Fetal cardiac dysfunction in pregnancies affected by intrahepatic cholestasis of pregnancy: A cohort study.

AIM: To analyze the presence of fetal myocardial dysfunction in intrahepatic cholestasis of pregnancy (ICP) at diagnosis. METHODS: This prospective cohort study included 49 pregnant participants with ICP at diagnosis and 49 nonaffected controls from a single public hospital. ICP was diagnosed based on clinical symptoms after excluding other causes of pruritus and presence of autoimmune diseases. Total bile acids were not obtained in this cohort. ICP pregnancies were assessed with a functional echocardiography at diagnosis including PR-interval, isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) for electrical, systolic, and diastolic function, respectively. Controls were assessed at recruitment. Perinatal outcomes were obtained from delivery books. The main outcome was the presence of PR-interval prolongation or first-degree fetal heart block, and echographic signs of diastolic and systolic dysfunction. RESULTS: Compared to controls, ICP were above upper limit in conjugated bilirubin (2.0% vs. 20.4%; p = 0.008), aspartate aminotransferase (2.0% vs. 24.5%; p = 0.002), and alanine aminotransferase (4.1% vs. 28.6%; p = 0.002). ICP was associated with a higher PR-interval (130 ± 12 ms vs. 121 ± 6 ms; p < 0.0001) with five first-degree fetal heart blocks. IRT was significantly higher in ICP (42 ± 6 ms vs. 37 ± 5 ms; p = 0.0001), with no differences in ICT and ET. PR-interval trend was only positively correlated with IRT in ICP pregnancies (p = 0.04 and p = 0.34, in ICP and controls, respectively). CONCLUSIONS: Our study demonstrates that fetuses affected by maternal ICP are associated with electrical and diastolic myocardial dysfunction. More studies focused on antenatal and postnatal functional echocardiography are necessary to validate our results and consider these markers in the clinical management of ICP pregnancies.

Congenital cytomegalovirus infection among twin pairs.

OBJECTIVE: The purpose of this study was to describe the fetal/neonatal cytomegalovirus (CMV) status according to chorionicity and outcome in twin pregnancies diagnosed with CMV. METHODS: An opportunistic diagnosis of CMV infection was performed in a tertiary referral center. All cases diagnosed in twin pregnancies (2006-2011) were included. Prenatal diagnosis was performed by CMV-DNA in the amniotic fluid (AF) of both fetuses only on the evidence of sonographic findings in either one or both twins. Neonatal screening was selectively assessed in symptomatic newborns, preterm, and infants born to HIV-infected mothers. Congenital infection was considered in the presence of CMV-DNA in AF, fetal tissues or newborn urine within the first 2 weeks of life, and symptomatic disease with clinical findings at birth or autopsy. RESULTS: A total of six twin pregnancies with congenital CMV infection were diagnosed, five dichorionic and one monochorionic diamniotic. Only one sibling was infected among dichorionic pregnancies, two diagnosed prenatally, and three after birth. In the monochorionic pregnancy, the diagnosis was performed prenatally and the two fetuses were infected and severely damaged. CONCLUSIONS: Congenital CMV infection in twins might be related, among other factors, to chorionicity, and in DC twins a non-concordant infection can be expected.

Severity of Fetal Brain Abnormalities in Congenital Heart Disease in Relation to the Main Expected Pattern of in utero Brain Blood Supply.

OBJECTIVES: We evaluated the hypothesis that in fetuses with congenital heart disease (CHD) there is a correlation between the expected pattern of in utero brain blood supply and the severity of neurodevelopmental impairment. METHODS: A total of 58 fetuses with CHD and 58 controls underwent a Doppler ultrasound and fetal MRI at 36-38 weeks. Fetuses with CHD were divided into two functional classes: class A with an expected severe reduction in oxygenated brain blood supply (left outflow tract obstruction and transposition of great vessels) and class B with theoretically near-normal or mildly impaired oxygenated brain blood supply (other CHD). Head biometry and cerebroplacental Doppler were assessed by ultrasound, and brain volumetry, cortical development and metabolism by MRI. RESULTS: Both class A and B CHD fetuses had significant differences in head biometry, brain perfusion, cortical development and brain metabolism compared with controls. However, there was a significant linear tendency for head biometry, cerebral Doppler, volumes, cortical sulcation and metabolic ratios across the three clinical groups, with signs of more severe brain alterations in type A CHD fetuses. CONCLUSIONS: All fetuses with CHD showed significant brain developmental changes, but differences were more pronounced in CHD associated with an expected severe reduction in oxygenated blood supply to the brain.

