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Objective To evaluate corpus callosum (CC) size by neurosonography (NSG) in fetuses with an isolated major congenital heart defect (CHD) and explore the association of CC size with the expected pattern of in-utero oxygen supply to the brain. Methods A total of 56 fetuses with postnatally confirmed isolated major CHD and 56 gestational-age-matched controls were included. Fetuses with CHD were stratified into two categories according to the main expected pattern of cerebral arterial oxygen supply: Class A, moderately to severely reduced oxygen supply (left outflow tract obstruction and transposition of the great arteries) and Class B, near normal or mildly impaired oxygenated blood supply to the brain (other CHD). Transvaginal NSG was performed at 32-36 weeks in all fetuses to evaluate CC length, CC total area and areas of CC subdivisions in the midsagittal plane. Results CHD fetuses had a significantly smaller CC area as compared to controls (7.91 +/- 1.30 vs 9.01 +/- 1.44 mm(2); P < 0.001), which was more pronounced in the most posterior part of the CC. There was a significant linear trend for reduced CC total area across the three clinical groups, with CHD Class-A cases showing more prominent changes (controls, 9.01 +/- 1.44 vs CHD Class B, 8.18 +/- 1.21 vs CHD Class A, 7.53 +/- 1.33 mm(2); P < 0.05). Conclusions Fetuses with major CHD had a smaller CC compared with controls, and the difference was more marked in the CHD subgroup with expected poorer brain oxygenation. Sonographic CC size could be a clinically feasible marker of abnormal white matter development in CHD. (c) 2021 International Society of Ultrasound in Obstetrics and Gynecology.

In general terms, fetal growth restriction (FGR) is considered the impossibility of achieving the genetically determined potential size. In the vast majority of cases, it is related to uteroplacental insufficiency. Although its origin remains unknown and causes are only known in 30% of cases, it is believed to be related to an interaction of environmental and genetic factors with either a fetal or maternal origin. One hypothesis is that alterations in the gastrointestinal microbiota composition, and thus alteration in the immune response, could play a role in FGR development. We performed an observational, prospective study in a subpopulation affected with FGR to elucidate the implications of this microbiota on the FGR condition. A total of 63 fetuses with FGR diagnosed in the third trimester as defined by the Delphi consensus, and 63 fetuses with fetal growth appropriate for gestational age will be recruited. Obstetric and nutritional information will be registered by means of specific questionnaires. We will collect maternal fecal samples between 30 to 36 weeks, intrapartum samples (maternal feces, maternal and cord blood) and postpartum samples (meconium and new-born feces at 6 weeks of life). Samples will be analyzed in the Department of Biochemistry and Molecular Biology II, Nutrition and Food Technology Institute of the University of Granada (UGR), for the determination of the gastrointestinal microbiota composition and its relationship with inflammatory biomarkers. This study will contribute to a better understanding of the influence of gastrointestinal microbiota and related inflammatory biomarkers in the development of FGR. Trial registration: NCT04047966. Registered August 7, 2019, during the recruitment stage. Retrospectively registered. Ongoing research., Instituto de Salud Calos III, Fondos de Desarrollo Regional Europeos (FEDER) PI17/01215

IntroductionThe adaptive changes of the foetal heart in intrauterine growth restriction can persist postnatally. Data regarding its consequences for early circulatory adaptation to extrauterine life are scarce. The aim of this study was to assess cardiac morphometry and function in newborns with late-onset intrauterine growth restriction to test the hypothesis that intrauterine growth restriction causes cardiac shape and functional changes at birth.MethodsA comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates.ResultsCompared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e′) diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group.ConclusionNeonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.

Objectives: Firstly, to describe the outcome of a series of fetuses with Ebstein’s anomaly (EA) and, secondly, to study the utility of different second-trimester echocardiographic parameters to predict fetal and neonatal mortality. Methods: 39 fetuses with EA diagnosed between 18 and 28 weeks of gestation were included. Fetal echocardiography included the cardiothoracic ratio (CTR); right atrial (RA) area index; displacement of the tricuspid valve (TV); tricuspid regurgitation; pulmonary artery; and ductus arteriosus flow characteristics. Additionally, 2 novel parameters were obtained: the relative RA area ratio (RA area/cardiac area) and the TV displacement index (TVDI, TV displacement distance/longi­tudinal diameter of the left ventricle). Correlation between the echocardiographic variables and the primary outcome of perinatal mortality or survival at 1 year of life was evaluated. Results: From the initial cohort, 8 cases were excluded due to complex congenital heart defects. Termination of pregnancy (TOP) was performed in 15 cases, and fetal death was diagnosed in 3 cases. In the live-born cohort of 13 patients, 4 died in the neonatal period, yielding a perinatal survival rate of 29 and 56%, respectively, after excluding TOP cases. Compared with survivors, nonsurvivors showed a significantly higher CTR (56.7 ± 16.2 vs. 42.6 ± 8.6; p = 0.04), relative RA area ratio (0.39 ± 0.13 vs. 0.25 ± 0.05; p = 0.01), and TVDI (0.62 ± 0.17 vs. 0.44 ± 0.12; p = 0.03) at diagnosis. The best model to predict perinatal mortality was obtained by using a scoring system which included the relative RA area ratio and TVDI (AUC 0.905 [95% CI 0.732–1.000]). Conclusions: Fetuses with a relative RA area ratio ≥0.29 and TVDI ≥0.65 at the second trimester have the highest risk of dying in the perinatal stage.

