Effect of cannula insertion site during fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia on preterm prelabor rupture of membranes.

OBJECTIVE: To assess whether the cannula insertion site on the maternal abdomen during fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) was associated with preterm prelabor rupture of membranes (PPROM) before balloon removal. METHODS: This was a multicenter retrospective study of consecutive pregnancies with isolated left- or right-sided CDH that underwent FETO in four centers between January 2009 and January 2021. The site for balloon insertion was categorized as above or below the umbilicus. One propensity score was analyzed in both groups to calculate an average treatment effect (ATE) by inverse probability of treatment weighting. Logistic regression and Cox proportional hazard regression including the ATE weights were performed to examine the effect size of entry point on the frequency and timing of PPROM before balloon removal. RESULTS: A total of 294 patients were included. The mean ± SD gestational age at PPROM was 33.45 ± 2.01 weeks and the mean rate of PPROM before balloon removal was 25.9% (76/294). Gestational age at FETO was later in the below-umbilicus group (mean ± SD, 29.47 ± 1.29 weeks vs 29.00 ± 1.25 weeks; P = 0.002) and the duration of FETO was longer in the above-umbilicus group (median, 14.49 min (interquartile range (IQR), 8.00-21.00 min) vs 11.00 min (IQR, 7.00-14.49 min); P = 0.002). After balancing for possible confounding factors, trocar entry point below the umbilicus did not increase the risk of PPROM before balloon removal (adjusted odds ratio, 1.56 (95% CI, 0.89-2.74); P = 0.120) and had no effect on the timing of PPROM before balloon removal (adjusted hazard ratio, 1.56 (95% CI, 0.95-2.55); P = 0.080). CONCLUSION: There was no evidence that uterine entry site for FETO was correlated with the risk of PPROM before balloon removal. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis.

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Curvas de aprendizaje del cierre de la espina bífida fetal mediante cirugía abierta y endoscópica: revisión sistemática y metaanálisis OBJETIVO: El ensayo del Estudio sobre la Gestión del Mielomeningocele (MOMS, por sus siglas en inglés) demostró la seguridad y eficacia de la cirugía fetal abierta para la espina bífida aperta (EBA). Las técnicas alternativas recientemente desarrolladas pueden reducir los riesgos de la madre sin comprometer los efectos neuroprotectores del feto. El objetivo de esta revisión sistemática fue evaluar la curva de aprendizaje (CA) de diferentes técnicas de cierre de la EBA fetal. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE, Web of Science, EMBASE, Scopus y Cochrane, así como en la literatura gris, para identificar artículos relevantes sobre cirugía fetal para la EBA, sin restricción de idioma, publicados entre enero de 1980 y octubre de 2018. Se examinaron sistemáticamente los estudios identificados y se seleccionaron los que informaban de todos los procedimientos consecutivos y con seguimiento postnatal ≥12 meses. Los estudios se incluyeron sólo si informaban sobre las variables de resultado necesarias para medir la CA, definidas por la seguridad y la eficacia para el feto. Dos autores recuperaron los datos de forma independiente, evaluaron la calidad de los estudios y clasificaron las observaciones en bloques de 30 pacientes. Para el metaanálisis, los datos se agruparon mediante un modelo de efectos aleatorios cuando fueron heterogéneos. Para medir la CA, se usaron dos métodos complementarios. En el método de división de grupos, la competencia se definió cuando el procedimiento proporcionó resultados comparables a los del ensayo MOMS para 12 variables de resultados que representaban el resultado quirúrgico inmediato, la neuroprotección neonatal a corto plazo y la neuroprotección a largo plazo a ≥12 meses de edad. Luego, cuando se dispuso de los datos brutos de los pacientes, se realizó un análisis de suma acumulada basado en un resultado binario compuesto que definió el éxito de la cirugía. El resultado compuesto combinó cuatro variables clínicamente relevantes en cuanto a la seguridad (ausencia de parto pretérmino extremo <30 semanas; ausencia de muerte fetal a ≤7 días después de la cirugía) y eficacia (reducción de la hernia del rombencéfalo y ausencia de cualquier tratamiento neonatal de dehiscencia o derrame de líquido cefalorraquídeo en el lugar del cierre). RESULTADOS: De los 6024 resultados de la búsqueda, se incluyeron 17 (0,3%) estudios, todos ellos con un riesgo de sesgo bajo, moderado o incierto. El cierre de la EBA fetal se realizó mediante histerotomía estándar (11 estudios), mini histerotomía (un estudio) o fetoscopia, ya fuera mediante el cierre exteriorizado del útero de una sola capa (un estudio), el cierre percutáneo de una sola capa (tres estudios) o el cierre percutáneo de dos capas (un estudio). Sólo se pudieron metaanalizar los resultados de la histerotomía estándar. En general, los resultados mejoraron significativamente con la experiencia. Se alcanzó la competencia después de 35 casos consecutivos para la histerotomía estándar y se predijo que se alcanzaría después de ≥57 casos para la mini histerotomía y ≥56 para la fetoscopia percutánea de dos capas. En el caso de las fetoscopias percutánea y exteriorizada del útero de una sola capa, no se alcanzó la competencia en los 81 y 28 casos disponibles para el análisis, respectivamente, y no se pudo realizar el análisis de predicción de la CA. CONCLUSIONES: El número de casos operados está correlacionado con el resultado del cierre de la EBA fetal, y el número de casos operados necesarios para alcanzar la competencia estuvo entre 35 para la histerotomía estándar y ≥56-57 para las operaciones con mínima agresividad. Las observaciones realizadas proporcionan información importante para las instituciones que buscan establecer un nuevo centro fetal, desarrollar una nueva técnica de cirugía fetal o entrenar a su equipo, e informar a los médicos que remiten a especialistas a los posibles pacientes y a terceros. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Copy number imbalances detected with a BAC-based array comparative genomic hybridization platform in congenital diaphragmatic hernia fetuses.

