Can growth in dichorionic twins be monitored with individualized growth assessment?

OBJECTIVE: To characterize fetal growth in dichorionic twins using individualized growth assessment (IGA), a method based on individual growth potential estimates. METHODS: This secondary analysis included 286 fetuses/neonates from 143 dichorionic twin pregnancies that were part of the ESPRiT (Evaluation of Sonographic Predictors of Restricted Growth in Twins) study. The sample was subcategorized according to birth weight into appropriate-for-gestational-age (AGA) (n = 243) and small-for-gestational-age (SGA) (n = 43) cohorts. Serial biometric scans evaluating biparietal diameter, head circumference (HC), abdominal circumference, femur diaphysis length and estimated weight at 2-week intervals were used to evaluate fetal growth, while measurements of birth weight, crown-heel length and HC determined neonatal growth outcome. Six abnormalities (hypoxic ischemic encephalopathy, periventricular leukomalacia, necrotizing enterocolitis, respiratory distress, sepsis and death) constituted the evaluated adverse neonatal outcomes (ANO). IGA was used to: evaluate differences in second-trimester growth velocities between singletons (from a published dataset) and dichorionic twins (138 AGA twins with normal third-trimester growth); describe the degree to which actual third-trimester growth in twins followed expected growth (111 AGA twins, normal fetal growth and neonatal growth outcomes); determine if the fetal growth pathology score 1 (-FGPS1) could detect, quantify and classify twin growth pathology (224 AGA, 42 SGA); and assess the relationship between -FGPS1 and ANO (24 SGA twins with progressive growth restriction confirmed by abnormal neonatal growth outcome). RESULTS: The differences in second-trimester growth velocity between singletons and twins (means and variances) were small and not statistically significant. Percent deviations from the expected third-trimester size trajectories were within the 95% reference ranges derived from singletons at 95.7% (1677/1752) of timepoints studied. Abnormal growth was detected in 37.9% of AGA twins and 85.7% of SGA twins. Growth restriction was more heterogeneous in AGA twins, while in SGA twins progressive growth restriction was the principal type (66.7%). -FGPS1 patterns previously defined in singletons classified 97.5% of pathological twin cases. In our most severe form of growth restriction (progressive), there were only three (12.5%) ANOs related to growth abnormalities, all in cases with -FGPS1 values more negative than -2.0%. Using these criteria, the frequency of ANO was 33%. CONCLUSIONS: With respect to growth, dichorionic twins can be considered as two singletons in the same uterus. Normally growing dichorionic twins have the same growth potential as singletons with normal growth outcome. These twins also follow expected third-trimester growth trajectories with the same precision as do singletons. Third-trimester growth pathology can be detected, quantified and classified using -FGPS1 as in singletons. Limited evidence of a relationship between fetal growth abnormalities and adverse neonatal outcome was found. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Second-trimester growth velocities in twin and singleton pregnancies.

OBJECTIVE: Previous small studies used individualized growth assessment (IGA) to characterize prenatal growth velocities of singletons and twins. We aimed to compare second-trimester growth velocities of individual anatomical parameters between monochorionic diamniotic (MCDA) twins, dichorionic diamniotic (DCDA) twins and singleton fetuses in a larger study. METHODS: This was a study of a novel cohort of 222 MCDA twins and previously published cohorts of 40 DCDA twins and 118 singletons with serial ultrasound data. Fetal biometric measurements of biparietal diameter, head circumference, abdominal circumference and femur diaphysis length from prenatal ultrasound examinations were used to calculate second-trimester growth velocities using direct calculation or linear regression analysis. Linear fit was assessed based on the coefficient of determination (R2 ). Mean growth velocities and variances were compared among the three groups. RESULTS: The majority of cases underwent three second-trimester ultrasound examinations with fetal biometry available. All fetuses had linear growth, with R2 > 99% for all parameters. Only 1-2% of all MCDA and DCDA anatomical parameters had abnormal growth velocity scores outside the 95% reference range for singletons. There were no significant differences in mean growth velocity for any parameter between MCDA twins and singletons. Femur diaphysis length growth velocity was significantly lower in DCDA twins than in both MCDA twins and singletons. There were no other significant differences among the groups. CONCLUSIONS: Expanding on prior work using IGA, we found that second-trimester growth velocity of the four major anatomical parameters overall was similar between twins and singletons and between MCDA and DCDA twins, supporting the use of singleton-derived growth standards for IGA in twins. Twin growth potential appears to be similar to that of singletons in the second trimester, suggesting that subsequent growth divergence may be due to third-trimester physiological or pathological changes in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Third-trimester growth diversity in small fetuses classified as appropriate-for-gestational age or small-for-gestational age at birth.

