The NICHD Fetal 3D Study: A Pregnancy Cohort Study of Fetal Body Composition and Volumes.

There's a paucity of robust normal fractional limb and organ volume standards from a large and diverse ethnic population. The Fetal 3D Study was designed to develop research and clinical applications for fetal soft tissue and organ volume assessment. The NICHD Fetal Growth Studies (2009-2013) collected 2D and 3D fetal volumes. In the Fetal 3D Study (2015-2019), sonographers performed longitudinal 2D and 3D measurements for specific fetal anatomical structures in research ultrasounds of singletons and dichorionic twins. The primary aim was to establish standards for fetal body composition and organ volumes, overall and by maternal race/ethnicity, and determine whether these standards vary for twins versus singletons. We describe the study design, methods, and details about reviewer training. Basic characteristics of this cohort, with their corresponding distributions of fetal 3D measurements by anatomical structure, are summarized. This investigation is responsive to critical data gaps in understanding serial changes in fetal subcutaneous fat, lean body mass, and organ volume in association with pregnancy complications. In the future, this cohort can answer critical questions regarding the potential influence of maternal characteristics, lifestyle factors, nutrition, and biomarker and chemical data on longitudinal measures of fetal subcutaneous fat, lean body mass, and organ volumes.

Maternal rest improves growth in small-for-gestational-age fetuses (<10th percentile).

BACKGROUND: Optimal management of fetuses diagnosed as small for gestational age based on an estimated fetal weight of <10th percentile represents a major clinical problem. The standard approach is to increase fetal surveillance with serial biometry and antepartum testing to assess fetal well-being and timing of delivery. Observational studies have indicated that maternal rest in the left lateral position improves maternal cardiac output and uterine blood flow. However, maternal bed rest has not been recommended based on the results of a randomized clinical trial that showed that maternal rest does not improve fetal growth in small-for-gestational-age fetuses. This study was conducted to revisit this question. OBJECTIVE: This study aimed to determine whether maternal bed rest was associated with an increase in the fetal biometric parameters that reflect growth after the diagnosis of a small-for-gestational-age fetus. STUDY DESIGN: A retrospective study was conducted on fetuses who were diagnosed as small for gestational age because of an estimated fetal weight of <10th percentile for gestational age. The mothers were asked to rest in the left lateral recumbent position. Fetal biometry was performed 2 weeks after the diagnosis. All fetuses before entry into the study had a previous ultrasound that demonstrated an estimated fetal weight of >10th percentile. To assess the response to bed rest, the change in fetal biometric parameters (estimated fetal weight, head circumference, abdominal circumference, and femur length) after the recommendation of bed rest was computed for 2 periods: (1) before the diagnosis of a weight of <10th percentile vs at the time of diagnosis of a weight of <10th percentile and (2) at the time of diagnosis of a weight of <10th percentile vs 2 weeks after maternal bed rest. For repeated measures, proportions were compared using the McNemar test, and percentile values were compared using the Kruskal-Wallis test. A P value of <.05 was considered significant. To describe changes in the estimated fetal weight without bed rest, 2 control groups in which the mothers were not placed on bed rest after the diagnosis of a small-for-gestational-age fetus were included. RESULTS: A total of 265 fetuses were observed before and after maternal bed rest. The following were observed in this study: (1) after 2 weeks of maternal rest, 199 of 265 fetuses (75%) had a fetal weight of >10th percentile; (2) the median fetal weight percentile increased from 6.8 (interquartile range, 4.4-8.4) to 18.0 (interquartile range, 9.5-29.5) after 2 weeks of bed rest; (3) similar trends were noted for the head circumference, abdominal circumference, and femur length. In the groups of patients who were not asked to be on bed rest, a reassignment to a weight of >10th percentile at a follow-up examination only occurred in 7 of 37 patients (19%) in the Texas-Michigan group and 13 of 111 patients (12%) in the Colorado group compared with the bed rest group (199/265 [75%]) (P<.001). CONCLUSION: Patients who were prescribed 2 weeks of bed rest after the diagnosis of a fetal weight of <10th percentile had an increase in weight of >10th percentile in 199 of 265 fetuses (75%). This increase in fetal weight was significantly higher than that in the 2 control groups in which bed rest was not prescribed. This observation suggests that bed rest improves fetal growth in a subset of patients.

Multiethnic growth standards for fetal body composition and organ volumes derived from 3D ultrasonography.

