Search

STUDY QUESTION Is early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes? SUMMARY ANSWER Larger embryonic crown–rump length (CRL) and embryonic volume (EV) are associated with lower odds of adverse birth outcomes, especially small for gestational age (SGA). WHAT IS ALREADY KNOWN Preterm birth, SGA, and congenital anomalies are the most prevalent adverse birth outcomes with lifelong health consequences as well as high medical and societal costs. In the late first and second trimesters of pregnancy, fetuses at risk for adverse birth outcomes can be identified using 2-dimensional ultrasonography (US). STUDY DESIGN, SIZE, DURATION Between 2009 and 2018, singleton pregnancies were enrolled in this ongoing prospective Rotterdam Periconception Cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 918 pregnant women from a tertiary hospital in the Netherlands. Pregnancy dating was based on either a regular menstrual cycle (for natural pregnancies) or a conception date (for ART pregnancies). CRL and EV were measured using Virtual Reality software on 3-dimensional (3D) ultrasound scans, repeatedly performed around 7, 9, and 11 weeks of gestation. The main outcome measure was adverse birth outcome, defined as the composite of SGA (birth weight <10th percentile), preterm birth (<37th week of gestation), congenital anomalies (Eurocat criteria), stillbirth (>16th week of pregnancy), or early neonatal mortality (≤7 days of life). Reference curves for CRL and EV were constructed. Cross-sectional (CRL/EV <20th percentile at 7, 9, and 11 weeks of gestation) and longitudinal (CRL/EV growth trajectories between 6th and 13th weeks) regression analyses were performed, with adjustments for the participants' educational level, smoking, parity, age, BMI, geographical background, mode of conception, and fetal sex. MAIN RESULTS AND THE ROLE OF CHANCE Of the 918 pregnant women included, the median age was 32.3 years, and 404 (44%) pregnancies had been conceived via ART. In 199 (22%) pregnancies, there was an adverse birth outcome. Regression analyses showed that at 7 weeks of gestation onwards, embryos with a CRL <20th percentile had an ∼2-fold increased odds of adverse birth outcome (adjusted odds ratio (aOR) 2.03, 95% CI 1.21—3.39, P  = 0.007). Similar associations were found for EV <20th percentile but were not statistically significant. These findings were mainly driven by the strong association between embryonic size and SGA (e.g. 7-week CRL: aOR 2.18 (1.16–4.09), P  = 0.02; 9-week EV: aOR 2.09 (1.10—3.97, P  = 0.02). Longitudinal growth trajectories of CRL, but not of EV, were associated with adverse birth outcomes. Both CRL and EV growth trajectories were associated with SGA. LIMITATIONS, REASONS FOR CAUTION The tertiary hospital population and the availability of sophisticated 3D-ultrasound techniques limit the generalizability of this study to general populations and settings. WIDER IMPLICATIONS OF THE FINDINGS Already very early in the first trimester of pregnancy, embryos with increased risks of an adverse birth outcome can be identified by using 3D-US and Virtual Reality. This expands the window of opportunity to enable the development of future interventions to potentially improve pregnancy outcomes and offspring health during their life-course. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER NL4115. [ABSTRACT FROM AUTHOR]

