Usefulness of lung-to-head ratio and intrapulmonary arterial Doppler in predicting neonatal morbidity in fetuses with congenital diaphragmatic hernia treated with fetoscopic tracheal occlusion.

OBJECTIVE: To explore the potential value of intrapulmonary artery Doppler velocimetry in predicting neonatal morbidity in fetuses with left-sided congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO). METHODS: Observed/expected lung-to-head ratio (O/E-LHR), and intrapulmonary Doppler pulsatility index and peak early-diastolic reversed flow were evaluated within 24 h before FETO in a consecutive cohort of 51 fetuses with left-sided CDH at between 24 and 33 weeks' gestation. Lung Doppler parameters were converted into Z-scores and defined as abnormal if the pulsatility index had a Z-score of > 1.0 or the peak early-diastolic reversed flow had a Z-score of > 3.5. The association of O/E-LHR and Doppler velocimetry with neonatal outcome was assessed using multiple linear or logistic regression analysis adjusted for gestational age at birth. RESULTS: Among the 26 fetuses that survived, 18 (69.2%) had normal and eight (30.8%) had abnormal Doppler values. O/E-LHR was not associated with neonatal morbidity in surviving fetuses. Compared with the group with normal Doppler parameters, cases with abnormal intrapulmonary Doppler were associated with a significant increase in the duration of mechanical ventilation (average increase of 21.2 (95% CI, 9.99-32.5) days; P < 0.01), conventional ventilation (15.2 (95% CI, 7.43-23.0) days; P < 0.01), high-frequency ventilation (6.34 (95% CI, 0.69-11.99) days; P < 0.05), nitric oxide therapy (5.73 (95% CI, 0.60-10.9) days; P < 0.05), oxygen support (36.5 (95% CI, 16.3-56.7) days; P < 0.01), parenteral nutrition (19.1 (95% CI, 7.53-30.7) days; P < 0.01) and stay in neonatal intensive care unit (42.7 (95% CI, 22.9-62.6) days; P < 0.001), and with significantly higher rates of high-frequency ventilation (87.5 vs. 44.4%;P < 0.05), oxygen requirement at 28 days of age (75.0 vs. 11.1%; P < 0.01), gastroesophageal reflux (62.5 vs. 22.2%; P < 0.05) and tube feeding at discharge (37.5 vs. 5.56%; P < 0.05). CONCLUSION: As previously reported, O/E-LHR did not predict neonatal morbidity. In contrast, intrapulmonary artery Doppler evaluation was predictive of neonatal morbidity in CDH fetuses treated with FETO.

Contribution of the myocardial performance index and aortic isthmus blood flow index to predicting mortality in preterm growth-restricted fetuses.

OBJECTIVES: To evaluate the predictive value for perinatal death of the myocardial performance index (MPI) and aortic isthmus flow index (IFI), as isolated parameters and in a combined model including currently used Doppler indices, in preterm growth restricted (IUGR) fetuses. METHODS: Umbilical artery, fetal middle cerebral artery (MCA) and ductus venosus (DV) pulsatility indices (PIs) were recorded, along with IFI and MPI, in a cohort of 97 preterm (delivered at between 24 and 34 weeks) IUGR fetuses. Logistic regression analysis was performed to identify those variables that were independently associated with perinatal mortality, and an algorithm to estimate probability of death was constructed including the best combination of parameters. RESULTS: With the exception of MCA, all Doppler indices were significantly associated with perinatal death as isolated parameters, but only DV-PI and MPI were found to be independent predictors on multivariate analysis. An algorithm combining DV atrial flow (positive or absent/reversed) and MPI (normal or above 95(th) percentile) had a better predictive accuracy than did any single parameter. The risk for death in IUGR fetuses below 28 weeks' gestation with present atrial flow in the DV and normal MPI was 18%, with either characteristic abnormal it was 70-73%, and with both abnormal it was 97%. The risk for death in IUGR fetuses above 28 weeks with present atrial flow in the DV and normal MPI was 0.1%, with either abnormal it was 6-7%, and with both abnormal it was 45%. CONCLUSIONS: MPI is an independent predictor of perinatal death in preterm IUGR fetuses with accuracy similar to that of DV flow. A combination of DV flow with MPI may better stratify the estimated probability of death. IFI does not add to the prediction of perinatal death when used in combination with DV flow.

Monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic flow (Type III): feasibility and perinatal outcome of fetoscopic placental laser coagulation.

OBJECTIVES: To assess the feasibility and impact on perinatal outcome of fetoscopic laser coagulation of placental anastomoses in monochorionic twins with selective intrauterine growth restriction (sIUGR) and intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery (Type III), in comparison with expectant management. METHODS: This is a descriptive study of the outcome of 18 cases of monochorionic twins with Type III sIUGR treated with laser, and 31 pregnancies managed expectantly over the same period. All newborns underwent neonatal brain ultrasound scans. Perinatal outcome and the incidence of neurological damage were compared between the two groups. RESULTS: Laser coagulation could be performed in only 88.9% (16/18) of cases owing to technical difficulties, and in 12.5% (2/16) a second procedure was required to achieve complete coagulation of the large artery-to-artery anastomosis. Mean gestational age at delivery was 31.0 (range, 26-33) weeks in the expectant management group and 32.6 (range, 23-38) weeks in the laser group (P = 0.32). Overall perinatal survival was 85.5% (53/62) and 63.9% (23/36), respectively (P = 0.02). Intrauterine demise of the smaller twin occurred in 19.4% (6/31) and 66.7% (12/18), respectively (P = 0.001), and was associated with death of the cotwin in 50% (3/6) and 0% (0/12) of these cases, respectively (P = 0.02). The prevalence of periventricular leukomalacia in the larger fetus was 4/28 (14.3%) in the expectant management group and 1/17 (5.9%) in the laser group (P = 0.63). CONCLUSIONS: Laser coagulation in sIUGR-iAREDF pregnancies is technically difficult and not always feasible. Placental dichorionization significantly increases the proportion of fetuses with intrauterine death of the growth-restricted twin, but it protects the normal twin from its cotwin's death in the event of demise of the growth-restricted twin.

Twin chorionicity and the risk of adverse perinatal outcome.

OBJECTIVE: To evaluate the impact of chorionicity on the perinatal outcomes of twin pregnancies complicated by twin-twin transfusion syndrome (TTS) or selective intrauterine growth restriction (sIUGR). METHOD: Pregnancies with 127 monochorionic (MC) and 109 dichorionic (DC) twins were followed up, and TTS and sIUGR incidence as well as morbidity and mortality were evaluated. RESULTS: The incidence of intrauterine fetal death was higher in MC than in DC pregnancies (6.5% vs. 1%), and higher in MC pregnancies complicated by TTS (5 deaths in 10 pregnancies [50%]) or sIUGR (2 in 9 [22%]). The incidence of sIUGR was similar in MC and DC pregnancies (7% vs. 5%), and the incidence of TTS was 8% in MC pregnancies (95% confidence interval, 3.2-12.8). Neonatal neurological and respiratory morbidity was higher among MC twins, and the increase in neonatal complications was linked to TTS and sIUGR. Uncomplicated MC and DC pregnancies had similar perinatal outcomes. CONCLUSION: The incidence of neonatal complications was higher in MC twins born of pregnancies complicated by TTS or sIUGR. Although the incidence of sIUGR was similar in MC and DC pregnancies, there was a trend towards worse outcomes in MC pregnancies affected by sIUGR.

Doppler changes in the main fetal brain arteries at different stages of hemodynamic adaptation in severe intrauterine growth restriction.

OBJECTIVE: To evaluate changes in the temporal evolution and regional distribution of arterial brain Doppler parameters in relation to different stages of hemodynamic adaptation in fetuses with severe intrauterine growth restriction (IUGR). METHODS: Thirty-six fetuses with severe IUGR ( 2 SD) were evaluated longitudinally with pulsed Doppler ultrasound at four different hemodynamic stages: Stage 1 (n = 36), mean UA-PI > 2 SD or absent UA end-diastolic flow; Stage 2 (n = 34), abnormal middle cerebral artery (MCA) PI (mean < 2 SD); Stage 3 (n = 30), reversed UA end-diastolic flow; Stage 4 (n = 12), absent or reversed atrial flow in the ductus venosus. In addition, 36 normally grown fetuses were studied for comparison. PI and time-averaged maximum velocity (TAMXV) in the MCA and the anterior cerebral (ACA), pericallosal (PER) and posterior cerebral (PCA) arteries were measured. RESULTS: In IUGR fetuses, PI values from all arteries were significantly reduced at Stage 2. At Stages 3 and 4, ACA-PI and PCA-PI did not change further, whereas MCA-PI and PER-PI showed a slight increase. In the ACA, MCA and PER, TAMXV in Stage 2 increased significantly. In Stages 3 and 4, ACA and PER-TAMXV remained unchanged, whereas MCA-TAMXV showed a slight decrease, mirroring the PI values. PCA-TAMXV values were similar to controls at all stages. CONCLUSION: In IUGR fetuses, the brain arteries differ in the magnitude and time sequence of Doppler parameters in relation to systemic hemodynamic adaptation, suggesting the existence of regional brain redistribution processes.

