Peri-conceptional maternal vulnerability risk score and embryonic growth: the Rotterdam Periconception Cohort

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RESEARCH QUESTION: What is the association of peri-conceptional maternal vulnerability, assessed through a weighted multi-domain risk score with embryonic growth? DESIGN: 638 pregnancies were included from the Rotterdam Periconception Cohort. Data on nine vulnerability factors (encompassing lifestyle, mental health and environmental factors) were obtained through self-administered questionnaires. The Periconceptional Vulnerability Risk Score (PVRS) was calculated using weighted estimates of associations between vulnerability factors and 'Big 3' pregnancy outcomes (congenital anomalies, preterm birth and small for gestational age). Embryonic growth was assessed by repeated first-trimester 3D transvaginal ultrasound measurements of crown-rump length and embyronic volume, analyzed with VR-software. RESULTS: For the total study population, the PVRS ranged from -0.071 to 0.320 (median 0.131). Higher PVRS values were significantly associated with reduced embryonic growth trajectories (CRL: β = -0.58 mm, 95% CI -0.94 to -0.23, P = 0.001; embryonic volume: β = -0.31 cm³, 95% CI -0.49 to -0.13, P = 0.001). Subgroup analyses revealed significant negative associations in naturally conceived pregnancies (CRL: β = -0.82 mm, 95% CI -1.48 to -0.16, P = 0.015; embryonic volume: β = -0.39 cm³, 95% CI -0.71 to -0.08, P = 0.015) and in overweight women (CRL: β = -0.91 mm, 95% CI -1.55 to -0.27, P = 0.006; embryonic volume: β = -0.51 cm³, 95% CI -0.82 to -0.21, P = 0.001). CONCLUSIONS: The PVRS provides a weighted measure of maternal vulnerability, significantly associated with reduced embryonic growth, particularly in naturally conceived pregnancies and overweight women. Although no causality can be inferred from this study, the observed associations suggest that a broad peri-conceptional vulnerability assessment could help to identify potentially modifiable risk factors.