BACKGROUND: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort. OBJECTIVE: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with conventional 2-dimensional measures where applicable. STUDY DESIGN: The National Institute of Child Health and Human Development Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to 5 scans per fetus (N=1730 fetuses). Abdominal subcutaneous tissue thickness was measured from 2-dimensional images and fetal limb soft tissue parameters extracted from 3-dimensional multiplanar views. Cerebellar, lung, liver, and kidney volumes were measured using virtual organ computer aided analysis. Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (fifth, 50th, 95th percentiles) were derived from 15 to 41 weeks' using linear mixed models for repeated measures with cubic splines. RESULTS: Subcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27 to 29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29 to 30 weeks. In contrast, growth patterns for 2-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the second trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid-arm and thigh circumferences were more linear. Cerebellar 2-dimensional diameter increased linearly, whereas cerebellar 3-dimensional volume growth gradually accelerated until 32 weeks followed by a more linear growth. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26 to 27 weeks for kidneys, and 29 weeks for liver. CONCLUSION: Growth patterns and timing of maximal growth for 3-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional 2-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic, or environmental influences and pregnancy complications, in ways not identifiable using corresponding 2-dimensional measures. Further investigation into the relationships of these 3-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

Predictors of height in Romanian infants 6-23 months old: findings from a national representative sample.

BACKGROUND: The research explored the association between infants' height and various demographic factors in Romania, a country where such critical information has been lacking. METHODS: This study was conducted on a nationally representative sample and used a family physicians database to determine a sample of 1532 children (713 girls and 819 boys) 6-23 months of age (M = 14.26; SD = 5.15). Infants' height-for-age z-scores (HAZ) were calculated using the World Health Organization's computing algorithm. A multiple regression analysis was conducted to investigate whether certain risk factors, such as infant mother's age, location, marital status, socioeconomic status (SES), as well as infant's term status at birth, age, anemia, minimum dietary diversity (MDD) and birth order, could significantly predict the HAZ. RESULTS: The study identified several significant predictors of height. Specifically, lower HAZ was associated with rural living, preterm birth, age 18-23 months, unmarried mothers, anemia, lack of MDD and being third or later born in the family. In contrast, higher HAZ was associated with medium or high maternal SES and older maternal age. CONCLUSIONS: The study underscores the importance of addressing these significant risk factors through distinct interventions to improve height outcomes in at-risk Romanian populations.

Impact of Pelvic Rest Recommendations on Follow-Up and Resolution of Placenta Previa and Low-Lying Placenta.

OBJECTIVE: To determine the rate of resolution of placenta previa and low-lying placenta (LLP) and the effect of pelvic rest recommendations on the timing of follow-up imaging. METHODS: Retrospective review of pregnancies with previa/LLP detected on mid-trimester exam at our ultrasound unit from 2019 to 2021. LLP was defined as the lower edge of placenta located within 2 cm of the internal cervical os. Previa was defined as any portion of the placenta touching with the internal os. Demographics, placental location, activity restrictions, and delivery outcomes were analyzed. Timing of follow-up imaging was stratified by individuals advised and not advised pelvic rest. RESULTS: Exactly 144 patients had previa and 266 had LLP on the mid-trimester exam with complete records. Previa resolution happened in 51.4% (74/144) of cases. Exactly 62% (46/74) of previa resolutions occurred by the 28-week ultrasound. Exactly 45% (65/144) of previa patients were advised pelvic rest. Most pelvic rest and non-pelvic rest patients had a 28-week scan. Even when clearance occurred, most patients in both groups had a repeat ultrasound at 32 weeks. Exactly 75% of LLP resolved by the 28-week scan, and the remainder by delivery. Exactly 12% (32/259) of LLP patients were advised pelvic rest. CONCLUSION: Most societies recommend follow-up imaging at 32 weeks; however, our results suggest this may be done sooner and closer to 28 weeks. Pelvic rest did not affect timing of repeat imaging or delivery.

The role of the fetal biophysical profile in the management of fetal growth restriction.