OBJECTIVE: We have shown previously that third-trimester growth in small fetuses (estimated fetal weight (EFW) < 10th percentile) with birth weight (BW) < 10th percentile is heterogeneous using individualized growth assessment (IGA). We aimed to test our hypothesis that individual growth patterns in small fetuses with BW > 10th percentile are also variable but in different ways. METHODS: This was a study of 191 cases with EFW < 10th percentile and BW > 10th percentile (appropriate-for-gestational-age (AGA) cohort), derived from the PORTO study. Composite size parameters were used to quantify growth pathology at individual third-trimester timepoints (individual composite prenatal growth assessment score (-icPGAS)). The fetal growth pathology score 1 (-FGPS1), calculated cumulatively from serial -icPGAS values, was used to characterize third-trimester growth patterns. Vascular-system evaluation included umbilical artery (UA) and middle cerebral artery (MCA) Doppler velocimetry. Outcome variables were birth age (preterm/term delivery) and BW (expressed as growth potential realization index for weight (GPRIWT ) and percentile). The findings from the AGA cohort were compared with those from small fetuses (EFW < 10th percentile) with BW < 10th percentile (small-for-gestational-age (SGA) cohort). RESULTS: The AGA cohort was found to have 134 fetuses (70%) with normal growth pattern and 57 (30%) with growth restriction based on IGA criteria. Seven growth-restriction -FGPS1 patterns were observed, including the previously defined progressive, late, adaptive and recovering types. The recovering type was the most common growth pattern in the AGA cohort (50.9%). About one-third of fetuses without any evidence of growth restriction had significant unexplained abnormalities in the UA (34%) and MCA (31%) and elevated mean GPRIWT values (113 ± 12.5%). Comparison of the AGA and SGA cohorts indicated a significant difference in the distribution of -FGPS1 growth patterns (P = 0.0001). Compared with the SGA cohort, the AGA cohort had more fetuses with a normal growth pattern (70% vs 38%) and fewer cases with growth restriction (30% vs 62%). While the recovering type was the most common growth-restriction pattern in the AGA cohort (51%), the progressive type was the primary growth-restriction pattern in the SGA cohort (44%). No difference in the incidence of MCA or UA abnormality was found between the SGA and AGA cohorts when comparing subgroups of more than 10 fetuses. CONCLUSIONS: Both normal-growth and growth-restriction patterns were observed in the AGA cohort using IGA, as seen previously in the SGA cohort. The seven types of growth restriction defined in the SGA cohort were also identified in AGA cases, but their distribution was significantly different. In one-third of cases without evidence of growth pathology in the AGA cohort, Doppler abnormalities in the UA and MCA were seen. This heterogeneity underscores the difficulty of accurate classification of fetal and neonatal growth status using conventional population-based methods. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

ISUOG Practice Guidelines: ultrasound assessment of fetal biometry and growth.

INTRODUCTION These Guidelines aim to describe appropriate assessment of fetal biometry and diagnosis of fetal growth disorders. These disorders consist mainly of fetal growth restriction (FGR), also referred to as intrauterine growth restriction (IUGR) and often associated with small­for­gestational age (SGA), and large­for­gestational age (LGA), which may lead to fetal macrosomia; both have been associated with a variety of adverse maternal and perinatal outcomes. Screening for, and adequate management of, fetal growth abnormalities are essential components of antenatal care, and fetal ultrasound plays a key role in assessment of these conditions. The fetal biometric parameters measured most commonly are biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur diaphysis length (FL). These biometric measurements can be used to estimate fetal weight (EFW) using various different formulae1. It is important to differentiate between the concept of fetal size at a given timepoint and fetal growth, the latter being a dynamic process, the assessment of which requires at least two ultrasound scans separated in time. Maternal history and symptoms, amniotic fluid assessment and Doppler velocimetry can provide additional information that may be used to identify fetuses at risk of adverse pregnancy outcome. Accurate estimation of gestational age is a prerequisite for determining whether fetal size is appropriate­for­gestational age (AGA). Except for pregnancies arising from assisted reproductive technology, the date of conception cannot be determined precisely. Clinically, most pregnancies are dated by the last menstrual period, though this may sometimes be uncertain or unreliable. Therefore, dating pregnancies by early ultrasound examination at 8­14 weeks, based on measurement of the fetal crown­rump length (CRL), appears to be the most reliable method to establish gestational age. Once the CRL exceeds 84 mm, HC should be used for pregnancy dating2­4. HC, with or without FL, can be used for estimation of gestational age from the mid­trimester if a first­trimester scan is not available and the menstrual history is unreliable. When the expected delivery date has been established by an accurate early scan, subsequent scans should not be used to recalculate the gestational age1. Serial scans can be used to determine if interval growth has been normal. In these Guidelines, we assume that the gestational age is known and has been determined as described above, the pregnancy is singleton and the fetal anatomy is normal. Details of the grades of recommendation used in these Guidelines are given in Appendix 1. Reporting of levels of evidence is not applicable to these Guidelines.

