequently develop HDP or GDM have a mild subclinical reduction in left ventricular function. In HDP cases, with or without GDM, there is evidence of impaired placentation and all biomarkers of impedance to peripheral blood flow are consistently increased. In contrast, in the GDM group without HDP, biomarkers of placental function are normal and those of impedance to peripheral blood flow are either marginally increased or not significantly different from those in normal pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal cardiac function at 19-23 weeks' gestation in prediction of gestational diabetes mellitus.

OBJECTIVES: To examine differences in maternal cardiovascular indices at 19-23 weeks' gestation between pregnancies that develop gestational diabetes mellitus (GDM) and those without GDM, and to determine whether such cardiovascular changes are the consequence of maternal demographic characteristics and medical history or GDM per se. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, and maternal echocardiography for assessment of E/A ratio, E/e' ratio, myocardial performance index, global longitudinal systolic strain, left ventricular ejection fraction, peripheral vascular resistance, left ventricular cardiac output and left ventricular mass indexed for body surface area. The measurements of the maternal cardiac indices were standardized to remove the effects of maternal characteristics and elements from the medical history, and the adjusted values in the GDM group were compared to those in the non-GDM group. Likelihood ratios were derived for those indices that were altered significantly in GDM, and these were used to modify the prior risk derived from maternal demographic characteristics and medical history. The area under the receiver-operating-characteristics curve and the detection rate of GDM, at 10%, 20% and 40% false-positive rates, in screening by a combination of maternal factors with cardiovascular indices were determined. RESULTS: The study population of 2853 pregnancies contained 199 (7.0%) that developed GDM. In pregnancies that developed GDM, there were significant differences from the non-GDM group in E/A ratio, E/e' ratio, myocardial performance index and global longitudinal systolic strain. After adjustment for maternal demographic characteristics and factors from the medical history known to affect cardiac indices, the only cardiovascular indices that were significantly different between the GDM and non-GDM groups were peripheral vascular resistance and myocardial performance index, both of which were marginally increased in the GDM group. The performance of screening for GDM by maternal demographic characteristics and medical history was not improved by the addition of cardiovascular indices. CONCLUSIONS: Women with GDM have subtle functional and hemodynamic cardiac changes prior to the development of GDM. These cardiac changes are mostly related to the adverse risk-factor profile of these women. Maternal cardiac assessment at 20 weeks does not offer additional predictive information for GDM development in pregnancy to that calculated based on demographic characteristics and medical history. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Cardiac function in gestational diabetes mellitus: A longitudinal study from fetal life to infancy.

OBJECTIVE: To determine whether cardiac functional and structural changes in fetuses of mothers with gestational diabetes mellitus (GDM) persist in the offspring beyond the neonatal period. DESIGN: Longitudinal study. SETTING: Fetal Medicine Unit in a UK teaching hospital. METHODS: 73 women with GDM and 73 women with uncomplicated pregnancy were recruited and fetal cardiac scans were performed at 35-36 weeks' gestation. Repeat echocardiogram was performed in their offspring during infancy. MAIN OUTCOME MEASURES: Fetal and infant cardiac functional and structural changes. RESULTS: Fetuses of mothers with GDM, compared with controls, had more globular right ventricles (sphericity index 0.7, interquartile range [IQR] 0.6/0.7 versus 0.6, IQR 0.5/0.6, P < 0.001) and reduced right global longitudinal systolic strain (-16.4, IQR -18.9/-15.3 versus -18.5, IQR -20.6/-16.8, P = 0.001) and left global longitudinal systolic strain (-20.1, IQR -22.5/-16.9 versus -21.3, IQR -23.5/-19.5), P = 0.021). In the GDM group, compared with controls, in infancy there was higher left ventricular E/e' (8.7, IQR 7.3/9.7 versus 7.9 IQR, 6.8/8.9 P = 0.011) and lower left ventricular global longitudinal systolic strain (-21.0, IQR -22.5/-19.4 versus -22.3, IQR -23.5/-20.7, P = 0.001) and tricuspid annular plane systolic excursion (13.8, IQR 12.7/16.1 versus 15.2, IQR 13.8/16.8, P = 0.003). These differences remained following multivariable analysis. CONCLUSION: Gestational diabetes mellitus is associated with alterations in fetal cardiac function and structure compared with controls and persistent cardiac changes in infancy. TWEETABLE ABSTRACT: Gestational diabetes mellitus, even when well controlled, is associated with fetal cardiac changes and these persist in infancy.

Influence of birth weight on fetal cardiac indices at 35-37 weeks' gestation.

OBJECTIVE: Echocardiographic studies have reported that fetuses with low birth weight, compared to those with normal birth weight, have globular hearts and reduced cardiac function. Dichotomizing continuous variables, such as birth weight, may be helpful in describing pathology in small studies but can prevent us from identifying physiological responses in relation to change in size. The aim of this study was to explore associations between fetal cardiac morphology and function and birth weight, as a continuous variable, as well as uterine artery (UtA) pulsatility index (PI), as an indirect measure of placental perfusion, and the cerebroplacental ratio (CPR), as an indirect measure of fetal oxygenation. METHODS: This was a prospective study of 1498 women with singleton pregnancy undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Pregnancies complicated by pregestational or gestational diabetes mellitus, chronic hypertension, pregnancy-induced hypertension or pre-eclampsia were excluded from the analysis. Conventional and more advanced echocardiographic modalities, such as speckle tracking, 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 indices. In addition, the PI of the UtA, umbilical artery (UA) and fetal middle cerebral artery (MCA) was determined and the CPR was calculated by dividing MCA-PI by UA-PI. Multiple linear regression models were used to assess determinants of fetal echocardiographic parameters. RESULTS: The study population included 146 (9.7%) small-for-gestational-age (SGA) fetuses with birth weight < 10th percentile and 68 (4.5%) with fetal growth restriction (FGR). In the SGA and FGR groups, compared to the non-SGA and non-FGR fetuses, respectively, there was a more globular right ventricle and reduced left and right ventricular systolic function, and, from the left ventricular diastolic functional indices, the E/A ratio was increased. There was a linear association of right ventricular sphericity index, indices of left and right ventricular systolic function and E/A ratio with birth-weight Z-score. There were no significant associations between cardiac morphological and functional indices and UtA-PI Z-score or CPR Z-score. CONCLUSIONS: This screening study at 35-37 weeks' gestation has demonstrated that birth weight is a determinant of fetal cardiac morphology and function but UtA-PI and CPR, as indirect measures of placental perfusion and fetal oxygenation, are not. This suggests that the differences in fetal cardiac indices between small and appropriately grown fetuses may be part of a normal physiological response to change in fetal size rather than part of a pathological adaptation to abnormal placental perfusion and fetal oxygenation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.