Non-invasive messenger RNA transcriptional evaluation in human kidney allograft dysfunction.

The aim of the present study was to evaluate messenger RNA expression in kidney allograft recipients. Forty-four kidney transplant recipients were evaluated up to three months after grafting. After transplantation, peripheral blood samples were drawn sequentially for real-time polymerase chain reaction analyses of perforin and TIM-3 genes. Biopsies were obtained to evaluate acute graft dysfunction and interpreted according to the Banff classification. Eight patients presented episodes of acute rejection. Recipients with rejection had significantly higher levels of TIM-3 mRNA transcripts compared to those without rejection (median gene expression 191.2 and 36.9 mRNA relative units, respectively; P<0.0001). Also, perforin gene expression was higher in patients with rejection (median gene expression 362.0 and 52.8 mRNA relative units; P<0.001). Receiver operating characteristic curves showed that the area under the curve (AUC) for the TIM-3 gene was 0.749 (95%CI: 0.670-0.827). Perforin gene mRNA expression provided an AUC of 0.699 (95%CI: 0.599 to 0.799). Overall accuracy of gene expression was 67.9% for the TIM-3 gene and 63.6% for the perforin gene. Combined accuracy was 76.8%. Negative predictive values were 95.3% for the TIM-3 gene, 95.5% for the perforin gene, and 95.4% in the combined analyses. Gene expression was significantly modulated by rejection treatment decreasing 64.1% (TIM-3) and 90.9% (perforin) compared to the median of pre-rejection samples. In conclusion, the longitudinal approach showed that gene profiling evaluation might be useful in ruling out the diagnosis of acute rejection and perhaps evaluating the efficacy of treatment.

Atom-Pair Kinetics with Strong Electric-Dipole Interactions.

Rydberg-atom ensembles are switched from a weakly to a strongly interacting regime via adiabatic transformation of the atoms from an approximately nonpolar into a highly dipolar quantum state. The resultant electric dipole-dipole forces are probed using a device akin to a field ion microscope. Ion imaging and pair-correlation analysis reveal the kinetics of the interacting atoms. Dumbbell-shaped pair-correlation images demonstrate the anisotropy of the binary dipolar force. The dipolar C_{3} coefficient, derived from the time dependence of the images, agrees with the value calculated from the permanent electric-dipole moment of the atoms. The results indicate many-body dynamics akin to disorder-induced heating in strongly coupled particle systems.

Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices.

OBJECTIVES: To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR). METHODS: This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples. RESULTS: There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia. CONCLUSION: The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Diagnostic accuracy of ultrasonography and magnetic resonance imaging for the detection of fetal anomalies: a blinded case-control study.

OBJECTIVES: To compare the accuracy of two-dimensional ultrasound (2D-US), three-dimensional ultrasound (3D-US) and magnetic resonance imaging (MRI) for the diagnosis of congenital anomalies without prior knowledge of indications and previous imaging findings. METHODS: This was a prospective, blinded case-control study comprising women with a singleton pregnancy with fetal congenital abnormalities identified on clinical ultrasound and those with an uncomplicated pregnancy. All women volunteered to undergo 2D-US, 3D-US and MRI, which were performed at one institution. Different examiners at a collaborating institution performed image interpretation. Sensitivity and specificity of the three imaging methods were calculated for individual anomalies, based on postnatal imaging and/or autopsy as the definitive diagnosis. Diagnostic confidence was graded on a four-point Likert scale. RESULTS: A total of 157 singleton pregnancies were enrolled, however nine cases were excluded owing to incomplete outcome, resulting in 148 fetuses (58 cases and 90 controls) included in the final analysis. Among cases, 13 (22.4%) had central nervous system (CNS) anomalies, 40 (69.0%) had non-CNS anomalies and five (8.6%) had both CNS and non-CNS anomalies. The main findings were: (1) MRI was more sensitive than 3D-US for diagnosing CNS anomalies (MRI, 88.9% (16/18) vs 3D-US, 66.7% (12/18) vs 2D-US, 72.2% (13/18); McNemar's test for MRI vs 3D-US: P = 0.046); (2) MRI provided additional information affecting prognosis and/or counseling in 22.2% (4/18) of fetuses with CNS anomalies; (3) 2D-US, 3D-US and MRI had similar sensitivity for diagnosing non-CNS anomalies; (4) specificity for all anomalies was highest for 3D-US (MRI, 85.6% (77/90) vs 3D-US, 94.4% (85/90) vs 2D-US, 92.2% (83/90); McNemar's test for MRI vs 3D-US: P = 0.03); and (5) the confidence of MRI for ruling out certain CNS abnormalities (usually questionable for cortical dysplasias or hemorrhage) that were not confirmed after delivery was lower than it was for 2D-US and 3D-US. CONCLUSIONS: MRI was more sensitive than ultrasonography and provided additional information that changed prognosis, counseling or management in 22.2% of fetuses with CNS anomalies. False-positive diagnoses for subtle CNS findings were higher with MRI than with ultrasonography. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Incidence, risk factors, and outcomes of delayed graft function in deceased donor kidney transplantation in a Brazilian center.

