TABLE 1

Prenatal Cerebral Findings in Infants with CHD

Study (First Author, Journal, Year of Publication)Study Design, No. InfantsCHDAgeMethodsFindings (Compared With Healthy Controls and/or Reference Values, Unless Otherwise Stated)a
Ruiz et al, Ultrasound Obstet Gynecol, 2016Retrospective study, N = 119MixedSecond and third trimesterUltrasound (biometry, Doppler)Normal MCA-PI and CPR during second trimester; 18% MCA-PI and CPR less than fifth percentile at first examination
Lower MCA-PI in group with severe impairment of cerebral blood flow
UA-PI increased with GA
Smaller HC and BPD at diagnosis which remained during pregnancy
Hahn et alb, Ultrasound Obstet Gynecol, 2016Retrospective study, N = 133SVASecond and third trimesterUltrasound (biometry, Doppler)Lower MCA-PI and decreased more as GA progressed
Smaller HC at 24–29 wk GA and >34 wk GA
Fetal HC predictor of neonatal HC from 30 wk GA
MCA-PI not associated with fetal and neonatal HC
Zeng et al, Ultrasound Obstet Gynecol, 2015Case-control study, N = 73/168MixedSecond and third trimesterUltrasound (biometry, Doppler)Lower MCA-PI
Total intracranial volume, frontal lobe volume, cerebellar volume, and thalamus volume progressively decreased from 28 wk GA
Largest decrease in frontal lobe volume, followed by total intracranial volume and cerebellar volume
Smaller HC and BPD from 33 wk GA
Zeng et alb, Ultrasound Obstet Gynecol, 2015Case-control study, N = 112/112Mixed20–30 wkUltrasound (Doppler)Lower MCA-PI in HLHS, MCA-PI tended to be lower in LSOL, normal MCA-PI in TGA and RSOL
Higher cerebral blood flow
Vascularization index, flow index, and vascularization flow index of the total intracranial volume and 3 main arteries higher in HLHS and LSOL and of the anterior cerebral artery in TGA
Masoller et al, Ultrasound Obstet Gynecol, 2014Case-control study, N = 95/95Mixed20–24 wkUltrasound (biometry, Doppler)Lower MCA-PI and CPR and higher fractional moving blood volume
Fractional moving blood volume >95th percentile in 81% compared with 11% in controls
No differences in MCA-PI and fractional moving blood volume between CHD diagnostic groups
Smaller BPD and HC
No differences in BPD and HC between CHD diagnostic groups
Williams et alb, Am Heart J, 2013Cohort study, N = 134SVA18–38 wkUltrasound (Doppler)MCA-PI at first fetal echocardiogram −0.95 ± 1.5
22% MCA-PI < −2.0 at least once across gestation
Yamamoto et al, Ultrasound Obstet Gynecol, 2013Case-control study, N = 89/89Mixed32 wkUltrasound (biometry, Doppler)Lower MCA-PI, higher UA-PI and lower CPR in HLHS and CoA
CoA with retrograde aortic arch flow, lower MCA-PI and CPR, and higher UA-PI compared with CoA with antegrade flow
Normal MCA-PI, UA-PI, and CPR in TGA and POTO
Smaller HC at birth in TGA and CoA
Szwast et al, Ultrasound Obstet Gynecol, 2012Retrospective study, N = 131/92SVA18–40 wkUltrasound (Doppler)Lower MCA-PI and lower CPR in aortic arch obstruction compared with controls and compared with pulmonary obstruction
MCA-PI decreased during gestation for aortic obstruction
MCA-PI increased during gestation for pulmonary obstruction
Normal UA-PI
Williams et alb,c, Ultrasound Obstet Gynecol, 2012Pilot study, N = 13Mixed20–24 wkUltrasound (Doppler)MCA-PI −1.7 ± 1.1
56% CPR < 1.0 (no z scores)
HLHS and TOF lowest MCA-PI (−2.4 and −2.01, respectively), TGA −0.75
Arduini et al, J Matern Fetal Neonatal Med, 2011Case-control study, N = 60/65Mixed30–38 wkUltrasound (biometry, Doppler)Lower MCA-PI and CPR (no z scores)
HLHS and CoA lowest and TOF and TGA highest CPR
Smaller HC and HC/AC
HLHS and CoA lowest and TOF and TGA highest HC/AC
