Corpus callosum size by neurosonography in fetuses with congenital heart defect and relationship with expected pattern of brain oxygen supply.

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 mm2 ; 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 mm2 ; 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. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

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 < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). 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).

Biventricular impact of mild to moderate fetal pulmonary valve stenosis.

OBJECTIVES: To define the pattern of fetal echocardiographic changes associated with isolated pulmonary valve stenosis (PS) and to correlate the echocardiographic findings with neonatal outcome and the need for postnatal pulmonary valvuloplasty within the first 12 months postpartum. METHODS: This was a prospective cohort study between January 2009 and October 2015 of 16 fetuses with isolated PS and 48 controls matched by gestational age at ultrasound examination (± 2 weeks) evaluated at the Fetal Cardiology Unit at BCNatal (Barcelona). Standard fetal ultrasound and comprehensive echocardiography, which included cardiovascular morphometric parameters, and systolic and diastolic functional and timing measurements, were performed in all cases. Baseline characteristics and perinatal outcome were retrieved from clinical records. Cases were followed up until 12 months of age, and admission to intensive care unit, days of hospitalization, need for prostaglandins and requirement for postnatal surgery were reviewed. Fetal PS cases were analyzed according to the need for postnatal pulmonary valvuloplasty. RESULTS: The study groups were similar in terms of baseline, fetal ultrasound and perinatal characteristics. Median gestational age at diagnosis of PS was 33.4 (range, 20.0-36.5) weeks. Most cases corresponded to mild or moderate PS; only three fetuses had reversed flow in the ductus arteriosus before delivery. Six (37.5%) newborns, including all three with reversed flow in the ductus arteriosus prenatally, required postnatal pulmonary valvuloplasty. Fetuses with PS presented with larger and more globular hearts, with increased myocardial wall thickness in the third trimester. Despite preserved right ventricular (RV) ejection fraction and systolic longitudinal motion, PS cases showed increased right cardiac output and signs of diastolic dysfunction, with higher ductus venosus pulsatility index (0.72 ± 0.32 vs 0.53 ± 0.16, P = 0.004) and tricuspid E/E' ratio (7.52 ± 3.07 vs 5.76 ± 1.79, P = 0.022). In addition, fetuses with PS displayed a compensatory increase in left ventricular (LV) radial and longitudinal motion, as shown by a higher ejection fraction (79.3 ± 8.23% vs 67.6 ± 11.3%, P = 0.003) and mitral annular-plane systolic excursion (5.94 ± 1.38 vs 5.0 ± 1.22 mm, P = 0.035). Finally, fetuses requiring postnatal pulmonary valvuloplasty showed a different pattern of echocardiographic findings from those not requiring valvuloplasty, with a significantly smaller RV and pulmonary valve diameter, reduced tricuspid annular-plane systolic excursion (5.08 ± 1.59 vs 8.07 ± 1.93 mm, P = 0.028), increased LV cardiac output (340 ± 16 vs 176 ± 44 mL/min/kg, P = 0.003) and more pronounced signs of LV diastolic dysfunction (mitral E' velocity, 5.78 ± 0.90 vs 8.16 ± 1.58 cm/s, P = 0.008). CONCLUSIONS: Fetuses with PS present with more hypertrophic, larger and more globular hearts in the third trimester of pregnancy, associated with a higher right cardiac output and impaired biventricular relaxation. In addition, signs of increased LV contraction were observed. Our data suggest that RV and LV functional parameters could be useful for predicting the need for postnatal pulmonary valvuloplasty. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal changes in fetal biometry and cerebroplacental hemodynamics in fetuses with congenital heart disease.