BACKGROUND: A high incidence of delayed graft function (DGF) after deceased donor kidney transplantation occurs in Brazil. The reasons for such have not been adequately studied. METHODS: We performed a retrospective cohort study of 346 kidney transplant recipients from deceased donors. DGF risk factors related to the recipient, donor, and transplantation surgery were analyzed and correlated with graft outcomes. A logistic regression analysis was used to identify independent risk factors and patient and graft survival were assessed using Kaplan-Meier curves. RESULTS: The incidence of DGF was 70.8% (245 cases). Our final model of multivariate analysis showed that DGF is associated (P < .05) with donor final serum creatinine (relative risk [RR], 1.84; 95% confidence interval [CI], 1.26-2.70), donor age (RR, 1.02 [1.0-1.033]), receiving a kidney from national offer (RR, 2.44 [1.06-5.59]), and need for antibody induction (RR, 2.87 [1.33-6.18]). Outcomes that were associated with DGF were longer length of hospital stay (32.5 ± 20.5 vs 18.8 ± 16.3 days; P = .01), higher incidence of acute rejection (37.8 vs 12.9%; P < .01), worse graft survival at 1 year (83.5% vs 93.9%; P < .01), and higher levels of serum creatinine at 3, 6, and 12 months (P < .05). There was no difference in patient survival and the occurrence of acute rejection did not influence the survival of patients or grafts. CONCLUSION: DGF was associated with higher donor final serum creatinine, donor age, receiving a kidney from the national supply, and need for antibody induction. Most importantly, DGF was associated with worse outcomes.

Evaluation of equations that estimate glomerular filtration rate in renal transplant recipients.

AIM: The accuracy of equations that estimate the glomerular filtration rate (GFR) in renal transplant patients has not been established; thus their performance was assessed in stable renal transplant patients. METHODS: Renal transplant patients (N.=213) with stable graft function were enrolled. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used as the reference method and compared with the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Mayo Clinic (MC) and Nankivell equations. Bias, accuracy and concordance rates were determined for all equation relative to CKD-EPI. RESULTS: Mean estimated GFR values of the equations differed significantly from the CKD-EPI values, though the correlations with the reference method were significant. Values of MDRD differed from the CG, MC and Nankivell estimations. The best agreement to classify the chronic kidney disease (CKD) stages was for the MDRD (Kappa=0.649, P<0.001), and for the other equations the agreement was moderate. The MDRD had less bias and narrower agreement limits but underestimated the GFR at levels above 60 mL/min/1.73 m2. Conversely, the CG, MC and Nankivell equations overestimated the GFR, and the Nankivell equation had the worst performance. The MDRD equation P15 and P30 values were higher than those of the other equations (P<0.001). CONCLUSION: Despite their correlations, equations estimated the GFR and CKD stage differently. The MDRD equation was the most accurate, but the sub-optimal performance of all the equations precludes their accurate use in clinical practice.

Magnetic resonance diffusion-weighted imaging: reproducibility of regional apparent diffusion coefficients for the normal fetal brain.