Congenital diaphragmatic hernia (CDH) is a phenotypically and genetically heterogeneous disorder, with a complex inheritance pattern. Structural abnormalities of almost all chromosomes have been described in association with CDH. We made a molecular analysis through array comparative genomic hybridization (array CGH) of a group of fetuses with prenatal ultrasound diagnosis of CDH and normal G-banded karyotypes. A whole genome BAC-array CGH, composed of approximately 5000 BAC clones, was carried out on blood samples from fetuses with prenatal ultrasound diagnosis of CDH and a normal karyotype (500-band level). All potential cytogenetic alterations detected on the arrays were reported. The array CGH analysis showed copy number gains and losses in 10 of 12 cases. Eighty-five clones showed genomic imbalances, and 29 clones displayed described copy number variations. We identified a recurrent gain in 17q12 in two of 12 cases, which has not been previously described. Our results may contribute to determining the effectiveness and applicability of array CGH for prenatal diagnosis purposes, and also to elucidate the submicroscopic genomic instability of CDH fetuses.

Fetal thigh volumetry by three-dimensional ultrasound: comparison between multiplanar and VOCAL techniques.

OBJECTIVES: To evaluate the agreement between multiplanar and Virtual Organ Computer-aided AnaLysis (VOCAL()) techniques for the measurement of total fetal thigh volume and to assess the repeatability and reproducibility of measurements performed using these methods; to derive birth weight-predicting models for both methods and to compare their accuracies. METHODS: This was a cross-sectional study of 150 singleton pregnancies at 30-42 weeks of gestation in which ultrasound volumes of the fetal thigh were obtained within 48 hours of delivery and measured using multiplanar and VOCAL techniques. Bland-Altman analyses were performed to determine the agreement between the two methods, and to evaluate intraobserver and interobserver variability in a subset of 40 patients. Birth weight-predicting models were derived using total fetal thigh volumes obtained using the VOCAL (ThiV) and multiplanar (ThiM) methods as independent variables. The accuracies of these formulas were compared. RESULTS: The mean percentage difference between measurements performed using the VOCAL technique and the multiplanar technique was -0.04 and the 95% limits of agreement were -8.17 and 8.09. The mean percentage difference and 95% limits of agreement between paired measurements in the assessment of intraobserver and interobserver variability were -1.10 (-7.67 to 5.47) and 0.61 (-7.68 to 8.91) for the VOCAL technique and 1.03 (-6.35 to 8.41) and -0.68 (-11.42 to 10.06) for the multiplanar method, respectively. The best-fit formulas for predicting birth weight (BW) were: BW = 1025.383 + 12.775x ThiV; and BW = 1033.286 + 12.733x ThiM. There was no significant difference between the accuracies of these formulas. CONCLUSIONS: There is good agreement between the VOCAL and multiplanar techniques for assessment of total fetal thigh volume. Measurements performed using both methods are repeatable and reproducible. For prediction of birth weight, the formulas generated in this study can be used interchangeably.