Pautas de ISUOG para la práctica: evaluación ecográfica de la biometría y el crecimiento fetal INTRODUCCIÓN: El objetivo de estas Pautas es describir la evaluación adecuada de la biometría fetal y el diagnóstico de los trastornos del crecimiento fetal. Estos trastornos consisten principalmente en la restricción del crecimiento fetal (RCF), también conocida como restricción del crecimiento intrauterino (RCIU), que a menudo está asociada con un tamaño pequeño para la edad gestacional (PEG) o grande para la edad gestacional (GEG), que pueden dar lugar a la macrosomía fetal; ambos se han asociado con una variedad de resultados maternos y perinatales adversos. La detección y el tratamiento adecuado de las anomalías del crecimiento fetal son componentes esenciales de la atención prenatal, y la ecografía fetal desempeña un papel fundamental en la evaluación de estas afecciones. Los parámetros biométricos fetales medidos con mayor frecuencia son (todas las siglas procedentes del inglés) el diámetro biparietal (BPD), el perímetro cefálico (HC), el perímetro abdominal (AC) y la longitud de la diáfisis del fémur (FL). Estas mediciones biométricas se pueden utilizar para estimar el peso del feto (PEF) mediante fórmulas diferentes1 . Es importante diferenciar entre el concepto de tamaño fetal en un momento dado y el crecimiento fetal en sí, siendo este último un proceso dinámico cuya evaluación requiere al menos dos ecografías separadas en el tiempo. La historia y los síntomas de la madre, la evaluación del líquido amniótico y la velocimetría Doppler pueden proporcionar información adicional que se puede utilizar para identificar los fetos bajo riesgo de resultados adversos del embarazo. La estimación precisa de la edad gestacional es un prerrequisito para determinar si el tamaño del feto es apropiado para la edad gestacional (AEG). Excepto en el caso de los embarazos procedentes de tecnologías de reproducción asistida, la fecha de concepción no se puede determinar con precisión. Clínicamente, la fecha de la mayoría de los embarazos se establece en función del último período menstrual, aunque a veces esto puede ser incierto o poco fiable. Por lo tanto, el fechado de los embarazos mediante ecografía temprana a las 8-14 semanas, mediante la medición de la longitud céfalo-caudal (LCC) fetal, parece ser el método más fiable para establecer la edad gestacional. Una vez que la LCC excede los 84 mm, se debe usar el HC2-4 para establecer la fecha del embarazo. El HC, con o sin FL, se puede utilizar para estimar la edad gestacional a partir de la mitad del primer trimestre si no se dispone de una ecografía del primer trimestre y el historial menstrual no es fiable. Cuando se ha establecido la fecha prevista del parto mediante una exploración temprana precisa, no se deben utilizar exploraciones posteriores para recalcular la edad gestacional1 . Las exploraciones en serie se pueden utilizar para determinar si el intervalo del crecimiento ha sido normal. En estas Pautas se asume que la edad gestacional es conocida y ha sido determinada según lo anterior, que el embarazo es de feto único y que la anatomía fetal es normal. En el Apéndice 1 se detallan los grados de recomendación utilizados en estas Pautas. El informe sobre los niveles de evidencia no es aplicable a estas Pautas.

Longitudinal assessment of lung area measurements by two-dimensional ultrasound in fetuses with isolated left-sided congenital diaphragmatic hernia.

