Effect of fetal hemodynamics on growth in fetuses with single ventricle or transposition of the great arteries.

OBJECTIVES: As birth weight is a critical predictor of outcome in neonates with congenital heart defect (CHD), the common problem of poor fetal growth in this population is clinically important. However, it is not well understood and the impact of fetal hemodynamics on fetal growth and birth weight in those with CHD has not been assessed. In this study, we sought to evaluate the association between combined cardiac output (CCO) and fetal middle cerebral artery (MCA) and umbilical artery (UA) pulsatility indices (PIs) and fetal growth in different subgroups of CHD, and to study the effects of fetal hemodynamics on late gestational weight gain. We hypothesized that fetuses with CHD will have lower CCO and be smaller at birth. METHODS: This was a retrospective review of fetal echocardiograms from 67 fetuses diagnosed with hypoplastic left heart syndrome (HLHS, n = 30), non-HLHS single ventricle (SV) (n = 20) or dextrotransposition of the great arteries (d-TGA, n = 17), compared with normal controls (n = 42). CCO was calculated using valvar area, velocity-time integral and heart rate and indexed to estimated fetal weight. MCA- and UA-PI were calculated using systolic, diastolic and mean velocities. Fetal biometry was recorded. Regression models were used to study trends in CCO, MCA- and UA-PI and fetal biometry over gestational age. To evaluate fetal weight gain in late gestation, Z-scores of estimated fetal weight at 30 weeks and birth weight were compared. Regression analysis was used to determine the associations of CCO, indexed CCO and MCA- and UA-PI at 30 weeks with birth weight, length and head circumference Z-scores, in addition to weight gain late in gestation. The gestational age of 30 weeks was chosen based on previous studies that found evidence of poor weight gain in fetuses with CHD in late gestation, starting at around that time. RESULTS: CCO increased with gestation in all four groups but the rate was slower in fetuses with HLHS and in those with SV. MCA-PI was lower in fetuses with HLHS compared with in those with non-HLHS-SV throughout gestation, suggesting different cerebral blood distribution. At the end of gestation, rate of fetal weight gain slowed in those with HLHS and in those with SV (similar to CCO curves), and head circumference growth rate slowed in all groups but controls. CCO, indexed CCO and MCA- and UA-PI did not correlate with any of the birth measurements or with weight gain late in gestation in fetuses with CHD. CONCLUSIONS: We found no associations of CCO or MCA- and UA-PI with late gestational weight gain or biometry at birth in fetuses with CHD. This does not support fetal hemodynamics as the primary driver of suboptimal fetal growth in fetuses with SV. Future research could further explain genetic and placental abnormalities that may affect fetal growth in those with CHD. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Association between fetal growth, cerebral blood flow and neurodevelopmental outcome in univentricular fetuses.

OBJECTIVE: To investigate the association of fetal growth and cerebrovascular resistance at different periods in gestation with neurodevelopment (ND) at 14 months in the univentricular subject. METHODS: We reviewed serial prenatal ultrasound (US) examinations from 133 infants enrolled in the Pediatric Heart Network's Single Ventricle Reconstruction or Infants with Single Ventricle trials, including a subset of 82 infants in whom ND was assessed at 14 months using mental (MDI) and psychomotor (PDI) developmental indices. US examinations were assigned to one of four gestational time periods: (1) 20-23 weeks, (2) 24-29 weeks, (3) 30-33 weeks and (4) ≥ 34 weeks. Middle cerebral artery (MCA) flow velocity was measured and pulsatility index (PI), a measure of downstream resistance, was calculated. Data on fetal head circumference (HC), femur length, abdominal circumference (AC) and estimated fetal weight (EFW) were collected and their Z-scores were calculated. We evaluated the rate of change of these parameters over time within individuals, tested correlations between fetal growth and ND and assessed predictors of ND using linear regression. RESULTS: The mean prenatal HC Z-score was < 0 at each gestational-age period and became more negative later in pregnancy. There was less growth in HC from time period 3 to period 4 compared with from period 2 to 3 (Δ HC Z-score, -0.07 ± 0.1 vs 0.11 ± 0.22, P = 0.03). Though ND did not correlate with HC, HC Z-score or MCA-PI Z-score, HC growth from period 2 to period 3 correlated with MDI (r = 0.45, P = 0.047). AC Z-score in period 4 predicted MDI (ß = 4.02, P = 0.04). EFW Z-score and AC Z-score in period 2 predicted PDI (ß = 10.6, P = 0.04 and ß = 3.29, P = 0.047, respectively). Lower MCA-PI at initial US predicted higher PDI (ß = -14.7, P = 0.03). CONCLUSION: In univentricular fetuses, lower cerebrovascular resistance may be protective for ND. Decreased fetal somatic growth may predict developmental abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Standardization of amniotic fluid leptin levels and utility in maternal overweight and fetal undergrowth.

