Development of Fetal Growth Charts in Twins Stratified by Chorionicity and Mode of Conception: A Retrospective Cohort Study in China
Introduction Twin pregnancies have been on the rise globally, primarily due to the increasing use of assisted reproductive technology (ART) and delayed childbirth. In fact, ART accounts for approximately one-third of all twin pregnancies. It is well-documented that fetal growth in twins is slower compared to singletons, typically starting from 28 to 32 weeks of gestation, which is attributed to the limited uterine space. Despite this, the clinical evaluation of intrauterine growth in twins still largely relies on growth standards established for singletons. This discrepancy has created a pressing need for the development of twin-specific biometry charts to accurately monitor fetal growth trajectories in twin pregnancies.
Several ultrasonographic reference charts for twins have been developed in recent years. However, many of these studies were based on small populations or did not exclude high-risk pregnancies, limiting their applicability. Additionally, evidence suggests that monochorionic diamniotic (MCDA) twins exhibit a slower growth rate compared to dichorionic diamniotic (DCDA) twins. Furthermore, ART has been shown to affect perinatal outcomes in twin pregnancies. Therefore, both chorionicity and mode of conception are critical factors that should be considered when developing fetal biometric references for twins.
Methods This retrospective longitudinal study was conducted at the International Peace Maternity & Child Health Hospital in Shanghai, China, from 2016 to 2019. The study included pregnant women who delivered twins or singletons during this period. The inclusion criteria required that deliveries occur at or beyond 34 weeks of gestation for twins and 37 weeks for singletons, with at least two sets of ultrasound measurements taken during the pregnancy. Exclusion criteria included uncertain chorionicity, monoamnionicity, key information deficits, fetal death, structural or chromosomal anomalies, and maternal complications such as hypertension or diabetes.
Gestational age was calculated based on the date of ovulation, embryo transfer, last menstrual period, or crown-rump length. Chorionicity was determined by the number of gestational sacs observed at 7 to 8 weeks of gestation and confirmed by ultrasound findings such as the “T sign” or “lambda sign” during the first trimester. Ultrasound examinations were performed every 3 to 4 weeks between 14 and 32 weeks, and every 2 weeks thereafter until delivery for singletons and DCDA twins. For MCDA twins, examinations were conducted every 2 weeks between 14 and 32 weeks and weekly beyond 32 weeks of gestation.
Fetal biometric measurements, including biparietal diameter (BPD), head circumference (HC), femur length (FL), humerus length (HL), anteroposterior trunk diameter (APTD), and transverse trunk diameter (TTD), were recorded at each visit. Estimated fetal weight (EFW) was calculated using Hadlock formulas, and abdominal circumference (AC) was derived from the mean arithmetic diameters of APTD and TTD.
Statistical analysis was performed using linear mixed models to test for differences in growth patterns between groups. The generalized additive model for location, scale, and shape (GAMLSS) was used to model the growth curves for each biometric parameter. Model selection was based on the generalized Akaike Information Criterion (GAIC), and centile curves were constructed for each biometric parameter according to chorionicity and mode of conception.
Results The study included 929 twin pregnancies and 2019 singleton pregnancies, with a total of 12,837 ultrasound observations for twins and 9,787 for singletons. Among the twin pregnancies, 148 were spontaneously conceived monochorionic diamniotic (SC-MCDA), 215 were spontaneously conceived dichorionic diamniotic (SC-DCDA), and 566 were ART-conceived dichorionic diamniotic (ART-DCDA) twins.
The results showed that SC-DCDA twins grew faster than SC-MCDA twins but slower than ART-DCDA twins, with all differences being statistically significant. All three twin groups exhibited significant differences compared to singletons, particularly during the third trimester. Customized fetal growth charts were constructed for each biometric parameter for SC-MCDA, SC-DCDA, and ART-DCDA twins.
The fetal biometric trajectories demonstrated characteristic patterns based on chorionicity and mode of conception. SC-MCDA twins had smaller biometric measurements compared to SC-DCDA twins, particularly in EFW, AC, FL, and HL. The growth velocity for EFW, BPD, HC, FL, and HL was also significantly different between SC-MCDA and SC-DCDA twins. Similarly, ART-DCDA twins showed significant differences in all six fetal biometric measurements compared to SC-DCDA twins.
Discussion The findings of this study highlight the importance of developing twin-specific fetal growth charts that account for both chorionicity and mode of conception. The slower growth rate observed in SC-MCDA twins compared to SC-DCDA twins is consistent with previous studies, which have shown that monochorionic twins generally exhibit slower growth rates. The higher growth rate observed in ART-DCDA twins suggests that the mode of conception may also play a role in fetal growth patterns.
The study’s strengths include its large sample size, longitudinal design, and strict inclusion criteria, which enhance the reliability of the findings. The use of the GAMLSS model, which allows for the modeling of median, standard deviation, skewness, and kurtosis, further improves the accuracy of the growth curves. Additionally, the comparison with singleton data underscores the intrinsic differences in growth patterns between twins and singletons, emphasizing the need for twin-specific growth standards.
However, the study has some limitations. It was conducted at a single center, which may limit the generalizability of the findings. Additionally, the small number of MCDA twins conceived through ART precluded their inclusion in the analysis. Despite these limitations, the study provides valuable insights into the growth patterns of twins and establishes a foundation for future research in this area.
Conclusion This study successfully developed a set of fetal growth charts for Chinese twins, stratified by chorionicity and mode of conception. The findings demonstrate that SC-MCDA twins grow slower than SC-DCDA twins, and ART-DCDA twins exhibit the highest growth rate. The customized growth charts provide a valuable tool for the accurate assessment of intrauterine growth in twins, addressing the limitations of using singleton-based standards. Future research should aim to validate these findings in larger, multi-center studies and explore the underlying mechanisms that contribute to the observed differences in growth patterns.
doi.org/10.1097/CM9.0000000000001616
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