OBJECTIVE: To evaluate the reproducibility of regional apparent diffusion coefficient (ADC) measurements of the normal fetal brain in the second and third trimesters of pregnancy. METHODS: Fifty normal singleton fetuses from healthy pregnant women between 19 and 37 weeks' gestation were studied without sedation. Single-shot diffusion-weighted images of the fetal brain were obtained using a 1.5-Tesla magnetic resonance scanner and a six-channel body array coil. ADC maps were created using 0 and 1000 b-values along three orthogonal directions. Two examiners independently measured ADC values in the cerebellar hemispheres (CH), pons, thalamus, basal ganglia (BG), centrum semiovale (CSO), and frontal (FWM), parietal (PWM), temporal (TWM) and occipital (OWM) white matter. Correlation between ADC values and menstrual age was assessed by linear regression analysis. The bias and agreement of ADC measurements were determined using Bland-Altman plots. RESULTS: ADC values either remained constant (BG, FWM, PWM, TWM, OWM, CSO) or decreased (CH, pons, thalamus) with advancing menstrual age. Mean intraobserver bias for ADC measurements was not significantly different from zero. Small interobserver differences in mean ADC measurements (i.e. a small mean bias) were detected for CH (1.26 ± 0.20 vs 1.20 ± 0.18 µm(2) /ms, P = 0.006), PWM (1.37 ± 0.29 vs 1.33 ± 0.26 µm(2) /ms, P = 0.02) and CSO (1.36 ± 0.29 vs 1.33 ± 0.28 µm(2) /ms, P < 0.0001). Measurement agreement was acceptable. CONCLUSIONS: ADC measurements in normal unsedated fetuses in the second and third trimesters are reproducible except for small differences for PWM, CH and CSO between examiners.

Noninvasive analyses of kidney injury molecule-1 messenger RNA in kidney transplant recipients with graft dysfunction.

BACKGROUND: Kidney graft fibrosis is a major factor related to chronic loss of kidney function. At present, the finding of fibrosis depends on the analysis of tissue in the renal biopsy, which has important limitations. In this study, we evaluated the messenger mRNA transcription and gene expression of kidney injury molecule-1 (KIM-1) in kidney tissue and in urinary sediment cells of kidney transplant patients with graft dysfunction aiming at the development of techniques that may allow the noninvasive diagnosis of interstitral fibrosis/tubular atrophy (IF/TA). PATIENTS AND METHODS: RNA extracted from cells in tissue and urine of 77 renal transplant patients whose biopsies were classified according to the Banff scheme-2007. Four diagnostic groups were established: (1) acute tubular necrosis (n = 9); (2) acute rejection (n = 49); (3) acute calcineurin inhibitors nephrotoxicity (n = 10); and (4) interstitial fibrosis and tubular atrophy (IFTA, n = 29). Tissue and urine cell RNA was amplified and quantification were made by real-time polymerase chain reactron. Data from the quantification of gene expression are presented as median and 25th to 75th percentiles. RESULTS: Messenger RNA levels of the KIM-1 gene were higher in the biopsies (26.17; 3.38-294.53) and urinary sediment cells (0.09; 0-5.81) of the patients classified as having IF/TA as compared with all others groups. A significant correlation between gene expression in samples of urine and tissue cells was found (P < .01). CONCLUSION: These initial data suggests that KIM-1 gene mRNA quantification can be used as a noninvasive biomarker of IF/TA.

Evaluation of adherence to immunosuppressive drugs in kidney transplantation by control of medication dispensing.

Nonadherence to immunosuppressive medications represents a burden to organ transplantation being associated with rejection episodes and graft loss. In this cross-sectional study we evaluated the prevalence and risk factors for nonadherence in kidney transplant patients by measuring the retrieval of the immunosuppressive drugs in the registry kept by the state Rio Grande do Sul public health system. We considered nonadherence the failure to retrieval of medication at least one time over a 1-year period of evaluation. In 288 patients evaluated, the frequency of failure to retrieve was 58.7%. Being fully employed (66.4% × 33.6%, P = .008) and younger age at transplantation (39 ± 13 × 46 ± 11, P = .011) were associated with nonadherence. Multivariate analysis showed a greater prevalence ratio (PR) of non- adherence in patients using tacrolimus. Estimated glomerular filtration rate was significantly lower in the nonadherence groups as compared with adherent groups (45.3 ± 21.6 × 51.3 ± 19.4, P = .016). In conclusion, we found a high prevalence of nonadherence to immunosuppressive drugs with association to active working situation and use of tacrolimus. Importantly, glomerular filtration rate was found to be lower in nonadherent patients.