BACKGROUND AND PURPOSE: Fetuses with isolated nonsevere ventriculomegaly (INSVM) are at risk of presenting neurodevelopmental delay. However, the currently used clinical parameters are insufficient to select cases with high risk and determine whether subtle changes in brain development are present and might be a risk factor. The aim of this study was to perform a comprehensive evaluation of cortical development in INSVM by magnetic resonance (MR) imaging and assess its association with neonatal neurobehavior. MATERIALS AND METHODS: Thirty-two INSVM fetuses and 29 healthy controls between 26-28 weeks of gestation were evaluated using MR imaging. We compared sulci and fissure depth, cortical maturation grading of specific areas and sulci and volumes of different brain regions obtained from 3D brain reconstruction of cases and controls. Neonatal outcome was assessed by using the Neonatal Behavioral Assessment Scale at a mean of 4 ± 2 weeks after birth. RESULTS: Fetuses with INSVM showed less profound and underdeveloped sulcation, including the Sylvian fissure (mean depth: controls 16.8 ± 1.9 mm, versus INSVM 16.0 ± 1.6 mm; P = .01), and reduced global cortical grading (mean score: controls 42.9 ± 10.2 mm, versus INSVM: 37.8 ± 9.9 mm; P = .01). Fetuses with isolated nonsevere ventriculomegaly showed a mean global increase of gray matter volume (controls, 276.8 ± 46.0 ×10 mm3, versus INSVM 277.5 ± 49.3 ×10 mm3, P = .01), but decreased mean cortical volume in the frontal lobe (left: controls, 53.2 ± 8.8 ×10 mm3, versus INSVM 52.4 ± 5.4 ×10 mm3; P = < .01). Sulcal depth and brain volumes were significantly associated with the Neonatal Behavioral Assessment Scale severity (P = .005, Nagelkerke R2 = 0.732). CONCLUSIONS: INSVM fetuses showed differences in cortical development, including regions far from the lateral ventricles, that are associated with neonatal neurobehavior. These results suggest the possible use of these parameters to identify cases at higher risk of altered neurodevelopment. ispartof: AMERICAN JOURNAL OF NEURORADIOLOGY vol:40 issue:9 pages:1567-1574 ispartof: location:United States status: published

Background Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Methods Eligible participants are women presenting at 20 to Discussion The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children’s neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. Trial registration NCT02996630, on 4th December 2016 (retrospectively registered).

A longitudinal study with dual x-ray absorptiometry disclosed that infants born large for gestational age from mothers without diabetes mellitus and without excessive gestational weight gain tend to be long with increased adipose tissue as newborns and tall and lean as toddlers.

Objectives To perform a comprehensive assessment of cortical development in fetuses with isolated nonsevere ventriculomegaly (INSVM) by neurosonography. Methods We prospectively included 40 fetuses with INSVM and 40 controls. INSVM was defined as atrial width between 10.0 and 14.9 mm without associated malformation, infection, or chromosomal abnormality. Cortical development was assessed by neurosonography at 26 and 30 weeks of gestation measuring depth of selected sulci and applying a maturation scale from 0 (no appearance) to 5 (maximally developed) of main sulci and areas. Results INSVM showed underdeveloped calcarine and parieto-occipital sulci. In addition, significant delayed maturation pattern was also observed in regions distant to ventricular system including Insula depth (controls 30.8 mm [SD 1.7] vs INSVM 31.7 mm [1.8]; P = .04), Sylvian fissure grading (>2 at 26 weeks: controls 87.5% vs INSVM 50%, P = .01), mesial area grading (>2 at 30 weeks: controls 95% vs INSVM 62.5%; P = .03), and cingulate sulcus grading (>2 at 30 weeks: controls 100% vs INSVM 80.5%; P = .01). Conclusions Fetuses with INSVM showed underdeveloped cortical maturation including also regions, where effect of ventricular dilatation is unlikely. These results suggest that in a proportion of fetuses with INSVM, ventricular dilation might be related with altered cortical architecture.

Background. Nerve growth factor (NGF) plays a key role in neuroprotection and developmental maturity. We assessed longitudinally the circulating concentrations of NGF in term healthy human newborns and infants as well as their association with prenatal growth and early postnatal feeding patterns.Methods. Circulating NGF and anthropometric measures (weight, length, body mass index, and ponderal index) were assessed longitudinally—at birth and at age 4 months—in 86 term infants born appropriate (AGA), small (SGA), or large for gestational age (LGA).Results. Cord blood NGF levels in SGA newborns were higher than those in AGA newborns (1.41 ± 0.2 pg/mL vs. 0.66 ± 0.1 pg/mL;p=0.02) and not different from those in LGA neonates (0.79 ± 0.2 pg/mL). At age 4 months, SGA-breastfed infants showed the highest NGF concentrations (p=0.02andp=0.01vs. AGA and SGA-formula-fed infants, respectively), while LGA infants depicted a marginal increase. NGF levels in cord blood correlated negatively with the ponderal index at birth (r=−0.36;p=0.0008).Conclusions. Circulating NGF is related to both prenatal growth and early postnatal nutrition. The maintenance of increased NGF concentrations in SGA-breastfed infants at age 4 months might be a potential mechanism to counterbalance potential risks for developing cognitive and psychomotor disadvantages.

