Please cite this paper as: Bergen N, Jaddoe V, Timmermans S, Hofman A, Lindemans J, Russcher H, Raat H, Steegers‐Theunissen R, Steegers E. Homocysteine and folate concentrations in early pregnancy ...and the risk of adverse pregnancy outcomes: the Generation R Study. BJOG 2012;119:739–751.
Objective To investigate associations between early pregnancy homocysteine, folate and vitamin B12 concentrations and placental weight, birthweight and adverse pregnancy outcomes.
Design Population‐based birth cohort study.
Setting Rotterdam, the Netherlands.
Population Cohort of 5805 pregnant women.
Methods To analyse homocysteine, folate and vitamin B12 concentrations, blood was drawn in early pregnancy. These concentrations were divided into quintiles. Information on birth outcomes was retrieved from medical records. Multivariate regression analyses were used.
Main outcome measures Placental weight, birthweight, small for gestational age at birth (SGA) (<5th centile), prematurity and pre‐eclampsia.
Results High homocysteine concentrations (highest quintile) were associated with lower placental weight (difference 30 g; P < 0.001) and birthweight (difference 110 g; P < 0.001), and increased risk of SGA odds ratio (OR) 1.7; P = 0.006 compared with lowest quintile (reference). Low folate concentrations (lowest quintile) were associated with lower placental weight (difference 26 g; P = 0.001) and birthweight (difference 125 g; P < 0.001), and increased risks of SGA (OR 1.9; P = 0.002), prematurity (OR 2.2; P = 0.002) and pre‐eclampsia (OR 2.1; P = 0.04) compared with highest quintile (reference). The risk of developing SGA and pre‐eclampsia was substantially higher in women who had higher homocysteine and lower folate concentrations. No associations were found with vitamin B12.
Conclusions Higher homocysteine and lower folate concentrations in early pregnancy are associated with lower placental weight and birthweight, and higher risk of adverse pregnancy outcomes. These findings suggest that high homocysteine and low folate concentrations in early pregnancy may adversely influence placentation and subsequently affect the success of pregnancy and birth outcomes.
BACKGROUND
Adverse reproductive performance has been linked to unhealthy dietary intake and lifestyles. Our objectives were to investigate the prevalence of unhealthy dietary intake and lifestyles ...before conception and to evaluate whether tailored preconception counselling modifies these behaviours.
METHODS
Between October 2007 and April 2009, 419 couples received tailored preconception dietary and lifestyle counselling at the outpatient clinic of Obstetrics and Gynaecology of the Erasmus University Medical Center Rotterdam, the Netherlands. A subgroup (n = 110 couples) was counselled twice with a fixed time interval of 3 months. Self-administered questionnaires were used for tailored dietary and lifestyle counselling. A cumulative score based on six Dutch dietary guidelines was displayed in the personal Preconception Dietary Risk score (PDR score). In a similar manner, the Rotterdam Reproduction Risk score (R3 score) was calculated from lifestyle factors (women: 13 items, men: 10 items). Univariate and paired tests were used.
RESULTS
Most couples (93.8%) were subfertile. At the second counselling, the percentage consuming the recommended intake of fruit had increased from 65 to 80 in women and from 49 to 68 in men and the percentage of women getting the recommended intake of fish increased from 39 to 52. As a consequence, the median PDR score was decreased women: 2.6 (95% CI 2.4–2.9) to 2.4 (95% CI 2.1–2.6), men: 2.5 (95% CI 2.3–2.7) to 2.2 (95% CI 1.9–2.4), both P < 0.05. The median R3 scores were also lower women: 4.7 (95% CI 4.3–5.0) to 3.1 (95% CI 2.8–3.4), men: 3.0 (95% CI 2.8–3.3) to 2.0 (95% CI 1.7–2.3), both P < 0.01 due to less alcohol use (−14.6%), more physical exercise and folic acid use in women, and less alcohol use in men (−19.4%) (all P < 0.01). The R3 scores in women and men were decreased in all ethnicity, educational level, neighbourhood and BMI categories. However, low educated women appeared to show a larger reduction than better educated women and men with a normal BMI to show a larger decrease than overweight men. The reduction in the PDR score of women was similar in both ethnic groups. More than 85% women and men found the counselling useful and around 70% would recommend it to others.
