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

Periconceptional maternal intake of ultra-processed foods, energy and macronutrients the impact on imaging markers of early utero-placental vascular development:The rotterdam

Background &amp; aims: The quantity and quality of maternal nutrition in the periconception period is an important determinant for embryonic and foetal development and subsequent pregnancy course and outcome. The intake of ultra-processed foods (UPF) has increased worldwide and adverse health outcomes have been reported. However, the impact of UPF intake on the placenta, essential for prenatal nourishment, is unknown. Therefore, we aim to investigate associations between the periconceptional maternal intake of UPF, energy and related macronutrients, and first-trimester utero-placental vascular development. Methods: We included 214 ongoing pregnancies in the Virtual Placenta study, a subcohort of the Rotterdam periconception cohort. At enrollment, participants filled out a food frequency questionnaire from which we calculated the average daily energy from UPF, total energy intake and macronutrient intake from UPF. At 7-9-11 weeks of gestation, we performed sequential three-dimensional power Doppler ultrasounds of the first-trimester utero-placental vasculature. Virtual Organ Computer-aided AnaLysis (VOCAL) software, Virtual Reality segmentation and a skeletonization algorithm were applied to measure placental volume (PV), utero-placental vascular volume (uPVV) and generate the utero-placental vascular skeleton (uPVS). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (end-, bifurcation-, crossing- or vessel point) and used to calculate density of vascular branching. Linear mixed models adjusted for confounders were used to investigate associations between maternal intake of UPF, total energy and macronutrients from UPF and PV, uPVV and uPVS characteristics. Results: Energy intake from UPF and total energy intake were not consistently associated with imaging markers of utero-placental vascular development. Higher carbohydrate intake of 10 g/day from UPF was associated with increased uPVS trajectories (end points (β = 0.34, 95%CI = 0.07; 0.61), bifurcation points (β = 0.38, 95%CI = 0.05; 0.70), vessel points (β = 0.957, 95%CI = 0.21; 1.71). No associations were observed with PV. Conclusions: Against our hypothesis, periconceptional maternal intake of UPF and total energy were not convincingly associated with impaired first-trimester utero-placental vascular development. Remarkably, the increased intake of carbohydrates from UPF, which is often considered ‘unhealthy’, is positively associated with first-trimester utero-placental vascular development. Given the complexity of diet, further research should elucidate what underlies these findings to be able to interpret how nutrition may impact utero-placental vascular development in early pregnancy. Clinical trial number: This study is registered at the Dutch Trial Register (NTR6854).</p

Innovative approach for first-trimester fetal organ volume measurements using a Virtual Reality system:The Generation R <i>Next</i> 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

Preconception and Early-Pregnancy Body Mass Index in Women and Men, Time to Pregnancy, and Risk of Miscarriage

