Real-world treatment patterns and outcomes using terlipressin in 203 patients with the hepatorenal syndrome.

BACKGROUND: Hepatorenal syndrome and acute kidney injury are common complications of decompensated cirrhosis, and terlipressin is recommended as first-line vasoconstrictor therapy. However, data on its use outside of clinical trials are lacking. AIMS: To assess practice patterns and outcomes around vasoconstrictor use for hepatorenal syndrome in UK hospitals. METHODS: This was a multicentre chart review study. Data were extracted from medical records of patients diagnosed with hepatorenal syndrome and treated by vasoconstrictor drugs between January 2013 and December 2017 at 26 hospitals in the United Kingdom. The primary outcome was improvement of kidney function, defined as complete response (serum creatinine improved to ≤1.5 mg/dL), partial response (serum creatinine reduction of ≥20% but >1.5 mg/dL) and overall response (complete or partial response). Other outcomes included need for dialysis, mortality, liver transplantation and adverse events. RESULTS: Of the 225 patients included in the analysis, 203 (90%) were treated with terlipressin (median duration, 6 days; range: 2-24 days). Mean (±standard deviation) serum creatinine at vasopressor initiation was 3.25 ± 1.64 mg/dL. Terlipressin overall response rate was 73%. Overall response was higher in patients with mild acute kidney injury (baseline serum creatinine <2.25 mg/dL), compared to those with moderate (serum creatinine ≥2.25 mg/dL and <3.5 mg/dL) or severe (serum creatinine ≥3.5 mg/dL). Ninety-day survival was 86% for all patients (93% for overall responders vs 66% for treatment nonresponders, P < 0.0001). CONCLUSION: Terlipressin is the most commonly prescribed vasoconstrictor for patients with hepatorenal syndrome in the United Kingdom. Treatment with terlipressin in patients with less severe acute kidney injury (serum creatinine <2.25 mg/dL) was associated with higher treatment responses, and 90-day survival.

Preconception use of cART by HIV-positive pregnant women increases the risk of infants being born small for gestational age.

BACKGROUND: The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands. MATERIALS AND METHODS: We included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015. Multivariate logistic regression analysis for single and multiple pregnancies was used to evaluate predictors of small for gestational age (SGA, birth weight <10th percentile for gestational age), low birth weight and preterm delivery. RESULTS: A total of 1392 children born to 1022 mothers were included. Of these, 331 (23.8%) children were SGA. Women starting cART before conception had an increased risk of having a SGA infant compared to women starting cART after conception (OR 1.35, 95% CI 1.03-1.77, p = 0.03). The risk for SGA was highest in women who started a protease inhibitor-(PI) based regimen prior to pregnancy, compared with women who initiated PI-based cART during pregnancy. While the association of preterm delivery and preconception cART was significant in univariate analysis, on multivariate analysis only a non-significant trend was observed (OR 1.39, 95% CI 0.94-1.92, p = 0.06) in women who had started cART before compared to after conception. In multivariate analysis, the risk of low birth weight (OR 1.34, 95% CI 0.94-1.92, p = 0.11) was not significantly increased in women who had started cART prior to conception compared to after conception. CONCLUSION: In our cohort of pregnant HIV-positive women, the use of cART prior to conception, most notably a PI-based regimen, was associated with intrauterine growth restriction resulting in SGA. Data showed a non-significant trend in the risk of PTD associated with preconception use of cART compared to its use after conception. More studies are needed with regard to the mechanisms taking place in the placenta during fetal growth in pregnant HIV-positive women using cART. It will only be with this knowledge that we can begin to understand the potential impact of HIV and cART on the fetus, in order to be able to determine the optimal individualised drug regimen for HIV-infected women of childbearing age.

Estimating the predictive ability of genetic risk models in simulated data based on published results from genome-wide association studies.