Itsukaichi et al, Fetal Diagn Ther, 20118Retrospective study, N = 44/140Mixed28–34 wkUltrasound (biometry, Doppler)MCA-RI measurements more often less than fifth percentile and UA-RI >90th percentile
Similar biometry measurements in fetuses <10th and >10th MCA-RI percentile
McElhinney et al, Ultrasound Med Biol, 2010Cohort study, N = 52 HLHSHLHS20–31 wkUltrasound (Doppler)Lower MCA-PI and RI in HLHS
Normal UA-PI and UA-RI
37% CPR <1.0 (no z scores)
Berg et al, Ultrasound Obstet Gynecol, 2009Case-control study, N = 113/1378Mixed19–41 wkUltrasound (biometry, Doppler)Smaller HC at birth, normal MCA-PI and CPR in TGA
Smaller HC at birth, lower MCA-PI and CPR in HLHS
Normal biometry and Doppler parameters in PA, AoS, and TOF
Guorong et al, Fetal Diagn Ther, 2009Case-control study, N = 45/275Mixed20–40 wkUltrasound (Doppler)Normal MCA-PI
MCA-PI tended to be lower in LSOL and was lower in congestive heart failure
Higher UA-PI and higher U/C PI ratios
No traditional “brain sparing” as MCA-PI was normal, whereas U/C PI was higher
Chen et al, Am J Perinatol, 2009Case-control study, N = 11/44Ebstein anomaly23–37 wkUltrasound (Doppler)Lower MCA-PI and CPR (no z scores)
Higher UA-PI and left ventricular myocardial performance index
Lower fetal cardiac profile score (median 1 point lower)
MCA-PI positive correlation with cardiovascular profile score and negative correlation with left ventricular myocardial performance index
Modena et al, Am J Obstet Gynecol, 2006Case-control study, N = 71/71Mixed24–28 wkUltrasound (Doppler)Normal MCA-PI, UA-PI, and CPR
MCA-PI more often less than fifth percentile (5/71 vs 0/71)
CPR more often less than fifth percentile (8/71 vs 2/71)
No difference in UA-PI >95th percentile (6/71 vs 3/71)
Kaltman et al, Ultrasound Obstet Gynecol, 2005Case-control study, N = 58/114Mixed20–40 wkUltrasound (Doppler)Lower MCA-PI in HLHS
Higher MCA-PI in RSOL compared with HLHS
Higher UA-PI in RSOL
U/C PI-ratio similar between diagnostic groups
Donofrio et al, Pediatr Cardiol, 2003Case-control study, N = 36/21MixedSecond and third trimesterUltrasound (Doppler)Lower MCA-RI and CPR
Normal UA-RI
HLHS and HRHS infants had highest incidence of abnormally low CPR (58% and 60%)
Jouannic et al, Ultrasound Obstet Gynecol, 2002Case-control study, N = 23/40TGA36–38 wkUltrasound (Doppler)Lower MCA-PI
Normal UA-PI, DV-PI, and Ao-PI (no z scores)
Meise et al, Ultrasound Obstet Gynecol, 2001Case-control study, N = 115/100Mixed19–41 wkUltrasound (Doppler)Normal MCA-PI
Higher UA-PI
No difference in UA-PI >95th percentile
Brossard-Racine et alc, Am J Neuroradiol, 2016Cohort study, N = 103MixedSecond and third trimesterMRI (structural)16% fetal brain abnormalities (6 mild ventriculomegaly, 4 increased extra-axial spaces, 2 white matter cysts, 2 inferior vermian hypoplasia, 1 white matter signal hyperintensity)
32% neonatal brain abnormalities, 27% acquired brain injury
Postnatally, a predominance of punctate white matter injury
Brossard-Racine et al, Am J Neuroradiol, 2014Case-control study, N = 144/194Mixed18–39 wkMRI (structural)23% brain injury compared with 1.5% for controls
Most common: mild unilateral ventriculomegaly and increased extra-axial CSF spaces
No association between type of brain injury and CHD diagnosis
Mlczoch et alb, Eur J Paediatr Neurol, 2013Retrospective study, N = 53Mixed20–37 wkMRI
(structural)39% brain injury (7 malformation, 5 acquired lesion, 9 asymmetry of the ventricles/wider CSF spaces)
Fetuses with similar PA and Ao size had higher prevalence of brain injury compared with fetuses with PA < Ao or Ao < PA
Schellen et al, Am J Obstet Gynecol, 2015Retrospective study, N = 24/24TOF25 wkMRI, volumeLower total brain volume and cortical and subcortical volumes from 20 wk GA