Study Question: CAN WE assess human prenatal cerebellar growth from the first until the third trimester of pregnancy and create growth trajectories to investigate associations with periconceptional maternal and fetal characteristics?Summary Answer: Prenatal growth trajectories of the human cerebellum between 9 and 32 weeks gestational age (GA) were created using three-dimensional ultrasound (3D-US) and show negative associations with pre-pregnancy and early first trimester BMI calculated from self-reported and standardized measured weight and height, respectively.What Is Known Already: The cerebellum is essential for normal neurodevelopment and abnormal cerebellar development has been associated with neurodevelopmental impairments and psychiatric diseases. Cerebellar development is particularly susceptible to exposures during the prenatal period, including maternal folate status, smoking habit and alcohol consumption.Study Design, Size, Duration: From 2013 until 2015, we included 182 singleton pregnancies during the first trimester as a subgroup in a prospective periconception cohort with follow-up until birth. For the statistical analyses, we selected 166 pregnancies ending in live born infants without congenital malformations.Participants/materials, Setting, Methods: We measured transcerebellar diameter (TCD) at 9, 11, 22, 26 and 32 weeks GA on ultrasound scans. Growth rates were calculated and growth trajectories of the cerebellum were created. Linear mixed models were used to estimate associations between cerebellar growth and maternal age, parity, mode of conception, geographic origin, pre-pregnancy and first trimester BMI, periconceptional smoking, alcohol consumption, timing of folic acid supplement initiation and fetal gender.Main Results and the Role Of Chance: In total, 166 pregnancies provided 652 (87%) ultrasound images eligible for TCD measurements. Cerebellar growth rates increased with advancing GA being 0.1691 mm/day in the first trimester, 0.2336 mm/day in the second trimester and 0.2702 mm/day in the third trimester. Pre-pregnancy BMI, calculated from self-reported body weight and height, was significantly associated with decreased cerebellar growth trajectories (β = -0.0331 mm, 95% CI = -0.0638; -0.0024, P = 0.035). A similar association was found between cerebellar growth trajectories and first trimester BMI, calculated from standardized measurements of body weight and height (β = -0.0325, 95% CI = -0.0642; -0.0008, P = 0.045, respectively).Limitations, Reasons For Caution: As the study population largely consisted of tertiary hospital patients, external validity should be studied in the general population. Whether small differences in prenatal cerebellar growth due to a higher pre-pregnancy and first trimester BMI have consequences for neurodevelopmental outcome needs further investigation.Wider Implications Of the Findings: Our findings further substantiate previous evidence for the detrimental impact of a higher maternal BMI on neurodevelopmental health of offspring in later life.Study Funding/competing Interest(s): This study was funded by the Department of Obstetrics and Gynecology, Erasmus MC University Medical Centre and Sophia Children's Hospital Fund, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared. [ABSTRACT FROM AUTHOR]

Study Question: Can growth trajectories of the human embryonic head be created using 3D ultrasound (3D-US) and virtual reality (VR) technology, and be associated with second trimester fetal head size and periconceptional maternal conditions? Summary Answer: Serial first trimester head circumference (HC) and head volume (HV) measurements were used to create reliable growth trajectories of the embryonic head, which were significantly associated with fetal head size and periconceptional maternal smoking, age and ITALIC! in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) treatment. What Is Known Already: Fetal growth is influenced by periconceptional maternal conditions. Study Design, Size, Duration: We selected 149 singleton pregnancies with a live born non-malformed fetus from the Rotterdam periconception cohort. Participants/materials, Setting, Methods: Bi-parietal diameter and occipital frontal diameter to calculate HC, HV and crown-rump length (CRL) were measured weekly between 9 + 0 and 12 + 6 weeks gestational age (GA) using 3D-US and VR. Fetal HC was obtained from second trimester structural anomaly scans. Growth trajectories of the embryonic head were created with general additive models and linear mixed models were used to estimate associations with maternal periconceptional conditions as a function of GA and CRL, respectively. Main Results: A total of 303 3D-US images of 149 pregnancies were eligible for embryonic head measurements (intra-class correlation coefficients >0.99). Associations were found between embryonic HC and fetal HC ( ITALIC! ρ = 0.617, ITALIC! P < 0.001) and between embryonic HV and fetal HC ( ITALIC! ρ = 0.660, ITALIC! P < 0.001) in ITALIC! Z-scores. Maternal periconceptional smoking was associated with decreased, and maternal age and IVF/ICSI treatment with increased growth trajectories of the embryonic head measured by HC and HV (All ITALIC! P < 0.05). Limitations, Reasons For Caution: The consequences of the small effect sizes for neurodevelopmental outcome need further investigation. As the study population consists largely of tertiary hospital patients, external validity should be studied in the general population. Wider Implications Of the Findings: Assessment of growth trajectories of the embryonic head may be of benefit in future early antenatal care. Study Funding/competing Interests: This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared. [ABSTRACT FROM AUTHOR]

