R.P.M. Steegers-Theunissen

Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease

Objective  To investigate the inter‐relation between mother and infant homocysteine, folate and vitamin B12 status and the risk of a child with congenital heart disease (CHD).

The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring.

Objective  The objective of this study was to test the hypothesis whether a maternal dietary pattern is associated with the risk of spina bifida (SB) in the offspring.

High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring

Objective  To study associations between maternal dietary and supplement intake of antioxidants vitamin E, retinol and congenital heart defects (CHDs).

An optimal periconception maternal folate status for embryonic size: the Rotterdam Predict study

To investigate the association between periconception maternal folate status and embryonic size.

Periconception maternal characteristics and embryonic growth trajectories: the Rotterdam Predict study

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.

A derangement of the maternal lipid profile is associated with an elevated risk of congenital heart disease in the offspring

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 Students 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.

A maternal dietary pattern characterised by fish and seafood in association with the risk of congenital heart defects in the offspring

Please cite this paper as: Obermann‐Borst S, Vujkovic M, de Vries J, Wildhagen M, Looman C, de Jonge R, Steegers E, Steegers‐Theunissen R. A maternal dietary pattern characterised by fish and seafood in association with the risk of congenital heart defects in the offspring. BJOG 2011; DOI: 10.1111/j.1471‐0528.2011.02984.x.

Low-dose folic acid supplementation does not influence plasma methionine concentrations in young non-pregnant women.

An elevated plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease and for having offspring with a neural-tube defect. Folate is a methyl donor in the remethylation of homocysteine into methionine. Although folic acid supplementation decreases tHcy concentrations, effects of folic acid supplementation on plasma methionine concentrations are unclear. There is also concern that folic acid supplementation negatively affects vitamin B12 status. We studied effects of low-dose folic acid supplementation on methionine and vitamin B12 concentrations in plasma. We also investigated whether baseline plasma methionine and tHcy concentrations correlated with the baseline folate and vitamin B12 status. For a period of 4 weeks, 144 young women received either 500 micrograms folic acid each day, or 500 micrograms folic acid and placebo tablets on alternate days, or a placebo tablet each day. Plasma methionine, tHcy and plasma vitamin B12 concentrations were measured at start and end of the intervention period. Folic acid supplementation had no effect on plasma methionine or plasma vitamin B12 concentrations although it significantly decreased tHcy concentrations. Plasma methionine concentrations showed no correlation with either tHcy concentrations (Spearman rs-0.01, P = 0.89), or any of the blood vitamin variables at baseline. Baseline tHcy concentrations showed a slight inverse correlation with baseline concentrations of plasma vitamin B12 (rs-0.25, P < 0.001), plasma folate (rs-0.24, P < 0.01) and erythrocyte folate (rs-0.19, P < 0.05). In conclusion, low-dose folic acid supplementation did not influence plasma methionine or plasma vitamin B12 concentrations. Furthermore, no correlation between plasma methionine concentrations and the blood folate and vitamin B12 status was shown.

The influence of IVF/ICSI treatment on human embryonic growth trajectories

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 = 0.03(4)√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.

Periconceptional maternal ‘high fish and olive oil, low meat’ dietary pattern is associated with increased embryonic growth: The Rotterdam Periconceptional Cohort (Predict) Study

To investigate the association between periconceptional maternal dietary pattern and first‐trimester embryonic growth.