Gestational hypertensive disorders and blood pressure and childhood cardiac outcomes: A prospective cohort study.

OBJECTIVE: To assess whether gestational hypertensive disorders and higher gestational blood pressure were associated with subclinical changes in offspring cardiac structure and function during childhood. DESIGN: Population-based prospective cohort study. SETTING: Rotterdam, the Netherlands. POPULATION: A cohort of 2502 mother-offspring pairs. METHODS: Maternal blood pressure was measured in early, mid and late pregnancy, and information on gestational disorders were obtained from medical records. Offspring cardiac measurements were assessed by Cardiovascular Magnetic Resonance at 10 years. MAIN OUTCOME MEASURES: Left and right ventricular end-diastolic volumes (LVEDVs and RVEDVs), and ejection fractions, and left ventricular mass (LVM). RESULTS: Offspring exposed to pre-eclampsia had a lower right ventricular ejection fraction (RVEF) (difference, -0.31 SDS; 95% CI -0.60, -0.02); however, no associations with other cardiac outcomes were present. Higher maternal diastolic blood pressure (DBP) in early and late pregnancy was associated with lower LVEDVs and RVEDVs (p < 0.05), with the strongest effect in early pregnancy. No associations of systolic blood pressure (SBP) with offspring outcomes were present. These associations persisted after additional adjustment for birth and child factors. Paternal SBP and DBP were not associated with offspring cardiac outcomes. CONCLUSIONS: No consistent associations of gestational hypertensive disorder status with childhood cardiac outcomes were present. Higher maternal DBP throughout pregnancy was associated with lower childhood LVEDVs and RVEDVs. Stronger maternal-offspring rather than paternal-offspring associations were present, which may suggest that suboptimal maternal gestational haemodynamic adaptations affects offspring cardiac structure through direct intrauterine effects. Further studies are needed to replicate these findings and examine the underlying mechanisms.

Associations of Fetal and Infant Growth Patterns With Early Markers of Arterial Health in School-Aged Children.

Importance: Fetal life and infancy might be critical periods for predisposing individuals to develop cardiovascular disease in adulthood. Objective: To examine the associations of fetal and infant weight growth patterns with early markers of arterial health. Design, Setting, and Participants: This population-based prospective cohort study was conducted from early fetal life onward among 4484 offspring of women in Rotterdam, the Netherlands, delivering between April 1, 2002, and January 31, 2006. Statistical analysis was performed between January 1 and August 31, 2021. Exposures: Estimated fetal weight was measured in the second and third trimester. Data on weight and gestational age at birth were collected from midwives. Infant weight was measured at 6, 12, and 24 months. Main Outcomes and Measures: The common carotid intima-media thickness (cIMT) and carotid distensibility were measured as early markers of arterial health. Results: Follow-up measurements were available for 4484 children (2260 girls [50.4%]; median age, 9.7 years [95% range, 9.3-10.5 years]; and 2578 [57.5%] of Dutch ethnicity). Gestational age at birth was not associated with markers of arterial health. A 500-g-higher birth weight was associated with increased cIMT (standard deviation score [SDS], 0.08 mm [95% CI, 0.05-0.10 mm]) and a lower carotid distensibility (SDS, -0.05 × 10-3 kPa-1; [95% CI, -0.08 to -0.03 × 10-3 kPa-1]). Compared with children with a birth weight of 2500 to 4500 g, those weighing more than 4500 g had the lowest carotid distensibility (difference in SDS, -0.22 × 10-3 kPa-1 [95% CI, -0.42 to -0.02 × 10-3 kPa-1]). Conditional regression analyses showed that higher third-trimester fetal weight and birth weight were associated with increased cIMT (difference in SDS: third-trimester fetal weight, 0.08 mm [95% CI, 0.04-0.12 mm]; birth weight, 0.05 mm [95% CI, 0.01-0.09 mm]) and that higher weight at 6, 12, and 24 months was associated with increased cIMT (difference in SDS: 6 months, 0.05 mm [95% CI, 0.01-0.10 mm]; 12 months, 0.06 mm [95% CI, 0.02-0.10 mm]; and 24 months, 0.07 mm [95% CI, 0.03-0.11 mm]) and lower carotid distensibility (difference in SDS: 6 months, -0.04 × 10-3 kPa-1 [95% CI, -0.09 to -0.001 × 10-3 kPa-1]; 12 months, -0.05 × 10-3 kPa-1 [95% CI, -0.09 to -0.01 × 10-3 kPa-1]; and 24 months, -0.10 × 10-3 kPa-1 [95% CI, -0.15 to -0.06 × 10-3 kPa-1]). Compared with children with normal fetal and infant growth, children with normal fetal growth that was followed by accelerated infant growth had the highest cIMT (SDS, 0.19 mm [95% CI, 0.07-0.31 mm]) and lowest carotid distensibility (SDS, -0.16 × 10-3 kPa-1 [95% CI, -0.28 to -0.03 × 10-3 kPa-1]). The observed associations were largely explained by childhood body mass index. Conclusions and Relevance: In this cohort study of 4484 children aged approximately 10 years, higher fetal and infant weight growth patterns were associated with early markers of impaired arterial health. Childhood body mass index seemed to be involved in the underlying pathways of the observed associations.

