Discrepancy in menstrual and ultrasound-based gestational age is associated with chromosomal aberrations and adverse pregnancy outcomes—Results from a nationwide cohort study

Introduction: In women with a regular cycle, reliable last menstrual period (LMP), and accurate crown–rump length (CRL) estimation, discrepancies in estimated date of delivery (EDD) may indicate impaired fetal growth and increased risk of morbidity. This study examines whether discrepancies between EDD based on LMP (EDD_LMP) and CRL (EDD_CRL) are associated with chromosomal aberrations, adverse pregnancy outcomes, and obstetric complications. Material and Methods: A Danish nationwide register-based cohort study including all singleton pregnancies with both CRL and LMP registered between 2008 and 2018. Exclusion criteria were uncertain LMP, irregular menstrual cycle, EDD discrepancies >±28 days, assisted reproductive technology, and missing outcome data. The cohort was stratified into seven groups according to EDD_LMP-EDD_CRL discrepancy. Negative discrepancies indicated smaller-than-expected CRL, positive discrepancies indicated larger-than-expected CRL, and ±3 days served as reference. Outcomes included chromosomal aberrations, major structural malformations, pregnancy loss, termination of pregnancy, fetal growth restriction, preterm birth, and obstetric complications (preeclampsia, preterm pre-labour rupture of membranes, placenta previa, and placental abruption). Prevalence with 95% confidence intervals and adjusted odds ratios (aOR) were calculated. Results: A total of 262 329 pregnancies were included; 16% had smaller and 21% had larger CRL than expected from LMP. Negative discrepancies were significantly associated with increased risk of chromosomal aberrations, adverse pregnancy outcomes, and obstetric complications. In the −8 to −14 days group, 1.28% had a chromosomal abnormality (aOR 2.77 [95% CI 2.30–3.31]), and risk remained elevated among pregnancies at low combined first-trimester screening risk (aOR 1.95 [1.55–2.43]). For triploidy and trisomy 18, 91% and 59% of cases, respectively, had discrepancies of <−3 days. In the −8 to −14 days group, adverse pregnancy outcome occurred in 11.0% (aOR 1.49 [1.40–1.59]), and 6.5% had obstetric complications, mainly preeclampsia (aOR 1.19 [1.10–1.29]). Conversely, positive discrepancies were associated with reduced risk of chromosomal abnormalities (aOR 0.67 [0.44–0.96]) and adverse pregnancy outcomes (aOR 0.77 [0.69–0.86]) in the +8 to +14 days group. Conclusions: A smaller than expected CRL was strongly associated with chromosomal aberrations, adverse pregnancy outcomes, and obstetric complications. Incorporating EDD discrepancies into risk algorithms for genetic disease, growth restriction, and preeclampsia may improve prediction and warrants further study.