Levels of Selenomonas species in generalized aggressive periodontitis.

BACKGROUND AND OBJECTIVE: To compare the levels of Selenomonas sputigena and uncultivated/unrecognized Selenomonas species in subgingival biofilms from periodontally healthy subjects and from subjects with generalized aggressive periodontitis. MATERIAL AND METHODS: Fifteen periodontally healthy subjects and 15 subjects with generalized aggressive periodontitis were recruited and their clinical periodontal parameters were evaluated. Nine subgingival plaque samples were collected from each subject and all were individually analyzed for the levels of 10 bacterial taxa, including cultured and uncultivated/unrecognized microorganisms, using the RNA-oligonucleotide quantification technique. Between-group differences in the levels of the test taxa were determined using the Mann-Whitney U-test. RESULTS: Subjects with generalized aggressive periodontitis showed significantly higher mean counts of Porphyromonas gingivalis, S. sputigena and the Mitsuokella sp. Human Oral Taxon (HOT) 131 (previously described as Selenomonas sp. oral clone CS002), while higher mean counts of Actinomyces gerencseriae and Streptococcus sanguinis were found in periodontally healthy subjects (p < 0.01). Selenomonas sp. HOT 146 was only detected in the generalized aggressive periodontitis group. In the generalized aggressive periodontitis group, the levels of P. gingivalis and S. sputigena were higher in deep sites (probing depth ≥ 5 mm) than in shallow sites (probing depth ≤ 3 mm) (p < 0.01). Furthermore, in subjects with generalized aggressive periodontitis, sites with probing depth of ≤ 3 mm harbored higher levels of these two species than sites with the same probing depth in periodontally healthy subjects. There were positive correlations between probing depth and the levels of P. gingivalis (r = 0.77; p < 0.01), S. sputigena (r = 0.60; p < 0.01) and Selenomonas dianae (previously described as Selenomonas sp. oral clone EW076) (r = 0.42, p < 0.05). CONCLUSION: S. sputigena and Mitsuokella sp. HOT 131 may be associated with the pathogenesis of generalized aggressive periodontitis, and their role in the onset and progression of this infection should be investigated further.

Transdermal nitroglycerin in patients with severe pre-eclampsia with placental insufficiency: effect on uterine, umbilical and fetal middle cerebral artery resistance indices.

OBJECTIVES: To evaluate the effect of transdermal nitroglycerin on Doppler velocity waveforms of the uterine, umbilical and fetal middle cerebral arteries in patients with severe pre-eclampsia. METHODS: This was a prospective study of 30 singleton pregnancies (gestational age range: 24-31 weeks) with severe pre-eclampsia and abnormal uterine and umbilical artery Doppler waveforms. We compared maternal blood pressure as well as the resistance index (RI) and the pulsatility index (PI) of the uterine, umbilical and fetal middle cerebral arteries before and after application of a transdermal nitroglycerin patch (average dose 0.4 mg/h) for a period of 3 days. Intra-day comparisons before and after administration of nitroglycerin and a comparison between days 0 (no patch) and 3 after administration of the first dose of nitroglycerin were performed using ANOVA for paired samples. RESULTS: A significant decrease in the PI and RI of the uterine (25.3 ± 4.9% and 21.2 ± 6.2%, respectively, P < 0.001) and umbilical (23.1 ± 6.9% and 19.7 ± 6.1%, respectively, P < 0.001) arteries was noted when comparing the first day without medication against the third day with the patch. No significant change in the PI and RI of the middle cerebral artery was observed. The mean arterial blood pressure decreased from 119.5 ± 4.5 mmHg to 114.8 ± 4.4 mmHg (P < 0.05). CONCLUSION: The use of transdermal nitroglycerin in patients with severe pre-eclampsia is associated with a significant reduction in the RI and PI of the uterine and umbilical arteries, as well as of maternal blood pressure. Transdermal nitroglycerin does not affect the RI and PI of the fetal middle cerebral artery.

