Study question: Are maternal characteristics and lifestyle factors associated with human embryonic growth trajectories?

Summary answer: Periconception maternal age is associated with increased, and smoking and alcohol use with decreased embryonic growth trajectories, estimated with crown-rump length (CRL) measurements.

What is known already: Fetal weight is associated with health and disease in later life. Maternal characteristics and lifestyle factors affect fetal growth in the second and third trimesters of pregnancy and at birth; however, little is known about the association of these characteristics with first trimester embryonic growth.

Study design, size, duration: In a tertiary centre, pregnant women were recruited and enrolled in a prospective periconception cohort study before 8 weeks of gestation. We selected 87 spontaneously conceived singleton pregnancies of women recruited in 2009 and 2010 that ended in non-malformed live births.

Participants/materials, setting, methods: We performed weekly three-dimensional ultrasound scans from enrolment up to 13 weeks of gestation. At enrolment, a questionnaire was completed. Embryonic CRL measurements were performed using the V-Scope software in the BARCO I-Space. Associations between maternal characteristics and embryonic growth were assessed using square root transformed CRL as response in linear mixed model analyses, adjusted for potential confounders.

Main results and the role of chance: Four hundred and ninety-six scans from 87 pregnancies were included. In the multivariable analysis, maternal age was positively associated with first trimester CRL (difference per maternal year of age 0.024√mm (95% confidence interval (CI) 0.009, 0.040), P = 0.001). At 6 and 12 weeks of gestation, the CRL of an embryo from a 40-year-old mother was estimated 2.0 mm (61%) and 7.2 mm (14%) larger, respectively, compared with an embryo from a 20-year-old mother. Smoking of 10 or more cigarettes per day was negatively associated with CRL (difference -0.211√mm (95% CI -0.416, -0.006), P = 0.04), with embryos that were 0.9 mm (18.7%) and 3.1 mm (5.5%) smaller at 6 and 12 weeks, respectively, compared with non-smokers. Periconception alcohol use was negatively associated with CRL growth rate (difference -0.0025√mm (95% CI -0.0047, -0.0003)/day gestational age, P = 0.022), with embryos that were 0.2 mm (3%) and 1.1 mm (2%) smaller at 6 and 12 weeks, respectively, compared with non-alcohol users. Parity, BMI and moment of initiation of folic acid use were not significantly associated with embryonic CRL.

Limitations, reasons for caution: Due to the selection of pregnancies in a tertiary centre and the small number of pregnancies, the external validity of the results has to be confirmed using larger sample sizes and other population-based periconception cohort studies.

Wider implications of the findings: The association of maternal age and smoking with embryonic growth is in line with previous literature, whereas the association between embryonic growth and alcohol use is a new finding. However, concerning exposure to alcohol, the effect estimate was small and it is questionable whether this is of clinical value. More research is warranted to unravel underlying mechanisms and to assess the implications for preconception and early pregnancy care, such as the development and implementation of effective lifestyle interventions.

Study funding/competing interest(s): The work was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest.