Which circulation?
Distinguish maternal vascular malperfusion (MVM) from fetal vascular malperfusion (FVM).
Journal club · MFM clinicians
CHD is associated with fetal-side placental vascular injury
Placental pathology in fetuses with and without congenital heart defects
PLACENTA
⇄causal direction unresolved
FETAL HEART
Doiron et al. · Pregnancy 2026;2:e70439
Dr. Chukwuma Onyeije · OpenMFM · September 2026
R1 · Association ≠ causation
Learning objectives
Separate mechanism, measurement, and management
Three questions organize the evidence.
What was measured?
Interpret the composite, absolute event frequencies, adjusted odds, and selected controls.
What changes care?
Separate biological insight from evidence supporting a clinical intervention.
R1; educational framework
Pathology framework
The placenta contains two distinct vascular compartments
The location of vascular injury matters.
Spiral arteries → intervillous space
Maternal blood
↓
Bathes the villous surface
↓
Bathes the villous surface
MVM: infarction, altered villous maturation, decidual vascular lesions.
EXCHANGE
across the villous barrier
across the villous barrier
Umbilical arteries → villous vessels
Fetal blood
↓
Returns via the umbilical vein
↓
Returns via the umbilical vein
FVM: injury involving fetal vessels and villi, including thrombosis and avascular villi.
Maternal and fetal blood normally occupy separate spaces. The terms identify different patterns of injury.
R1 methods; R2
Biological hypothesis
The placenta–heart axis has several plausible causal directions
Post-delivery histology cannot reveal which process came first.
Shared developmental influences↙ ↘Placenta + fetal heart
Placental vascular dysfunction⇢Altered fetal cardiac loading
Abnormal fetal cardiac physiology⇢Altered placental perfusion
These are mechanistic hypotheses. This case-control study does not distinguish among them.
R1 discussion; R3
Study design
117 CHD cases were matched with 234 selected controls
Single-center deliveries, January 2011–June 2021.
117
CHD cases
Prenatal diagnosis confirmed by postnatal echocardiography.
234
Controls without CHD
Placentas were sent for pathology for a clinical indication.
1:2 matching · maternal age + gestational age at delivery (within 1 week)
Who was excluded?
Multiple gestations, other major fetal anomalies, aneuploidy, and unavailable reviewable placental slides. This is a selected singleton cohort, not a sample of all CHD pregnancies.
The control group is clinically selected; its lesion frequency is not a healthy-population baseline.
R1 methods; Table 1
Critical appraisal
Blinded rereview improves consistency, not representativeness
Three pediatric pathologists assessed deidentified slides using a standardized worksheet.
Blinded to CHD
Reviewers did not know cardiac defect status or pregnancy outcomes, except gestational age and birthweight.
Same lesion checklist
A worksheet based on Amsterdam terminology directed assessment of cases and controls.
Selection remains
Original gross descriptions varied. Available specimens and clinically indicated control submissions limit generalizability.
Standardized assessment reduces measurement bias; it cannot remove selection bias.
R1 methods and limitations
Endpoint definition
The FVM composite includes three different finding groups
Any included finding could meet the authors’ endpoint.
Vascular thrombosis
Fetal vascular thrombosis.
Villous lesions
Stromal vascular karyorrhexis or avascular villi.
Cord abnormalities
Hypercoiling, hypocoiling, two-vessel cord, or marginal insertion.
An FVM composite event is not synonymous with severe histologic FVM.
Sensitivity analysis
The authors report that the CHD association persisted when cord abnormalities were removed from the composite. Numerical estimates from supplemental analyses were not available in the supplied PDF.
R1 methods; Table 2; sensitivity-analysis narrative; R2
Primary finding
The FVM composite occurred in 47.9% versus 32.5%
More CHD pregnancies met the study’s fetal-side composite.