Birth-weight prediction by two- and three-dimensional ultrasound imaging.

OBJECTIVES: To compare the accuracies of birth-weight predicting models derived from two-dimensional (2D) ultrasound parameters and from total fetal thigh volumes measured by three-dimensional (3D) ultrasound imaging; and to compare the performances of these formulae with those of previously published equations. METHODS: A total of 210 patients were evaluated to create a formula-generating group (n = 150) and a prospective-validation group (n = 60). Polynomial regression analysis was performed on the first group to generate one equation based on 2D ultrasound measurements, one based on fetal thigh volume measured by the multiplanar technique (ThiM) and one based on fetal thigh volume obtained by the Virtual Organ Computer-aided AnaLysis (VOCAL()) method (ThiV). Paired-samples t-tests with Bonferroni adjustments were used to compare the performances of these equations in the formula-finding and the prospective-validation groups. The same approach was used to compare the accuracies of the new 2D and 3D formulae with those of both original and modified 2D equations from previous publications, as well as the 3D model reported by Chang et al. RESULTS: The formulae with the best fit for the prediction of birth weight were: estimated fetal weight (EFW) = - 562.824 + 11.962x AC x FDL + 0.009 x BPD(2)x AC(2) (where AC is abdominal circumference, FDL is femur diaphysis length and BPD is biparietal diameter), EFW = 1033.286 + 12.733 x ThiM, and EFW = 1025.383 + 12.775 x ThiV. For both the formula-generating and the prospective-validation groups, there were no significant differences between the accuracies of the new 2D and 3D models in the prediction of birth weight. When applied to our population, the performances of the modified and original versions of the previously published 2D equations and the performance of the original 3D formula reported by Chang et al. were all significantly worse than our models. CONCLUSIONS: We believe that the greatest sources of discrepancy in estimation of birth weight are the phenotypic differences among patients used to create each of the formulae mentioned in this study. Our data reinforce the need for customized birth-weight prediction formulae, regardless of whether 2D or 3D measurements are employed.

Assessment of lung area in fetuses with congenital diaphragmatic hernia.

OBJECTIVE: To compare the intra- and interobserver agreement of three different methods of measuring lung area in fetuses with congenital diaphragmatic hernia (CDH). METHODS: In 71 fetuses with isolated CDH at 21-33 weeks' gestation, the area of the contralateral lung was assessed by firstly, manual tracing of lung borders, secondly, multiplication of the longest diameter of the lung by its widest perpendicular diameter, and thirdly, multiplication of the anteroposterior (AP) diameter of the lung at the mid-clavicular line by the perpendicular diameter at the midpoint of the AP diameter (AP method). In 30 fetuses the measurements were made by two observers and Bland-Altman analysis was used to compare the measurement agreement and bias for each observer and between the two observers. RESULTS: The area obtained by the AP method was similar to that obtained by the manual tracing method, but the area by the longest diameter approach was bigger by 34.4% (95% CI, - 2.4% to 71.1%). The 95% confidence intervals of the difference in paired measurements of lung areas by the same observer and by two different observers were narrower in the manual tracing method than in the multiplying diameters methods. CONCLUSIONS: In CDH the most reproducible measurement of fetal lung area is provided by manual tracing of the limits of the lungs, rather than by multiplication of lung diameters.

Comparison of fetal lung area to head circumference ratio with lung volume in the prediction of postnatal outcome in diaphragmatic hernia.

OBJECTIVES: To compare prediction of postnatal survival in isolated diaphragmatic hernia by prenatal two-dimensional (2D) versus three-dimensional (3D) sonographic assessment of the contralateral lung. METHODS: The lung area to head circumference ratio (LHR) of the contralateral lung was measured and expressed as a percentage of the normal mean for gestation (O/E) in 47 fetuses with isolated diaphragmatic hernia at 26 (range, 21-36) weeks of gestation. The lung area was measured by tracing the limits of the lungs (LHR trace) and by multiplying the longest diameter by its perpendicular (LHR diameters). The contralateral lung volume was measured by the Virtual Organ Computer-Aided anaLysis method and the O/E was calculated. Regression analysis was used to determine the significance of the LHRs and volume in the prediction of postnatal survival. RESULTS: The survival rate was 59.6% (28 of 47). There were significant associations between O/E LHR trace and O/E LHR diameters, and between each O/E LHR and O/E volume, but multiple regression analysis demonstrated that significant prediction of survival was provided only by O/E LHR trace and intrathoracic herniation of the liver. CONCLUSIONS: In diaphragmatic hernia prenatal prediction of postnatal outcome is better by 2D measurement of LHR trace than it is by 3D measurement of lung volume.

Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia.

OBJECTIVE: To assess the value of antenatally determined observed to expected fetal lung area to head circumference ratio (LHR) in the prediction of postnatal survival in isolated, congenital diaphragmatic hernia (CDH). METHODS: Two groups of fetuses were examined. The first group included 650 normal fetuses at 12-32 weeks' gestation, and the data collected were used to establish a normal range of observed to expected LHR with gestational age. The second group included the data of a retrospective multicenter study of 354 fetuses with isolated CDH in which the LHR was measured on one occasion at 18-38 weeks' gestation. The patients were divided into those with left-sided CDH with and without intrathoracic herniation of the liver and right-sided CDH. Regression analysis was used to determine the significant predictors of postnatal survival. RESULTS: In both the normal fetuses and those with CDH the LHR increased but the observed to expected LHR did not change significantly with gestational age. In normal fetuses the mean observed to expected LHR in the left lung was 100% (95% CI, 61-139%) and in the right lung it was 100% (95% CI, 67-133%). In fetuses with CDH the mean observed to expected LHR was 39% (range 7-79%). Regression analysis demonstrated that significant predictors of survival were the observed to expected LHR (odds ratio (OR) 1.09, 95% CI, 1.06-1.12), side of CDH (left side OR 11.14, 95% CI, 3.41-36.39) and gestational age at delivery (OR 1.18, 95% CI, 1.02-1.36). CONCLUSION: In CDH, the LHR increases while observed to expected LHR is independent of gestational age. In fetuses with both left- and right-sided CDH, measurement of the observed to expected LHR provides a useful prediction of subsequent survival.

Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation.

OBJECTIVE: To establish reference intervals for the fetal right, left and total lung volumes and heart volume between 12 and 32 weeks of gestation. METHODS: Fetal lung and heart volumes were measured using three-dimensional (3D) ultrasound in 650 normal singleton pregnancies at 12-32 weeks. The VOCAL (Virtual Organ Computer-aided AnaLysis) technique was used to obtain a sequence of six sections of each lung and the heart around a fixed axis, each after a 30 degrees rotation from the previous one. The rotation axis for the lungs extended from the apex to the upper limit of the diaphragm dome, and the rotation axis for the heart extended from its apex to its connection to the great vessels. The contour of each of these organs was drawn manually in the six different rotation planes to obtain the 3D volume measurement. In 60 cases the fetal lungs and heart volumes were measured by the same sonographer twice and also by a second sonographer once in order to compare the measurements and calculate intra- and interobserver agreement. RESULTS: The total lung volume and heart volume increased with gestation, from respective mean values of 1.6 and 0.6 mL at 12 weeks to 10.9 and 4.3 mL at 20 weeks and 49.3 and 26.6 mL at 32 weeks. The right to left lung volume ratio did not change significantly with gestation (median, 0.7), whereas the heart to total lung volume ratio increased with gestation from about 0.3 at 12 weeks to 0.5 at 32 weeks. In the Bland-Altman plot, the difference between paired measurements by two sonographers was, in 95% of the cases, less than 0.05, 0.5 and 1.9 mL for each lung at 12-13, 19-22 and 29-32 weeks, respectively, and the corresponding values for the heart volumes were 0.04, 0.4 and 2.3 mL. CONCLUSIONS: In normal fetuses the lung and heart volumes increase between 12 and 32 weeks of gestation. The extent to which in pathological pregnancies possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined.