Growth-restricted fetuses are at risk of hypoxemia, acidemia, and stillbirth because of progressive placental dysfunction. Current fetal well-being, neonatal risks following delivery, and the anticipated rate of fetal deterioration are the major management considerations in fetal growth restriction. Surveillance has to quantify the fetal risks accurately to determine the delivery threshold and identify the testing frequency most likely to capture future deterioration and prevent stillbirth. From the second trimester onward, the biophysical profile score correlates over 90% with the current fetal pH, and a normal score predicts a pH >7.25 with a 100% positive predictive value; an abnormal score on the other hand predicts current fetal acidemia with similar certainty. Between 30% and 70% of growth-restricted fetuses with a nonreactive heart rate require biophysical profile scoring to verify fetal well-being, and an abnormal score in 8% to 27% identifies the need for delivery, which is not suspected by Doppler findings. Future fetal well-being is not predicted by the biophysical profile score, which emphasizes the importance of umbilical artery Doppler and amniotic fluid volume to determine surveillance frequency. Studies with integrated surveillance strategies that combine frequent heart rate monitoring with biophysical profile scoring and Doppler report better outcomes and stillbirth rates of between 0% and 4%, compared with those between 8% and 11% with empirically determined surveillance frequency. The variations in clinical behavior and management challenges across gestational age are better addressed when biophysical profile scoring is integrated into the surveillance of fetal growth restriction. This review aims to provide guidance on biophysical profile scoring in the in- and outpatient management of fetal growth restriction.

Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction.

Cardiac Size, Shape, and Ventricular Contractility in Fetuses at Sea Level With an Estimated Weight Less-than 10th Centile.

OBJECTIVES: To investigate cardiac size, shape, and ventricular contractility in fetuses with estimated fetal weight (EFW) <10th centile at sea level (Houston). METHODS: A prospective ultrasound study examined 37 fetuses with EFW <10th centile at sea level. High-frequency cine clips were used to evaluate the 4-chamber view including end-diastolic measurements and global sphericity index. The size, shape, and contractility of both ventricles were analyzed with speckle tracking methods. Z scores were calculated using the mean ± standard deviation (SD) derived from normal controls. Measurements were abnormal if their Z score values were <-1.65 or >+1.65. The proportion of small fetuses with abnormal parameters was compared to normal reference ranges. Results were compared to a similar published study of small fetuses at higher altitude in Denver. RESULTS: About one-third of Houston fetuses with EFW <10th centile had enlarged globular shaped 4-chamber hearts with increased right ventricle (RV) area, RV basal-apical length, RV base width, and left ventricle (LV) basal-apical length measurements. Bilateral ventricular hypertrophy was often present. An increased proportion of Houston fetuses had increased ventricular contractility. However, decreased ventricular contractility was more prevalent for higher altitude fetuses. CONCLUSIONS: Third trimester fetuses at sea level, with an EFW <10th centile, were often associated with enlarged and globular-shaped hearts. They had increased global and longitudinal ventricular contractility as compared to controls. Higher altitude fetuses also had enlarged globular-shaped hearts but with a greater proportion of cases having decreased ventricular contractility as compared to the sea level cohort.

Is ventriculomegaly and hindbrain herniation seen before and after prenatal neural tube defect repair associated with a worse functional level than anatomical level at birth?

OBJECTIVE: To determine if the evaluation of the fetal ventricular system and hindbrain herniation (HBH) is associated with motor outcome at birth in prenatally repaired open neural tube defect (NTD). METHODS: Retrospective cohort study of 47 patients with NTD who underwent prenatal repair (17 fetoscopic; 30 open-hysterotomy). At referral and 6 weeks postoperatively, the degree of HBH, ventricular atrial widths and ventricular volume were evaluated by MRI. Head circumference and ventricular atrial widths were measured on ultrasound at referral and during the last ultrasound before delivery. Anatomic level of the lesion (LL) was determined based on the upper bony spinal defect detected by ultrasound. We considered the functional level as worse than anatomical level at birth when the motor level was equal or worse than the anatomical LL. RESULTS: 26% (12/47) of the cases showed worse functional level than anatomical level at birth. Having a HBH below C1 at the time of referral was associated with a worse functional level than anatomical level at birth (OR = 9.7, CI95 [2.2-42.8], p < 0.01). None of the other brain parameters showed a significant association with motor outcomes at birth. CONCLUSIONS: HBH below C1 before surgery was associated with a worse functional level than anatomical level at birth.

Fetal Weight Estimation Using Automated Fractional Limb Volume With 2-Dimensional Size Parameters in Diabetic Pregnancies.

