Growth patterns and cerebroplacental hemodynamics in fetuses with congenital heart disease

Abstract

Objectives: Congenital heart disease (CHD) has been associated with reduced fetal head circumference (HC), although the underlying pathophysiology remains undetermined. We aimed to define trends in fetal growth and cerebroplacental Doppler flow, and to investigate their relationship, in fetuses with CHD.

Methods: This was a retrospective study in two fetal medicine units in The Netherlands. We included all fetuses with CHD in whom Doppler flow patterns (middle cerebral artery (MCA) pulsatility index (PI), umbilical artery (UA) PI and cerebroplacental ratio (CPR)) and biometry (HC and abdominal circumference (AC)) had been measured serially after 19 weeks' gestation between January 2010 and November 2016. Fetuses were categorized into three groups based on the expected cerebral arterial oxygen saturation of their particular type of CHD: normal; mild to moderately reduced; severely reduced. Trends over time in Z-scores were analyzed using a linear mixed-effects model.

Results: A total of 181 fetuses fulfilled the inclusion criteria. Expected cerebral arterial oxygen saturation in CHD was classified as normal in 44 cases, mild to moderately reduced in 84 and severely reduced in 53. In the cohort overall, average trends over time were significant for both HC and AC Z-scores. HC Z-scores showed a tendency to decrease until 23 weeks, then to increase until 33 weeks, followed by another decrease in the late third trimester. AC Z-scores increased progressively with advancing gestation. MCA-PI and UA-PI Z-scores showed significant trends throughout pregnancy, but CPR Z-scores did not. There were no associations between expected cerebral arterial oxygen saturation and fetal growth. Average trends in MCA-PI Z-scores were significantly different between the three subgroups, whereas those in UA-PI Z-scores and in CPR Z-scores were similar between the subgroups. There was no significant association between MCA-PI and HC Z-scores.

Conclusions: Fetal biometry and Doppler flow patterns are within normal range in fetuses with CHD, but show trends over time. Head growth in fetuses with CHD is not associated with cerebral blood flow pattern or placental function and HC is not influenced by the cerebral arterial oxygen saturation. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Keywords: Doppler flow patterns; congenital heart disease; growth; head circumference; oxygenation.

Figure 1

Classification of fetal congenital heart defects according to expected cerebral arterial oxygen saturation, with three examples from each category (adapted from Rudolph)13, 14, 30. Numbers are saturations (in percent) based on lamb experiments; values may be lower in human fetuses. Arrows indicate flow hemodynamics. In (a–c) are examples of those classified as having expected normal cerebral arterial oxygen saturation: (a) normal heart; (b) coarctation of the aorta; (c) mild to moderate aortic stenosis. In (d–f) are those classified as having expected mild to moderately reduced cerebral arterial oxygen saturation: (d) tetralogy of Fallot; (e) pulmonary atresia with intact septum; (f) critical aortic stenosis. In (g–i) are those classified as having expected severely reduced cerebral arterial oxygen saturation: (g) transposition of the great arteries (TGA) with ventricular septal defect; (h) TGA with intact interventricular septum; (i) hypoplastic left heart syndrome (aortic and mitral atresia). Ao, descending aorta; DA, arterial duct; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PV, pulmonary veins; RA, right atrium; RV, right ventricle; SVC, superior vena cava.

Figure 2

Averaged trends in Z‐scores of fetal growth and Doppler flow patterns in fetuses with congenital heart disease. (a) Head circumference (HC); (b) abdominal circumference (AC); (c) middle cerebral artery pulsatility index (MCA‐PI); (d) umbilical artery pulsatility index (UA‐PI); (e) cerebroplacental ratio (CPR). Gray dots are individual measurements, gray lines are individual trends and dark gray shading shows 95% CIs for fitted model.

Figure 3

Averaged trends in Z‐scores of fetal growth and Doppler flow patterns in three subgroups of fetuses with congenital heart disease, classified according to whether cerebral arterial oxygen saturation would be expected to be normal (), mild to moderately reduced () or severely reduced (). 95% CIs of fitted model are shaded gray. (a) Head circumference (HC); (b) abdominal circumference (AC); (c) middle cerebral artery pulsatility index (MCA‐PI); (d) umbilical artery pulsatility index (UA‐PI); (e) cerebroplacental ratio (CPR).

Figure 4

Averaged trends in Z‐score of middle cerebral artery pulsatility index (MCA‐PI) for normal head circumference (HC) (solid lines) and for abnormal HC (dashed lines) at last measurement before birth in fetuses with congenital heart disease (CHD): (a) entire cohort; (b) three subgroups according to whether CHD type would be expected to have normal (), mild to moderately reduced () or severely reduced () cerebral arterial oxygen saturation. 95% CIs of fitted model are shaded gray for total cohort only; those for CHD subgoups were broad and overlapping.