CHD 56 / 117
47.9%
No CHD 76 / 234
32.5%
+15.4 percentage points
Observed difference in this cohort
1.88 crude OR
95% CI 1.20–2.97 · conditional logistic regression
R1 Table 2 · Primary composite
Adjusted analysis
The FVM association persisted after adjustment
Adjusted odds ratio 2.01 · 95% confidence interval 1.14–3.56.
Adjustment set and interpretation
Race/ethnicity, payer, hypertension, diabetes, tobacco use, FGR, and BMI. Maternal age and delivery gestational age were matching variables.
An odds ratio is not a risk ratio. The estimate does not mean twice the absolute probability of FVM, and adjustment cannot establish causation.
The association is robust to measured covariates; causal direction remains unresolved.
R1 Figure 1A; Table 2
Composite components
Villous injury gives the composite more clinical detail
Component categories overlap and should not be added together.
| Finding | CHD · n=117 | No CHD · n=234 | p |
|---|---|---|---|
| Villous lesions | 31 (26.5%) | 25 (10.7%) | 0.0001 |
| Avascular villi | 26 (22.2%) | 23 (9.8%) | 0.002 |
| Two-vessel cord | 8 (6.8%) | 2 (0.9%) | 0.003 |
| Fetal vascular thrombosis | 15 (12.8%) | 22 (9.4%) | 0.326 |
The composite result does not mean every FVM component was increased.
Interpret component p-values cautiously
Components were compared using chi-square or Fisher’s exact tests. No multiplicity correction is described. These exploratory comparisons are less definitive than the primary composite analysis.
R1 Table 2
Other primary outcome
MVM was not significantly increased in this cohort
A nonsignificant result does not establish equivalence.
CHD 44 / 117
37.6%
No CHD 75 / 234
32.1%
Adjusted OR 1.32 · 95% CI 0.72–2.42
Controls had more chronic hypertension and diabetes. This may affect the MVM comparison.
Why earlier studies can differ
Carreon et al. reported increased MVM in a different cohort. Differences in control selection, lesion definitions, and pathology methods may contribute to heterogeneity; this explanation is an inference, not a tested finding.
R1 Table 1, Table 2, Figure 1B; R6
Secondary findings
Chorangiosis and smaller placentas support further investigation
Both findings provide context for a possible oxygenation pathway.
12.0% vs 4.7%
CHD versus controls · p=0.013
Increased terminal villous capillaries; associated with chronic low-grade hypoxia.
Smaller placentas were reported with CHD
The main text reports more placentas below the 10th weight percentile.
Exact size estimates are not plotted because supplemental denominators were unavailable for verification.
These findings neither date hypoxia nor establish it as the cause of the cardiac defect.
R1 results, p.5 and discussion; R4
FGR and sensitivity analyses
FGR does not fully account for the observed association
FGR occurred in 32/117 CHD pregnancies versus 32/234 controls: 27.4% versus 13.7%.
FVM association persisted
Adjusted OR 2.01 (95% CI 1.14–3.56).
Conclusion remained similar
The authors report persistence in their sensitivity analysis.
FGR could be a confounder, mediator, or shared consequence.
Why adjustment is not a mechanism test
The correct role of FGR in a causal model is uncertain. Adding or removing it cannot establish the sequence linking CHD, growth, and placental pathology. Supplemental effect estimates were not supplied.
R1 Table 1; Figure 1A; sensitivity-analysis narrative
Cardiac phenotypes
Cardiac subtype patterns remain exploratory
Small groups limit interpretation of left-sided, right-sided, septal, and conotruncal lesions.
Left-sided
Example: hypoplastic left heart
Right-sided
Example: tricuspid atresia
Septal
Examples: VSD / ASD
Conotruncal
Example: transposition
The authors describe more of several lesions in the septal group. This does not establish a subtype-specific surveillance strategy.
Evidence boundary
Groups followed the study’s primary-lesion classification. Exact subtype sizes and rates from Table S2 were not available for independent verification; no numerical subtype ranking is presented.
