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Metabolic dynamics and prediction of sFGR and adverse fetal outcomes: a prospective longitudinal cohort study
Nana Huang1,2,3, Wei Chen1,2,4,5,6, Hai Jiang1,2,3
1Department of Obstetrics and Gynecology, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing, 100191, China.
Insights
Maternal plasma metabolites in early pregnancy can predict selective fetal growth restriction (sFGR) and fetal brain injury. Specific metabolite combinations in the first and second trimesters show high accuracy for early detection and intervention in monochorionic diamniotic twin pregnancies.
Area of Science:
- Perinatal medicine
- Metabolomics
- Neurodevelopmental disorders
Background:
- Selective fetal growth restriction (sFGR) affects 15% of monochorionic diamniotic (MCDA) twin pregnancies, increasing risks of mortality and long-term neurological issues.
- Current prediction and intervention strategies for sFGR are limited by a lack of longitudinal cohort studies.
Purpose of the Study:
- To identify predictive biomarkers for sFGR and associated fetal brain injury using a prospective longitudinal cohort study.
- To evaluate the neurocognitive behavioral development of infants affected by sFGR.
Main Methods:
- Quantified 25 key metabolites in maternal and cord plasma across trimesters from 337 samples.
- Assessed fetal growth and brain injury via ultrasonography and long-term neurodevelopment using the Ages and Stages Questionnaire-third edition (ASQ-3).
- Correlated metabolite levels with ultrasound and ASQ-3 data; developed predictive models for sFGR and fetal brain injury.
Main Results:
- Differential metabolite patterns varied throughout pregnancy, with a peak in the second trimester.
- A combination of L-phenylalanine, L-leucine, and L-isoleucine in the second trimester predicted sFGR occurrence with high accuracy (AUC: 0.878).
- Specific metabolite combinations in the first and second trimesters accurately identified fetal brain injury and correlated with long-term neurodevelopment (AUC: 0.94).
Conclusions:
- Maternal plasma metabolites from the first and second trimesters are superior biomarkers for predicting sFGR and fetal brain injury compared to later samples.
- Identified metabolites offer potential for early prediction and targeted interventions in clinical settings for sFGR.
Background:
Selective fetal growth restriction (sFGR) is an extreme complication that significantly increases the risk of perinatal mortality and long-term adverse neurological outcomes in offspring, affecting approximately 15% of monochorionic diamniotic (MCDA) twin pregnancies. The lack of longitudinal cohort studies hinders the early prediction and intervention of sFGR.
Methods:
We constructed a prospective longitudinal cohort study of sFGR, and quantified 25 key metabolites in 337 samples from maternal plasma in the first, second, and third trimester and from cord plasma. In particular, our study examined fetal growth and brain injury data from ultrasonography and used the Ages and Stages Questionnaire-third edition subscale (ASQ-3) to evaluate the long-term neurocognitive behavioral development of infants aged 2-3 years. Furthermore, we correlated metabolite levels with ultrasound data, including physical development and brain injury indicators, and ASQ-3 data using Spearman's-based correlation tests. In addition, special combinations of differential metabolites were used to construct predictive models for the occurrence of sFGR and fetal brain injury.
Results:
Our findings revealed various dynamic patterns for these metabolites during pregnancy and a maximum of differential metabolites between sFGR and MCDA in the second trimester (n = 8). The combination of L-phenylalanine, L-leucine, and L-isoleucine in the second trimester, which were closely related to fetal growth indicators, was highly predictive of sFGR occurrence (area under the curve [AUC]: 0.878). The combination of L-serine, L-histidine, and L-arginine in the first trimester and creatinine in the second trimester was correlated with long-term neurocognitive behavioral development and showed the capacity to identify fetal brain injury with high accuracy (AUC: 0.94).
Conclusions:
The performance of maternal plasma metabolites from the first and second trimester is superior to those from the third trimester and cord plasma in discerning sFGR and fetal brain injury. These metabolites may serve as useful biomarkers for early prediction and promising targets for early intervention in clinical settings.