BACKGROUND: There is increasing interest in investigating genetic risk models in empirical studies, but such studies are premature when the expected predictive ability of the risk model is low. We assessed how accurately the predictive ability of genetic risk models can be estimated in simulated data that are created based on the odds ratios (ORs) and frequencies of single-nucleotide polymorphisms (SNPs) obtained from genome-wide association studies (GWASs). METHODS: We aimed to replicate published prediction studies that reported the area under the receiver operating characteristic curve (AUC) as a measure of predictive ability. We searched GWAS articles for all SNPs included in these models and extracted ORs and risk allele frequencies to construct genotypes and disease status for a hypothetical population. Using these hypothetical data, we reconstructed the published genetic risk models and compared their AUC values to those reported in the original articles. RESULTS: The accuracy of the AUC values varied with the method used for the construction of the risk models. When logistic regression analysis was used to construct the genetic risk model, AUC values estimated by the simulation method were similar to the published values with a median absolute difference of 0.02 [range: 0.00, 0.04]. This difference was 0.03 [range: 0.01, 0.06] and 0.05 [range: 0.01, 0.08] for unweighted and weighted risk scores. CONCLUSIONS: The predictive ability of genetic risk models can be estimated using simulated data based on results from GWASs. Simulation methods can be useful to estimate the predictive ability in the absence of empirical data and to decide whether empirical investigation of genetic risk models is warranted.

[Biobanks and the return of results to donors]. / Biobanken en de terugkoppeling van onderzoeksbevindingen aan donoren.

Biobanks should return clinically significant and actionable research findings to donors who have given physical material to the biobank. Because the clinical significance of a research finding is hard to determine for the individual donor, a procedure to decide on clinical significance should be incorporated into a structure for the actual feedback of research results. Most published studies show that donors expect return of individual research results, but there is almost no experience with it. Explorative questionnaire-based research among Dutch biobanks from the BioBanking Medical Research Infrastructure (BBMRI.NL) shows that a substantial group of biobanks can return individual research findings from data analysis. On the basis of these experiences a return of results policy may be drafted that answers to the interests of donors and the possibilities of biobanks.

Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.

Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4 to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.

A common genetic variant at 15q25 modifies the associations of maternal smoking during pregnancy with fetal growth: the generation R study.

OBJECTIVE: Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics. METHODS: This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy. RESULTS: Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences -0.23 mm (95%CI -0.45 to -0.00) and -0.41 mm (95%CI -0.69 to -0.13), respectively] and a smaller birth length [difference -2.61 mm (95%CI -5.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference -33 grams (95%CI -55 to -10)], and tended to be associated with birth weight [difference -38 grams (95%CI -89 to 13)]. This association persisted after adjustment for smoking quantity. CONCLUSIONS: Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene--fetal smoke exposure interactions.

Assessment of maternal smoking status during pregnancy and the associations with neonatal outcomes.

INTRODUCTION: Single assessment of smoking during pregnancy may lead to misclassification due to underreporting or failure of smoking cessation. We examined the percentage of mothers who were misclassified in smoking status based on single assessment, as compared with repeated assessment, and whether this misclassification leads to altered effect estimates for the associations between maternal smoking and neonatal complications. METHODS: This study was performed in 5,389 mothers participating in a prospective population-based cohort study in the Netherlands. Smoking status was assessed 3 times during pregnancy using questionnaires. Information on birth weight and neonatal complications was obtained from hospital records. RESULTS: For categorizing mothers per smoking status, Cohen's Kappa coefficient was .86 (p < .001) between single and repeated assessments. Of all mothers who reported nonsmoking or first trimester-only smoking in early pregnancy, 1.7% (70 of 4,141) and 33.7% (217 of 643), respectively, were reclassified to continued smoking based on repeated assessment. Younger, shorter lower educated mothers who had non-European ethnicity experienced more stress, consumed more alcohol, and did not use folic acid supplements had higher risk of underreporting their smoking status or failure of smoking cessation. Marginal differences were found on the associations of maternal smoking with neonatal complications between single or repeated assessment. CONCLUSIONS: Our results suggest that single assessment of smoking during pregnancy leads to underestimation of the continued smoking prevalence, especially among mothers who reported quitting smoking in first trimester. However, this underestimation does not materially change the effect estimates for the associations between maternal smoking and neonatal outcomes.

Folic acid supplements modify the adverse effects of maternal smoking on fetal growth and neonatal complications.