OBJECTIVE: To evaluate lung growth in healthy fetuses and those with congenital diaphragmatic hernia (CDH) using two-dimensional (2D) ultrasound. METHODS: Fetal right lung measurements obtained by 2D ultrasound between 19 and 37 weeks' gestation were evaluated longitudinally in 66 healthy fetuses and 52 fetuses with isolated left-sided CDH. Right lung areas were determined by the 'tracing' and 'longest-diameters' methods and, subsequently, lung area-to-head circumference ratios (LHRs) were calculated. Functions fitted to these size parameters with respect to gestational age were evaluated for three sets of group-wise comparisons: (1) healthy vs CDH fetuses; (2) different degrees of severity of CDH; and (3) CDH fetuses that survived vs those that died by 6 months postpartum. RESULTS: There was a significantly slower increase in right lung areas and LHRs with advancing gestational age in CDH fetuses than in healthy individuals (P < 0.05). Compared to those with milder forms of CDH, lung areas and LHRs of fetuses with more severe forms displayed a smaller increase (P < 0.05) and LHRs of fetuses with severe CDH did not increase during pregnancy (P > 0.05). Individuals who died postpartum did not show any increase in LHR (P > 0.05) throughout gestation. CONCLUSIONS: The right lung area and LHR, calculated using either the longest-diameters or tracing method, display reduced growth rates during gestation in cases of isolated left-sided CDH as compared with healthy fetuses. The growth curve characteristics of fetal lung areas and LHRs may be useful for predicting neonatal mortality.

Quantitative characterization of dense body, autophagic vacuole, and acid phosphatase-bearing particle populations during the early phases of glucagon-induced autophagy in rat liver.

Quantitative characterization of dense body, autophagic vacuole and acid phosphatase-bearing particle populations of rat liver have been made at 10 min intervals during the first 50 min following the intraperitoneal administration of glucagon. Beginning 10 to 20 min postinjection, increases in the number of autophagic vacuoles and in the osmotic sensitivity of acid phosphatase-bearing particles were observed, associated with a progressive disappearance of dense bodies. These changes appeared to reach a maximum 50 min after treatment. The average volume of autophagic vacuoles was found to be 440-870% greater than that of normal dense bodies during this time period. No consistent change in total acid phosphatase activity was noted. A detailed study of autophagic vacuole profile populations revealed the presence of five different types of profiles, two of which, types I and II, accounted for 76.3-94.4% of the profiles examined. Type I profiles primarily contained elements of the endoplasmic reticulum, free ribosomes, and ground cytoplasm. Type II profiles had mitochondrial profiles as their principal constituent, but endoplasmic reticulum and free ribosomes were also seen. At all time points type I profiles predominated, comprising 55-69% of the profiles found. Both profile types were bounded by single and double limiting membranes, the former being predominate. A time-dependent change in the ratio of single to double membrane-limited profiles could not be demonstrated. Morphometric parameters derived from profile size distributions indicated that the number of types I and II autophagic vacuoles increased with time, the rate being greater for the type II particle, except between 40 and 50 min. The average volume of the type II autophagic vacuole was consistently greater than that of the type I.

Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes.

The response of rat liver lysosomes to an intraperitoneal injection of glucagon has been evaluated from studies on the mechanical fragility, osmotic sensitivity, and sedimentation properties of these subcellular particles. It has been found that about (1/2) hr after the injection of glucagon the hepatic lysosomes exhibit a fairly sudden increase in their sensitivity to mechanical stresses and to exposure to a decreased osmotic pressure. At the same time, their sedimentation properties undergo complex changes characterized mainly by a significant increase in the sedimentation coefficient of a considerable proportion of the total particles. In addition, glucagon causes an increase in the proportion of slowly sedimenting particles, with the result that the distribution of sedimentation coefficients within the total population tends to become bimodal. The latter change is more pronounced for acid phosphatase, less so for cathepsin D, and barely detectable for acid deoxyribonuclease. All these modifications are maximal between 45 and 90 min after injection and regress to normal within approximately 4 hr. With the exception of the increase in the slow component, for which no explanation can be advanced at the present time, they are consistent with the hypothesis that glucagon causes an increase in lysosomal size, and may be related to the autophagic-vacuole formation known to occur after glucagon administration.