OBJECTIVES: To examine the effect of adding automated fetal fractional limb volume (FLV) with conventional 2-dimensional (2D) fetal weight estimation procedures in a cohort of diabetic pregnancies. METHODS: A pilot study of diabetic pregnancies measured standard fetal biometry within 7 days of delivery. Fractional arm volume (AVol) and fractional thigh volume (TVol) soft tissue parameters were measured with a commercially available automated software utility (5D Limb Vol; Samsung Medison Co, Ltd, Seoul, Korea). Three conventional weight prediction models that included only 2D size parameters were compared to FLV models that included AVol or TVol. Estimated and actual birth weight (BW) were assessed for the mean percent difference ± standard deviation of the percent differences. Systematic errors were evaluated by the Student t test, and random errors were compared by the Pitman test for correlated variances. The proportion of neonates with estimated fetal weight within 10% of BW was compared between groups by the McNemar test. RESULTS: Ninety gravid women were enrolled with pregestational (26.7%) or gestational (73.3%) diabetes. All prediction models were accurate, with the exception of small underestimations by the model of Schild et al (-3.8%; Ultrasound Obstet Gynecol 2004; 23:30-35). Random errors for the AVol (6.2%) and TVol (6.9%) models were significantly more precise than the other 3 prediction models: Hadlock et al (7.8%; Am J Obstet Gynecol 1985; 151:333-337), INTERGROWTH-21st (8.0%; Ultrasound Obstet Gynecol 2017; 49:478-486), and Schild et al (8.6%; P < .01). The greatest proportion of cases with BW ±10% was also classified by the AVol (91.1%) and TVol (91.1%) models, followed by Hadlock (83.3%), INTERGROWTH-21st (78.9%), and Schild (76.7%) predictions. CONCLUSIONS: The addition of automated FLV measurements to conventional 2D biometry was associated with improved weight predictions in this cohort of diabetic pregnancies.

Umbilical Artery Doppler Patterns and Right Ventricular Outflow Abnormalities in Twin-Twin Transfusion Syndrome.

OBJECTIVES: To evaluate the association of abnormal Doppler velocimetric patterns in the umbilical arteries (UAs) and right ventricular outflow tract abnormalities (RVOTAs) in twin- twin transfusion syndrome (TTTS) cases. METHODS: This retrospective study involved women who had laser surgery for TTTS between January 2012 and May 2018 at a single institution. The prevalence of an RVOTA in either twin was compared among TTTS cases in which both twins had positive end-diastolic flow (EDF) in the UA and those in which either twin had intermittent or persistent absent/reversed UA EDF. Nonparametric tests were used for comparisons. Logistic regression was performed to identify variables associated with an RVOTA in either twin, adjusted for moderate or severe tricuspid regurgitation, right ventricular hypertrophy, right ventricular systolic or diastolic dysfunction, the Quintero stage, and other confounders. P < .05 was considered significant. RESULTS: A total of 126 consecutive TTTS cases were included. Right ventricular outflow tract abnormalities were seen in 8.7% (11of 126) of cases, all in recipient twins. Significant differences in the rate of RVOTAs in the recipient twin were seen between TTTS cases with intermittent absent/reversed UA EDF and those with positive UA EDF (26.9% [7 of 26] versus 3.7% [3 of 82]; P = .002]. However, no significant differences were noted among the other study groups. Intermittent absent/reversed UA EDF was associated with a significantly increased risk for an RVOTA (adjusted odds ratio, 20.6 [95% confidence interval, 3.1-138]; P = .002) after adjusting for confounders. CONCLUSIONS: Intermittent changes in vascular impedance to UA flow may contribute to the pathogenesis of acquired right-sided cardiac lesions in the recipient twin affected with TTTS.

Fetal Weight Estimation Using Automated Fractional Limb Volume With 2-Dimensional Size Parameters: A Multicenter Study.