Maternal smoking during pregnancy leads to increased risks of neonatal complications. The use of folic acid supplements might reduce the adverse effects of smoking. We examined whether folic acid supplement use modifies the associations of maternal smoking with first trimester plasma homocysteine concentrations, fetal growth characteristics, and risks of neonatal complications. The associations were studied in 6294 mothers participating in a prospective population-based cohort study in The Netherlands. Main outcomes measurements were first trimester plasma homocysteine concentrations, fetal growth characteristics, and neonatal complications, including preterm birth, low birth weight, and small-size-for-gestational-age. Continued maternal smoking was associated with higher first trimester plasma homocysteine concentrations [difference 0.52 µmol/L (95% range = 0.20, 2.14)], lower third trimester fetal weight (difference -44 g (95% CI = -57, -31)], and birth weight [difference -148 g (95% CI = -179, -118)]. There were significant interactions between maternal smoking and folic acid supplements on all outcome measures (all P-interaction < 0.040). Among mothers who continued smoking during pregnancy, those who did not use folic acid supplements had the highest risk of delivering a child with low birth weight [OR = 3.45 (95% CI = 1.25, 9.54)] compared to those who did use periconceptional folic acid supplements. No significant effects were observed for the risks of preterm birth and small-size-for-gestational-age at birth. Our results suggest that some adverse effects of maternal smoking on fetal growth and neonatal outcomes might be reduced by the use of folic acid supplements. The observed interaction seems to be mainly driven by smoking in the first trimester only.

Blood pressure in different gestational trimesters, fetal growth, and the risk of adverse birth outcomes: the generation R study.

Researchers have suggested that maternal hypertensive disorders during pregnancy affect fetal growth. The authors examined the associations between systolic and diastolic blood pressures in different trimesters of pregnancy and both repeatedly measured fetal growth characteristics and the risks of adverse birth outcomes. The present study (2001-2005) was performed in 8,623 women who were participating in a population-based prospective cohort study from fetal life onwards. Blood pressure and fetal growth characteristics were assessed in each trimester of pregnancy. Information on hypertensive complications and adverse birth outcomes was obtained from medical records. The results suggested that higher blood pressure was associated with smaller fetal head circumference and femur length, as well as lower fetal weight from the third trimester onward. An increase in blood pressure from the second trimester to the third trimester was associated with an increased risk of adverse birth outcomes. Compared with women who did not experience hypertension during pregnancy, women with preeclampsia had increased risks of having children who were preterm (odds ratio = 5.89, 95% confidence interval: 2.63, 13.14), had a low birth weight (odds ratio = 8.94, 95% confidence interval: 6.19, 12.90), or were small for their gestational age (odds ratio = 5.03, 95% confidence interval: 3.31, 7.62). The present results suggest that higher maternal blood pressure is associated with impaired fetal growth during the third trimester of pregnancy and increased risks of adverse birth outcomes.

Blood pressure tracking during pregnancy and the risk of gestational hypertensive disorders: the Generation R Study.

AIMS: Blood pressure tracking can be used to examine the predictability of future values by early measurements. In a population-based prospective cohort study, among 8482 pregnant women, we examined whether blood pressure in early pregnancy tracks to third trimester and whether this tracking is influenced by maternal characteristics and is associated with the risk of gestational hypertensive disorders. METHODS AND RESULTS: Blood pressure was measured in each trimester of pregnancy. Information about doctor-diagnosed pregnancy-induced hypertension and preeclampsia was obtained from medical records. Correlation coefficients between first and third trimester for systolic and diastolic blood pressure were 0.47 and 0.46, respectively. The odds ratio for staying in the highest tertile from first to third trimester for systolic blood pressure was 3.09 [95% confidence interval (CI): 2.73, 3.50] and for diastolic blood pressure 3.28 (95% CI: 2.90, 3.69). Blood pressure tracking coefficients were lower in younger, shorter, and non-European women and in women with higher gestational weight gain. Systolic and diastolic blood pressure changes from second to third trimester, but not from first to second trimester, were positively associated with the risks of pregnancy-induced hypertension and preeclampsia. CONCLUSION: Blood pressure tracks moderately during pregnancy and is influenced by maternal characteristics. Second to third trimester increases in systolic and diastolic blood pressure are associated with an increased risk of gestational hypertensive disorders.

