Fetal cerebrovascular response to maternal hyperoxygenation in congenital heart disease: effect of cardiac physiology

Ultrasound Obstet Gynecol. 2021 May;57(5):769-775. doi: 10.1002/uog.22024. Epub 2021 Apr 13.


Objective: Fetal cerebrovascular resistance is influenced by several factors in the setting of intact autoregulation to allow for normal cerebral blood flow and oxygenation. Maternal hyperoxygenation (MH) allows for acute alterations in fetal physiology and can be a tool to test cerebrovascular reactivity in late-gestation fetuses. In this study, we utilized MH to evaluate cerebrovascular reactivity in fetuses with specific congenital heart disease (CHD).

Methods: This was a cross-sectional study of fetuses with complex CHD compared to controls without CHD. CHD cases were grouped according to physiology into: left-sided obstructive lesion (LSOL), right-sided obstructive lesion (RSOL) or dextro-transposition of the great arteries (d-TGA). Subjects underwent MH testing during the third-trimester fetal echocardiogram. The pulsatility index (PI) was calculated for the fetal middle cerebral artery (MCA), umbilical artery (UA) and branch pulmonary artery (PA). The change in PI from baseline to during MH was compared between each CHD group and controls.

Results: Sixty pregnant women were enrolled (CHD, n = 43; control, n = 17). In the CHD group, there were 27 fetuses with LSOL, seven with RSOL and nine with d-TGA. Mean gestational age was 33.9 (95% CI, 33.6-34.2) weeks. At baseline, MCA-PI Z-score was lowest in the LSOL group (-1.8 (95% CI, -2.4 to -1.2)) compared with the control group (-0.8 (95% CI, -1.3 to -0.3)) (P = 0.01). In response to MH, MCA-PI Z-score increased significantly in the control and d-TGA groups but did not change significantly in the LSOL and RSOL groups. The change in MCA-PI Z-score was significantly higher in the control group than in the LSOL group (0.9 (95% CI, 0.42-1.4) vs 0.12 (95% CI, -0.21 to 0.45); P = 0.03). This difference was more pronounced in the LSOL subgroup with retrograde aortic arch flow. Branch PA-PI decreased significantly in response to MH in all groups, with no difference in the change from baseline to MH between the groups, while UA-PI was unchanged during MH compared with at baseline.

Conclusions: The fetal cerebrovascular response to MH varies based on the underlying CHD diagnosis, suggesting that cardiovascular physiology may influence the autoregulatory capacity of the fetal brain. Further studies are needed to determine the clinical implications of these findings on long-term neurodevelopment in these at-risk children. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Keywords: congenital heart disease; fetal cerebrovascular resistance; fetal echocardiogram; maternal hyperoxia; middle cerebral artery pulsatility index.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological
  • Adult
  • Case-Control Studies
  • Cerebrovascular Circulation*
  • Cross-Sectional Studies
  • Echocardiography
  • Female
  • Fetal Therapies / methods*
  • Fetus / embryology
  • Fetus / physiopathology
  • Gestational Age
  • Heart Defects, Congenital / diagnostic imaging
  • Heart Defects, Congenital / embryology*
  • Heart Defects, Congenital / physiopathology
  • Humans
  • Middle Cerebral Artery / diagnostic imaging
  • Middle Cerebral Artery / embryology
  • Middle Cerebral Artery / physiopathology
  • Oxygen Inhalation Therapy / methods*
  • Placental Circulation*
  • Pregnancy
  • Pregnancy Trimester, Third
  • Pulmonary Artery / diagnostic imaging
  • Pulmonary Artery / embryology
  • Pulmonary Artery / physiopathology
  • Pulsatile Flow
  • Ultrasonography, Prenatal
  • Umbilical Arteries / diagnostic imaging
  • Umbilical Arteries / embryology
  • Umbilical Arteries / physiopathology