Childhood Blood Pressure, Carotid Intima Media Thickness, and Distensibility After In Utero Exposure to Gestational Hypertensive Disorders.

Background Offspring exposed to gestational hypertensive disorders have higher blood pressure and increased risk of stroke in later life. Gestational hypertensive disorders might influence vascular development in the offspring, predisposing them to a higher blood pressure and stroke in later life. Methods and Results In a population-based cohort among 4777 mother-offspring pairs, we examined whether gestational hypertension, preeclampsia, and higher gestational blood pressure across the full blood pressure spectrum were associated with offspring blood pressure, carotid intima media thickness, and distensibility at the age of 10 years. Offspring exposed to gestational hypertension, but not preeclampsia, had higher systolic and diastolic blood pressure (0.17 [95% CI, 0.02-0.31] and 0.23 [95% CI, 0.08-0.38] increases in standard deviation scores, respectively), whereas no associations with intima media thickness and distensibility were present. Higher maternal systolic and diastolic blood pressure in early, mid, and late pregnancy were associated with higher offspring systolic and diastolic blood pressure and lower distensibility (P values <0.05), but not with intima media thickness. The associations were not explained by maternal, birth, or child factors. Paternal systolic and diastolic blood pressure were also associated with these offspring outcomes (P values <0.05), with a comparable strength as maternal-offspring associations. Conclusions Gestational hypertension and higher gestational blood pressure, even below the diagnostic threshold for gestational hypertensive disorders, are associated with higher offspring blood pressure and lower carotid distensibility. No associations were found for preeclampsia with offspring vascular outcomes. As maternal-offspring and paternal-offspring associations were comparable, these associations are more likely driven by genetic predisposition and shared lifestyle rather than by a direct intrauterine effect.

Innovative approach for first-trimester fetal organ volume measurements using a Virtual Reality system: The Generation R Next Study.

INTRODUCTION: To investigate the reproducibility of first-trimester fetal organ volume measurements using three-dimensional (3D) ultrasound and a Virtual Reality system. METHODS: Within a population-based prospective cohort study, 3D ultrasound datasets of 25 first-trimester fetuses were collected by three sonographers. We used the V-scope application to perform Virtual Reality volume assessments of the fetal heart, lungs, and kidneys. All measurements were performed by two independent researchers. RESULTS: Intraobserver analyses for volume measurements of the fetal heart, lungs, and kidneys showed intraclass correlation coefficients ≥0.86, mean differences ≤8.3%, and coefficients of variation ≤22.8%. Interobserver analyses showed sufficient agreement for right lung volume measurements, but consistent measurement differences between observers for left lung, heart, and kidney volume measurements (p-values <0.05). CONCLUSION: We observed sufficient intraobserver reproducibility, but overall suboptimal interobserver reproducibility for first-trimester fetal heart, lung, and kidney volume measurements using an innovative Virtual Reality approach. In the current stage, these measurements might be promising for the use in research settings. The reproducibility of the measurements might be further improved by novel post-processing algorithms.

Maternal Iron Status in Early Pregnancy and Blood Pressure Throughout Pregnancy, Placental Hemodynamics, and the Risk of Gestational Hypertensive Disorders.

BACKGROUND: In nonpregnant populations, higher serum ferritin, which reflects high iron stores, is associated with an increased risk of hypertension. We hypothesized that a dysregulated maternal iron status in early pregnancy may lead to impaired gestational hemodynamic adaptations, leading to an increased risk of gestational hypertensive disorders. OBJECTIVES: We examined the associations of maternal iron status with maternal blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders. METHODS: In a population-based prospective cohort study among 5983 pregnant women, we measured maternal serum ferritin, transferrin saturation, serum iron, and transferrin concentrations at a median of 13.2 weeks gestation (95% range, 9.6-17.6). Maternal blood pressure was measured in early pregnancy, mid pregnancy, and late pregnancy, and placental hemodynamic parameters in mid pregnancy and late pregnancy were measured by ultrasound. Information on gestational hypertensive disorders was collected from medical records. We examined the associations of maternal early pregnancy iron status with maternal systolic and diastolic blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders using linear and logistic regression models. RESULTS: Higher maternal early pregnancy serum ferritin concentrations were associated with higher systolic and diastolic blood pressure throughout pregnancy in the basic models (P values < 0.05). After adjustment for maternal inflammation, sociodemographic and lifestyle factors, higher maternal early pregnancy serum ferritin concentrations were only associated with a higher early pregnancy diastolic blood pressure [0.27 (95% CI, 0.03-0.51) mmHg per SD score increase in serum ferritin] and with a higher mid pregnancy umbilical artery pulsatility index (P < 0.05). No associations with the risk of gestational hypertensive disorders were present. CONCLUSIONS: No consistent associations were present of maternal iron status in early pregnancy with gestational hemodynamic adaptations or the risks of gestational hypertensive disorders. Further studies are needed to examine the potential role of iron metabolism in the development of gestational hypertensive disorders within higher-risk populations.