Association of brain metabolism with sulcation and corpus callosum development assessed by MRI in late-onset small fetuses.

OBJECTIVE: We sought to determine the relationship between fetal brain metabolism and microstructure expressed by brain sulcation, and corpus callosum (CC) development assessed by fetal brain magnetic resonance (MR) imaging and proton MR spectroscopy ((1)H-MRS). STUDY DESIGN: A total of 119 fetuses, 64 that were small for gestational age (estimated fetal weight <10th centile and normal umbilical artery Doppler) and 55 controls underwent a 3T MR imaging/(1)H-MRS exam at 37 weeks. Anatomical T2-weighted images were obtained in the 3 orthogonal planes and long echo time (TE) (1)H-MRS acquired from the frontal lobe. Head biometrics, cortical fissure depths (insula, Sylvian, parietooccipital, cingulate, and calcarine), and CC area and biometries were blindly performed by manual and semiautomated delineation using Analyze software and corrected creating ratios for biparietal diameter and frontooccipital diameter, respectively, for group comparison. Spectroscopic data were processed using LCModel software and analyzed as metabolic ratios of N-acetylaspartate (NAA) to choline (Cho), Cho to creatine (Cr), and myo-inositol (Ino) to Cho. Differences between cases and controls were assessed. To test for the association between metabolic ratios and microstructural parameters, bivariate correlation analyses were performed. RESULTS: Spectroscopic findings showed decreased NAA/Cho and increased Cho/Cr ratios in small fetuses. They also presented smaller head biometrics, shorter and smaller CC, and greater insular and cingulate depths. Frontal lobe NAA/Cho significantly correlated with biparietal diameter (r = 0.268; P = .021), head circumference (r = 0.259; P = .026), CC length (r = 0.265; P = .026), CC area (r = 0.317; P = .007), and the area of 6 from the 7 CC subdivisions. It did not correlate with any of the cortical sulcation parameters evaluated. None of the other metabolic ratios presented significant correlations with cortical development or CC parameters. CONCLUSION: Frontal lobe NAA/Cho levels-which are considered a surrogate marker of neuronal activity-show a strong association with CC development. These results suggest that both metabolic and callosal alterations may be part of the same process of impaired brain development associated with intrauterine growth restriction.

Neurosonographic assessment of the corpus callosum as imaging biomarker of abnormal neurodevelopment in late-onset fetal growth restriction.

OBJECTIVE: To explore corpus callosum (CC) developmental differences by ultrasound in late-onset small fetuses compared with adequate for gestational age (AGA) controls. STUDY DESIGN: Ninety four small (estimated fetal weight <10th centile) and 71 AGA fetuses were included. Small fetuses were further subdivided into fetal growth restriction (IUGR, n = 64) and small for gestational age (SGA, n = 30) based on poor perinatal outcome factors, that is, birth weight <3rd centile and/or abnormal cerebroplacental ratio and/or uterine artery Doppler. The entire cohort was scanned to assess CC by transvaginal neurosonography obtaining axial, coronal and midsagittal images. CC length, thickness, total area and the areas after a subdivision in 7 portions were evaluated by semiautomatic software. Furthermore, the weekly average growth of the CC in each study group was calculated and compared. RESULTS: Small fetuses showed significantly shorter (small fetuses: 0.49 vs. AGA: 0.52; p < 0.01) and smaller CC (1.83 vs. 2.03; p < 0.01) with smaller splenium (0.47 vs. 0.55; p < 0.01) compared to controls. The CC growth rate was also reduced when compared to controls. Changes were more prominent in small fetuses with abnormal cerebroplacental Doppler suggesting fetal growth restriction. CONCLUSIONS: Neurosonographic assessment of CC showed significantly altered callosal development, suggesting in-utero brain reorganization in small fetuses. This data support the potential value of CC assessment by US to monitor brain development in fetuses at risk.

Corpus callosum differences assessed by fetal MRI in late-onset intrauterine growth restriction and its association with neurobehavior.