R1 methods and discussion
Clinical application
Established clinical findings should drive antenatal decisions
The study evaluated pathology, not an intervention.
CHD + higher FVM frequency
This paper establishes no new testing interval, medication indication, or delivery threshold.
Respond to diagnosed FGR
SMFM defines FGR as EFW or AC below the 10th percentile.
Once FGR is diagnosed, assess umbilical artery Doppler every 1–2 weeks, with escalation for abnormal flow and clinical context.
Apply the established pathway in context
SMFM recommends offering diagnostic testing with chromosomal microarray when FGR coexists with a fetal malformation, regardless of gestational age. Coordinate management with the fetal cardiac and obstetric picture. Post-delivery pathology is not a validated prenatal FVM test.
Clinical inference: integrate pathology with growth, Doppler, and cardiac findings; avoid attributing every lesion to CHD.
R1; R5 (SMFM recommendations 1, 6, 9)
Clinical Pearls
Retain six distinctions
What to remember six months from now.
Compartment
MVM and FVM represent different injury patterns.
Composite
Know what qualifies as an FVM event.
Magnitude
Read absolute frequencies alongside odds ratios.
Selection
Clinically selected controls shape the comparison.
Causation
Adjustment cannot establish temporal direction.
Action
Use established clinical indications to guide care.
R1; R2; R5
Evidence & Controversies
The association is clearer than its clinical actionability
The next study must connect timing, phenotype, and outcomes.
Known in this cohort
A higher FVM composite with CHD persisted after adjustment. MVM was not significantly different.
Uncertain
Causal direction, lesion severity, external validity, subtype effects, and incremental prognostic value.
Why results differ
Studies use different controls, definitions, and review methods. MVM findings are not uniform.
Next research
Prospective recruitment, standardized blinded sampling, prenatal measures, and linked neonatal outcomes.
R1; R3; R6
References
Follow each claim to its source
Primary results are transcribed from the supplied Doiron et al. article.
- R1 · Primary studyDoiron TE, Besmer S, Guerrero J, Salas J, Fox L, Zantow E, Chavan NR. Placental pathology in fetuses with and without congenital heart defects. Pregnancy. 2026;2:e70439.
- R2 · Pathology consensusKhong TY, Mooney EE, Ariel I, et al. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med. 2016;140(7):698–713.
- R3 · Mechanistic contextBurton GJ, Jauniaux E. Development of the Human Placenta and Fetal Heart: Synergic or Independent? Front Physiol. 2018;9:373.
- R4 · ChorangiosisVafaei H, Karimi Z, Akbarzadeh-Jahromi M, Asadian F. Association of placental chorangiosis with pregnancy complication and prenatal outcome: a case-control study. BMC Pregnancy Childbirth. 2021;21:99.
- R5 · Clinical guidanceSociety for Maternal-Fetal Medicine; Martins JG, Biggio JR, Abuhamad A. SMFM Consult Series #52: Diagnosis and management of fetal growth restriction. Am J Obstet Gynecol. 2020;223(4):B2–B17.
- R6 · Comparative cohortCarreon CK, Ronai C, Hoffmann JK, Tworetzky W, Morton SU, Wilkins-Haug LE. Maternal Vascular Malperfusion and Anatomic Cord Abnormalities Are Prevalent in Pregnancies With Fetal Congenital Heart Disease. Prenat Diagn. 2025;45(10):1325–1333. Published online August 30, 2024.
Source scope and disclosures
Doiron et al.: Saint Louis University Graduate Medical Education Advanced Health Data Research Training Grant for statistical support; authors declared no conflicts. Supplemental tables were not supplied. Supporting reference records and clinical guidance were checked September 14, 2026. Original educational diagrams; no study images reproduced.
Educational content for clinicians. Apply current guidance and individual clinical context.
References verified September 14, 2026