Objective
To investigate the association between periconception maternal folate status and embryonic size.
Design
Prospective periconception cohort study.
Setting
Erasmus University Medical Centre, ...Rotterdam, the Netherlands.
Population
Seventy‐seven singleton pregnancies recruited in 2009 and 2010.
Methods
We recruited women before 8 weeks of gestation and performed weekly three‐dimensional ultrasound scans from enrolment up to 13 weeks of gestation. As a measure of embryonic growth, crown–rump length (CRL) measurements were performed using V‐Scope software in the BARCO I‐Space. Maternal blood was collected to determine first‐trimester long‐term red blood cell (RBC) folate status. Non‐malformed live births were included in the analysis. We calculated quartiles of RBC folate, square root‐transformed CRL data and performed multivariable linear mixed model analyses.
Main outcome measures
Serial first‐trimester CRL measurements.
Results
In total, 484 ultrasound scans were performed in 77 women, in 440 (90.7%) of which CRLs could be measured. RBC folate in the third quartile (1513–1812 nmol/l) was significantly associated with an increased CRL compared with the first two quartiles (814–1512 nmol/l) and the upper quartile (1813–2936 nmol/l; Poverall = 0.03; adjusted for gestational age, smoking, body mass index and fetal sex). Compared with the third quartile, embryos in the upper quartile were 24.2% smaller at 6+0 weeks 4.1 mm (95% confidence interval 3.5, 4.7) versus 5.4 mm (95% confidence interval 4.8, 6.1) and 7.6% smaller at 12+0 weeks 55.1 mm (95% confidence interval 52.9, 57.3) versus 59.6 mm (95% confidence interval 57.4, 62.0) of gestation.
Conclusions
This study suggests that a very high maternal periconception folate status is associated with reduced embryonic size. Whether these effects are beneficial or harmful requires further investigation.
We study the shapes of galaxy dark matter haloes by measuring the anisotropy of the weak gravitational lensing signal around galaxies in the second Red-sequence Cluster Survey (RCS2). We determine ...the average shear anisotropy within the virial radius for three lens samples: the “all” sample, which contains all galaxies with 19 < mr′ < 21.5, and the “red” and “blue” samples, whose lensing signals are dominated by massive low-redshift early-type and late-type galaxies, respectively. To study the environmental dependence of the lensing signal, we separate each lens sample into an isolated and clustered part and analyse them separately. We address the impact of several complications on the halo ellipticity measurement, including PSF residual systematics in the shape catalogues, multiple deflections, and the clustering of lenses. We estimate that the impact of these is small for our lens selections. Furthermore, we measure the azimuthal dependence of the distribution of physically associated galaxies around the lens samples. We find that these satellites preferentially reside near the major axis of the lenses, and constrain the angle between the major axis of the lens and the average location of the satellites to ⟨θ⟩ = 43.7° ± 0.3° for the “all” lenses, ⟨θ⟩ = 41.7° ± 0.5° for the “red” lenses and ⟨θ⟩ = 42.0° ± 1.4° for the “blue” lenses. We do not detect a significant shear anisotropy for the average “red” and “blue” lenses, although for the most elliptical “red” and “blue” galaxies it is marginally positive and negative, respectively. For the “all” sample, we find that the anisotropy of the galaxy-mass cross-correlation function ⟨f − f45⟩ = 0.23 ± 0.12, providing weak support for the view that the average galaxy is embedded in, and preferentially aligned with, a triaxial dark matter halo. Assuming an elliptical Navarro-Frenk-White profile, we find that the ratio of the dark matter halo ellipticity and the galaxy ellipticity fh = eh/eg = 1.50-1.01+1.03, which for a mean lens ellipticity of 0.25 corresponds to a projected halo ellipticity of eh = 0.38-0.25+0.26 if the halo and the lens are perfectly aligned. For isolated galaxies of the “all” sample, the average shear anisotropy increases to ⟨f-f45⟩ = 0.51-0.25+0.26 and fh = 4.73-2.05+2.17, whilst for clustered galaxies the signal is consistent with zero. These constraints provide lower limits on the average dark matter halo ellipticity, as scatter in the relative position angle between the galaxies and the dark matter haloes is expected to reduce the shear anisotropy by a factor ~2.
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.
Abstract
STUDY QUESTION
Is the maternal cardiovascular (CV) risk profile associated with human embryonic growth trajectories and does the mode of conception affect this association?