Gestational-age-adjusted reference values for the modified myocardial performance index for evaluation of fetal left cardiac function.

OBJECTIVE: It has been shown that the modified myocardial performance index (Mod-MPI) is associated with higher reproducibility than conventional MPI because it uses mitral and aortic valve 'clicks' to calculate each time period. We aimed to construct normal reference values for the Mod-MPI after 19 weeks' gestation. METHODS: The Mod-MPI was calculated in the left ventricle of 557 normal fetuses at 19-39 weeks' gestation. The isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT) and ejection time (ET) were measured using the Doppler signals (clicks) of the opening and closing of the mitral and aortic valves as landmarks. Mod-MPI was calculated as (ICT + IRT)/ET. RESULTS: Throughout gestation, there was a small increase in the Mod-MPI (at 19 weeks it was 0.35 +/- 0.027 (mean +/- SD); at 39 weeks, 0.37 +/- 0.029; Mod-MPI = 0.33 + 0.001x gestational age (GA) (weeks), r(2) = 0.017). Of the three components, ICT remained constant, IRT increased (IRT = 0.028 + 2.52 x GA (weeks)), and ET slightly decreased (ET = 0.184 - 3.65 x GA (weeks)). Fetal heart rate (FHR) had no effect on the Mod-MPI, but the duration of IRT, ICT and ET decreased by 13-15% when FHR increased from 130 to 160 beats per minute. CONCLUSION: The GA-adjusted reference values for the Mod-MPI and the three time periods used for its calculation can be applied to fetal cardiac evaluation in the presence of pregnancy-associated complications.

Evaluation of fetal regional cerebral blood perfusion using power Doppler ultrasound and the estimation of fractional moving blood volume.

OBJECTIVE: To standardize the evaluation of regional fetal brain blood perfusion, using power Doppler ultrasound (PDU) to estimate the fractional moving blood volume (FMBV) and to evaluate the reproducibility of this estimation. METHODS: Brain blood perfusion was evaluated in 35 normally grown fetuses at 28-30 weeks of gestation, using PDU. The following cerebral regions were included in the PDU color box: anterior sagittal, complete sagittal, basal ganglia, and cerebellar. Ten consecutive good-quality images of each anatomical plane were recorded and the delimitation of the region of interest (ROI) was performed off-line. FMBV was quantified in the ROI of all images and the mean considered as the final value. Differences between regions, variability, reproducibility and agreement between observers were assessed. RESULTS: Power Doppler images of the described anatomical planes were obtained in all cases, regardless of fetal position. The median time for the acquisition of the images was 7 (range 4-12) min. Mean (range) FMBV values were: anterior sagittal, 16.5 (10.7-22.8)%, inter-patient coefficient of variation (CV) 0.22; complete sagittal, 13.5 (8.8-16.1)%, CV 0.27; basal ganglia, 18.3 (10.7-27.6)%, CV 0.27; and cerebellar, 6.6 (3.0-11.0)%, CV 0.38. There were statistically significant differences in FMBV between cerebellar and complete sagittal ROIs with the frontal and basal ganglia regions. Reproducibility analyses showed an intraclass correlation coefficient of 0.91 (95% CI 0.67-0.97) and an interclass correlation coefficient of 0.87 (95% CI 0.70-0.94). Interobserver agreement showed a mean difference between observers of -0.2 (SD 2.7) with 95% limits of agreement -5.6 to 5.2. CONCLUSIONS: When the regions of interest are well defined, the FMBV estimate offers a method to quantify blood flow perfusion in different fetal cerebral areas. There appear to be regional differences in FMBV within the fetal brain.

