Impact of first-trimester anomaly scan on health-related quality of life and healthcare costs:a scoping review

Importance: The first-trimester anomaly scan (FTAS) has the potential to detect major congenital anomalies in an early stage of pregnancy. Due to this potential early detection, there is a trend to introduce FTAS in regular care. Data regarding the impact of FTAS on the patient’s perspective are limited. Objective: To provide an overview of the literature assessing the impact of the FTAS on health-related quality of life (HRQoL) and healthcare costs. Evidence acquisition: Literature search was performed in Embase, PubMed, Medline Ovid, Cochrane Library database, Web-of-Science, and Google Scholar were searched. All studies that reported the performance of a nuchal translucency measurement with a basic fetal assessment HRQoL or healthcare costs of FTAS were included. Studies solely describing screening of chromosomal anomalies were excluded. Three authors independently screened the studies and extracted the data. Results were combined using descriptive analysis. PROSPERO registration number: CRD42016045190. Results: The search yielded 3242 articles and 16 were included. Thirteen articles (7045 pregnancies) examined the relationship between FTAS and HRQoL. Anxiety scores were raised temporarily before FTAS and returned to early pregnancy baseline following the absence of anomalies. Depression scores did not change significantly as a result of FTAS. Three articles studied healthcare costs. These studies, published before 2005, found a combination of FTAS and second-trimester anomaly scan (STAS) resulted in an increased amount of detected anomalies when compared to a STAS-only regimen. However, the combination would also be more costly. Conclusions: Women experience anxiety in anticipation of the FTAS result and following a reassuring FTAS result, anxiety returns to the baseline level. FTAS seems to be a reassuring experience. The included studies on costs showed the addition of FTAS is likely to increase the number of detected anomalies against an increase in healthcare costs per pregnancy. Review registration: PROSPERO CRD42016045190.</p

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes:The Rotterdam Periconception Cohort

STUDY QUESTION: Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? SUMMARY ANSWER: Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (&lt;p3), compared to women using only FA. WHAT IS KNOWN ALREADY: Periconceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA. STUDY DESIGN, SIZE, DURATION: A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires. MAIN RESULTS AND THE ROLE OF CHANCE: This study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (&lt;p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA. LIMITATIONS, REASONS FOR CAUTION: Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS. WIDER IMPLICATIONS OF THE FINDINGS: Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended.</p

Maternal lifestyle risk factors and human embryonic morphologic development:the Generation R Next study

Inadequate folic acid supplement use is associated with decelerated embryonic development. This emphasises the importance of preconceptional counselling on healthy lifestyle choices to create an optimal environment for the developing embryo

Towards segmentation and spatial alignment of the human embryonic brain using deep learning for atlas-based registration

We propose an unsupervised deep learning method for atlas based registration to achieve segmentation and spatial alignment of the embryonic brain in a single framework. Our approach consists of two sequential networks with a specifically designed loss function to address the challenges in 3D first trimester ultrasound. The first part learns the affine transformation and the second part learns the voxelwise nonrigid deformation between the target image and the atlas. We trained this network end-to-end and validated it against a ground truth on synthetic datasets designed to resemble the challenges present in 3D first trimester ultrasound. The method was tested on a dataset of human embryonic ultrasound volumes acquired at 9 weeks gestational age, which showed alignment of the brain in some cases and gave insight in open challenges for the proposed method. We conclude that our method is a promising approach towards fully automated spatial alignment and segmentation of embryonic brains in 3D ultrasound

Artificial intelligence for automated Carnegie staging of the human embryo in three-dimensional ultrasound:the Rotterdam periconception cohort

Since automatic Carnegie staging using AI is real-time and does not require a VR set-up adoption in clinical practice becomes feasible. In future work, we aim to enhance interpretability by analysing the specific morphological aspects in ultrasound scans utilised by the algorithm to assign the Carnegie stage. Understanding the morphological aspects linked to the Carnegie stage by the algorithm might lead to more in-depth insight into the patterns of normal and abnormal morphological development across pregnancie

Periconceptional maternal and paternal alcohol consumption and embryonic and fetal development:the Rotterdam periconception cohort