SUMMARY ANSWER
...This small study suggests that the maternal CV risk profile is inversely associated with first trimester embryonic growth trajectories in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) pregnancies, but not in spontaneously conceived pregnancies.
WHAT IS KNOWN ALREADY
Maternal high-blood pressure and smoking affect placental function, accompanied by increased risk of fetal growth restriction and low-birthweight. Mothers who experience pregnancies complicated by fetal growth restriction are at increased risk of CV disease in later life.
STUDY DESIGN, SIZE, DURATION
In a prospective periconception birth cohort conducted in a tertiary hospital, 111 singleton ongoing pregnancies with reliable pregnancy dating, no pre-existing maternal disease and no malformed live borns were investigated.
PARTICIPANTS/MATERIALS, SETTINGS, METHODS
Spontaneously conceived pregnancies with a reliable first day of the last menstrual period and a regular menstrual cycle of 25–31 days only (n = 66) and IVF/ICSI pregnancies (n = 45) were included. Women underwent weekly three-dimensional ultrasound scans (3D US) from 6- to 13-week gestational age. To estimate embryonic growth, serial crown-rump length (CRL) measurements were performed using the V-Scope software in a BARCO I-Space. Maternal characteristics and CV risk factors were collected by self-administered questionnaires. The CV risk profile was created based on a score of risk factors, including maternal age, body-mass index, CV disease in the family, diet and smoking. Quartiles of the CV risk score were calculated. Associations between the CV risk score and embryonic growth were assessed using square root transformed CRL in multivariable linear mixed model analyses.
MAIN RESULTS AND THE ROLE OF CHANCE
From the 111 included pregnancies, 696 3D US data sets were obtained of which 637 (91.5%) CRLs could be measured. In the total group, The CV risk score was inversely, but not significantly associated with embryonic growth (−0.03√mm; P = 0.291). Stratified by mode of conception, the CV risk score was inversely and significantly associated with embryonic growth (β = −0.04√mm; P = 0.025, adjusted for possible confounders) in the IVF/ICSI group. Compared with the first quartile, embryos in the upper quartile were 10.4% smaller at 6+0 weeks (4.4 versus 4.9 mm) and 3.1% smaller at 12+0 weeks (56.5 versus 58.4 mm) of gestation. Although the CV risk score was slightly, but significantly, higher in women conceiving spontaneously compared with those undergoing IVF/ICSI treatment CV risk score = 2.06 (SD: 1.23) and 1.60 (SD: 1.15), respectively, no association was established with embryonic growth in that particular group.
LIMITATIONS, REASONS FOR CAUTION
Participants included in the present cohort are women with a singleton ongoing pregnancy without any pre-existing disease and selected from a tertiary hospital. Hence, they represent a selected group of women. Larger and population-based periconception birth cohort studies are recommended to demonstrate external validity.
WIDER IMPLICATIONS OF THE FINDINGS
Differences in embryonic growth between pregnancies conceived spontaneously and after IVF/ICSI treatment in relation with CV risk factors substantiate the importance of more investigation into differences in sensitivity of endometrial, endothelial, placental and embryonic tissues.
STUDY FUNDING/COMPETING INTEREST(S)
Funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. The authors declare no conflict of interest.
STUDY QUESTION
Is in vitro fertilization treatment with or without intracytoplasmatic sperm injection (IVF/ICSI) associated with changes in first and second trimester embryonic and fetal growth ...trajectories and birthweight in singleton pregnancies?
SUMMARY ANSWER
Embryonic and fetal growth trajectories and birthweight are not significantly different between pregnancies conceived with IVF/ICSI treatment and spontaneously conceived pregnancies with reliable pregnancy dating.
WHAT IS KNOWN ALREADY
IVF/ICSI treatment has been associated with increased risks of preterm birth, fetal growth restriction and low birthweight. Decreased first-trimester crown-rump length (CRL) in the general population has been inversely associated with the same adverse pregnancy outcomes.