Major dietary patterns and blood pressure patterns during pregnancy: the Generation R Study.

OBJECTIVE: We sought to evaluate associations between dietary patterns and systolic blood pressure (SBP) and diastolic blood pressure during pregnancy. STUDY DESIGN: This was a prospective study of 3187 pregnant women. Participants completed a food-frequency questionnaire in early pregnancy. The Mediterranean dietary pattern, comprising high intake of vegetables, vegetable oils, pasta, fish, and legumes, and the Traditional dietary pattern, comprising high intake of meat and potatoes, were identified using factor analysis. RESULTS: A higher SBP was observed among mothers with high Traditional pattern adherence. Low adherence to the Mediterranean pattern was also associated with higher SBP but only in early and mid pregnancy. A higher diastolic blood pressure throughout pregnancy was observed in mothers with high adherence to the Traditional pattern and low adherence to the Mediterranean pattern. These effect estimates were most pronounced in mid pregnancy. CONCLUSION: Low adherence to a Mediterranean and high adherence to a Traditional dietary pattern is associated with a higher blood pressure in pregnancy.

Maternal age during pregnancy is associated with third trimester blood pressure level: the generation R study.

BACKGROUND: We hypothesized that hemodynamic adaptations related to pregnancy and ageing might be associated with differences in blood pressure levels during pregnancy between younger and older women. This might partly explain the increased risk of gestational hypertensive disorders with advanced maternal age. We examined the associations of maternal age with systolic and diastolic blood pressure in each trimester of pregnancy and the risks of gestational hypertensive disorders. METHODS: The study was conducted among 8,623 women participating in a population-based prospective cohort study from early pregnancy onwards. Age was assessed at enrolment. Blood pressure was measured in each trimester. Information about gestational hypertensive disorders was available from medical records. RESULTS: In second and third trimester, older maternal age was associated with lower systolic blood pressure (-0.9 mm Hg (95% confidence interval: -1.4, -0.3) and -0.6 mm Hg (95% confidence interval: -1.1, -0.02) per additional 10 maternal years, respectively). Older maternal age was associated with higher third trimester diastolic blood pressure (0.5 mm Hg (95% confidence interval: 0.04, 0.9) per additional 10 maternal years). Maternal age was associated with pregnancy-induced hypertension among overweight and obese women. CONCLUSION: Older maternal age is associated with lower second and third trimester systolic blood pressure, but higher third trimester diastolic blood pressure. These blood pressure differences seem to be small and within the physiological range. Maternal age is not consistently associated with the risks of gestational hypertensive disorders. Maternal body mass index might influence the association between maternal age and the risk of pregnancy-induced hypertension.

Maternal caffeine intake, blood pressure, and the risk of hypertensive complications during pregnancy. The Generation R Study.

BACKGROUND: Caffeine intake has been suggested to be associated with the risk of hypertension. Less is known about the associations of caffeine intake on maternal cardiovascular adaptations during pregnancy. We examined the associations of caffeine intake in different trimesters of pregnancy with repeatedly measured blood pressure and the risks of pregnancy-induced hypertension and pre-eclampsia in a population-based cohort of 7,890 pregnant women. METHODS: In each trimester caffeine intake and systolic and diastolic blood pressure were assessed by questionnaires and physical examinations, respectively. Information about hypertensive complications was obtained from medical records. RESULTS: Our longitudinal analyses revealed no significant differences for both systolic and diastolic blood pressure. The cross-sectional analyses showed that higher caffeine intake tended to be associated with higher systolic blood pressure in first and third trimester (P trend <0.05), but not in second trimester. Caffeine intake was not consistently associated with diastolic blood pressure levels, or the risk of pregnancy-induced hypertension. As compared to women with caffeine intake of <2 units/day, those using 2-3.9 units/day had a lower risk of pre-eclampsia (odds ratio 0.63 (95% confidence interval: 0.40, 0.96)). CONCLUSIONS: Higher caffeine intake during pregnancy seems to be associated with elevated systolic blood pressure levels in first and third trimester, but not with diastolic blood pressure levels. We did not find evidence of significant adverse associations of caffeine intake on maternal cardiovascular adaptations during pregnancy. The unexpected finding of a possible protective association with moderate caffeine intake deserves further investigation.