Localization of Na + , K + -ATPase and other enzymes in teleost pseudobranch. II. Morphological characterization of intact pseudobranch, subcellular fractions, and plasma membrane substructure.

The pseudobranch of the pinfish Lagodon rhomboides is an unusually homogeneous and structurally simple tissue, well suited to cell fractionation studies. Its principal cell type, closely related to the chloride cells of teleost gill, is characterized by numerous mitochondria in close association with abundant tubular invaginations of the plasma membrane. Other cytoplasmic organelles are rarely encountered. In broken fresh pseudobranch cells negatively stained with ammonium molybdate, a 40 A particulate layer was observed on the intracellular surface of the tubular plasma membrane fragments. Nuclear (N), mitochondrial-light mitochondrial (M+L), and microsomal (P) fractions, obtained by differential centrifugation, were characterized by examination of fixed, embedded pellets and unfixed preparations negatively stained with ammonium molybdate and potassium phosphotung-state. Mitochondria, in orthodox configuration and retaining their outer membranes, were observed in M+L and N. Significant amounts of tubular, sheetlike, or vesicular membrane fragments were observed in all three fractions. Many such fragments, when negatively stained, showed the 40 A particulate surface layer characteristic of plasma membrane invaginations, and in some cases 20-A projections could be resolved on the opposite (extracellular) surface. Since these morphological observations, together with previously presented biochemical data, suggest a plasma membrane localization of Na(+), K(+)-ATPase, the possible association of the enzyme with membrane projections is discussed.

Localization of Na + , K + -ATPase and other enzymes in teleost pseudobranch. I. Biochemical characterization of subcellular fractions.

In an effort to determine the subcellular localization of sodium- and potassium-activated adenosine triphosphatase (Na(+), K(+)-ATPase) in the pseudobranch of the pinfish Lagodon rhomboides, this tissue was fractionated by differential centrifugation and the activities of several marker enzymes in the fractions were measured. Cytochrome c oxidase was found primarily in the mitochondrial-light mitochondrial (M+L) fraction. Phosphoglucomutase appeared almost exclusively in the soluble (S) fraction. Monoamine oxidase was concentrated in the nuclear (N) fraction, with a significant amount also in the microsomal (P) fraction but little in M+L or S. Na(+), K(+)-ATPase and ouabain insensitive Mg(2+)-ATPase were distributed in N, M+L, and P, the former having its highest specific activity in P and the latter in M+L. Rate sedimentation analysis of the M+L fraction indicated that cytochrome c oxidase and Mg(2+)-ATPase were associated with a rapidly sedimenting particle population (presumably mitochondria), while Na(+), K(+)-ATPase was found primarily in a slowly sedimenting component. At least 75% of the Na(+), K(+)-ATPase in M+L appeared to be associated with structures containing no Mg(2+)-ATPase. Kinetic properties of the two ATPases were studied in the P fraction and were typical of these enzymes in other tissues. Na(+), K(+)-ATPase activity was highly dependent on the ratio of Na(+) and K(+) concentrations but independent of absolute concentrations over at least a fourfold range.

Fetal growth parameters and birth weight: their relationship to neonatal body composition.

OBJECTIVES: The main goal was to investigate the relationship between prenatal sonographic parameters and birth weight in predicting neonatal body composition. METHODS: Standard fetal biometry and soft tissue parameters were assessed prospectively in third-trimester pregnancies using three-dimensional ultrasonography. Growth parameters included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), mid-thigh circumference and femoral diaphysis length (FDL). Soft tissue parameters included fractional arm volume (AVol) and fractional thigh volume (TVol) that were derived from 50% of the humeral or femoral diaphysis lengths, respectively. Percentage of neonatal body fat (%BF) was determined within 48 h of delivery using a pediatric air displacement plethysmography system based on principles of whole-body densitometry. Correlation and stepwise multiple linear regression analyses were performed with potential prenatal predictors and %BF as the outcome variable. RESULTS: Eighty-seven neonates were studied with a mean +/- SD %BF of 10.6 +/- 4.6%. TVol had the greatest correlation with newborn %BF of all single-parameter models. This parameter alone explained 46.1% of the variability in %BF and the best stepwise multiple linear regression model was: %BF = 0.129 (TVol) - 1.03933 (P < 0.001). Birth weight similarly explained 44.7% of the variation in %BF. AC and estimated fetal weight (EFW) accounted for only 24.8% and 30.4% of the variance in %BF, respectively. Skeletal growth parameters, such as FDL (14.2%), HC (7.9%) and BPD (4.0%), contributed the least towards explaining the variance in %BF. CONCLUSIONS: During the late third trimester of pregnancy %BF is most highly correlated with TVol. Similar to actual birth weight, this soft tissue parameter accounts for a significant improvement in explaining the variation in neonatal %BF compared with fetal AC or EFW alone.