Prevalence and microbiological diversity of Archaea in peri-implantitis subjects by 16S ribosomal RNA clonal analysis.

BACKGROUND AND OBJECTIVE: This study evaluated the prevalence and the molecular diversity of Archaea in the subgingival biofilm samples of subjects with peri-implantitis. MATERIAL AND METHODS: Fifty subjects were assigned into two groups: Control (n = 25), consisting of subjects with healthy implants; and Test (n = 25), consisting of subjects with peri-implantitis sites, as well as a healthy implant. In the Test group, subgingival biofilm samples were taken from the deepest sites of the diseased implant. In both groups, subgingival biofilm was collected from one site with a healthy implant and from one site with a periodontally healthy tooth. DNA was extracted and the 16S ribosomal RNA gene was amplified with universal primer pairs for Archaea. Amplified genes were cloned and sequenced, and the phylotypes were identified by comparison with known 16S ribosomal RNA sequences. RESULTS: In the Control group, Archaea were detected in two and three sites of the implant and the tooth, respectively. In the Test group, Archaea were detected in 12, 4 and 2 sites of diseased implants, healthy implants and teeth, respectively. Diseased implants presented a significantly higher prevalence of Archaea in comparison with healthy implants and natural teeth, irrespective of group. Over 90% of the clone libraries were formed by Methanobrevibacter oralis, which was detected in both groups. Methanobacterium congelense/curvum was detected in four subjects from the Test group and in two subjects from the Control group. CONCLUSION: Although M. oralis was the main species of Archaea associated with both healthy and diseased implant sites, the data indicated an increased prevalence of Archaea in peri-implantitis sites, and their role in pathogenesis should be further investigated.

Quantitative analyses of kidney injury molecule-1 messenger RNA in kidney transplant recipients with graft dysfunction.

BACKGROUND: Kidney injury molecule-1 (KIM-1), a type I transmembrane protein that is not expressed in normal renal tissue, shows increased expression in dedifferentiated cells within damaged regions of the proximal tubule. We evaluated mRNA transcription of the KIM-1 gene in renal tissue of kidney transplant patients who were experiencing graft dysfunction searching for an accurate biomarker of kidney graft injury. PATIENTS AND METHODS: mRNA analysis was performed on 59 biopsies from kidney transplant patients who had been classified according to the Banff 1997 scheme. Biopsies were categorized in 5 diagnostic groups: acute tubular necrosis (ATN) with superimposed acute rejection episode (ARE), ATN; ARE; calcineurin inhibitor nephrotoxicity (CIN); or interstitial fibrosis and tubular atrophy (IFTA). Amplified tissue RNA was quantified by real-time polymerase chain reaction. RESULTS: Renal tissue evaluations showed significantly increased KIM-1 mRNA expression as shown by median values, 25-75 percentiles, and averages of the logarithmic transformation: namely, CIN group (50.6; 1.8-285, 1; 1.24) and IFTA group (7.5; 1.26-14.6; 0.62), displayed significant differences (P > .05). In contrast, expression was lower among the ATN (0.47; 0.28-1.06; -0.13); ARE (0.21; 0.11-0.78; -0.45), and ATN+ARE (0.46; 0.06-3.27; -0.25) cohorts. CONCLUSION: These preliminary data suggested that KIM-1 mRNA might be useful biomarker of tubular damage associated with CIN and IFTA.

Iliac crest angle: a novel sonographic parameter for the prediction of Down syndrome risk during the second trimester of pregnancy.