Importance: Obesity in women is associated with reduced fertility and an increased risk of miscarriage. These associations might also be present across the full range of body mass index (BMI) categories as well as among men. Objective: To investigate the associations of preconception BMI in both partners with time to pregnancy and miscarriage. Design, Setting, and Participants: This population-based prospective cohort study was conducted in Rotterdam, the Netherlands, between August 9, 2017, and July 1, 2021. A total of 3604 women and their partners were included from the preconception period onward with follow-up until birth. The date of analysis was July 12, 2024. Exposure: Body mass index (calculated as weight in kilograms divided by height in meters squared) measured in preconception or early pregnancy. Main Outcome and Measures: Fecundability, defined as the probability of conceiving within 1 month; subfertility, defined as time to pregnancy or duration of actively pursuing pregnancy of more than 12 months or use of assisted reproductive technology; and miscarriage, defined as pregnancy loss before 22 weeks of gestation. These measures were assessed using questionnaires and via the obstetric caregiver. Results: The study population for time-to-pregnancy analyses consisted of 3033 episodes among women (median age, 31.6 years [IQR, 29.2-34.5 years]; median BMI, 23.5 [IQR, 21.2-26.5]) and 2288 episodes among men (median age, 33.4 years [IQR, 30.5-36.8 years]; median BMI, 24.9 [IQR, 23.0-27.4]). The study population for miscarriage analyses consisted of 2770 pregnancy episodes among women (median age, 31.5 years [IQR, 28.9-34.3 years]; median BMI, 23.5 [IQR, 21.3-26.7]) and 2189 pregnancy episodes among men (median age, 33.5 years [IQR, 30.4-36.8 years]; median BMI, 25.0 [IQR, 23.0-27.5]). Higher BMI in women and men was associated with lower fecundability: for every unit increase in BMI, fecundability decreased (fecundability ratio [FR]: women, 0.98 [95% CI, 0.97-0.99]; men, 0.99 [95% CI, 0.98-1.00]). Women with overweight (FR, 0.88 [95% CI, 0.80-0.98]) and obesity (FR, 0.72 [95% CI, 0.63-0.82]) had lower fecundability compared with women with normal weight. Compared with normal weight in women, underweight (odds ratio [OR], 1.88 [95% CI, 1.22-2.88]), overweight (OR, 1.35 [95% CI, 1.11-1.63]), and obesity (OR, 1.67 [95% CI, 1.30-2.13]) were associated with increased odds of subfertility. In men, obesity was associated with increased odds of subfertility (OR, 1.69 [95% CI, 1.24-2.31]). Compared with normal weight in women, overweight (OR, 1.49 [95% CI, 1.12-1.98]) and obesity (OR, 1.44 [95% CI, 1.00-2.08]) were associated with increased odds of miscarriage. Conclusions and Relevance: In this cohort study, BMI outside of the normal category in women and men during the preconception or early-pregnancy periods was associated with time to pregnancy and miscarriage. Optimizing BMI in women and men from the preconception period onward might be an important strategy to improve fertility outcomes.</p

PCOS: Backgrounds, evidence and problems in diagnosing the syndrome

PCOS constitutes a heterogeneous clinical picture harbouring different subsets of patients. Recently an attempt was made to define the diagnosis of PCOS based on existing clinical evidence. Oligo- or anovulation, clinical or biochemical hyperandrogenism and polycystic ovaries constitute the key clinical features on which the diagnosis should be based. No single diagnostic criterion is sufficient for clinical diagnosis. Based on this new consensus the spectrum of women with PCOS has been considerably broadened. The purpose of this paper is to review the evidence for this new classification and to address problems in diagnosing PCOS using these new criteria.</p

Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients' offspring

Objectives To study pregnancy outcomes in a closely monitored, well-defined cohort of women with rheumatoid arthritis (RA). In particular, pregnancy outcomes of women that used a TNFi during pregnancy. Methods Patients were derived from a prospective study on pregnancy and RA (Preconception Counseling in Active RA study) and treated according to a treatment protocol aimed at minimal disease activity. Multivariate linear regression analysis was used to describe which variables influenced birth weight. Results 188 patients were included, 92 (48.9%) patients with RA used a TNFi during pregnancy. Disease Activity Score in 28 joints C reactive protein (DAS28CRP) was low at all time points during pregnancy (DAS28CRP in the third trimester: 2.17 (SD 0.73). TNFi use was not associated with an increase of adverse pregnancy outcomes such as low birth weight (<2500 g), (emergency) caesarian section, hypertensive disorders or congenital malformations. TNFi use resulted in less children born small-for-gestational age (p=0.05), however, did not increase the risk of large-for-gestational age (p=0.73). Mean birth weight was 173 g higher in women that used a TNFi during pregnancy (3.344 kg vs 3.171 kg, p=0.03). In the multivariate analysis, maternal age (β -0.023, 95% CI -0.040 to -0.0065, p=0.007), TNFi use (β 0.20, 95% CI 0.066, 0.34, p=0.004), diabetes mellitus (β 0.37, 95% CI 0.12, 0.63, p=0.004) and gestational age (β 0.18, 95% CI 0.15, 0.2, p<0.001) were statistically significant associated with birth weight. Conclusions This is the first study to show that TNFi use during pregnancy is associated with increased birth weight of offspring of women with well-controlled RA. The underlying mechanism of TNF-inhibition on birth weight and the long-term consequences for the offspring should be explored in future research