Objective Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI. Methods A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3rd and 9th centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was 95th centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler. Results Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P

Objective: To assess cardiovascular function and damage in term small-for-gestational-age (SGA) and intrauterine growth-restricted (IUGR) fetuses by echocardiography and biomarkers in cord blood. Methods: This was a cohort study including 60 normal fetuses and 47 term small fetuses subclassified as small for gestational age (SGA) with estimated fetal weight (EFW) between the 3rd and 9th centiles and normal fetoplacental Doppler (n = 14) or intrauterine growth restriction (IUGR, n = 33) if EFW 95th centile. Fetal echocardiography included left myocardial performance index (MPI) and annular plane systolic excursion. Fetal B-type natriuretic peptide (BNP), troponin-I, heart-type fatty acid-binding proteins (H-FABP), and homocysteine concentrations were measured in cord blood collected at delivery. Results: Both SGA and IUGR cases presented echocardiographic signs of systolic and diastolic dysfunction with increased MPI (mean controls 0.43 [SD 0.12], SGA 0.47 [0.03], and IUGR 0.57 [0.08], p < 0.01) and decreased mitral annular plane systolic excursion (controls 6.0 mm [1.0], SGA 5.5 mm [0.6], and IUGR 4.9 mm [0.8], p = 0 01). IUGR fetuses presented increased levels of cord blood BNP (controls 17.2 pg/mL [11.5], SGA 22.4 pg/mL [10.7], and IUGR 31.2 pg/mL [26.8], p < 0.01). Troponin I was increased in both SGA and IUGR cases (controls 0.004 ng/mL [0.007], SGA 0.012 ng/mL [0.02], and IUGR 0.018 ng/mL [0.05], p < 0.01). H-FABP and homocysteine showed similar values among groups. Conclusions: Cardiac dysfunction and cell damage is a common feature of term SGA and IUGR fetuses despite of the severity criteria for perinatal outcome. Further research is needed to evaluate the potential long-term consequences on their cardiovascular system.

Sexagenarians born large are at lower risk for type 2 diabetes than those born small, a key feature of their body composition being a higher muscle mass, which explains their higher body mass index and also their lower fat-to-lean-mass ratio. Myogenesis is completed in early infancy under the inhibitory control of myostatin. We tested whether large-born infants from nondiabetic mothers develop an early surplus of lean mass while having a lower myostatinemia. Design, Methods, Study Participants, and Main Outcomes: In a longitudinal study (0-4 mo), we compared the body composition and endocrine markers (fasting glucose, insulin, IGF-1, high molecular weight adiponectin) of breast-fed appropriate- vs large-for-gestational-age infants (n = 125) from nondiabetic mothers. Circulating myostatin concentrations were assayed after collection of the above-mentioned data.The study was conducted at the University Hospital for Women and Children.There were no interventions.Between 0-4 months, large-for-gestational-age infants switched from an adipose to a lean body composition (due to a nearly 20% excess of lean mass) and to an insulin-sensitive and hyperadiponectinemic state while having low IGF-1 concentrations and the lowest myostatinemia hitherto reported in the human (all between P ≤ .01 and P ≤ .0001).Large-born infants from nondiabetic mothers were found to combine a low myostatinemia with an excess of lean mass. The fetal-neonatal control of myostatinemia deserves further attention because it could become a target of interventions that aim at reducing the risk for diabetes in later life by augmenting myogenesis in early life.

Background: Prenatal growth restraint is associated with increased oxidative stress - as judged by mitochondrial dysfunction - in pregnancies complicated by preeclampsia or diabetes, but it is uncertain whether this is also the case in uncomplicated pregnancies. We assessed the link between fetal growth restraint and placental mitochondrial dysfunction, as reflected by changes in mitochondrial DNA (mtDNA) content and superoxide dismutase (SOD) activity. Methods: After uncomplicated pregnancies, placentas (n = 48) were collected at term delivery of singleton infants who were appropriate for gestational age (AGA) or small for gestational age (SGA) (n = 24 in each subgroup). Placental mtDNA content was assessed by real-time PCR, placental SOD activity by colorimetry, and citrate synthase activity - to determine mitochondrial mass - by the spectrophotometric method. Results: Placentas of SGA infants had a lower mtDNA content (p = 0.015) and a higher SOD activity (p = 0.001) than those of AGA controls. These differences were maintained after normalization of the mtDNA content by citrate synthase activity. In placentas of SGA infants, there was a negative association between mtDNA content and SOD activity (r = -0.58, p = 0.008). Conclusions: Fetal growth restraint is accompanied by adaptive changes in the mitochondrial function of the placenta, also in uncomplicated pregnancies.