A classification system for selective intrauterine growth restriction in monochorionic pregnancies according to umbilical artery Doppler flow in the smaller twin.

OBJECTIVES: To evaluate a classification of selective intrauterine growth restriction (sIUGR) in monochorionic (MC) twins based on the characteristics of umbilical artery (UA) Doppler flow in the smaller twin, in terms of association with clinical outcome and with the pattern of placental anastomoses. METHODS: One hundred and thirty-four MC twins diagnosed with sIUGR at 18-26 weeks were classified as Type I (UA Doppler with positive diastolic flow, n = 39), Type II (persistent absent or reversed end-diastolic flow, n = 30) and Type III (intermittent absent or reversed end-diastolic flow, n = 65). Perinatal outcome, placental sharing and the pattern of anastomoses were compared with those in 76 uncomplicated MC twins. RESULTS: Mean gestational age at delivery was 35.5 (range, 30-38) weeks in controls, 35.4 (range, 16-38) weeks in Type I, 30.7 (range, 27-40) weeks in Type II (P < 0.0001) and 31.6 (range, 23-39) weeks in Type III (P < 0.0001) pregnancies. Fetal weight discordance was significantly higher in Type II (38%) and Type III (36%) than in Type I (29%) (P < 0.0001) pregnancies. Deterioration of the growth-restricted fetus occurred in 90% of Type II cases, compared with 0% and 10.8% of Types I and III, respectively (P < 0.001). Unexpected intrauterine fetal death of the smaller twin occurred in 15.4% of Type III cases, compared with 2.6% and 0% of Types I and II respectively (P < 0.05). Parenchymal brain lesions in the larger twin were observed in 19.7% of Type III cases and less than 5% in the other groups (P < 0.05). Placental discordance (larger/smaller) was 1.3 in controls, compared with 1.8, 2.6 and 4.4 in Types I, II and III, respectively (P < 0.01). The proportion of cases with arterioarterial anastomoses > 2 mm in diameter was 55% in controls, 70% in Type I, 18% in Type II (P < 0.01) and 98% in Type III (P < 0.01). CONCLUSION: sIUGR can be classified on the basis of umbilical artery Doppler into three types that correlate with different clinical behavior and different patterns of placental anastomoses. This classification may be of help in clinical decision-making and when comparing clinical studies.

Hypertrophic cardiomyopathy-like changes in monochorionic twin pregnancies with selective intrauterine growth restriction and intermittent absent/reversed end-diastolic flow in the umbilical artery.

OBJECTIVE: To evaluate the prevalence of hypertrophic cardiomyopathy-like (HCL) changes in monochorionic twins with selective intrauterine growth restriction (sIUGR) and intermittent absent/reversed end-diastolic flow (iAREDF), also defined as Type III sIUGR, and the clinical relevance of this condition. METHODS: A total of 80 pregnancies with sIUGR were studied, 40 with, and 40 without iAREDF. HCL changes were defined as an increased thickness of either left or right ventricular wall (mean > 2 SD) estimated with M-mode ultrasonography. Data were plotted on normal reference values constructed from 75 uncomplicated monochorionic twin pregnancies (150 fetuses) at 22-34 weeks' gestation. Perinatal outcomes in pregnancies with and without HCL changes were compared. RESULTS: In the group with iAREDF, 8/40 of the larger twins (20%) had HCL changes (five bilaterally, two in the right, and one in the left ventricle) as compared with 1/40 (2.5%) in fetuses without iAREDF (P = 0.03). No differences were observed in the smaller twin (1/40 in both groups). HCL changes were not associated with a significant increment in perinatal mortality as only one large fetus from the group with iAREDF died in utero. In the remaining 10 cases, no differences in the intertwin weight discordance, placental surface discordance, or rate of neonatal neurological damage were observed. However, all 10 presented mildly abnormal neonatal cardiac findings that resolved over time with no apparent short-term impact on cardiac function. CONCLUSIONS: HCL changes in the larger twin should be regarded as part of the spectrum of findings in Type III monochorionic-sIUGR (presenting iAREDF). This finding does not seem to be associated with an increased rate of short-term neurological or cardiac complications.