STUDY DESIGN, SIZE, DURATION
In a prospective periconception birth cohort study conducted in a tertiary centre, 146 singleton pregnancies with reliable pregnancy dating and nonmalformed live borns were investigated, comprised of 88 spontaneous and 58 IVF/ICSI pregnancies.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Serial 3D ultrasound scans were performed from 6 to 12 weeks of gestation. As estimates of embryonic growth, CRL and embryonic volume (EV) were measured using the I-Space virtual reality system. General characteristics were obtained from self-administered questionnaires at enrolment. Fetal growth parameters at 20 weeks and birthweight were obtained from medical records. To assess associations between IVF/ICSI and embryonic growth trajectories, estimated fetal weight and birthweight, stepwise linear mixed model analyses and linear regression analyses were performed using square root transformed CRL and fourth root transformed EV.
MAIN RESULTS AND THE ROLE OF CHANCE
In 146 pregnancies, 934 ultrasound scans were performed of which 849 (90.9%) CRLs and 549 (58.8%) EVs could be measured. Embryonic growth trajectories were comparable between IVF/ICSI pregnancies and spontaneously conceived pregnancies (CRL: βIVF/ICSI = 0.10√mm; P = 0.10; EV: βIVF/ICSI = 0.034√cm³; P = 0.13). Estimated fetal weight and birthweight were also comparable between both groups (βIVF/ICSI = 6 g; P = 0.36 and βIVF/ICSI = 80 g; P = 0.24, respectively).
LIMITATIONS, REASONS FOR CAUTION
Variations in embryonic growth trajectories of spontaneously conceived pregnancies with reliable pregnancy dating may partially be a result of less precise pregnancy dating and differences in endometrium receptivity compared with IVF/ICSI pregnancies.
WIDER IMPLICATIONS OF THE FINDINGS
The absence of a significant difference in embryonic and fetal growth trajectories suggests safety of IVF/ICSI treatment with regard to early embryonic growth. However, further research is warranted to ascertain the influence of IVF/ICSI treatments in a larger study population, and to estimate the impact of the underlying causes of the subfertility and other periconceptional exposures on human embryonic and fetal growth trajectories.
FUNDING STATEMENT
This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Centre.
CONFLICT OF INTEREST
No competing interests are declared.
Abstract Background and aims Maternal hyperglycaemia and hyperhomocysteinaemia are risk factors for congenital heart disease (CHD). These metabolic derangements and deranged lipid levels are ...associated with adult cardiovascular disease. We examined whether maternal lipid levels are associated with the risk of CHD offspring. Methods and Results From 2003 onwards, a case-control study was conducted. Participants were mothers of children with ( n = 261) and without ( n = 325) CHD. At around 16 months after the index-pregnancy, maternal lipid levels were determined. Maternal characteristics and lipid levels were compared by Student’s t -test. In a multivariable logistic regression model, risk estimates were calculated for associations between CHD and lipid levels. Adjustments were made for maternal age, diabetes, ethnicity, body mass index (BMI), parity, periconception folic acid use and total homocysteine levels. Outcome measures are presented in (geometric) means (p5–p95) and odds ratios (ORs) with 95% confidence intervals (CIs). Case mothers showed higher cholesterol (4.9 vs. 4.7 mmol l−1 , P < 0.05), low-density lipoprotein (LDL)-cholesterol (3.2 vs. 3.0 mmol l−1 , P < 0.05), apolipoprotein B (84.0 vs. 80.0 mg dl−1 , P < 0.01) and homocysteine (10.8 vs. 10.2 μmol l−1 , P < 0.05) than controls. LDL-cholesterol above 3.3 mmol l−1 (OR 1.6 (95%CI, 1.1–2.3)) and apolipoprotein B above 85.0 mg dl−1 were associated with an almost twofold increased CHD risk (OR 1.8 (95%CI, 1.2–2.6)). This was supported by elevated CHD risks per unit standard deviation increase in cholesterol (OR 1.2 (95% CI 1.03–1.5)), LDL-cholesterol (OR 1.3 (95%CI, 1.1–1.6) and apolipoprotein B (OR 1.3 (95% CI 1.1–1.6)). Apolipoprotein B was most strongly associated with CHD risk. Conclusion A mildly deranged maternal lipid profile is associated with an increased risk of CHD offspring.