OBJECTIVES: To develop new fetal weight prediction models using automated fractional limb volume (FLV). METHODS: A prospective multicenter study measured fetal biometry within 4 to 7 days of delivery. Three-dimensional data acquisition included the automated FLV that was based on 50% of the humerus diaphysis (fractional arm volume [AVol]) or 50% of the femur diaphysis (fractional thigh volume [TVol]) length. A regression analysis provided population sample-specific coefficients to develop 4 weight estimation models. Estimated and actual birth weights (BWs) were compared for the mean percent difference ± standard deviation of the percent differences. Systematic errors were analyzed by the Student t test, and random errors were compared by the Pitman test. RESULTS: A total of 328 pregnancies were scanned before delivery (BW range, 825-5470 g). Only 71.3% to 72.6% of weight estimations were within 10% of actual BW using original published models by Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337) and INTERGROWTH-21st (Ultrasound Obstet Gynecol 2017; 49:478-486). All predictions were accurate by using sample-specific model coefficients to minimize bias in making these comparisons (Hadlock, 0.4% ± 8.7%; INTERGROWTH-21st, 0.5% ± 10.0%; AVol, 0.3% ± 7.4%; and TVol, 0.3% ± 8.0%). Both AVol- and TVol-based models improved the percentage of correctly classified BW ±10% in 83.2% and 83.9% of cases, respectively, compared to the INTERGROWTH-21st model (73.8%; P < .01). For BW of less than 2500 g, all models slightly overestimated BW (+2.0% to +3.1%). For BW of greater than 4000 g, AVol (-2.4% ± 6.5%) and TVol (-2.3% ± 6.9%) models) had weight predictions with small systematic errors that were not different from zero (P > .05). For these larger fetuses, both AVol and TVol models correctly classified BW (±10%) in 83.3% and 87.5% of cases compared to the others (Hadlock, 79.2%; INTERGROWTH-21st, 70.8%) although these differences did not reach statistical significance. CONCLUSIONS: In this cohort, the inclusion of automated FLV measurements with conventional 2-dimensional biometry was generally associated with improved weight predictions.

Fetal Tachycardia Is an Independent Risk Factor for Chromosomal Anomalies in First-Trimester Genetic Screening.

OBJECTIVES: The association of an abnormal fetal heart rate (FHR) and chromosomal anomalies in the first trimester of pregnancy remains unclear, probably because of the lack of control for known confounding factors. This study was designed to determine whether an increased FHR is an independent risk factor for chromosomal anomalies between 11 and 14 weeks' gestation. METHODS: This cohort study included women who underwent first-trimester genetic screening between 2011 and 2014 at a single institution. A multivariable logistic regression analysis was performed to determine whether an FHR of 170 beats per minute (bpm) or higher, derived from a receiver operating characteristic curve, is an independent risk factor for all chromosomal anomalies while controlling for known confounding factors. P < .05 was considered significant. RESULTS: An FHR of 170 bpm or higher was observed in 7% (228 of 3254), and chromosomal anomalies were present in 1.0% (31 of 3254) of the population. A higher proportion of fetuses with an FHR of 170 bpm or higher had chromosomal anomalies compared to those with an FHR lower than 170 bpm. An FHR of 170 bpm or higher was an independent risk factor for chromosomal anomalies after controlling for known confounding factors. Of note, in the group of fetuses with a nuchal translucency above the 95th percentile, the frequency of chromosomal anomalies was significantly higher among fetuses with an FHR of 170 bpm or higher compared to those with an FHR lower than 170 bpm. CONCLUSIONS: Fetal tachycardia is a risk factor for chromosomal anomalies during first-trimester genetic screening, independent of increased nuchal translucency, nuchal septations, and maternal age.

Characterization of Placental Microvasculature Using Superb Microvascular Imaging.

Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA) uses clutter suppression to extract flow signals at rapid frame rates, which provides high-resolution vessel-branching details without the need for contrast agents. The potential diagnostic benefits of SMI, as described in other areas of medicine, requires further exploration during pregnancy. In this pictorial essay, we demonstrate the complementary use of SMI compared to conventional Doppler ultrasound and how it may improve our ability to characterize placental microvascular patterns without the need for ultrasound contrast agents.

Cerebral oxygen metabolism during and after therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: a feasibility study using magnetic resonance imaging.