Background: Stress during treatment at the Neonatal Intensive Care Unit (NICU) has long-term negative consequences on preterm infants' development., Aims: We developed an instrument suited to validly determine the cumulative stress exposure for preterm infants in a NICU., Study Design: This survey study made use of two consecutive questionnaires., Subjects: NICU nurses and physicians from the nine NICUs in the Netherlands., Outcome Measures: First, respondents rated the relevance of 77 items encompassing potentially stressful procedures, commented on their comprehensibility and the comprehensiveness of the list. We calculated the content validity per item (CVI-I) and included only the relevant items in a second questionnaire in which the participants rated the stressfulness from 0 (not stressful) to 10 (extremely stressful). A stressfulness index - representing the median score - was calculated for each included item., Results: Based on the CVI-I of the 77 items, step 1 resulted in 38 items considered relevant to quantify stress in preterm infants during the first 28 days of life. This list of 38 items exists of 34 items with a CVI-I if 0.78 or higher, one of these items was split into two items, and three items were added to improve comprehensiveness. The stressfulness index ranged from five to nine., Conclusions: The NeO-stress score consists of stressful items including their severity index and was developed to determine cumulative stress exposure of preterm infants. Evaluating the cross-cultural validity, correlating it to behavioural and biological stress responses, and evaluating its ability to predict preterm infants at risk for the negative effects following stress might expand the possibilities for this instrument., Competing Interests: Conflict of interest None declared., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To explore, based on the existing body of literature, main characteristics of prenatal counseling for parents at risk for extreme preterm birth., Methods: A scoping review was conducted searching Embase, Medline, Web of Science, Cochrane, CINAHL, and Google Scholar., Results: 46 articles were included. 27 of them were published between 2017 and 2021. More than half of them were conducted in the United States of America. Many different study designs were represented. The following characteristics were identified: personalization, parent-physician relationships, shared decision-making, physician bias, emotions, anxiety, psychosocial factors, parental values, religion, spirituality, hope, quality of life, and uncertainty., Conclusions: Parental values are mentioned in 37 of the included articles. Besides this, uncertainty, shared decision-making, and emotions are most frequently mentioned in the literature. However, reflecting on the interrelation between all characteristics leads us to conclude that personalization is the most notable trend in prenatal counseling practices. More and more, it is valued to adjust the counseling to the parent(s)., Practice Implications: This scoping review emphasizes again the complexity of prenatal counseling at the limit of viability. It offers an exploration of how it is currently approached, and reflects on how future research can contribute to optimizing it., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: In infants born very preterm, monitoring of early brain growth could contribute to prediction of later neurodevelopment. Therefore, our aim was to investigate associations between 2 early cranial ultrasound markers (corpus callosum-fastigium and corpus callosum length) and neurodevelopmental outcome and the added value of both markers in the prediction of neurodevelopmental outcome based on neonatal risk factors and head circumference in very preterm infants., Materials and Methods: This prospective observational study included 225 infants born at <30 weeks' gestational age, of whom 153 were without any brain injury on cranial ultrasound. Corpus callosum-fastigium and corpus callosum length and head circumference were measured at birth, 29 weeks' gestational age, transfer from the neonatal intensive care unit to a level II hospital, and 2 months' corrected age. We analyzed associations of brain markers and their growth with cognitive, motor, language, and behavioral outcome at 2 years' corrected age., Results: In infants without brain injury, greater corpus callosum-fastigium length at 2 months was associated with better cognitive outcome. Corpus callosum length at 2 months was positively associated with cognitive, motor, and language outcome. Faster growth of the corpus callosum length between birth and 2 months was associated with better cognitive and motor function. Prediction of neurodevelopmental outcome based on neonatal risk factors with or without head circumference was significantly improved by adding corpus callosum length., Conclusions: Both corpus callosum-fastigium and corpus callosum length on cranial ultrasound are associated with neurodevelopmental outcome of very preterm infants without brain injury at 2 years, but only corpus callosum length shows the added clinical utility in predicting neurodevelopmental outcome., (© 2022 by American Journal of Neuroradiology.)