OBJECTIVE: The aim of this study is to evaluate corpus callosum (CC) development by Magnetic Resonance Imaging (MRI) in late-onset intrauterine growth restricted (IUGR) fetuses compared to appropriate for gestational age and its association with neurobehavioral outcome. METHOD: One hundred and seventeen late-onset IUGR and 73 control fetuses were imaged using a 3T MRI scanner at term, obtaining T2 half-Fourier acquisition single-shot turbo spin-echo anatomical slices. CC length, thickness, total area and the areas after a subdivision in 7 portions were assessed. Neonatal Behavioral Assessment Scale test was performed on IUGR newborns at 42 ± 1 weeks. RESULTS: IUGR fetuses showed significantly smaller CC (Total CC Area IUGR: 1.3996 ± 0.26 vs. AGA: 1.664 ± 0.31; p < 0.01) and smaller subdivision areas as compared with controls. The differences were slightly more pronounced in fetuses with very low birth weight and/or abnormal brain and/or abnormal uterine Doppler. CC measurements were significantly associated with neurobehavioral outcome in IUGR cases. CONCLUSIONS: CC development was significantly altered in late-onset IUGR fetuses and correlated with worse neurobehavioral performance. CC could be further explored as a potential imaging biomarker to predict abnormal neurodevelopment in pregnancies at risk.

Brainstem and cerebellar differences and their association with neurobehavior in term small-for-gestational-age fetuses assessed by fetal MRI.

OBJECTIVE: We tested the hypothesis whether small-for-gestational-age (SGA) fetuses have different brain stem and cerebellar morphometry when compared with appropriate-for-gestational-age (AGA) fetuses and whether the differences in these structures were associated with their neonatal neurobehavior. STUDY DESIGN: Magnetic resonance imaging was performed on 51 SGA fetuses and 47 AGA fetuses at 37 weeks' gestation. Pontine width, medullar width, vermian width and height, cerebellar primary fissure's depth, and cerebellar volume were measured and corrected by biparietal diameter and cerebellar volume by total intracranial volume. Ratios were compared between cases and control subjects. The association between morphometric differences and neurobehavioral outcome in SGAs was tested. RESULTS: Brainstem and cerebellar ratios were significantly larger in SGA fetuses: pontine width, SGA 0.143 ± 0.01 vs AGA 0.135 ± 0.01 (P < .01); medullar width, SGA 0.088 ± 0.01 vs AGA 0.083 ± 0.01 (P = .03); vermian width, SGA 0.181 ± 0.03 vs AGA 0.162 ± 0.02 (P < .01); vermian height, SGA 0.235 ± 0.03 vs AGA 0.222 ± 0.01 (P < .01); cerebellar volume, SGA 0.042 ± 0.01 vs AGA 0.038 ± 0.00 (P = .04); with deeper cerebellar primary fissure in SGAs, SGA 0.041 ± 0.01 vs AGA 0.035 ± 0.01 (P = .01). Medullar, cerebellar biometries, and volumetry were significantly associated with different Neonatal Behavioral Assessment Scale cluster scores in SGA infants. CONCLUSION: Brain stem and cerebellar morphometric measurements are significantly different in term SGA fetuses, which are associated significantly with their neurobehavioral outcome. This finding supports the existence of brain microstructural changes in SGA fetuses and lays the basis for potential image biomarkers to detect fetuses who are at risk.

Differences in cortical development assessed by fetal MRI in late-onset intrauterine growth restriction.

OBJECTIVE: The objective of the study was to evaluate cortical development parameters by magnetic resonance imaging (MRI) in late-onset intrauterine growth-restricted (IUGR) fetuses and normally grown fetuses. STUDY DESIGN: A total of 52 IUGR and 50 control fetuses were imaged using a 3T MRI scanner at 37 weeks of gestational age. T2 half-Fourier acquisition single-shot turbo spin-echo anatomical acquisitions were obtained in 3 planes. Cortical sulcation (fissures depth corrected by biparietal diameter), brain volumetry, and asymmetry indices were assessed by means of manual delineation and compared between cases and controls. RESULTS: Late-onset IUGR fetuses had significantly deeper measurements in the left insula (late-onset IUGR: 0.293 vs control: 0.267; P = .02) and right insula (0.379 vs 0.318; P < .01) and the left cingulate fissure (0.096 vs 0.087; P = .03) and significantly lower intracranial (441.25 cm(3) vs 515.82 cm(3); P < .01), brain (276.47 cm(3) vs 312.07 cm(3); P < .01), and left opercular volumes (2.52 cm(3) vs 3.02 cm(3); P < .01). IUGR fetuses showed significantly higher right insular asymmetry indices. CONCLUSION: Late-onset IUGR fetuses had a different pattern of cortical development assessed by MRI, supporting the existence of in utero brain reorganization. Cortical development could be useful to define fetal brain imaging-phenotypes characteristic of IUGR.