Three-dimensional evaluation of mid-facial hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To investigate the mid-facial hypoplasia of fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation, by three-dimensional (3D) evaluation of the maxilla and the nasal bones. METHODS: A 3D volume of the fetal head was obtained before fetal karyotyping at 11 + 0 to 13 + 6 (median 12) weeks of gestation in 80 fetuses that were subsequently found to have trisomy 21 and in 862 fetuses subsequently found to be chromosomally normal. The multiplanar mode was used to obtain a sequence of transverse views of the fetal face and to demonstrate the maxilla, the adjacent rami of the mandible and the nasal bones. The maxillary depth, defined as the distance between the alveolus of the maxilla in the midline anteriorly and the midpoint of the line joining the rami posteriorly, was measured. Ossification of the nasal bones was considered to be normal if both bones were more echogenic than the overlying skin. RESULTS: In the chromosomally normal group the maxillary depth increased linearly with crown-rump length (CRL) from 3.1 mm at a CRL of 45 mm to 4.8 mm at a CRL of 84 mm, and in the trisomy 21 fetuses the depth was significantly smaller than normal (mean difference = - 0.3 mm, P < 0.001). There was no significant association between the delta maxillary depth and delta nuchal translucency thickness in either the trisomy 21 or the chromosomally normal fetuses. Impaired ossification of the nasal bones was observed in 3.1% of the chromosomally normal fetuses and in 60.0% of those with trisomy 21. The mean maxillary depth was significantly smaller in fetuses demonstrating impaired ossification than in those with normal ossification of the nasal bones (mean difference = -0.2 mm; 95% CI, -0.3 to -0.1, P = 0.001). CONCLUSIONS: In a high proportion of fetuses with trisomy 21 there is sonographic evidence of mid-facial hypoplasia at 11 + 0 to 13 + 6 weeks of gestation.

Relationship between lung-to-head ratio and lung volume in normal fetuses and fetuses with diaphragmatic hernia.

OBJECTIVE: To examine the relationship between the fetal lung area and lung area to head circumference ratio (LHR) and lung volume by three-dimensional (3D) ultrasonography in normal fetuses and in fetuses with unilateral congenital diaphragmatic hernia (CDH). METHODS: In 64 fetuses with CDH at median 26 (range, 20-32) weeks of gestation the contralateral lung volume, lung area and LHR were measured and the values were compared to those of 650 normal fetuses at 12-32 weeks. In the normal fetuses both lungs were assessed but in the 64 fetuses with CDH only the contralateral lung was measured because the ipsilateral lung could be visualized adequately in only 40 (62.5%) of the cases. Regression analysis was used to assess the significance of the association between lung volume and lung area or LHR. In the fetuses with CDH, the observed to expected ratios for lung area and LHR were calculated. The expected lung area and LHR were the normal median for a given lung volume. The significance of the differences between the observed to expected lung area and LHR in fetuses with CDH and normal fetuses was determined. In the 64 fetuses with CDH and in 64 normal fetuses, matched for gestational age, the lung length between the apex and the superior aspect of the diaphragm dome was also recorded. RESULTS: In normal fetuses the median lung area and LHR in both the left and right lungs increased significantly with lung volume. In the fetuses with CDH, the lung area and lung volume for gestation were substantially lower than in normal fetuses and the ratios of observed to expected lung area and LHR for a given lung volume were significantly lower than the respective values in normal fetuses. Additionally, the mean lung length was 13% greater and the mean lung area was 44% smaller than the respective values in the normal controls matched for gestational age. CONCLUSIONS: The finding of a significant association between LHR and lung volume has validated the use of LHR in the assessment of lung growth. However, the study has also demonstrated that in fetuses with CDH, LHR underestimates the actual lung volume, because the herniated viscera cause a greater lateral, rather than vertical, compression of the contralateral lung.

Left and right lung volumes in fetuses with diaphragmatic hernia.

OBJECTIVE: To compare the volume of the ipsilateral and contralateral lungs in fetuses with congenital diaphragmatic hernia (CDH). METHODS: Left and right lung volumes were measured using three-dimensional (3D) ultrasonography in 42 fetuses with CDH at median 26 (range, 20-32) weeks of gestation. Each value was then expressed as a difference, in standard deviations, from the normal mean for gestation, previously established from the study of 650 normal fetuses at 12-32 weeks (Z-score). The Mann-Whitney U-test was used to determine the significance of the differences between the measurements in fetuses with CDH and normal fetuses and between the ipsilateral and contralateral lungs in fetuses with left- and right-sided CDH. RESULTS: There were 34 fetuses with left-sided CDH and eight with right-sided CDH. In CDH both the ipsilateral and contralateral lung volumes were substantially lower than in normal fetuses. In left CDH the left lung volume was 4.03 (median; range, 3.11-4.78) SDs below the normal mean for gestation, and the respective values for the right lung were 3.04 (median; range, 1.78-4.31) SDs (P < 0.001 for both). In right CDH, the left lung volume was 2.91 (median; range, 1.62-4.07) SDs below the normal mean for gestation and the respective values for the right lung were 4.35 (median; range, 3.07-4.99) SDs (P < 0.001 for both). In both left and right diaphragmatic hernia the deficit in the volume of the ipsilateral lung was significantly greater than the deficit in the contralateral lung. CONCLUSIONS: In fetuses with CDH both the ipsilateral and contralateral lung volumes are substantially lower than in normal fetuses.

