Prenatal diagnosis and pregnancy outcome of major structural anomalies detectable in the first trimester: A population-based cohort study in the Netherlands

Background: Prenatal diagnosis of several major congenital anomalies can be achieved in the first trimester of pregnancy.

Objective: This study investigates the timing of diagnosis and pregnancy outcome of foetuses and neonates with selected structural anomalies in the Northern Netherlands over a 10-year period when the prenatal screening programme changed significantly, but no first-trimester anatomical screening was implemented.

Methods: We performed a population-based retrospective cohort study with data from the EUROCAT Northern Netherlands database on pregnancies with delivery or termination of pregnancy for fetal anomaly (TOPFA) date between 2010 and 2019. The analysis was restricted to anomalies potentially detectable in the first trimester of pregnancy in at least 50% of cases, based on previously published data. These included: anencephaly, encephalocele, spina bifida, holoprosencephaly, tricuspid/pulmonary valve atresia, hypoplastic left heart, abdominal wall and limb reduction defects, lethal skeletal dysplasia, megacystis, multiple congenital anomalies. The primary outcome was the timing of diagnosis of each structural anomaly. Information on additional investigations, genetic testing and pregnancy outcome (live birth, TOPFA and foetal/neonatal death) was also collected.

Results: A total of 478 foetuses were included; 95.0% (n = 454) of anomalies were detected prenatally and 5.0% (n = 24) postpartum. Among the prenatally detected cases, 31% (n = 141) were diagnosed before 14 weeks of gestation, 65.6% (n = 298) between 14-22 weeks and 3.3% (n = 15) after 22 weeks. Prenatal genetic testing was performed in 80.4% (n = 365) of cases with prenatally diagnosed anomalies, and the results were abnormal in 26% (n = 95). Twenty-one% (n = 102) of pregnancies resulted in live births and 62.8% (n = 300) in TOPFA. Spontaneous death occurred in 15.9% (n = 76) of cases: in-utero (6.1%, n = 29), at delivery (7.7%, n = 37) or in neonatal life (2.1%, n = 10).

Conclusion: Major structural anomalies amenable to early diagnosis in the first trimester of pregnancy are mostly diagnosed during the second trimester in the absence of a regulated first-trimester anatomical screening programme in the Netherlands and are associated with TOPFA and spontaneous death, especially in cases with underlying genetic anomalies.