Maternal smoking and blood pressure in different trimesters of pregnancy: the Generation R study.

OBJECTIVE: Smoking during pregnancy is a risk factor for various adverse birth outcomes but lowers the risk of preeclampsia. Cardiovascular adaptations might underlie these associations. We examined the associations of smoking in different trimesters of pregnancy with repeatedly measured blood pressure and the risks of preeclampsia and pregnancy-induced hypertension in a low-risk population-based cohort of 7106 pregnant women. METHODS: This study was embedded in a population-based prospective cohort study from early pregnancy onwards. Smoking and systolic and diastolic blood pressures were assessed by questionnaires and physical examinations in each trimester of pregnancy. Information about preeclampsia and pregnancy-induced hypertension was obtained from medical records. RESULTS: Compared to nonsmoking women, both first-trimester-only and continued smoking were associated with a steeper increase for systolic blood pressure and a lowest mid-pregnancy level and steeper increase thereafter for diastolic blood pressure throughout pregnancy. We did not find any significant associations in risk of preeclampsia for first-trimester-only smoking (odds ratio of 1.28, 95% confidence interval 0.74, 2.21) and continued smoking (odds ratio of 0.83, 95% confidence interval 0.50, 1.36), respectively. CONCLUSIONS: Our results suggest that both first-trimester-only and continued smoking are associated with persistent maternal cardiovascular adaptations during pregnancy. Strategies for prevention of smoking during pregnancy should be focused on the preconception period. The effects of early and late-pregnancy smoking on the risk of preeclampsia should be further explored. Our results should be carefully interpreted to the general population of pregnant women.

Associations of light and moderate maternal alcohol consumption with fetal growth characteristics in different periods of pregnancy: the Generation R Study.

BACKGROUND: Excessive alcohol consumption during pregnancy has adverse effects on fetal growth and development. Less consistent associations have been shown for the associations of light-to-moderate maternal alcohol consumption during pregnancy with health outcomes in the offspring. Therefore, we examined the associations of light-to-moderate maternal alcohol consumption with various fetal growth characteristics measured in different periods of pregnancy. METHODS: This study was based on 7333 pregnant women participating in a population-based cohort study. Alcohol consumption habits and fetal growth were assessed in early (gestational age <17.9 weeks), mid- (gestational age 18-24.9 weeks) and late pregnancy (gestational age > or =25 weeks). We assessed the effects of different categories of alcohol consumption (no; less than one drink per week; one to three drinks per week; four to six drinks per week; one drink per day and two to three drinks per day) on repeatedly measured fetal head circumference, abdominal circumference and femur length. RESULTS: In total, 37% of all mothers continued alcohol consumption during pregnancy, of whom the majority used less than three drinks per week. We observed no differences in growth rates of fetal head circumference, abdominal circumference or femur length between mothers with and without continued alcohol consumption during pregnancy. Compared with mothers without alcohol consumption, mothers with continued alcohol consumption during pregnancy had an increased fetal weight gain [difference 0.61 g (95% confidence interval: 0.18, 1.04) per week]. Cross-sectional analyses in mid- and late pregnancy showed no consistent associations between the number of alcoholic consumptions and fetal growth characteristics. All analyses were adjusted for potential confounders. CONCLUSIONS: Light-to-moderate maternal alcohol consumption during pregnancy does not adversely affect fetal growth characteristics. Further studies are needed to assess whether moderate alcohol consumption during pregnancy influences organ growth and function in postnatal life.

Maternal caffeine intake from coffee and tea, fetal growth, and the risks of adverse birth outcomes: the Generation R Study.