Assessment of lung area in normal fetuses at 12-32 weeks.

OBJECTIVE: To establish reference intervals with gestation for the right and left lung areas and lung area to head circumference ratio (LHR). METHODS: This was a cross-sectional study of 650 normal singleton pregnancies at 12-32 weeks of gestation. We measured the left and right lung areas on the cross-sectional plane of the thorax, used for examination of the four-chamber view of the heart, by three different techniques: firstly, manual tracing of the limits of the lungs; secondly, multiplication of the longest diameter of the lung by its longest perpendicular diameter; thirdly, multiplication of the anteroposterior diameter of the lung at the mid-clavicular line by the perpendicular diameter at the midpoint of the anteroposterior diameter. RESULTS: The respective mean left and right lung areas (manual tracing) increased with gestational age, from 36 and 58 mm(2) at 12 weeks to 220 and 325 mm(2) at 20 weeks and 594 and 885 mm(2) at 32 weeks. This 16-fold increase in lung area was accompanied by a four-fold increase in head circumference. Consequently, the left and right LHR increased with gestational age. The most reproducible way of measuring the lung area was by manual tracing of the limits of the lungs and the least reproducible was by multiplying the longest diameter of the lungs by their longest perpendicular diameter. Furthermore, the method employing the longest diameter, compared with the tracing method, overestimated both the left and the right lung areas by about 45% and the method employing the anteroposterior diameter overestimated the area of the right lung by about 35%, but not that of the left lung. CONCLUSIONS: In the antenatal prediction of pulmonary hypoplasia by the assessment of lung area it is important to take gestational age into account. Dividing the lung area by the head circumference does not correct for the gestation-related increase in lung area. Reproducible measurement of the lung area is provided by manual tracing of the limits of the lungs, rather than by multiplication of lung diameters.

Fetal trunk and head volume measured by three-dimensional ultrasound at 11 + 0 to 13 + 6 weeks of gestation in chromosomally normal pregnancies.

OBJECTIVE: To establish the relationship between fetal trunk and head volume measured by three-dimensional (3D) ultrasound and gestational age at 11 + 0 to 13 + 6 weeks of gestation. METHODS: The fetal trunk and head volume were measured using 3D ultrasound in 417 chromosomally normal fetuses from singleton pregnancies at 11 + 0 to 13 + 6 (median, 12 + 0) weeks of gestation. Regression analysis was used to determine the significance of the association between fetal volume and gestational age. The Bland-Altman analysis was used to compare the measurement agreement and bias for a single examiner and between different examiners. RESULTS: The fetal trunk and head volume increased linearly with gestation from a mean of 5.8 mL at 11 + 0 weeks to 33.3 mL at 13 + 6 weeks and 1 SD was 4.4 mL. There was also a significant linear association between fetal volume and crown-rump length (CRL), from a mean of 5.1 mL at a CRL of 45 mm to 37.5 mL at a CRL of 84 mm and 1 SD was 2.7 mL. However, within this gestational range, a doubling in CRL, from a mean of 48 mm at 11 + 0 weeks to 79 mm at 13 + 6 weeks, was associated with a 5-6-fold increase in fetal volume. The mean difference in fetal volume between paired measurements by the same sonographer was -0.87 mL (95% limits of agreement, -2.31 to 4.05 mL) and the mean difference between paired measurements by two sonographers was -1.09 mL (-5.49 to 3.32 mL). CONCLUSIONS: 3D ultrasound can provide a reproducible measurement of the fetal trunk and head volume in early pregnancy. At between 11 + 0 and 13 + 6 weeks there is a 5-6-fold increase in fetal volume but only a doubling in CRL.