Higher ventricular volumes and cerebrospinal fluid spaces
Normal intracranial cavity volume and cerebellar volume
Al Nafisi et al, J Cardiovasc Magn Reson, 20139Case-control study, N = 22/12 controlsMixed30–39 wkMRI, volume6 fetuses brain weights less than fifth percentile, 0 controls brain weights <25th percentile
19% lower combined ventricular output
Sun et al, Circulation, 2015Case-control study, N = 30/30Mixed36 wkMRI (volume, O2 saturation)Smaller brain volume
10% lower aorta oxygen saturation with cerebral blood flow and extraction being normal. As a result, 15% reduction in cerebral oxygen delivery and 32% reduction in oxygen consumption
Reduced cerebral oxygen consumption associated with a mean 13% reduction in brain volume or 1 SD reduction in estimated brain weight z score
Limperopoulos et al, Circulation, 2010Case-control study, N = 55/50Mixed25–37 wkMRI (volume, metabolism)Significantly and progressively smaller total brain volume and intracranial cavity volume
Lower NAA/Cho during the third trimester
7 CHD fetuses had cerebral lactate compared with 0 controls
Absence of antegrade aortic flow and presence of lactate predictors of low NAA/Cho
Masoller et al, Fetal Diagn Ther, 2016Case-control study, N = 58/58Mixed36–38 wkUltrasound (Doppler)Lower MCA-PI and CPR and higher frontal fractional moving blood volume
MRI (volume, metabolism)Lower MCA-PI and CPR in fetuses with impaired cerebral blood flow than fetuses with near-normal or mildly impaired cerebral blood flow
Smaller total and intracranial brain volume, decreased cortical development, and altered metabolism
Fetuses with impairment of blood flow to the cerebrum had more severe abnormalities on MRI than fetuses with near-normal/mildly impaired blood flow to the cerebrum
Masoller et alb, Ultrasound Obstet Gynecol, 2016Case-control study, N = 58/58Mixed36–38 wkUltrasound (Doppler)Lower MCA-PI and CPR and higher fractional moving blood volume
MRI (volume, metabolism)Smaller HC and BPD
Smaller brain, intracranial, and opercular volume and decreased sulcation
Increased Ino/Cho and decreased NAA/Cho and Cho/Cr ratios
MCA-PI, CPR, and fetal HC at mid gestation were independent predictors of abnormal brain development
Clouchoux et al, Cereb Cortex, 2013Case-control study, N = 18/30HLHS25–37 wkUltrasound (Doppler)Smaller brain volumes, which became progressively greater after 30 wk GA, smaller gyrification index, and smaller surface area
MRI, volume3–4 wk sulcation delay
Low CPR and absence of antegrade aortic flow associated with decreased cortical gray matter, white matter, subcortical matter, and decreased cortical surface area
  • AC, abdominal circumference; Ao, aorta; Ao-PI, pulsatility index of the aorta; AoS, aortic stenosis; BPD, biparietal diameter; CoA, coarctation of the aorta; CSF, cerebrospinal fluid; DV-PI, pulsatility index of the ductus venosus; GA, gestational age; HC/AC, head circumference/abdominal circumference; HRHS, hypoplastic right heart syndrome; LSOL, left-sided obstructive lesion; MCA-RI, resistance index of the middle cerebral artery; POTO, pulmonary outflow tract obstruction; RSOL, right-sided obstructive lesion; SVA, single ventricle anomaly; TOF, tetralogy of Fallot; UA-RI, resistance index of the umbilical artery; U/C PI, pulsatility index of the umbilical artery/pulsatility index of the middle cerebral artery.

  • a Doppler parameters and biometry measurements are reported as z scores unless otherwise stated.

  • b Articles that also address neurodevelopmental outcome.

  • c Articles that also address postnatal findings.