Systemic lupus erythematosus and COVID-19 during pregnancy

Background: The ongoing corona virus disease 2019 (COVID-19) pandemic is having a worldwide impact. Valuable information on the clinical characteristics of COVID-19 in pregnant patients with an autoimmune disease, such as systemic lupus erythematosus (SLE), is currently lacking. Methods: Herein, we describe the clinical presentation of 2 pregnant patients with SLE and mild symptomatic COVID-19 infection. Results: In both pregnant SLE patients, a watchful-waiting approach without initiation of treatment for COVID-19 was taken. No adverse outcomes were reported and both pregnancies resulted in healthy neonates born at term. In one patient we observed a flare in SLE disease activity, most likely attributed to discontinuing SLE treatment. Conclusion: Our report highlights the importance of multidisciplinary collaboration between health care professionals as well as individualized treatment decisions during unprecedented periods such as the current COVID-19 pandemic. Discontinuation of immunosuppressive drugs during the acute phase of a COVID-19 infection should be considered on a case-by-case basis. Maternal treatment decisions should be in line with current recommendations for treatment of rheumatic and musculoskeletal diseases during COVID-19 infection and in line with treatment of COVID- 19 during pregnancy

Assessment of First-Trimester Utero-Placental Vascular Morphology by 3D Power Doppler Ultrasound Image Analysis Using a Skeletonization Algorithm: The Rotterdam Periconception Cohort

Abnormal uteroplacental vascular development is one of the primary causes of the major disorders of pregnancy. Identification of this aberrant development in the preconception stage and in the first trimester, when measures to prevent complications are most effective, remains a challenge. Recent advances in offline imaging processing and Doppler techniques have allowed ultrasonographic analysis of placental volume (PV) and uteroplacental vascular volume (uPVV) in the first trimester. The ability of ultrasound to assess specific vascular morphology is not fully understood. The aim of this study was to investigate morphologic development of the first-trimester human uteroplacental vasculature in vivo using 3-dimensional power Doppler ultrasound and advanced image processing to generate the uteroplacental vascular skeleton (uPVS). Data were obtained from the VIRTUAL Placenta study, an ongoing observational study including adult women carrying a singleton pregnancy at less than 10-week gestational age (GA). At least 2 study visits were scheduled in the first trimester, at 7, 9, and 11 weeks' GA. The image quality of ultrasound scans was scored on a 4-point scale ranging between 0 (optimal) and 3 (unusable), and PV was measured using VOCAL software. The uPVV was measured using a virtual reality desktop system with the V-scope volume-rendering application. A skeletonization algorithm was then applied to the uPVV segmentation to generate the uPVS, and 7 morphological uPVS characteristics were used to determine the density of vascular branching within the placenta. A total of 214 women from the VIRTUAL cohort were eligible for inclusion, and 81% of all ultrasound data were of sufficient quality for generation of the uPVS. The distribution of endpoints, vessel points, bifurcation points, and crossing points in the uPVS and the distribution of uPVS characteristics per cm3 uPVV show consistent morphologic patterns throughout the first trimester. Moderate to strong positive correlations between uPVS characteristics and PV and strong positive correlations between uPVS characteristics and uPVV were identified. All uPVS characteristics increased significantly through the first trimester, except for uPVS average length, which remained constant between 7, 9, and 11 weeks' GA. When stratifying for placenta-related complications among the cohort, no significant differences in the uPVS characteristics were seen at 7 weeks' GA (n = 94). However, at 9 weeks (n = 170), there were significantly fewer number of vessel points (P = 0.040), bifurcation points (P = 0.050), crossing points (P = 0.020), and a shorter total network length (P = 0.023) among pregnancies with placenta-related complications. At 11 weeks' GA (n = 129), uPVS average vascular thickness was significantly lower in pregnancies with placenta-related complications (P = 0.007), but no other uPVS differences were observed. At 11 weeks' GA, pregnancies with placenta-related complications were found to have an increased density of vascular branching in the uPVV. The results of this study demonstrate a quantitative morphologic analysis of the human uteroplacental vasculature in the first trimester of pregnancy and key differences in the vascular morphology between pregnancies with and without placenta-related complications

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