Fractional limb volume--a soft tissue parameter of fetal body composition: validation, technical considerations and normal ranges during pregnancy.

OBJECTIVES: The main goals were to provide normal reference ranges for fractional limb volume as a new index of generalized fetal nutritional status, to evaluate the reproducibility of fractional fetal limb volume measurements during the second and third trimesters of pregnancy, and to demonstrate technical considerations for this technique. METHODS: This was a prospective, cross-sectional study of gravid women during mid to late pregnancy. Fractional limb volumes were based on either 50% of humeral or femoral diaphysis length. Each partial volume was subdivided into five equidistant slices that were centered along the mid-arm or mid-thigh. Slices were traced manually to obtain fractional arm (AVol) or fractional thigh (TVol) volume. Reproducibility studies were performed, using Bland-Altman plots, to assess blinded interobserver and intraobserver measurement bias and agreement. Selected images were chosen to demonstrate technical factors for the acquisition and analysis of these parameters. Reference charts were established to describe normal ranges for AVol and TVol. RESULTS: Three hundred and eighty-seven subjects were scanned to include 380 AVol (range, 1.1-68.3 mL) and 378 TVol (range 2.0-163.2 mL) measurements between 18.0 and 42.1 weeks' menstrual age. No gender differences were found in these soft tissue measurements (AVol, P = 0.90; TVol, P = 0.91; Mann-Whitney test). Intraobserver mean bias +/- SD and 95% limits of agreement (LOA) for fractional limb volumes were: 2.2 +/- 4.2% (95% LOA, - 6.0 to 10.5%) for AVol and 2.0 +/- 4.2% (95% LOA, - 6.3 to 10.3%) for TVol. Interobserver bias and agreement were - 1.9 +/- 4.9% (95% LOA, - 11.6 to 7.8%) for AVol and - 2.0 +/- 5.4% (95% LOA, - 12.5 to 8.6%) for TVol. Technical factors were related to image optimization, transducer pressure, fetal movement, soft tissue compression and amniotic fluid volume. CONCLUSIONS: Fractional limb volume assessment may improve the detection and monitoring of malnourished fetuses because this soft tissue parameter can be obtained quickly and reproducibly during mid to late pregnancy. Careful attention should be placed on technical factors that can potentially affect optimal acquisition and analysis of these volume measurements.

New fetal weight estimation models using fractional limb volume.

OBJECTIVES: The main goal of this study was to determine the accuracy and precision of new fetal weight estimation models, based on fractional limb volume and conventional two-dimensional (2D) sonographic measurements during the second and third trimesters of pregnancy. METHODS: A prospective cross-sectional study of 271 fetuses was performed using three-dimensional ultrasonography to extract standard measurements-biparietal diameter (BPD), abdominal circumference (AC) and femoral diaphysis length (FDL)-plus fractional arm volume (AVol) and fractional thigh volume (TVol) within 4 days of delivery. Weighted multiple linear regression analysis was used to develop 'modified Hadlock' models and new models using transformed predictors that included soft tissue parameters for estimating birth weight. Estimated and observed birth weights were compared using mean percent difference (systematic weight estimation error) and the SD of the percent differences (random weight estimation error). The proportion of newborns with estimated birth weight within 5 or 10% of actual birth weight were compared using McNemar's test. RESULTS: Birth weights in the study group ranged from 235 to 5790 g, with equal proportions of male and female infants. Six new fetal weight estimation models were compared with the results for modified Hadlock models with sample-specific coefficients. All the new models were very accurate, with mean percent differences that were not significantly different from zero. Model 3 (which used the natural logarithms of BPD, AC and AVol) and Model 6 (which used the natural logarithms of BPD, AC and TVol) provided the most precise weight estimations (random error = 6.6% of actual birth weight) as compared with 8.5% for the best original Hadlock model and 7.6% for a modified Hadlock model using sample-specific coefficients. Model 5 (which used the natural logarithms of AC and TVol) classified an additional 9.1% and 8.3% of the fetuses within 5% and 10% of actual birth weight and Model 6 classified an additional 7.3% and 4.1% of infants within 5% and 10% of actual birth weight. CONCLUSION: The precision of fetal weight estimation can be improved by adding fractional limb volume measurements to conventional 2D biometry. New models that consider fractional limb volume may offer novel insight into the contribution of soft tissue development to weight estimation.