BACKGROUND: Therapeutic hypothermia is the standard-of-care treatment for infants diagnosed with moderate-to-severe hypoxic-ischemic encephalopathy (HIE). MRI for assessing brain injury is usually performed after hypothermia because of logistical challenges in bringing acutely sick infants receiving hypothermia from the neonatal intensive care unit (NICU) to the MRI suite. Perhaps examining and comparing early cerebral oxygen metabolism disturbances to those after rewarming will lead to a better understanding of the mechanisms of brain injury in HIE and the effects of therapeutic hypothermia. OBJECTIVE: The objectives were to assess the feasibility of performing a novel T2-relaxation under spin tagging (TRUST) MRI technique to measure venous oxygen saturation very early in the time course of treatment, 18-24 h after the initiation of therapeutic hypothermia, to provide a framework to measure neonatal cerebral oxygen metabolism noninvasively, and to compare parameters between early and post-hypothermia MRIs. MATERIALS AND METHODS: Early (18-24 h after initiating hypothermia) MRIs were performed during hypothermia treatment in nine infants with HIE (six with moderate and three with severe HIE). Six infants subsequently had an MRI after hypothermia. Mean values of cerebral blood flow, oxygen extraction fraction, and cerebral metabolic rate of oxygen from MRIs during hypothermia were compared between infants with moderate and severe HIE; and in those with moderate HIE, we compared cerebral oxygen metabolism parameters between MRIs performed during and after hypothermia. RESULTS: During the initial hypothermia MRI at 23.5±5.2 h after birth, infants with severe HIE had lower oxygen extraction fraction (P=0.04) and cerebral metabolic rate of oxygen (P=0.03) and a trend toward lower cerebral blood flow (P=0.33) compared to infants with moderate HIE. In infants with moderate HIE, cerebral blood flow decreased and oxygen extraction fraction increased between MRIs during and after hypothermia (although not significantly); cerebral metabolic rate of oxygen (P=0.93) was not different. CONCLUSION: Early MRIs were technically feasible while maintaining hypothermic goal temperatures in infants with HIE. Cerebral oxygen metabolism early during hypothermia is more disturbed in severe HIE. In infants with moderate HIE, cerebral blood flow decreased and oxygen extraction fraction increased between early and post-hypothermia scans. A comparison of cerebral oxygen metabolism parameters between early and post-hypothermia MRIs might improve our understanding of the evolution of HIE and the benefits of hypothermia. This approach could guide the use of adjunctive neuroprotective strategies in affected infants.

Ecology shapes the evolutionary trade-off between predator avoidance and defence in coral reef butterflyfishes.

Antipredator defensive traits are thought to trade-off evolutionarily with traits that facilitate predator avoidance. However, complexity and scale have precluded tests of this prediction in many groups, including fishes. Using a macroevolutionary approach, we test this prediction in butterflyfishes, an iconic group of coral reef inhabitants with diverse social behaviours, foraging strategies and antipredator adaptations. We find that several antipredator traits have evolved adaptively, dependent primarily on foraging strategy. We identify a previously unrecognised axis of diversity in butterflyfishes where species with robust morphological defences have riskier foraging strategies and lack sociality, while species with reduced morphological defences feed in familiar territories, have adaptations for quick escapes and benefit from the vigilance provided by sociality. Furthermore, we find evidence for the constrained evolution of fin spines among species that graze solely on corals, highlighting the importance of corals, as both prey and structural refuge, in shaping fish morphology.

Individualized growth assessment: conceptual framework and practical implementation for the evaluation of fetal growth and neonatal growth outcome.

Fetal growth abnormalities can pose significant consequences on perinatal morbidity and mortality of nonanomalous fetuses. The most widely accepted definition of fetal growth restriction is an estimated fetal weight less than the 10th percentile for gestational age according to population-based criteria. However, these criteria do not account for the growth potential of an individual fetus, nor do they effectively separate constitutionally small fetuses from ones that are malnourished. Furthermore, conventional approaches typically evaluate estimated fetal weight at a single time point, rather than using serial scans, to evaluate growth. This article provides a conceptual framework for the individualized growth assessment of a fetus/neonate based on measuring second-trimester growth velocity of fetal size parameters to estimate growth potential. These estimates specify size models that generate individualized third-trimester size trajectories and predict birth characteristics. Comparisons of measured and predicted values are used to separate normally growing fetuses from those with growth abnormalities. This can be accomplished with individual anatomical parameters or sets of parameters. A practical and freely available software (Individualized Growth Assessment Program) has been developed to allow implementation of this approach for clinical and research purposes.

Obstetric and gynecologic ultrasound curriculum and competency assessment in residency training programs: consensus report.