Research question: What is the impact of maternal and paternal alcohol consumption in the periconception period on embryonic and fetal development assessed using three-dimensional ultrasound and virtual reality techniques? Design: This prospective observational study was embedded in the Rotterdam periconception cohort (Predict study). Participating women received longitudinal three-dimensional transvaginal ultrasound examinations from week 7 to week 12 of gestation to measure crown–rump length and embryonic volume. Mid-pregnancy fetal size parameters and birth weight were retrieved from medical files. Participants completed a periconception exposure questionnaire and a validated food frequency questionnaire. Linear mixed models were used to analyse the association between parental alcohol consumption, and embryonic and fetal developmental parameters. Results: In total, 1141 female and 987 male participants were included in the analyses. Moderate maternal alcohol consumption in the periconception period resulted in a smaller head circumference (β = -1.85, SE = 0.84, P = 0.03), abdominal circumference (β = -2.65, SE = 0.93, P = 0.004), femur length (β = -0.56, SE = 0.22, P = 0.01) and estimated fetal weight (β = -9.36, SE = 4.35, P = 0.03) at 20 weeks of gestation. Paternal alcohol consumption showed significant positive associations, mainly with fetal size parameters (abdominal circumference: β = 0.033, SE = 0.01, P = 0.008; estimated fetal weight: β = 0.131, SE = 0.06, P = 0.03). Conclusions: Moderate maternal alcohol consumption is negatively associated with fetal growth parameters. Moreover, alcohol is proven to be a strong teratogen, and its consumption before and during pregnancy should be discouraged in both women and men as it affects several parameters of embryonic and fetal development.</p

Artificial intelligence for automated detection of congenital brain anomalies in the first trimester:the Rotterdam Periconception Cohort

Here, we showed the first steps towards automatic detection of brain anomalies in first trimester pregnancies using 3D ultrasound images. The next step is to evaluate if the abnormal features correspond with the brain anomalies. In the future, we will extend this algorithm towards a broader age range and towards all anatomical structures to enable automated congenital anomaly screening during the first trimester

Sublobar Pulmonary Resection in Children With Congenital Lung Abnormalities:A Systematic Review

Background:Lobectomy is currently the advised resection for symptomatic congenital lung abnormalities (CLA). Sublobar surgery is suggested as an alternative that enables to conserve healthy lung parenchyma. This systematic review aims to explore the outcomes of sublobar surgery in CLA patients as well as the corresponding surgical terminology and techniques. Methods: A systematic literature search was performed in adherence to PRISMA-P guidelines. The target population consists of children undergoing sublobar pulmonary resection for CLA. All studies were independently assessed by two reviewers, and evaluated by a third reviewer in case of disagreement. Results: The literature search yielded 901 studies of which 18 studies were included, comprising 1167 cases. The median chest tube insertion duration was 3.6 days (range 2.0–6.9 days), the median hospital admission was 4.9 days (range 2.0–14.5 days), and residual disease was diagnosed in 2% – leading to re-operation in 70%. The median incidence of postoperative complications was 15% (range 0–67%). Follow-up imaging was standard-of-care in 2/3 of studies. Due to the absence of standardised terminology, operative details and specification of resection type did not typically relate between studies. Conclusions: Sublobar resection of CLA lesions could be a viable alternative to lobectomy in certain cases, with the advantage of conserving healthy lung parenchyma. Peri- and postoperative complications are comparable with those reported for conventional lobectomy. The incidence of residual disease following sublobar surgery appears to be lower than commonly stated. To improve comparability between studies, we recommend reporting perioperative characteristics in a structured format. Level of evidence: Level IV.</p

Periconceptional Maternal One-Carbon Biomarkers are Associated with Embryonic Development According to the Carnegie Stages