CONCLUSIONS
Tailored preconception counselling about unhealthy dietary and lifestyle behaviours of subfertile couples in an outpatient tertiary clinic is feasible and seems to decrease the prevalence of harmful behaviours in the short term. These results with subfertile couples are promising and illustrate their opportunities to contribute to reproductive performance and pregnancy outcome.
BACKGROUND
Subfertility and poor nutrition are increasing problems in Western countries. Moreover, nutrition affects fertility in both women and men. In this study, we investigate the association ...between adherence to general dietary recommendations in couples undergoing IVF/ICSI treatment and the chance of ongoing pregnancy.
METHODS
Between October 2007 and October 2010, couples planning pregnancy visiting the outpatient clinic of the Department of Obstetrics and Gynaecology of the Erasmus Medical Centre in Rotterdam, the Netherlands were offered preconception counselling. Self-administered questionnaires on general characteristics and diet were completed and checked during the visit. Six questions, based on dietary recommendations of the Netherlands Nutrition Centre, covered the intake of six main food groups (fruits, vegetables, meat, fish, whole wheat products and fats). Using the questionnaire results, we calculated the Preconception Dietary Risk score (PDR), providing an estimate of nutritional habits. Dietary quality increases with an increasing PDR score. We define ongoing pregnancy as an intrauterine pregnancy with positive heart action confirmed by ultrasound. For this analysis we selected all couples (n= 199) who underwent a first IVF/ICSI treatment within 6 months after preconception counselling. We applied adjusted logistic regression analysis on the outcomes of interest using SPSS.
RESULTS
After adjustment for age of the woman, smoking of the woman, PDR of the partner, BMI of the couple and treatment indication we show an association between the PDR of the woman and the chance of ongoing pregnancy after IVF/ICSI treatment (odds ratio 1.65, confidence interval: 1.08–2.52; P= 0.02. Thus, a one-point increase in the PDR score associates with a 65% increased chance of ongoing pregnancy.
CONCLUSIONS
Our results show that increasing adherence to Dutch dietary recommendations in women undergoing IVF/ICSI treatment increases the chance of ongoing pregnancy. These data warrant further confirmation in couples achieving a spontaneous pregnancy and in randomized controlled trials.
BACKGROUND This study investigates whether dietary patterns, substantiated by biomarkers, are associated with semen quality. METHODS In 161 men of subfertile couples undergoing in vitro fertilization ...treatment in a tertiary referral clinic in Rotterdam, the Netherlands, we assessed nutrient intakes and performed principal component factor analysis to identify dietary patterns. Total homocysteine (tHcy), folate, vitamin B12 and B6 were measured in blood and seminal plasma. Semen quality was assessed by sperm volume, concentration, motility, morphology and DNA fragmentation index (DFI). Linear regression models analyzed associations between dietary patterns, biomarkers and sperm parameters, adjusted for age, body mass index (BMI), smoking, vitamins and varicocele. RESULTS The ‘Health Conscious’ dietary pattern shows high intakes of fruits, vegetables, fish and whole grains. The ‘Traditional Dutch’ dietary pattern is characterized by high intakes of meat, potatoes and whole grains and low intakes of beverages and sweets. The ‘Health Conscious’ diet was inversely correlated with tHcy in blood (β = −0.07, P = 0.02) and seminal plasma (β = −1.34, P = 0.02) and positively with vitamin B6 in blood (β = 0.217, P = 0.01). An inverse association was demonstrated between the ‘Health Conscious’ diet and DFI (β = −2.81, P = 0.05). The ‘Traditional Dutch’ diet was positively correlated with red blood cell folate (β = 0.06, P = 0.04) and sperm concentration (β = 13.25, P = 0.01). CONCLUSIONS The ‘Health Conscious’ and ‘Traditional Dutch’ dietary pattern seem to be associated with semen quality in men of subfertile couples.
BACKGROUND
Congenital heart defects (CHDs) are the most common major malformations in newborns. In this study we examined the associations between the occurrence of CHDs in children and ...periconceptional occupational parental exposures to chemicals.