Individualized growth assessment of fetal thigh circumference using three-dimensional ultrasonography.

OBJECTIVES: To develop individualized growth assessment (IGA) standards for upper (ThC(u)) and middle (ThC(m)) fetal thigh circumferences using three-dimensional ultrasonography. METHODS: A prospective, longitudinal sonographic study of 30 fetuses was performed beginning at 18 weeks' menstrual age. Second-trimester sonographic parameters were measured from three-dimensional volume data to establish IGA standards. Normal infant growth outcomes were confirmed using modified Neonatal Growth Assessment Scores (m(3)NGAS(51)). ThC(u) and ThC(m) were studied in more detail. Rossavik growth model specification procedures, based on the slopes of the second-trimester growth curves, were developed for both ThC(u) and ThC(m). Third-trimester growth trajectories and birth measurements were subsequently predicted for these parameters. Percentage deviations during the third trimester and percentage differences at actual birth age were used to compare observed and predicted measurements. The 95% ranges for Growth Potential Realization Index (GPRI) values for both types of thigh circumference were determined. Values for m(3)NGAS(51) using GPRI(ThC(u)), GPRI(ThC(m)) and GPRI(ThC(o)) (original method) were compared. RESULTS: The 30 newborns had no postnatal evidence of abnormal growth. Two examiners demonstrated a satisfactory measurement bias of mean +/- SD 2.1 +/- 3.6 (95% limits of agreement,-4.9 to 9.1)% for ThC(m) and 3.3 +/- 4.1 (95% limits of agreement,-4.8 to 11.4)% for ThC(u). Rossavik functions fitted parameter trajectories well, with mean R(2) values of 99.5 +/- 0.4% for ThC(u) and 99.6 +/- 0.3% for ThC(m). By fixing coefficients k at their mean values, their respective fits did not change, and the variabilities of coefficients c and s were significantly reduced. For ThC(u), coefficient c was significantly related to the second-trimester slope (R(2)=98.6%), as was s to c(R(2)=91.0%). For ThC(m), coefficient c was significantly related to the second-trimester slope (R(2)=98.6%), as was s to c(R(2)=85.6%). Third-trimester growth trajectories, derived from second-trimester slopes for individual fetuses, had third-trimester deviations of 0.07 +/- 3.7% for ThC(u) and-0.04 +/- 3.7% for ThC(m). Percentage differences at birth age were 16.8 +/- 10.2% for ThC(u) and 8.9 +/- 9.5% for ThC(m). With correction for systematic overestimations, the mean GPRI values were 103.7 (95% range, 90-121)% for ThC(u) and 101.6 (95% range, 88-118)% for ThC(m). Corresponding mean +/- SD m(3)NGAS(51) values, using GPRI(ThC(u)), GPRI(ThC(m)) and GPRI(ThC(o)), were 203 +/- 11%, 201 +/- 10% and 200 +/- 9%, respectively. CONCLUSIONS: Fetal thigh circumference can be measured reliably and evaluated using standard IGA methods. Both ThC(u) and ThC(m) give similar results in the third trimester but neonatal thigh circumference predictions are improved by using ThC(m). Corresponding GPRI(ThC(m)) values are closer to the ideal value of 100% and can be used in m(3)NGAS(51) calculations for assessment of neonatal growth outcome.

Fetal ventricular pacing for hydrops secondary to complete atrioventricular block.

The advent of ultrasound recording has expanded the capabilities for treatment of the fetus in utero. The diagnosis of specific disease processes has allowed for prenatal intervention by new techniques designed to improve fetal survival. The application of ventricular pacing in a hydropic fetus with complete atrioventricular (AV) block is reported. Complete AV block resulted from maternal collagen vascular disease. The application of ventricular pacing was to allow for further in utero development and for reversal of hydrops fetalis after improvement in cardiac output. Despite fetal death 4 hours after placement of the ventricular pacing lead, this procedure when applied earlier in the development of hydrops may allow for fetal survival. Ventricular pacing was accomplished without apparent trauma to mother or fetus and no evidence of fetal injury was seen at necropsy. Therefore, in the fetus who would otherwise die in utero before the point of viability ex utero, fetal ventricular pacing may be a rational alternative to current observation.