OBJECTIVE: Leptin is an adipokine that regulates energy homeostasis. The objective of this study was to establish a gestational age-specific standard for amniotic fluid leptin (AFL) levels and examine the relationship between AFL, maternal overweight and fetal growth restriction. STUDY DESIGN: Amniotic fluid was obtained at mid-gestation from singleton gravidas, and leptin was quantified using enzyme-linked immunosorbent assay. Amniotic fluid samples from 321 term pregnancies were analyzed. Clinical data, including fetal ultrasound measurements and maternal and infant characteristics, were available for a subset of patients (n=45). RESULTS: The median interquartile range AFL level was significantly higher at 14 weeks' gestation (2133 pg ml(-1) (1703 to 4347)) than after 33 weeks' gestation (519 pg ml(-1) (380 to 761), P trend<0.0001), an average difference of 102 pg ml(-1) per week. AFL levels were positively correlated with maternal pre-pregnancy body mass index (BMI) (r=0.36, P=0.03) adjusting for gestational age at measurement, but were not associated with fetal growth. CONCLUSIONS: AFL levels are higher at mid-gestation than at late gestation, and are associated with maternal pre-pregnancy BMI.

Assessment of fetal cardiomyopathy in early-stage twin-twin transfusion syndrome: comparison between commonly reported cardiovascular assessment scores.

OBJECTIVES: To assess the relationship between commonly reported fetal cardiomyopathy scoring systems in early-stage twin-twin transfusion syndrome (TTTS). METHODS: We reviewed retrospectively 100 cases of Quintero Stages I and II TTTS referred to our center for evaluation from 2008 to 2010. The cases were divided into groups of 25, representing each of four grades of TTTS cardiomyopathy as assessed by Cincinnati stage: no cardiomyopathy, Stage IIIa, Stage IIIb and Stage IIIc. Spearman correlation (rs ) was calculated between the Children's Hospital of Philadelphia (CHOP) score, cardiovascular profile score (CVPS), Cincinnati stage and myocardial performance index (MPI). RESULTS: There was a weak correlation between the Cincinnati stage and the CHOP score (rs = 0.36) and CVPS (rs = -0.39), while correlation was strong between the CHOP score and CVPS (rs = -0.72). MPI elevation was concordant with Cincinnati stage more frequently (82% of cases) than were ventricular hypertrophy (43%) or atrioventricular valve regurgitation (28%). 51% of fetuses with minimally elevated CHOP score (0-1) and 48% of fetuses with minimally depressed CVPS (9-10) had significant elevation (Z-score ≥ +3) in right ventricular or left ventricular MPI. CONCLUSIONS: MPI has a strong influence on grading the severity of fetal cardiomyopathy using the Cincinnati stage among fetuses with mild TTTS. Furthermore, significant elevation of the MPI is common among fetuses with mild disease as assessed by the CHOP score and CVPS. These differences should be understood when assessing and grading cardiomyopathy in TTTS, particularly in early (Quintero Stages I and II) disease.

Estimated cardiac output and cardiovascular profile score in fetuses with high cardiac output lesions.

OBJECTIVE: High cardiac output lesions are associated with an increased risk of fetal death, largely as a result of cardiac failure and hydrops fetalis. The cardiovascular profile score (CVPS) has been used to characterize cardiovascular wellbeing, and has been linked to fetal outcomes in other conditions. We aimed to test the hypothesis that elevated combined cardiac output (CCO) in fetuses with high output lesions may be associated with worsening cardiovascular status, as evidenced by a lower CVPS. METHODS: A retrospective review was performed of fetuses with high cardiac output lesions that underwent echocardiography between July 2006 and November 2010. Diagnoses included sacrococcygeal teratoma, placental chorioangioma and vein of Galen aneurysm. Fetal echocardiographic evaluation included assessment of CVPS, as well as Doppler/two-dimensional estimation of CCO, indexed to estimated fetal weight (CCOi). The relationship between CCO and CVPS was assessed. RESULTS: A total of 35 fetuses were studied: 27 had sacrococcygeal teratoma, seven had chorioangioma and one had vein of Galen aneurysm. There was a significant inverse relationship between mean logCCOi and CVPS (r2 = 0.48, P = 0.008). Of 31 patients with clinical outcome data, 10 experienced either in-utero demise or intervention; 80% of these fetuses had a CVPS of < 8. CONCLUSIONS: There is an inverse relationship between CCO and CVPS in the fetus with high cardiac output lesions. As a measure of fetal cardiovascular wellbeing in this population, the CVPS may be a useful tool for stratifying risk and for selection for intervention in these fetuses.

Prevalence and progression of recipient-twin cardiomyopathy in early-stage twin-twin transfusion syndrome.