Objective: There is no international consensus on what type of guideline is preferred for care at the limit of viability. We aimed to conceptualize what type of guideline is preferred by Dutch healthcare professionals: 1) none; 2) gestational-age-based; 3) gestational-age-based-plus; or 4) prognosis-based via a survey instrument. Additional questions were asked to explore the grey zone and attitudes towards treatment variation., Finding: 769 surveys were received. Most of the respondents (72.8%) preferred a gestational-age-based-plus guideline. Around 50% preferred 24 +0/7 weeks gestational age as the lower limit of the grey zone, whereas 26 +0/7 weeks was the most preferred upper limit. Professionals considered treatment variation acceptable when it is based upon parental values, but unacceptable when it is based upon the hospital's policy or the physician's opinion., Conclusion: In contrast to the current Dutch guideline, our results suggest that there is a preference to take into account individual factors besides gestational age., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Children born preterm are at risk of visuospatial attention orienting and processing dysfunctions, which can be quantified early in life using visually-guided eye movement responses., Aims: To identify the prevalence and perinatal risk factors for visuospatial attention orienting and processing dysfunctions in children born preterm of 1 year of corrected age (CA)., Study Design: 123 children born between 26 and 33 weeks of gestation underwent a nonverbal visuospatial test at 1y CA, using an eye tracking-based paradigm. For the detected high-salient (cartoon and contrast), intermediate-salient (form and motion) and low-salient (color) stimuli, we quantified the reaction time to fixation (RTF). RTFs were compared to normative references from an age-matched control group (N = 38). The prevalence of perinatal risk factors (gestational age and weight, indices of neurological damage, overal sickness, respiratory failure, and retinopathy) was compared between the groups with normal and delayed RTFs., Results: At 1y CA, the preterm group had 7-20% less detected stimuli than the control group, particularly for intermediate and low-salient stimuli. Compared to normative RTFs, modest delays were found for high-salient cartoon (in 19% of preterm children) and contrast (8%), intermediate-salient motion (23%) and form (21%), and low-salient color stimuli (8%). These children had a significantly higher prevalence of perinatal risk factors for respiratory failure and intraventricular hemorrhages., Conclusions: Children born between 26 and 32 weeks have a modest risk (8-23%) of visuospatial attention and processing dysfunction. This warrants early monitoring and support of general visual development in preterm children at risk of respiratory distress and disrupted cerebral blood flow., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: Infants born preterm are commonly diagnosed with structural brain lesions known to affect long-term neurodevelopment negatively. Yet, the effects of preterm birth on brain development in the absence of intracranial lesions remain to be studied in detail. In this study, we aim to quantify long term consequences of preterm birth on brain development in this specific group., Materials and Methods: Neonatal cranial sonography and follow-up T1-weighted MR imaging and DTI were performed to evaluate whether the anatomic characteristics of the cerebrum and cerebellum in a cohort of school-aged children (6-12 years of age) were related to gestational age at birth in children free of brain lesions in the perinatal period., Results: In the cohort consisting of 36 preterm (28-37 weeks' gestational age) and 66 term-born infants, T1-weighted MR imaging and DTI at 6-12 years revealed a reduction of cerebellar white matter volume (β = 0.387, P < .001), altered fractional anisotropy of cerebellar white matter (β = -0.236, P = .02), and a reduction of cerebellar gray and white matter surface area (β = 0.337, P < .001; β = 0.375, P < .001, respectively) in relation to birth age. Such relations were not observed for the cerebral cortex or white matter volume, surface area, or diffusion quantities., Conclusions: The results of our study show that perinatal influences that are not primarily neurologic are still able to disturb long-term neurodevelopment, particularly of the developing cerebellum. Including the cerebellum in future neuroprotective strategies seems therefore essential., (© 2018 by American Journal of Neuroradiology.)

Background and Purpose: Most ultrasound markers for monitoring brain growth can only be used in either the prenatal or the postnatal period. We investigated whether corpus callosum length and corpus callosum-fastigium length could be used as markers for both prenatal and postnatal brain growth., Materials and Methods: A 3D ultrasound study embedded in the prospective Rotterdam Periconception Cohort was performed at 22, 26 and 32 weeks' gestational age in fetuses with fetal growth restriction, congenital heart defects, and controls. Postnatally, cranial ultrasound was performed at 42 weeks' postmenstrual age. First, reliability was evaluated. Second, associations between prenatal and postnatal corpus callosum and corpus callosum-fastigium length were investigated. Third, we created reference curves and compared corpus callosum and corpus callosum-fastigium length growth trajectories of controls with growth trajectories of fetuses with fetal growth retardation and congenital heart defects., Results: We included 199 fetuses; 22 with fetal growth retardation, 20 with congenital heart defects, and 157 controls. Reliability of both measurements was excellent (intraclass correlation coefficient ≥ 0.97). Corpus callosum growth trajectories were significantly decreased in fetuses with fetal growth restriction and congenital heart defects (β = -2.295; 95% CI, -3.320-1.270; P < .01; β = -1.267; 95% CI, -0.972-0.562; P < .01, respectively) compared with growth trajectories of controls. Corpus callosum-fastigium growth trajectories were decreased in fetuses with fetal growth restriction (β = -1.295; 95% CI, -2.595-0.003; P = .05)., Conclusions: Corpus callosum and corpus callosum-fastigium length may serve as reliable markers for monitoring brain growth from the prenatal into the postnatal period. The clinical applicability of these markers was established by the significantly different corpus callosum and corpus callosum-fastigium growth trajectories in fetuses at risk for abnormal brain growth compared with those of controls., (© 2017 by American Journal of Neuroradiology.)