We present the results of a weak gravitational lensing analysis to determine whether the stellar mass or else the velocity dispersion is more closely related to the amplitude of the lensing signal ...around galaxies, hence to the projected distribution of dark matter. The lensing signal on smaller scales than the virial radius corresponds most closely to the lensing velocity dispersion in the case of a singular isothermal profile, but is also sensitive on larger scales to the clustering of the haloes. We have selected over 4000 lens galaxies at a redshift z < 0.2 with concentrated (or bulge-dominated) surface brightness profiles from the ~300 square degree overlap between the Red-sequence Cluster Survey 2 (RCS2) and the data release 7 (DR7) of the Sloan Digital Sky Survey (SDSS). We consider both the spectroscopic velocity dispersion and a model velocity dispersion (a combination of the stellar mass, the size, and the Sérsic index of a galaxy). Comparing the model and spectroscopic velocity dispersion we find that they correlate well for galaxies with concentrated brightness profiles. We find that the stellar mass and the spectroscopic velocity dispersion trace the amplitude of the lensing signal on small scales equally well. The model velocity dispersion, however, does significantly worse. A possible explanation is that the halo properties that determine the small-scale lensing signal – mainly the total mass – also depend on the structural parameters of galaxies, such as the effective radius and Sérsic index, but we lack data for a definitive conclusion.
We use weak gravitational lensing to analyse the dark matter haloes around satellite galaxies in galaxy groups in the Canada-France-Hawaii Telescope Lensing Survey (CFHTLenS) data set. This data set ...is derived from the Canada-France-Hawaii Telescope Legacy Survey Wide survey, and encompasses 154 deg2 of high-quality shape data. Using the photometric redshifts, we divide the sample of lens galaxies with stellar masses in the range 109-1010.5 M into those likely to lie in high-density environments (HDE) and those likely to lie in low-density environments (LDE). Through comparison with galaxy catalogues extracted from the Millennium Simulation, we show that the sample of HDE galaxies should primarily (∼61 per cent) consist of satellite galaxies in groups, while the sample of LDE galaxies should consist of mostly (∼87 per cent) non-satellite (field and central) galaxies. Comparing the lensing signals around samples of HDE and LDE galaxies matched in stellar mass, the lensing signal around HDE galaxies clearly shows a positive contribution from their host groups on their lensing signals at radii of ∼500-1000 kpc, the typical separation between satellites and group centres. More importantly, the subhaloes of HDE galaxies are less massive than those around LDE galaxies by a factor of 0.65 ± 0.12, significant at the 2.9σ level. A natural explanation is that the haloes of satellite galaxies are stripped through tidal effects in the group environment. Our results are consistent with a typical tidal truncation radius of ∼40 kpc.
The authors study the shapes of galaxy dark matter haloes by measuring the anisotropy of the weak gravitational lensing signal around galaxies in the second Red-sequence Cluster Survey. They ...determine the average shear anisotropy within the virial radius for three lens samples: the all sample, and the red and blue samples, whose lensing signals are dominated by massive low-redshift early-type and late-type galaxies, respectively. To study the environmental dependence of the lensing signal, they separate each lens sample into an isolated and clustered part and analyse them separately. They find that these satellites preferentially reside near the major axis of the lenses, and constrain the angle between the major axis of the lens and the average location of the satellites to ... for the all lenses, ... for the red lenses and ... for the blue lenses. For isolated galaxies of the all sample, the average shear anisotropy increases to ... and ..., whilst for clustered galaxies the signal is consistent with zero. (ProQuest: ... denotes formulae/symbols omitted.)
We present a weak gravitational lensing analysis of 815 square degree of \(i\)-band imaging from the Kilo-Degree Survey (KiDS-\(i\)-800). In contrast to the deep \(r\)-band observations, which take ...priority during excellent seeing conditions and form the primary KiDS dataset (KiDS-\(r\)-450), the complementary yet shallower KiDS-\(i\)-800 spans a wide range of observing conditions. The overlapping KiDS-\(i\)-800 and KiDS-\(r\)-450 imaging therefore provides a unique opportunity to assess the robustness of weak lensing measurements. In our analysis, we introduce two new `null' tests. The `nulled' two-point shear correlation function uses a matched catalogue to show that the calibrated KiDS-\(i\)-800 and KiDS-\(r\)-450 shear measurements agree at the level of \(1 \pm 4\)\%. We use five galaxy lens samples to determine a `nulled' galaxy-galaxy lensing signal from the full KiDS-\(i\)-800 and KiDS-\(r\)-450 surveys and find that the measurements agree to \(7 \pm 5\)\% when the KiDS-\(i\)-800 source redshift distribution is calibrated using either spectroscopic redshifts, or the 30-band photometric redshifts from the COSMOS survey.
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