OBJECTIVE: The management of twin-twin transfusion syndrome (TTTS) in its early stages (Quintero Stages I and II) is controversial. We describe the prevalence, severity, incidence and rate of progression of recipient-twin cardiomyopathy in Stages I and II TTTS. METHODS: Among 451 cases of TTTS evaluated between 2004 and 2009, 123 (27.3%) cases of Stages I and II were reviewed. Echocardiography was used to 'upstage' cases based on the presence or absence of mild (IIIA), moderate (IIIB), or severe (IIIC) recipient cardiomyopathy. Progression was defined by worsening in the degree of recipient-twin cardiomyopathy from initial presentation or failure to respond to amnioreduction. Outcome data included progression of recipient-twin cardiomyopathy, treatment and survival to birth. Data were compared by the chi-square, Fisher's exact test or t-test as appropriate. RESULTS: Seventy-seven of 123 (62.6%) cases were Quintero Stage I and 46/123 (37.4%) Quintero Stage II. Eighty (65.0%) were upstaged to Cincinnati Stage IIIA (n = 25), IIIB (n = 23) or IIIC (n = 32). Management included observation in 11 (8.9%), amnioreduction in 26 (21.1%), amnioreduction followed by selective fetoscopic laser photocoagulation (SFLP) in 43 (35.0%) and primary SFLP in 43 (35.0%). Of 80 cases managed by observation or amnioreduction initially, 43 (53.8%) progressed within a mean duration of 1.4 ± 1.5 weeks. The incidence of progression increased significantly as degree of recipient-twin cardiomyopathy at presentation worsened: Stage I, 9/27 (33.3%); Stage II, 8/15 (53.3%); Stage IIIA, 8/16 (50.0%); Stage IIIB, 10/10 (100%); and Stage IIIC, 8/12 (66.7%) (χ(2) = 14, P < 0.01). Overall fetal survival was 205 out of 244 (84.0%). Fetal survival with observation only was 81.8% (18/22), with amnioreduction only it was 92.3% (48/52), with initial observation or amnioreduction followed by SFLP it was 86.9% (73/84) and with primary SFLP it was 76.7% (66/86). CONCLUSION: Echocardiography demonstrates a high incidence of recipient-twin cardiomyopathy in early-stage TTTS. The more advanced the recipient-twin cardiomyopathy is, the more likely is progression to occur during observation or following amnioreduction.

Twin-reversed arterial perfusion sequence: pre- and postoperative cardiovascular findings in the 'pump' twin.

OBJECTIVES: To assess cardiovascular findings in twin-reversed arterial perfusion (TRAP) sequence pre- and post-therapy and compare these findings to traditional obstetric markers, defined as acardius to pump twin weight ratio and presence of polyhydramnios. METHODS: This was a retrospective review of 27 cases of TRAP sequence diagnosed between 2004 and 2008. Echocardiographic data included indexed cardiac output and functional and anatomic parameters. Ultrasound reports were reviewed for acardius to pump twin weight ratio and polyhydramnios. We assessed the relationship between cardiac output and the remaining cardiac/obstetric variables obtained pre- and post-treatment. RESULTS: Twenty-three subjects had complete echocardiographic data sets at initial evaluation (mean gestational age, 20.4 +/- 2.5 weeks) and, of these, post-treatment echocardiographic evaluation was available in 10. Six of seven (86%) pump twins with elevated indexed cardiac output had significant cardiovascular compromise. Most fetuses with abnormal cardiac output or right ventricular dysfunction normalized post-therapy. There was no relationship between cardiac output and obstetric markers. CONCLUSIONS: Elevated indexed cardiac output is strongly associated with cardiovascular compromise. Traditional obstetric prognosticators do not correlate with cardiovascular derangements. In pump twins with cardiac compromise, postoperative cardiovascular status improves acutely. Given this analysis, we conclude that assessment of cardiovascular findings should be incorporated into the management and treatment of TRAP sequence.

Purpura fulminans associated with Streptococcus pneumoniae infection in a child.

BACKGROUND: Neisseria meningitidis is the most frequent isolate associated with purpura fulminans in children. Although Streptococcus pneumoniae infection has been associated with purpura fulminans, with the exception of one adult, it has only been reported in immunocompromised hosts. PURPOSE: We report an apparently previously healthy child who presented with purpura fulminans associated with pneumococcal meningitis. METHODS: Case report and review of the medical literature from September 1966 to June 1997, using a MEDLINE search. CONCLUSION: While systemic pneumococcal infection is common in childhood, progression to purpura fulminans does not typically occur in overtly healthy children. Our patient illustrates that invasive pneumococcal infection should be considered and empirically treated in a child who presents with purpura fulminans, even in the absence of preexisting functional or anatomic asplenia.

Left bundle branch block in infants with dilated cardiomyopathy conveys a poor prognosis.

We describe three infants <3 months of age seen consecutively with dilated cardiomyopathy who presented initially with left bundle branch block on the surface 12-lead electrocardiogram. Each infant subsequently had a poor outcome: two died and one required heart transplantation. These results suggest that the presence of left bundle branch block on the 12-lead electrocardiogram conveys a poor prognosis in infants with dilated cardiomyopathy.