Background and Purpose: Preterm neonates are at risk for neurodevelopmental impairment, but reliable, bedside-available markers to monitor preterm brain growth during hospital stay are still lacking. The aim of this study was to assess the feasibility of corpus callosum-fastigium length as a new cranial sonography marker for monitoring of preterm brain growth., Materials and Methods: In this longitudinal prospective cohort study, cranial ultrasound was planned on the day of birth, days 1, 2, 3, and 7 of life; and then weekly until discharge in preterm infants born before 29 weeks of gestational age. Reproducibility and associations between clinical variables and corpus callosum-fastigium growth trajectories were studied., Results: A series of 1-8 cranial ultrasounds was performed in 140 infants (median gestational age at birth, 27(+2) weeks (interquartile range, 26(+1) to 28(+1); 57.9% male infants). Corpus callosum-fastigium measurements showed good-to-excellent agreement for inter- and intraobserver reproducibility (intraclass correlation coefficient >0.89). Growth charts for preterm infants between 24 and 32 weeks of gestation were developed. Male sex and birth weight SD score were positively associated with corpus callosum-fastigium growth rate., Conclusions: Corpus callosum-fastigium length measurement is a new reproducible marker applicable for bedside monitoring of preterm brain growth during neonatal intensive care stay., (© 2016 by American Journal of Neuroradiology.)

Background and Purpose: Neonatal DTI enables quantitative assessment of microstructural brain properties. Although its use is increasing, it is not widely known that vast differences in tractography results can occur, depending on the diffusion tensor estimation methodology used. Current clinical work appears to be insufficiently focused on data quality and processing of neonatal DTI. To raise awareness about this important processing step, we investigated tractography reconstructions of the fornix with the use of several estimation techniques. We hypothesized that the method of tensor estimation significantly affects DTI tractography results., Materials and Methods: Twenty-eight DTI scans of infants born <29 weeks of gestation, acquired at 30-week postmenstrual age and without intracranial injury observed, were prospectively collected. Four diffusion tensor estimation methods were applied: 1) linear least squares; 2) weighted linear least squares; 3) nonlinear least squares, and 4) robust estimation of tensors by outlier rejection. Quality of DTI data and tractography results were evaluated for each method., Results: With nonlinear least squares and robust estimation of tensors by outlier rejection, significantly lower mean fractional anisotropy values were obtained than with linear least squares and weighted linear least squares. Visualized quality of tract reconstruction was significantly higher by use of robust estimation of tensors by outlier rejection and correlated with quality of DTI data., Conclusions: Quality assessment and choice of processing methodology have considerable impact on neonatal DTI analysis. Dedicated acquisition, quality assessment, and advanced processing of neonatal DTI data must be ensured before performing clinical analyses, such as associating microstructural brain properties with patient outcome., (© 2014 by American Journal of Neuroradiology.)

Extracorporeal membrane oxygenation (ECMO) is a valuable treatment modality in neonates with reversible cardiopulmonary failure in therapy-resistant pulmonary hypertension after perinatal asphyxia, septic shock or ECMO cardiopulmonary resuscitation. Neonates with severe perinatal asphyxia are currently treated with therapeutic hypothermia to improve neurological outcome. Consequently, therapeutic hypothermia may be indicated in the neonatal ECMO population. Both ECMO and hypothermia have been associated with changes in drug disposition. However, little is known about the combined effects of these treatment modalities. This review will explore the available literature, identify possible changes in pharmacokinetics and make suggestions for future research directions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)