Fetal head-to-trunk volume ratio in chromosomally abnormal fetuses at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To determine the pattern of early growth disturbance in chromosomally abnormal fetuses by comparing the volume of the fetal head to that of the trunk. METHODS: The fetal trunk and head volume was measured using three-dimensional (3D) ultrasound in 145 chromosomally abnormal fetuses at a median gestational age of 12 (range, 11 + 0 to 13 + 6) weeks. The head volume was measured separately and then subtracted from the total head and trunk volume to obtain the volume of the fetal trunk. The head-to-trunk ratios were then calculated and the Mann-Whitney U-test was used to determine the significance of differences from 500 chromosomally normal fetuses. RESULTS: The fetal head volume for crown-rump length (CRL) was significantly smaller than normal in trisomy 21, trisomy 13 and Turner syndrome (P < 0.001, P < 0.001 and P = 0.001, respectively), whereas no significant differences were found in trisomy 18 and triploidy (P = 0.139 and P = 0.070, respectively). The fetal trunk volume for CRL was significantly smaller in all chromosomal abnormalities (P < 0.001) except Turner syndrome (P = 0.134). The head-to-trunk ratio for CRL was significantly larger in trisomy 18, trisomy 13 and triploidy (P < 0.001), but normal in trisomy 21 (P = 0.221) and Turner syndrome (P = 0.768). CONCLUSIONS: In trisomy 21 and Turner syndrome, the growth deficit was symmetrical with the head and trunk being equally affected, whereas in triploidy and trisomies 18 and 13 there was asymmetrical growth restriction with the trunk being more severely compromised than the head.

Fetal trunk and head volume in chromosomally abnormal fetuses at 11+0 to 13+6 weeks of gestation.

OBJECTIVE: To examine the pattern of growth in chromosomally abnormal fetuses at 11+0 to 13+6 weeks of gestation and compare the trunk and head volume to crown-rump length (CRL) in defining the growth deficit in such fetuses. METHODS: The fetal trunk and head volume was measured using three-dimensional (3D) ultrasound in 140 chromosomally abnormal fetuses at 11+0 to 13+6 (median 12) weeks of gestation, and the values were compared to 500 chromosomally normal fetuses. In each chromosomally abnormal fetus, the observed fetal trunk and head volume was subtracted from the expected mean (delta value) of the chromosomally normal fetuses of the same gestational age, and this difference was expressed as a percentage of the appropriate normal mean. The Mann-Whitney U-test was used to determine the significance of differences between the chromosomally normal and abnormal groups. RESULTS: In trisomy 21 (n=72) and Turner syndrome (n=14) fetuses, compared to chromosomally normal fetuses, the CRL for gestation was similar (P=0.335 and P=0.317, respectively), but the fetal trunk and head volume was about 10-15% lower (P<0.001 and P=0.004, respectively). In trisomy 18 (n=29), trisomy 13 (n=14) and triploidy (n=11), the deficit in volume was about 45% (P<0.001), whereas the deficit in CRL was less than 15% (P<0.001). CONCLUSIONS: In the quantification of the degree of early growth impairment in chromosomally abnormal fetuses, measurement of the fetal trunk and head volume using 3D ultrasound may be better than measurement of CRL.

Placental volume measured by three-dimensional ultrasound at 11 to 13 + 6 weeks of gestation: relation to chromosomal defects.

OBJECTIVE: To determine the potential value of measuring the placental volume at 11 to 13 + 6 weeks of gestation in screening for chromosomal defects. METHODS: The placental volume was measured using three-dimensional ultrasound in 500 consecutive singleton pregnancies immediately before chorionic villus sampling for fetal karyotyping at 11 to 13 + 6 (median, 12) weeks of gestation. RESULTS: The fetal karyotype was normal in 417 pregnancies and abnormal in 83. In the chromosomally normal group the mean placental volume increased significantly with gestation from a mean of 51 mL (5th and 95th centiles: 31.2 and 82.4 mL) at 11 weeks to 91 mL (5th and 95th centiles: 55.7 and 147.2 mL) at 13 + 6 weeks. In the chromosomally abnormal group the mean placental volume for gestational age was not significantly different from normal in trisomy 21 and Turner syndrome, but it was smaller in trisomies 13 and 18. CONCLUSIONS: The measurement of the placental volume at 11 to 13 + 6 weeks of gestation is unlikely to be a useful predictor of the major chromosomal defects. In trisomies 13 and 18 the small placental volume may be due to early-onset fetal growth restriction, which could be the consequence of impaired placental function.