METHODS
In an age-matched case–control study with standardized data collection at c. 15 months after birth, 424 mothers and 421 fathers of a child with CHD and 480 mothers and 477 fathers of a non-malformed child, filled out questionnaires on periconceptional general and job characteristics. A job exposure matrix, which links the information on job title and a description of work tasks to an expert judgement on exposure to chemicals in the workplace, was used.
RESULTS
The overall prevalence of occupational exposure to chemicals was 5.0 in cases and 6.2% in controls for mothers odds ratio (OR) adjusted = 0.92; 95% confidence interval (CI): 0.26–3.25, while 22.3 and 15.9% for fathers, respectively (OR adjusted = 1.23; 95% CI: 0.39–3.91). No association of maternal occupational exposure to chemicals with risk of CHDs was found. Paternal exposure to phthalates was associated with a higher incidence of CHDs in general (OR adjusted = 2.08; 95% CI: 1.27–3.40). Paternal exposure to phthalates was associated with perimembranous ventricular septal defect (OR adjusted = 2.84; 95% CI: 1.37–5.92), to polychlorinated compounds with atrioventricular septal defect (OR adjusted = 4.22; 95% CI: 1.23–14.42) and to alkylphenolic compounds with coarctation of the aorta (OR adjusted = 3.85; 95% CI: 1.17–12.67).
CONCLUSIONS
Periconceptional paternal (but not maternal) occupational exposure to certain chemicals is associated with an increased risk of CHDs in children. The results, however, must be interpreted cautiously as exposure probabilities are a crude measure of exposure.
BACKGROUND Most reproductive failures originate during the periconceptional period and are influenced by the age and the lifestyle of parents-to-be. We advance the hypothesis that these failures can ...arise as a partial consequence of derangements to one-carbon (1-C) metabolism (i.e. metabolic pathways that utilize substrates/cofactors such as methionine, vitamin B12, folate). 1-C metabolic pathways drive the synthesis of proteins, biogenic amines and lipids required for early growth, together with the synthesis and methylation of DNA and histones essential for the regulation of gene expression. We review how deficiencies in periconceptional 1-C metabolism affect fertility and development together with underlying mechanisms derived from animal studies. METHODS A literature search was performed using PubMed and bibliographies of all relevant original research articles and reviews. RESULTS We define 'periconception' as a 5-6-month period in women embracing oocyte growth, fertilization, conceptus formation and development to Week 10 of gestation (coinciding with the closure of the secondary palate in the embryo). During this period significant epigenetic modifications to chromatin occur that correspond with normal development. Subtle variations in 1-C metabolism genes and deficiencies in 1-C substrates/cofactors together with poor lifestyle, such as smoking and alcohol consumption, disturb 1-C metabolism and contribute to subfertility and early miscarriage and compromise offspring health. Procedures used in assisted reproduction can also disturb these metabolic pathways and contribute to poor pregnancy outcomes. CONCLUSIONS Evidence presented indicates that parental nutrition and other lifestyle factors during the periconceptional period can affect reproductive performance via 1-C metabolic pathways. This knowledge provides opportunities for treatment and prevention of reproductive failures and future non-communicable diseases.
Objective
To investigate whether first‐trimester maternal haemodynamic adaptation impacts placental, embryonic and fetal development as well as birth outcomes in pregnancies with and without ...placenta‐related complications.
Design
Prospective observational cohort.
Setting
A Dutch tertiary hospital.
Population
Two hundred and fourteen ongoing pregnancies.
Methods
At 7, 9 and 11 weeks of gestation, we assessed maternal haemodynamic adaptation (mean arterial blood pressure MAP, uterine artery UtA blood flow) and placental development (placental volume PV, uteroplacental vascular volume uPVV) using three‐dimensional power Doppler ultrasound volumes, and embryonic development (crown–rump length, embryonic volume). At 22 and 32 weeks of gestation, fetal development was assessed by estimated fetal weight. Birth outcomes (birthweight, placental weight) were extracted from medical records. Linear mixed modelling and linear regression analyses were applied.
Main outcome measures
Birthweight centile and placental weight.