Associations of dietary glycemic index and load during pregnancy with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders.

PURPOSE: The aim of this study was to examine the associations of dietary glycemic index and load with gestational blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. METHODS: In a population-based cohort among 3378 pregnant Dutch women, dietary glycemic index and load were assessed from food frequency questionnaires at median 13.4 (95% range 9.9-22.9) weeks gestation. Blood pressure was measured in early-, mid- and late-pregnancy. Placental hemodynamic parameters were measured in mid- and late-pregnancy by ultrasound. Data on gestational hypertensive disorders was acquired from medical records. RESULTS: Mean dietary glycemic index (SD) was 58 (3) and mean dietary glycemic load (SD) was 155 (47). Dietary glycemic index was not associated with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. Higher dietary glycemic load SDS was associated with a higher diastolic blood pressure in early-pregnancy, remaining after adjustment for socio-demographic and lifestyle factors ((0.98 (95% CI 0.35-1.61) mmHg per SDS increase in glycemic load). No other associations of glycemic load with blood pressure or placental hemodynamic parameters and the risk of gestational hypertensive disorders were present. No significant associations of dietary glycemic index and load quartiles with longitudinal blood pressure patterns from early to late-pregnancy were present. CONCLUSION: Within this low-risk pregnant population, we did not find consistent associations of dietary glycemic index and load with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. Further studies need to assess whether the effects on gestational hemodynamic adaptations are more pronounced among high-risk women with an impaired glucose metabolism.

First trimester fetal proportion volumetric measurements using a Virtual Reality approach.

OBJECTIVE: To establish feasibility and reproducibility of fetal proportion volumetric measurements, using three-dimensional (3D) ultrasound and a Virtual Reality (VR) system. METHODS: Within a population-based prospective birth cohort, 3D ultrasound datasets of 50 fetuses in the late first trimester were collected by three ultrasonographers in a single research center. V-scope software was used for volumetric measurements of total fetus, extremities, head-trunk, head, trunk, thorax, and abdomen. All measurements were performed independently by two researchers. Intraobserver and interobserver reproducibility were analyzed using Bland and Altman methods. RESULTS: Intraobserver and interobserver analyses of volumetric measurements of total fetus, head-trunk, head, trunk, thorax and abdomen showed intraclass correlation coefficients above 0.979, coefficients of variation below 7.51% and mean difference below 3.44%. The interobserver limits of agreement were within the ±10% range for volumetric measurements of total fetus, head-trunk, head and trunk. The interobserver limits of agreement for extremities, thorax and abdomen were -26.09% to 4.77%, -14.14% to 10.00% and -14.47% to 8.83%, respectively. CONCLUSION: First trimester fetal proportion volumetric measurements using 3D ultrasound and VR are feasible and reproducible, except volumetric measurements of the fetal extremities. These novel volumetric measurements may be used in future research to enable detailed studies on first trimester fetal development and growth.

Associations of DASH Diet in Pregnancy With Blood Pressure Patterns, Placental Hemodynamics, and Gestational Hypertensive Disorders.

Background The Dietary Approaches to Stop Hypertension (DASH) diet improves blood pressure in nonpregnant populations. We hypothesized that adherence to the DASH diet during pregnancy improves hemodynamic adaptations, leading to a lower risk of gestational hypertensive disorders. Methods and Results We examined whether the DASH diet score was associated with blood pressure, placental hemodynamics, and gestational hypertensive disorders in a population-based cohort study among 3414 Dutch women. We assessed DASH score using food-frequency questionnaires. We measured blood pressure in early-, mid-, and late pregnancy (medians, 95% range: 12.9 [9.8-17.9], 20.4 [16.6-23.2], 30.2 [28.6-32.6] weeks gestation, respectively), and placental hemodynamics in mid- and late pregnancy (medians, 95% range: 20.5 [18.7-23.1], 30.4 [28.5-32.8] weeks gestation, respectively). Information on gestational hypertensive disorders was obtained from medical records. Lower DASH score quartiles were associated with a higher mid pregnancy diastolic blood pressure, compared with the highest quartile (P<0.05). No associations were present for early- and late pregnancy diastolic blood pressure and systolic blood pressure throughout pregnancy. Compared with the highest DASH score quartile, the lower DASH score quartiles were associated with a higher mid- and late pregnancy umbilical artery pulsatility index (P≤0.05) but not with uterine artery resistance index. No associations with gestational hypertensive disorders were present. Conclusions A higher DASH diet score is associated with lower mid pregnancy diastolic blood pressure and mid- and late pregnancy fetoplacental vascular function but not with uteroplacental vascular function or gestational hypertensive disorders within a low-risk population. Further studies need to assess whether the effects of the DASH diet on gestational hemodynamic adaptations are more pronounced among higher-risk populations.