Moray AA, Robertson CMT, Bond GY, Abeysekera JB, Mohammadian P, Dinu IA, Atallah J, Switzer HN, Hornberger LK.Pediatr Cardiol. 2023 Apr;44(4):816-825. doi: 10.1007/s00246-022-03062-0.
Take home points:
- Multivariable regression analysis showed an inverse relationship between 3rd trimester Umbilical Artery-Pulsatility Index for all CHD and cognitive, motor, and language neurodevelopmental domains.
- Higher UA-PI in third trimester, may suggest delayed neurodevelopmental outcomes at 2 years.
Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch.
Introduction:
Major congenital heart disease (CHD) is associated with impaired neurodevelopment. The most prevalent morbidity associated with CHD is that of impaired neurodevelopment (ND), a finding attributed to abnormal physiology, perioperative, demographic, and social factors as well as associated genetic syndromes.
Doppler parameters suggesting placental insufficiency, including increased umbilical arterial (UA) and reduced middle cerebral arterial (MCA) pulsatility index (PI) a feature suggesting cerebral vasodilation or brain sparing, are prevalent in critical CHD although their association with long term abnormal ND remains incompletely examined.
Patient cohort:
Major CHD identified on fetal echocardiography, confirmed postnatally and at the time of cardiac surgery, and prospectively followed by the Western Canadian CPTFP were included. Major CHD was defined as having undergone one of the following eligible surgeries: bypass at≤6 weeks, shunts including systemic to pulmonary, Sano or bidirectional Glenn at≤6 months or isomerism/heterotaxy syndrome with any surgery at≤12 months.
Exclusion criteria included incomplete/absent prenatal Doppler data and factors influencing ND or growth namely genetic syndromes, multiple pregnancies, significant extracardiac anomalies and preterm birth at≤35 weeks. Additionally, fetuses with arrhythmias affecting Doppler measurements were excluded. The cohort was divided into 5 CHD subgroups based on surgical outcomes and anatomic subtypes: single ventricle (SV) and biventricular outcome (BV) groups; DTGA, HLHS and conotruncal (CT) anomalies groups.
Two-year somatic data (head circumference, length and weight) was collected at routine follow up with Z-scores used for analysis. Years of schooling determined maternal education and the Blishen Index assessed socio-economic status (SES). Certified pediatric psychologists administered the Bayley III to assess 2-year cognitive, language and motor ND outcomes. There were six 2-year outcomes of interest: 3 growth variables (length, weight, head circumference) and the 3 Bayley III test scores (cognitive, language, motor).
Fetal Parameters vs 2‑Year Neurodevelopmental and Growth Outcomes
On univariate analysis, higher 3rd trimester UA-PI Z-score was associated with lower ND scores in all three domains as well as the 2-year weight Z-score for the entire cohort. 2nd trimester UA-PI and 2nd and 3rd trimester MCA-PI did not show an association with ND or growth outcomes.
Multiple regression models for ND consisted of 3rd trimester UA-PI Z-score, sex, cumulative cardiopulmonary bypass time prior to 2-year assessment, and highest SES index. 3rd trimester UA-PI Z-scores and cumulative cardiopulmonary bypass times showed significant association with 2-year ND outcomes in all 3 domains, with a greater effect size for UA-PI (Table 4).
Higher 3rd trimester UA-PI Z-scores were significantly associated with lower 2-year cognition scores for the entire cohort, SV and HLHS subgroups, lower 2-year motor scores for the entire group, HLHS, SV and BV groups and lower 2-year language score for the entire group but not any subgroups.
Multivariable regression analysis, after adjusting for sex and SES index, showed no association of 3rd trimester UA-PI Z-score with 2-year growth, although the total number of open sternum days was significantly associated with 2-year length and weight Z-scores, and total cross clamp time across surgeries with 2-year head circumference Z-score.
Conclusion
In conclusion, the findings suggest an important inverse relationship between 3rd trimester UA-PI and 2-year ND outcomes across a spectrum of major fetal CHD. This relationship, most striking in HLHS and SVs may reflect their unique pathophysiologies that likely have impaired cerebral O2 delivery from a combination of placental insufficiency, intracardiac mixing and, for some, reduced cerebral blood flow.