OBJECTIVES: To validate a new sonographic technique for the display and measurement of fetal iliac crest angle (ICA), and to determine the relative contribution of standardized fetal pelvic measurements for estimating risk of Down syndrome during the second trimester of pregnancy. METHODS: Three-dimensional ultrasonography of the fetal pelvis was performed during a second-trimester scan for genetic amniocentesis. A coronal view of the 'virtual pelvis' was obtained by applying a maximum intensity projection algorithm to visualize both iliac wings. Two different ICAs were measured from a coronal projection of the fetal pelvis (ICA-coronal 1 and ICA-coronal 2); the latter approach relied on using ischial tuberosities as reference landmarks. Next, a coronal projection of the fetal pelvis was rotated to demonstrate a rendered view of the axial fetal pelvis. Axial inner (ICA-inner), middle (ICA-middle) and outer (ICA-outer) ICAs were measured. The maximum anterior iliac distance measurement was defined as the widest separation between the most anterior points of the rendered iliac crests. The reproducibility of each ICA method was analyzed using Bland-Altman statistics. Simple and multiple logistic regression analysis determined the relative contribution of each parameter as a prenatal predictor of Down syndrome. RESULTS: Ninety-four normal fetuses and 19 fetuses with Down syndrome were examined. The ICA-middle and ICA-coronal 2 parameters were the most reproducible angle measurements. The mean +/- SD ICA-middle measurement for fetuses with Down syndrome was significantly greater than that for normal subjects (94.5 +/- 9.8 degrees vs. 83.1 +/- 6.5 degrees ; P < 0.001). The mean +/- SD ICA-coronal 2 angle measurement for fetuses with Down syndrome was slightly greater than that for normal subjects (57.9 +/- 5.5 degrees vs. 51.9 +/- 7.1 degrees ; P = 0.0014). A multiple logistic regression model including ICA-middle and ICA-coronal 2 provided a predictive ability of 88.1% based on the area under the receiver-operating characteristics curve. This combination had a sensitivity of 94.4% for a false-positive rate of 5% in the detection of Down syndrome. CONCLUSIONS: Standardized iliac crest measurements of the fetal pelvis can be used to identify some fetuses at risk for trisomy 21 during the second trimester of pregnancy.

Non-invasive fetal lung assessment using diffusion-weighted imaging.

OBJECTIVES: The main goal was to develop a reproducible method for estimating the diffusion of water in human fetal lung tissue using diffusion-weighted imaging (DWI). A secondary objective was to determine the relationship of the apparent diffusion coefficients (ADCs) in the fetal lung to menstrual age and total lung volume. METHODS: Normal pregnant volunteers were scanned on a 1.5-Tesla (T) magnetic resonance imaging (MRI) system. The MRI system was equipped with 40-mT/m gradients (slew rate 200 T/m/s, rise time 0.2 ms). A six-channel body array coil was used for signal reception. Single-shot DWI utilized TE/TR 125/3400 ms, slice thickness 4 mm, field of view 280 mm x 280 mm, interslice gap 0.8 mm and a matrix of 128 x 128. The voxel size was 2.5 mm x 2.5 mm x 4.0 mm. Two b-values (0 and 1000) were chosen along three orthogonal directions. ADC maps were created using assigned b-values. Simple linear regression was performed with Pearson correlation coefficient. Interexaminer and intraexaminer bias, and 95% limits of agreement (LOA) were determined using Bland-Altman plots. RESULTS: Forty-seven scans were performed at a mean +/- SD of 29.2 +/- 4.5 weeks. The median coefficient of variation for ADC was 5.6% (interquartile range, 4.0-8.1%). No differences in ADC values were found between right and left lungs. Normally distributed ADC measurements were not significantly correlated with either total lung volume (r(2) = 0.0001, P = 0.94) or menstrual age (r(2) = 0.003, P = 0.70). The mean ADC value was 1.75 (95% CI, 1.63-1.86). Mean +/- SD intraexaminer bias was -0.15 +/- 2.3 (95% LOA, -4.7 to + 4.4) and interexaminer bias was 2.2 +/- 3.5 (95% LOA, -4.7 to + 9.1). CONCLUSIONS: Our findings suggest that ADC measurements of the fetal lung are reproducible between blinded examiners and are independent of menstrual age, as well as lung volume.