STUDY QUESTION: Is periconceptional maternal one-carbon (I-C) metabolism associated with embryonic morphological development in non-malformed ongoing pregnancies? SUMMARY ANSWER: Serum vitamin B12, red blood cell (RBC) folate and plasma total homocysteine (tHcy) are associated with embryonic development according to the Carnegie stages. WHAT IS KNOWN ALREADY: Derangements in maternal I-C metabolism affect reproductive and pregnancy outcomes, as well as future health of the offspring. STUDY DESIGN, SIZE, DURATION: Between 2010 and 2014, women with singleton ongoing pregnancies were enrolled in a prospective periconceptional cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 234 pregnancies, including 138 spontaneous or IUI pregnancies with strict pregnancy dating and 96 pregnancies derived from IVF, ICSI or cryopreserved embryo transfer (IVF/ICSI pregnancies), underwent longitudinal transvaginal three-dimensional ultrasound (3D US) scans from 6+0 up to 10+2 weeks of gestation. Carnegie stages were defined using internal and external morphologic criteria in a virtual reality system. Maternal venous blood samples were collected at enrollment for serum vitamin B12, RBC folate and plasma tHcy assessment. Associations between biomarker concentrations and longitudinal Carnegie stages were investigated using linear mixed models. MAIN RESULTS AND THE ROLE OF CHANCE: We performed a median of three 3D US scans per pregnancy (range 1-5) resulting in 600 good quality data sets for the Carnegie stage annotation (80.5%). Vitamin B12 was positively associated with embryonic development in the total study population (\u3b2 = 0.001 (95% CI: 0.000; 0.002), P < 0.05) and in the subgroup of strictly dated spontaneous pregnancies (\u3b2 = 0.002 (95% CI: 0.001; 0.003), P < 0.05). Low vitamin B12 concentrations (-2SD, 73.4 pmol/l) were associated with delayed embryonic development by 1.4 days (95% CI: 1.3-1.4) compared with high concentrations (+2SD, 563.1 pmol/l). RBC folate was positively associated with Carnegie stages only in IVF/ICSI pregnancies (\u3b2 = 0.001 (95% CI: 0.0005; 0.0015), P < 0.05). In this group, low RBC folate concentrations (-2SD, 875.4 nmol/l) were associated with a 1.8-day delay (95% CI: 1.7-1.8) in development compared with high concentrations (+2SD, 2119.9 nmol/l). tHcy was negatively associated with embryonic development in the total study population (\u3b2 = -0.08 (95% CI: -0.14; -0.02), P < 0.01), as well as in the IVF/ICSI subgroup (\u3b2 = -0.08 (95% CI: -0.15; -0.01), P < 0.05). High tHcy concentrations (+2SD, 10.4 \ub5mol/l) were associated with a delay of 1.6 days (95% CI: 1.5-1.7) in embryonic development compared with low concentrations (-2SD, 3.0 \ub5mol/l). LIMITATIONS, REASONS FOR CAUTION: The study was performed in a tertiary care center, resulting in high rates of folic acid supplement use and comorbidity that may reduce the external validity of our findings. WIDER IMPLICATIONS OF THE FINDINGS: In periconceptional care, maternal I-C biomarkers should be taken into account as predictors of embryonic morphological development. Combining embryonic size measurements with morphological assessment could better define normal embryonic development. STUDY FUNDING/COMPETING INTEREST(S): The work was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. RPMST is CSO of the startup company Slimmere Zorg and CEO of eHealth Care Solutions. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable

First trimester anomaly scan using virtual reality (VR FETUS study): study protocol for a randomized clinical trial

BACKGROUND: In recent years it has become clear that fetal anomalies can already be detected at the end of the first trimester of pregnancy by two-dimensional (2D) ultrasound. This is why increasingly in developed countries the first trimester anomaly scan is being offered as part of standard care. We have developed a Virtual Reality (VR) approach to improve the diagnostic abilities of 2D ultrasound. Three-dimensional (3D) ultrasound datasets are used in VR assessment, enabling real depth perception and unique interaction. The aim of this study is to investigate whether first trimester 3D VR ultrasound is of additional value in terms of diagnostic accuracy for the detection of fetal anomalies. Health-related quality of life, cost-effectiveness and also the perspective of both patient and ultrasonographer on the 3D VR modality will be studied. METHODS: Women in the first trimester of a high risk pregnancy for a fetus with a congenital anomaly are eligible for inclusion. This is a randomized controlled trial with two intervention arms. The control group receives 'care as usual': a second trimester 2D advanced ultrasound examination. The intervention group will undergo an additional first trimester 2D and 3D VR ultrasound examination. Following each examination participants will fill in validated questionnaires evaluating their quality of life and healthcare related expenses. Participants' and ultrasonographers' perspectives on the 3D VR ultrasound will be surveyed. The primary outcom