Results
In placenta‐related complications (n= 55, 25.7%), reduced haemodynamic adaptation, i.e. higher UtA pulsatility index (PI) and resistance index (RI) trajectories, was associated with smaller increase in PV (β = −0.559, 95% CI −0.841 to −0.278, P< 0.001; β = −0.579, 95% CI −0.878 to −0.280, P< 0.001) and uPVV trajectories (UtA PI: β = −0.301, 95% CI −0.578 to −0.023, P= 0.034). At birth, reduced haemodynamic adaptation was associated with lower placental weight (UtA PI: β = −0.502, 95% CI −0.922 to −0.082, P= 0.022; UtA RI: β = −0.435, 95% CI −0.839 to −0.032, P= 0.036). In pregnancies without placenta‐related complications, higher MAP trajectories were positively associated with birthweight centile (β = 0.398, 95% CI 0.049–0.748, P= 0.025).
Conclusions
Reduced first‐trimester maternal haemodynamic adaptation impacts both placental size and vascularisation and birthweight centile, in particular in pregnancies with placenta‐related complications.
Tweetable
Reduced first‐trimester maternal haemodynamic adaptation to pregnancy impairs early placental development.
BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to ...update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.
Abstract Introduction Offspring exposed to preeclampsia (PE) show an increased risk of cardiovascular disease in adulthood. We hypothesize that this is mediated by a disturbed vascular development of ...the placenta, umbilical cord and fetus. Therefore, we investigated associations between early-onset PE (EOPE), late-onset PE (LOPE) and features of placental and newborn vascular health. Methods We performed a nested case-control study in The Rotterdam Periconceptional Cohort, including 30 PE pregnancies (15 EOPE, 15 LOPE) and 218 control pregnancies (164 uncomplicated controls, 54 complicated controls including 28 fetal growth restriction, 26 preterm birth) and assessed macroscopic and histomorphometric outcomes of the placenta and umbilical cord. Results A significant association was observed between PE and a smaller umbilical vein area and wall thickness, independent of gestational age and birth weight. In EOPE we observed significant associations with a lower weight, length and width of the placenta, length of the umbilical cord, and thickness and wall area of the umbilical vein and artery. These associations attenuated after gestational age and birth weight adjustment. In LOPE a significant association with a larger placental width and smaller umbilical vein wall thickness was shown, independent of gestational age and birth weight. Discussion. Our study suggests that PE is associated with a smaller umbilical cord vein area and wall thickness, independent of gestational age and birth weight, which may serve as a proxy of disturbed cardiovascular development in the newborn. Follow-up studies are needed to ultimately predict and lower the risk of cardiovascular disease in offspring exposed to PE.
BACKGROUND Maternal hyperhomocysteinemia is detrimental for reproduction, but the effects on embryo quality are unknown. The aim of this study was to investigate whether biomarkers of the ...homocysteine pathway are associated with in vitro fertilization (IVF) outcome. METHODS In a prospective study, we investigated biomarkers of the homocysteine pathway for associations with embryo quality and biochemical pregnancy in women undergoing IVF or intracytoplasmic sperm injection treatment (n = 181). In the treatment cycle, blood and monofollicular fluid samples were collected for determination of folate, cobalamin and total homocysteine (tHcy) concentrations. RESULTS Of all the women in the study, 67% used folic acid supplements. In blood, a significant correlation was established between high cobalamin and better embryo quality standardized adjusted regression coefficient: −0.17, 95% confidence interval (CI): −0.30, −0.01. In monofollicular fluid of non-supplemented women, high cobalamin correlated with better embryo quality (estimate: −0.87; 95% CI: −1.68, −0.06), whereas high tHcy resulted in poor embryo quality (estimate: 1.01; 95% CI: 0.08, 1.95). However, in monofollicular fluid of supplemented women, high tHcy correlated with better embryo quality (estimate: −0.58; 95% CI: −1.12, −0.04). In the total group, a 2-fold increase of monofollicular fluid folate corresponded with a 3.3 times higher chance (95% CI: 1.09, 9.71) of achieving pregnancy. CONCLUSIONS An optimal homocysteine pathway in follicular fluid is associated with a better embryo quality and chance of pregnancy.
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