BACKGROUND: Caffeine is a widely used and accepted pharmacologically active substance. The effect of caffeine intake during pregnancy on fetal growth and development is still unclear. OBJECTIVE: We examined the associations of maternal caffeine intake, on the basis of coffee and tea consumption, with fetal growth characteristics measured in each trimester of pregnancy and the risks of adverse birth outcomes. DESIGN: Associations were studied in 7346 pregnant women participating in a population-based prospective cohort study from early pregnancy onward in the Netherlands (2001-2005). Caffeine intake in the first, second, and third trimesters was on the basis of coffee and tea consumption and was assessed by questionnaires. Fetal growth characteristics were repeatedly measured by ultrasound. Information about birth outcomes was obtained from hospital records. RESULTS: We observed no consistent associations of caffeine intake with fetal head circumference or estimated fetal weight in any trimester. Higher caffeine intake was associated with smaller first-trimester crown-rump length, second- and third-trimester femur length, and birth length (P for trend <0.05). Offspring of mothers who consumed > or =6 caffeine units/d tended to have increased risks of small-for-gestational-age infants at birth. CONCLUSIONS: Our results suggest that caffeine intake of > or =6 units/d during pregnancy is associated with impaired fetal length growth. Caffeine exposure might preferentially adversely affect fetal skeletal growth. Further studies are needed to assess these associations in non-European populations and to assess the postnatal consequences.

Maternal calcium intake during pregnancy and blood pressure in the offspring at age 3 years: a follow-up analysis of the Project Viva cohort.

A previous analysis of the Project Viva cohort (eastern Massachusetts, 1999-2002 recruitment) found an association between higher second-trimester supplemental maternal calcium intake and lower systolic blood pressure in offspring at 6 months. The authors analyzed 5,527 systolic blood pressure measurements from 1,173 mother-child pairs from this same cohort when the children were aged 3 years. They estimated the change in offspring blood pressure for a 500-mg difference in maternal total, dietary-only, and supplemental-only calcium intake during the first 2 trimesters of pregnancy. Mean daily total calcium intake was 1,311 mg (standard deviation, 421) in the first trimester and 1,440 mg (standard deviation, 386) in the second trimester. Mean systolic blood pressure of the offspring at age 3 years was 92.1 mm Hg (standard deviation, 10.3). None of the maternal calcium intake measures during the first and second trimesters was associated with systolic blood pressure in the offspring. For example, for each 500-mg increment in maternal total elemental calcium intake in the second trimester, child's 3-year systolic blood pressure was 0.1 mm Hg lower (95% confidence interval: -0.9, 0.6). Maternal calcium intake during pregnancy was not associated with offspring blood pressure at the age of 3 years.

The Generation R Study Biobank: a resource for epidemiological studies in children and their parents.

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. In total, 9,778 mothers were enrolled in the study. Prenatal and postnatal data collection is conducted by physical examinations, questionnaires, interviews, ultrasound examinations and biological samples. Major efforts have been conducted for collecting biological specimens including DNA, blood for phenotypes and urine samples. In this paper, the collection, processing and storage of these biological specimens are described. Together with detailed phenotype measurements, these biological specimens form a unique resource for epidemiological studies focused on environmental exposures, genetic determinants and their interactions in relation to growth, health and development from fetal life onwards.

Moderate alcohol consumption during pregnancy and the risk of low birth weight and preterm birth. The generation R study.

PURPOSE: To examine the associations of alcohol consumption in different periods of pregnancy with the risks of low birth weight and preterm birth. METHODS: This study was based on 7141 subjects participating in a population-based prospective cohort study from early pregnancy. Alcohol consumption was assessed in early, mid, and late pregnancy. Birth outcomes were birth weight in grams, low birth weight (<2500 g), small size for gestational age at birth (< -2 standard deviation scores) and preterm birth (gestational age <37 weeks). RESULTS: Overall, alcohol consumption during pregnancy was not associated with adverse birth outcomes. However, dose-response analyses showed tendencies toward adverse effects of average consumption of 1 or more alcoholic drinks per day in early pregnancy on birth weight (difference -129 g [95% confidence interval (CI): -271, 12]), low birth weight (adjusted odds ratio [aOR] 4.81 [95% CI: 1.10, 21.08]), small size for gestational age at birth (aOR 1.45 [95% CI: 0.33, 6.44]) and preterm birth (aOR 2.51 [95% CI: 0.92, 6.81]). Similar effects were found in late pregnancy. CONCLUSION: Average consumption of one or more but not less than one alcoholic drink per day in early or late pregnancy seems to be associated with adverse birth outcomes in the offspring.