Abstract and Introduction
Abstract
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.
Introduction
High embryonic growth and development rate in the first trimester renders this one of the most vulnerable periods in life. However, until recently, prenatal care and research have focused predominantly on fetal growth in the second half of pregnancy and birthweight. Fetal and newborn weight is associated with health and disease in later life (Gluckman et al., 2008). More recently, embryonic crown-rump length (CRL) at the end of the first trimester has been associated with fetal growth, birthweight and the risk of being born small for gestational age (SGA) or with a low birthweight (Smith et al., 1998; Bukowski et al., 2007; Mook-Kanamori et al., 2010).
During pregnancy the mother is the environment of the developing embryo and fetus (Steegers-Theunissen and Steegers, 2003). Whereas a multitude of maternal characteristics and lifestyle factors, such as parity and smoking, have been linked to birthweight (Gardosi et al., 1992; Wang et al., 2002), few studies have focused on the influence of periconception maternal characteristics and lifestyle on first trimester embryonic size (Bottomley et al., 2009; Bakker et al., 2010; Mook-Kanamori et al., 2010; Prabhu et al., 2010; Sarris et al., 2010). Moreover, to date longitudinal data on embryonic growth remain scarce (Bottomley and Bourne, 2009).
As a result of the development of transvaginal three-dimensional (3D) ultrasound techniques over the last few decades, visualization of the first trimester embryo has improved tremendously. The use of these novel ultrasound techniques in combination with the virtual reality technology of the BARCO I-Space and V-scope visualization software enables depth perception and thus an actual view of the third dimension (Koning et al., 2009). Together, these technological developments have enabled highly precise and reliable performance of early first trimester embryonic measurements in vivo (Verwoerd-Dikkeboom et al., 2008, 2010; Rousian et al., 2010) and have improved the means to assess longitudinally embryonic growth from early in the first trimester of pregnancy onwards.
The aim of this study is to investigate associations between periconception maternal characteristics and first trimester embryonic growth trajectories using longitudinal CRL measurements.