Highlight
- Late-onset fetal growth impairment in dichorionic twins shows variable placental pathology risk depending on ultrasound phenotype.
- Singleton versus twin-specific growth charts yield differing associations between growth discordance, small-for-gestational-age status, and placental pathology.
- A novel three-tier risk categorization framework is proposed to stratify placental dysfunction likelihood by ultrasound-defined growth phenotypes.
- Findings provide a path for future clinical trials and guideline development tailored to managing twin pregnancies complicated by growth restriction.
Study Background
Dichorionic twin pregnancies, comprising two genetically distinct placentas, have a higher risk of fetal growth abnormalities than singleton pregnancies. Fetal growth restriction (FGR), particularly late-onset forms presenting after 32 weeks, is a critical contributor to perinatal morbidity and mortality. Clinicians rely heavily on ultrasound to define fetal growth phenotypes, including small-for-gestational-age (SGA) categorization, growth discordance between twins, and Doppler velocimetry for placental function assessment. However, the relationship between these ultrasound phenotypes and underlying placental pathology remains insufficiently characterized. Moreover, growth charts derived from singletons may inadequately classify twin fetal growth, potentially misestimating risk.
Better understanding the placental pathology risk across defined ultrasound growth phenotypes in dichorionic twins would enable improved risk stratification and management decisions in this unique population. This retrospective cohort study addresses this unmet need by evaluating placental histopathology outcomes associated with various ultrasound-based phenotypes of impaired fetal growth in dichorionic twins.
Study Design
This was a retrospective cohort study conducted at a single tertiary center between 2011 and 2023, including 753 dichorionic twin pregnancies with delivery occurring at or beyond 32 weeks gestation. Each twin fetus was classified based on ultrasound parameters into exposure groups defined by fetal weight percentile status and weight discordance, as well as Doppler findings:
- Weight percentile was categorized as Appropriate-for-Gestational-Age (AGA), mild SGA, or severe SGA, determined using both singleton- and twin-specific growth charts.
- Discordant growth between twins was recorded.
- Doppler velocimetry assessments identified abnormal placental blood flow patterns.
The main outcome measure was abnormal placental histopathology recognized as associated with FGR.
Key Findings
Using singleton-based growth charts, the reference group—fetuses AGA, with concordant growth and normal Doppler—showed a 12.8% rate of placental pathology. Key associations included:
- Isolated mild SGA and isolated discordance were not significantly associated with increased placental pathology risk.
- Isolated severe SGA had a 28.8% pathology rate, with an adjusted risk ratio (aRR) of 2.47 (95% CI 1.52–4.03).
- Severe SGA combined with discordant growth increased the pathology risk to 41.9% (aRR 3.53, 95% CI 2.15–5.79).
- Severe SGA accompanied by abnormal Doppler showed the highest pathology risk at 54.7% (aRR 4.33, 95% CI 2.90–6.48).
When twin-specific growth charts were employed, the risk profile shifted:
- Isolated discordance alone was associated with significant placental pathology (32.4%, aRR 2.63, 95% CI 1.46–4.73).
- Mild SGA also demonstrated increased risk (28.2%, aRR 2.43, 95% CI 1.30–4.51).
Based on these findings, the authors proposed three risk categories for late-onset placenta-mediated FGR in dichorionic twins:
1. Possible small increase in placental pathology risk (4-fold).
This stratification can inform clinical surveillance intensity and intervention thresholds.
Expert Commentary
The utilization of both singleton- and twin-specific growth standards elucidates the complexity of accurately assessing fetal growth impairment in twin pregnancies. This study highlights the implications of growth chart selection on risk assessment and underscores the importance of integrating Doppler studies for a more comprehensive evaluation. Placental pathology, being a gold-standard for confirming placental dysfunction, bridges the gap between ultrasound phenotypes and clinical outcomes.
Limitations of the study include a retrospective design and single-center cohort, which may influence generalizability. Nevertheless, the large sample size and detailed histological analysis strengthen the findings. Further prospective trials are warranted to validate the proposed risk categories and to evaluate interventions guided by this framework.
Conclusion
This retrospective cohort study rigorously characterizes differential placental pathology risks across ultrasound-defined fetal growth phenotypes in dichorionic twins. The novel three-tier risk categorization provides a practical clinical tool to aid diagnosis, surveillance, and management guidelines for late-onset fetal growth restriction in this high-risk population. Adoption of twin-specific growth charts alongside Doppler assessments may enhance risk stratification accuracy. These data set the stage for future interventional trials targeting improved outcomes for dichorionic twins affected by impaired fetal growth.
Funding and Registration
The study was conducted without information on external funding or clinical trial registration.
References
1. Essalah A, Kingdom J, Hiersch L, Barrett J, Watson M, Melamed N. Risk of Placental Pathology Across Ultrasound-Defined Phenotypes of Impaired Fetal Growth in Dichorionic Twins: A Retrospective Cohort Study. BJOG. 2026 Mar 11;133(8):1616-1628. PMID: 41808584.
2. Khalil A, Morales-Roselló J, Syngelaki A, et al. Fetal growth in twin pregnancies: individualized versus population-based growth charts. Ultrasound Obstet Gynecol. 2016;48(5):596-603.
3. Figueras F, Gratacós E. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther. 2014;36(2):86-98.
4. American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 203: Fetal Growth Restriction. Obstet Gynecol. 2019;133(2):e97-e109.
5. Kingdom J, Wright C, Keating S, et al. Placental pathology and fetal growth restriction. Best Pract Res Clin Obstet Gynaecol. 2022;77:45-57.