Ultrasound imaging has become integral to the practice of obstetrics and gynecology. With increasing educational demands and limited hours in residency programs, dedicated time for training and achieving competency in ultrasound has diminished substantially. The American Institute of Ultrasound in Medicine assembled a multisociety task force to develop a consensus-based, standardized curriculum and competency assessment tools for obstetric and gynecologic ultrasound training in residency programs. The curriculum and competency assessment tools were developed based on existing national and international guidelines for the performance of obstetric and gynecologic ultrasound examinations and thus are intended to represent the minimum requirement for such training. By expert consensus, the curriculum was developed for each year of training, criteria for each competency assessment image were generated, the pass score was established at, or close to, 75% for each, and obtaining a set of 5 ultrasound images with pass score in each was deemed necessary for attaining each competency. Given the current lack of substantial data on competency assessment in ultrasound training, the task force expects that the criteria set forth in this document will evolve with time. The task force also encourages use of ultrasound simulation in residency training and expects that simulation will play a significant part in the curriculum and the competency assessment process. Incorporating this training curriculum and the competency assessment tools may promote consistency in training and competency assessment, thus enhancing the performance and diagnostic accuracy of ultrasound examination in obstetrics and gynecology.

Clinical assessment and brain findings in a cohort of mothers, fetuses and infants infected with ZIKA virus.

BACKGROUND: Congenital Zika virus (ZIKV) infection can be detected in both the presence and absence of microcephaly and manifests as a number of signs and symptoms that are detected clinically and by neuroimaging. However, to date, qualitative and quantitative measures for the purpose of diagnosis and prognosis are limited. OBJECTIVES: Main objectives of this study conducted on fetuses and infants with confirmed congenital Zika virus infection and detected brain abnormalities were (1) to assess the prevalence of microcephaly and the frequency of the anomalies that include a detailed description based on ultrasound and magnetic resonance imaging in fetuses and ultrasound, magnetic resonance imaging, and computed tomography imaging postnatally, (2) to provide quantitative measures of fetal and infant brain findings by magnetic resonance imaging with the use of volumetric analyses and diffusion-weighted imaging, and (3) to obtain additional information from placental and fetal histopathologic assessments and postnatal clinical evaluations. STUDY DESIGN: This is a longitudinal cohort study of Zika virus-infected pregnancies from a single institution in Colombia. Clinical and imaging findings of patients with laboratory-confirmed Zika virus infection and fetal brain anomalies were the focus of this study. Patients underwent monthly fetal ultrasound scans, neurosonography, and a fetal magnetic resonance imaging. Postnatally, infant brain assessment was offered by the use of ultrasound imaging, magnetic resonance imaging, and/or computed tomography. Fetal head circumference measurements were compared with different reference ranges with <2 or <3 standard deviations below the mean for the diagnosis of microcephaly. Fetal and infant magnetic resonance imaging images were processed to obtain a quantitative brain volumetric assessment. Diffusion weighted imaging sequences were processed to assess brain microstructure. Anthropometric, neurologic, auditory, and visual assessments were performed postnatally. Histopathologic assessment was included if patients opted for pregnancy termination. RESULTS: All women (n=214) had been referred for Zika virus symptoms during pregnancy that affected themselves or their partners or if fetal anomalies that are compatible with congenital Zika virus syndrome were detected. A total of 12 pregnant patients with laboratory confirmation of Zika virus infection were diagnosed with fetal brain malformations. Most common findings that were assessed by prenatal and postnatal imaging were brain volume loss (92%), calcifications (92%), callosal anomalies (100%), cortical malformations (89%), and ventriculomegaly (92%). Results from fetal brain volumetric assessment by magnetic resonance imaging showed that 1 of the most common findings associated with microcephaly was reduced supratentorial brain parenchyma and increased subarachnoid cerebrospinal fluid. Diffusion weighted imaging analyses of apparent diffusion coefficient values showed microstructural changes. Microcephaly was present in 33.3-58.3% of the cases at referral and was present at delivery in 55.6-77.8% of cases. At birth, most of the affected neonates (55.6-77.8%) had head circumference measurements >3 standard deviations below the mean. Postnatal imaging studies confirmed brain malformations that were detected prenatally. Auditory screening results were normal in 2 cases that were assessed. Visual screening showed different anomalies in 2 of the 3 cases that were examined. Pathologic results that were obtained from 2 of the 3 cases who opted for termination showed similar signs of abnormalities in the central nervous system and placental analyses, including brain microcalcifications. CONCLUSION: Congenital microcephaly is not an optimal screening method for congenital Zika virus syndrome, because it may not accompany other evident and preceding brain findings; microcephaly could be an endpoint of the disease that results from progressive changes that are related to brain volume loss. Long-term studies are needed to understand the clinical and developmental relevance of these findings.