OBJECTIVES: To determine the longitudinal behavior of fetal biometric measures and cerebroplacental hemodynamics throughout gestation in fetuses with congenital heart disease (CHD). METHODS: Fetal biometry and Doppler hemodynamics (uterine artery (UtA), umbilical artery (UA) and fetal middle cerebral artery (MCA)) were measured serially in a cohort of consecutive fetuses diagnosed with CHD. Evaluations were made at various time points, from diagnosis (20-25 weeks) to delivery, with at least two measurements per fetus that were at least 2 weeks apart. Fetuses were classified into three groups according to the pattern of blood supply to the brain (placental vs systemic) that would be expected on the basis of the type of CHD. All parameters were transformed into Z-scores. A linear mixed model to analyze repeated measurements was constructed for each parameter to assess its behavior throughout gestation. RESULTS: Four hundred and forty-four ultrasound examinations were performed in 119 CHD fetuses, with a median of two measurements per fetus. The fetuses presented a small head at diagnosis (biparietal diameter (BPD) Z-score, -1.32 ± 0.99; head circumference (HC) Z-score, -0.79 ± 1.02), which remained small throughout gestation. UtA and UA pulsatility indices (PI) showed a significant increase towards the end of pregnancy, whereas no significant changes were observed in MCA-PI or cerebroplacental ratio (CPR) with gestational age. Both MCA and CPR presented significant differences in longitudinal behavior between CHD groups, while BPD and HC did not. CONCLUSIONS: CHD fetuses have a relatively small head from the second trimester of pregnancy, regardless of the type of CHD anomaly, and increasing resistance in the UtA and UA as pregnancy progresses, suggestive of increasing degree of placental impairment. Our findings indicate the early onset of mechanisms that could lead to poorer neurodevelopment later in life. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Mid-gestation brain Doppler and head biometry in fetuses with congenital heart disease predict abnormal brain development at birth.

OBJECTIVES: Fetuses with congenital heart disease (CHD) show evidence of abnormal brain development before birth, which is thought to contribute to adverse neurodevelopment during childhood. Our aim was to evaluate whether brain development in late pregnancy can be predicted by fetal brain Doppler, head biometry and the clinical form of CHD at the time of diagnosis. METHODS: This was a prospective cohort study including 58 fetuses with CHD, diagnosed at 20-24 weeks' gestation, and 58 normal control fetuses. At the time of diagnosis, we recorded fetal head circumference (HC), biparietal diameter, middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and brain perfusion by fractional moving blood volume. We classified cases into one of two clinical types defined by the expected levels (high or low) of placental (well-oxygenated) blood perfusion, according to the anatomical defect. All fetuses underwent subsequent 3T-magnetic resonance imaging (MRI) at 36-38 weeks' gestation. RESULTS: Abnormal prenatal brain development was defined by a composite score including any of the following findings on MRI: total brain volume < 10(th) centile, parietoccipital or cingulate fissure depth < 10(th) centile or abnormal metabolic profile in the frontal lobe. Logistic regression analysis demonstrated that MCA-PI (odds ratio (OR), 12.7; P = 0.01), CPR (OR, 8.7; P = 0.02) and HC (OR, 6.2; P = 0.02) were independent predictors of abnormal neurodevelopment; however, the clinical type of CHD was not. CONCLUSIONS: Fetal brain Doppler and head biometry at the time of CHD diagnosis are independent predictors of abnormal brain development at birth, and could be used in future algorithms to improve counseling and targeted interventions. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease.

OBJECTIVES: To evaluate the associations between congenital heart disease (CHD) and head biometry and cerebrovascular blood flow dynamics at the time of diagnosis of CHD in the second trimester of pregnancy. METHODS: This was a study of 95 consecutive fetuses diagnosed with CHD. At the time of diagnosis, fetal biometry was performed and brain perfusion was assessed by middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and fractional moving blood volume (FMBV). The results were compared with those of 95 normal fetuses matched for gestational age. RESULTS: Median gestational age at diagnosis was 22 + 3 (range, 20 + 0 to 23 + 5) weeks. Fetuses with CHD showed significantly lower MCA-PI and CPR Z-scores (-0.23 vs 0.34 and -0.37 vs 0.30, respectively; both P < 0.001) and higher FMBV Z-scores (2.35 vs 0.15; P < 0.001). FMBV > 95(th) percentile was observed in 81.1% of cases as compared with 10.5% in controls (P < 0.001). Moreover, cases showed significantly smaller biparietal diameter (BPD) and head circumference (HC) Z-scores (-1.61 vs -0.43 and -0.89 vs 0.09, respectively; both P < 0.001), with a higher proportion of BPD and HC measurements below the 5(th) percentile compared with controls (51.6% vs 13.7% and 26.3% vs 4.2%, respectively; both P < 0.001). These findings were more pronounced in those cases with types of CHD associated with compromised oxygenated blood delivery to the brain, such as left outflow tract obstruction and transposition of the great arteries. CONCLUSIONS: A high proportion of fetuses with CHD have a smaller head and increased brain perfusion already in the second trimester, suggesting an early onset of the mechanisms leading to poorer neurodevelopment later in life.

