Maternal Glycemic Status and Longitudinal Fetal Body Composition and Organ Volumes Based on Three-Dimensional Ultrasonography.

OBJECTIVE: Gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth as measured by two-dimensional ultrasonography. Whether fetal three-dimensional (3D) soft tissue and organ volumes provide additional insight into fetal overgrowth is unknown. RESEARCH DESIGN AND METHODS: We prospectively evaluated longitudinal 3D fetal body composition and organ volumes in a diverse US singleton pregnancy cohort (2015-2019). Women were diagnosed with GDM, impaired glucose tolerance (IGT), or normal glucose tolerance (NGT). Up to five 3D ultrasound scans measured fetal body composition and organ volumes; trajectories were modeled using linear mixed models. Overall and weekly mean differences in fetal 3D trajectories were tested across glycemic status, adjusted for covariates. RESULTS: In this sample (n = 2,427), 5.2% of women had GDM, and 3.0% had IGT. Fetuses of women who developed GDM compared with NGT had larger fractional arm and fractional fat arm volumes from 26 to 35 weeks, smaller fractional lean arm volume from 17 to 22 weeks, and larger abdominal area from 24 to 40 weeks. Fetuses of women with IGT had similar growth patterns, which manifested later in gestation and with larger magnitudes, and had larger fractional lean arm volume. No overall differences were observed among thigh or organ volumes across glycemic status. CONCLUSIONS: Body composition differed in fetuses of GDM-complicated pregnancies, including larger arm and abdominal measures across the second and third trimesters. Patterns were similar in IGT-complicated pregnancies except that they occurred later in gestation and with larger magnitudes. Future research should explore how lifestyle and medication may alter fetal fat accumulation trajectories among hyperglycemic pregnancies.

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 Bonferroni Multiple Comparison 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.

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.

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.

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.

The Relation between Negative Automatic Thoughts and Psychological Inflexibility in Schizophrenia.

BACKGROUND: Schizophrenia is one of the most severe disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) spectrum. Negative automatic thoughts (NAT), cognitive fusion (CF), and experiential avoidance (EA), as part of psychological inflexibility (PI), can be considered important dysfunctional cognitive processes in schizophrenia. METHODS: In the present study, two samples were included: a target group consisting of 41 people with schizophrenia (23 females; aged 44.98 ± 11.74), and a control group consisting of 40 individuals with end-stage chronic kidney disease (CKD) (27 males; aged 60.38 ± 9.14). RESULTS: Differences were found between the two groups, with patients with schizophrenia showing an increased frequency of NAT, as well as higher levels of CF and EA (psychological inflexibility), compared to the control group. NAT were the mediator in the relation between the schizophrenia diagnosis and CF, as well as EA. CONCLUSION: Individuals with schizophrenia present a specific dysfunctional pattern of cognitive functioning, in which negative automatic thoughts represent a distinctive pathway to cognitive fusion and experiential avoidance.

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.

Standards for evaluating neonatal growth outcomes using individualized pathological growth potential realization indices.

OBJECTIVE: Provide standards for detecting neonatal growth abnormalities with the average pathological Growth Potential Realization Index (av. pGPRI). METHODS: Individualized Growth Assessment (IGA) evaluations of 117 neonates with normal growth outcomes were carried out using measurements of WT, HC, AC, ThC and CHL. Growth Potential Realization Index (GPRI) values for each parameter were calculated from predicted and actual birth measurements, the former obtained using Rossavik size models derived from the second-trimester growth potential estimates. Subtraction of either the upper and lower boundaries of GPRI reference ranges from these GPRI measurements gave + pGPRI and - pGPRI measurements. GPRI's within their reference ranges were assigned pGPRI values of zero. Average values for these two types of pGPRI's were calculated for the WT, HC, CHL set (n = 117) and the WT, HC, AC, ThC, CHL set (n = 112). RESULTS: The 95% reference ranges for the av. +pGPRI's and av. -pGPRI's in the WT, HC, CHL set were 0% to +0.50% and 0% to -0.40%, respectively. In the WT, HC, AC, ThC, CHL set, the comparable results were 0% to +0.50% and 0% to -0.72%. CONCLUSION: Standards are provided for classifying neonatal growth outcomes with a parameter quantifying growth pathology that was based on individualized growth potentials.

Individualized growth assessment in pregnancies complicated by fetal gastroschisis.

OBJECTIVE: Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases. STUDY DESIGN: Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements. RESULTS: Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (n = 19), there was 84% agreement between IGA and conventional methods in determining pathological growth in both the 3rd trimester and at birth. In the growth restriction and recovery group (n = 7), there was 71% agreement both in the 3rd trimester and at birth between IGA and conventional methods. In the progressive growth restriction group (n = 5), there was 100% agreement in the 3rd trimester and 60% agreement at birth between IGA and conventional methods. CONCLUSION: We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns - one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.