A simplified method for determining individual growth curve standards.

To simplify the procedure for obtaining individual growth curve standards, we investigated the use of models derived from the slopes of growth curves determined before 26 weeks' menstrual age. In serial examinations of 33 normal fetuses between 15-38 weeks, we obtained measurements of the biparietal diameter (BPD), head circumference, abdominal circumference, femur diaphysis length, head profile area, abdominal profile area, head cube, and abdominal cube. Rossavik models fitted to these data provided estimates of the coefficients c and s, and fitting linear models to the data before 26 weeks gave estimates of growth curve slopes. Slopes were also estimated from two data points at approximately 16 and 25 weeks. Regression analysis demonstrated a strong linear relationship between loge c and loge SLOPE1 (R2 = 87.3-98.4%), and between s and c (R2 = 64.9-90.3%). Using these relationships, growth models were determined from the slope values. Comparisons between observed measurements and those predicted by these models for the period after 26 weeks indicated that the methods of slope calculation were equally accurate in predicting future growth, and that this accuracy was very similar to that obtained with models based on regression analysis. These results demonstrate that individual growth curve standards for at least eight anatomic parameters during the last 14 weeks of pregnancy can be determined from the data obtained in two examinations before 26 weeks' menstrual age.

Individual growth curve standards in triplets: prediction of third-trimester growth and birth characteristics.

We investigated the ability of Rossavik growth models, determined from measurements obtained before 24 weeks (head circumference [HC], abdominal circumference [AC], femur diaphysis length, and estimated fetal weight [EFW]) or 25 weeks (thigh circumference), to predict third-trimester growth and birth characteristics in normally growing triplets. Comparisons of coefficient c values for six anatomical measurements indicated no statistically significant differences in the second-trimester growth of triplets, twins, and singletons. Third-trimester triplet values for HC, AC, and femur diaphysis length were predicted with an accuracy of +/- 6-8%. For thigh circumference and EFW, the comparable values were +/- 17 and +/- 15%, respectively. The HC at birth was predicted without bias; the random error was approximately -27 to 9.0%. Weight, AC, and thigh circumference were systematically overestimated (16.5, 20.9, and 16.3%, respectively). After correction for systematic errors, these characteristics could be predicted with random errors of -13.0 to 9.5% (weight), -12.0 to 2.8% (AC), and -16.7 to 11.3% (thigh circumference). Growth Potential Realization Index values had means of approximately 100% and ranges from 90-121%. The mean triplet value of the Neonatal Growth Assessment Score was 13.6, ranging from 2.8-26.5. These results are similar to those for singletons and twins and indicate that individual assessment of growth in triplets can be performed with the same methods used for both singletons and twins.

Flow velocity waveforms of the umbilical and cerebral arteries before and after intravascular transfusion.

Thirteen intravascular transfusions were performed in 13 human fetuses who were anemic because of severe red-cell alloimmunization. To investigate the status of the umbilical and cerebral circulations by pulsed Doppler ultrasound, we studied the fetal middle cerebral artery (N = 13), internal carotid artery (N = 11), anterior cerebral artery (N = 11), and umbilical artery (N = 13) before, within the first 2 hours after, and the day after intravascular transfusion. The gestational age at the time of transfusion was 21-31 weeks (mean +/- SD 25 +/- 3.1). The fetal hematocrits before transfusion ranged from 12-32% (23.4 +/- 6.1), whereas the hematocrit after transfusion was between 25-42% (35 +/- 5). The net blood volume transfused (volume infused--volume removed) ranged between 7.5-31.0 mL (16.0 +/- 7.4). The hematocrit of the transfused blood varied between 68-81% (74 +/- 4). Repeated-measures analysis of variance indicated significant differences in the pulsatility index values of the four vessels studied. The same analysis indicated significant differences in the pulsatility index values at the three time points. Multiple comparison tests showed that the pulsatility index was reduced significantly immediately after transfusion for each vessel studied, but returned to pretransfusion levels by the next day. These data suggest a change in vascular impedance soon after transfusion as a consequence of direct intravascular transfusion.