Intravenous ferrous sucrose versus placebo in addition to oral iron therapy for the treatment of severe postpartum anaemia: a randomised controlled trial.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of intravenous iron versus placebo added to standard oral iron therapy in the treatment of severe postpartum anaemia. DESIGN: A randomised, double-blind, parallel-group, placebo-controlled clinical trial was performed in a single centre. SETTING: Hospital Clinic of Barcelona, Barcelona, Spain. POPULATION: A cohort of 72 women with severe postpartum anaemia (6.0-8.0 g/dl) treated with oral ferrous sulphate (two tablets of 525 mg). METHODS: Women were randomised to receive either intravenous ferrous sucrose (200 mg/24 hours for two consecutive days) or intravenous placebo, in addition to standard iron therapy. Clinical and laboratory data were obtained at 1, 2, and 6 weeks. MAIN OUTCOME MEASURES: Haemoglobin and haematocrit at 1, 2, and 6 weeks. Other haematological and clinical parameters, psychological status, and adverse side effects were also evaluated. RESULTS: Haemoglobin and haematocrit values were comparable in women receiving intravenous iron or placebo in addition to oral iron therapy at any of the time points. At 6 weeks, haemoglobin level (mean ± SD) was 12.2 ± 1.0 versus 12.2 ± 0.9 g/dl, with a mean difference of -0.03 (95% CI -0.6 to 0.6), in the placebo and in the intravenous iron groups, respectively. No differences were found between clinical symptoms of anaemia, psychological status, and adverse side effects between groups. CONCLUSIONS: Intravenous iron added to oral iron therapy did not show significant benefits over placebo, neither in haemoglobin rise nor in symptoms or adverse side effects.

Isolated ventricular septal defects in the era of advanced fetal echocardiography: risk of chromosomal anomalies and spontaneous closure rate from diagnosis to age of 1 year.

OBJECTIVES: To evaluate, in a cohort of 248 fetuses seen at a tertiary referral center, the frequency of isolated ventricular septal defects (VSD) among all congenital heart defects (CHD), the association with chromosomal and postnatal anomalies and the rate of spontaneous closure. METHODS: This was a 6-year study on 10,800 women referred for fetal echocardiography, with 995 confirmed cases of CHD. The prevalence and characteristics of VSDs were analyzed, including follow-up until 1 year of age. Multivariate binary logistic regression analysis was performed to test the independent contribution of the ratio of the diameter of the VSD to that of the aorta (VSD/aorta ratio) (< 0.5 or ≥ 0.5) and location of VSD (perimembranous or muscular) in the prediction of spontaneous closure before the age of 1 year. RESULTS: Two hundred and forty-eight VSDs (24.9% of all CHDs) were diagnosed, of which 216 (87.1%) were muscular and 32 (12.9%) perimembranous. Median gestational age at diagnosis was 30.4 (range, 17-41) weeks and mean size 2.6 ± 0.77 mm. Clinically relevant chromosomal anomalies were found in one (3.1%) perimembranous VSD compared with none in 216 muscular defects (P = 0.12). Postnatal malformations were diagnosed in eight of the 211 cases (3.8%) evaluated at 12 months postpartum. Spontaneous closure occurred prenatally in 13 fetuses (5.2%) and postnatally in 151 of the 198 infants (76.3%) who had an open VSD at birth. Closure was predicted by the VSD/aorta ratio (odds ratio (OR) 0.445 (95% CI, 0.216-0.914); P < 0.03) and location (OR 0.385 (95% CI, 0.160-0.926); P < 0.03). CONCLUSIONS: In our fetal cardiology unit, isolated muscular VSD is today the most prevalent CHD. In contrast to the findings of postnatal studies, muscular VSDs were more common than perimembranous VSDs. Perimembranous VSDs were associated with a higher risk of chromosomal anomalies than were muscular VSDs, which had a similar risk to those of normal pregnancies. Spontaneous closure of the VSD was frequent and occurred in most cases postnatally.