Maternal lipid levels in early pregnancy as a predictor of childhood lipid levels: a prospective cohort study.

BACKGROUND: Maternal lipid levels in early pregnancy are associated with maternal health and foetal growth. It is however unclear if maternal lipids in early pregnancy can be used to predict childhood lipid levels. The aim of this study is to assess the association between maternal and offspring childhood lipid levels, and to investigate the influence of maternal BMI and diet on these associations. METHODS: This study included 2692 women participating in the Generation R study, an ongoing population-based prospective cohort study from early life onwards. Women with an expected delivery date between 2002 and 2006 living in Rotterdam, the Netherlands were included. Total cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL-c) were measured in early pregnancy (median 13.2 weeks [90% range 10.6; 17.1]). Low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated. Corresponding lipid measurements were determined in 2692 children at the age of 6 (median 6.0 years [90% range 5.7; 7.5]) and 1673 children 10 years (median 9.7 years [90% range 9.5; 10.3]). Multivariate linear regression analysis was used to examine the association between maternal lipid levels in early pregnancy and the corresponding childhood lipid measurements at the ages of 6 and 10 years while adjusting for confounders. RESULTS: Maternal lipid levels in early pregnancy are positively associated with corresponding childhood lipid levels 6 and 10 years after pregnancy, independent of maternal body mass index and diet. CONCLUSIONS: Maternal lipid levels in early pregnancy may provide an insight to the lipid profile of children years later. Gestational lipid levels may therefore be used as an early predictor of children's long-term health. Monitoring of these gestational lipid levels may give a window-of-opportunity to start early interventions to decrease offspring's lipid levels and possibly diminish their cardiovascular risk later in life. Future studies are warranted to investigate the genetic contribution on maternal lipid levels in pregnancy and lipid levels of their offspring years later.

Design and overview of the Origins of Alzheimer's Disease Across the Life course (ORACLE) study.

Brain development and deterioration across the lifespan are integral to the etiology of late-life neurodegenerative disease. Factors that influence the health of the adult brain remain to be elucidated and include risk factors, protective factors, and factors related to cognitive and brain reserve. To address this knowledge gap we designed a life-course study on brain health, which received funding through the EU ERC Programme under the name Origins of Alzheimer's Disease Across the Life course (ORACLE) Study. The ORACLE Study is embedded within Generation R, a prospective population-based cohort study of children and their parents, and links this with the Rotterdam Study, a population-based study in middle-aged and elderly persons. The studies are based in Rotterdam, the Netherlands. Generation R focuses on child health from fetal life until adolescence with repeated in-person examinations, but has also included data collection on the children's parents. The ORACLE Study aims to extend the parental data collection in nearly 2000 parents with extensive measures on brain health, including neuroimaging, cognitive testing and motor testing. Additionally, questionnaires on migraine, depressive symptoms, sleep, and neurological family history were completed. These data allow for the investigation of longitudinal influences on adult brain health as well as intergenerational designs involving children and parents. As a secondary focus, the sampling is enriched by mothers (n = 356) that suffered from hypertensive disorders during pregnancy in order to study brain health in this high-risk population. This article provides an overview of the rationale and the design of the ORACLE Study.

Hypertensive Disorders of Pregnancy and Cognitive Impairment: A Prospective Cohort Study.

OBJECTIVE: To determine the association between hypertensive disorders of pregnancy (HDP) and cognitive impairment 15 years after pregnancy, we measured cognitive performance in 115 women with a history of HDP and in 481 women with a previous normotensive pregnancy. METHODS: This was a nested cohort study embedded in a population-based prospective cohort from early pregnancy onwards. Cognitive function was assessed with cognitive tests 15 years after the index pregnancy (median 14.7 years, 90% range [13.9-16.1]). Cognitive performance was measured in different cognitive domains: executive function, processing speed, verbal memory, motor function, and visuospatial ability. A global cognition factor (g-factor) was derived from principal component analysis. RESULTS: Of the women with HDP, 80 (69.6%) had gestational hypertension (GH) and 35 (30.4%) had preeclampsia. Women with HDP had a lower g-factor than women with a previous normotensive pregnancy (mean -0.22, 90% range [-2.06-1.29]). HDP was negatively associated with the 15-word learning test: immediate recall (-0.25, 95% CI [-0.44 to -0.06]) and delayed recall (-0.30, 95% CI [-0.50 to -0.10]). Women with GH perform significantly worse on their 15-word learning test than women with a previous normotensive pregnancy. CONCLUSION: A history of HDP is independently associated with poorer working memory and verbal learning 15 years after pregnancy. This association is mainly driven by women with GH. Clinicians and women who experienced HDP should be aware of this risk.

Gestational lipid profile as an early marker of metabolic syndrome in later life: a population-based prospective cohort study.

BACKGROUND: In pregnancy lipid levels increase with gestation resembling an atherogenic lipid profile. Currently it is unclear whether gestational lipid levels are associated with an adverse cardiovascular risk profile later in life. The aim of this study is to assess the association between gestational lipid levels and lipid levels and prevalence of the metabolic syndrome (MS) six years after pregnancy. METHODS: In plasma of 3510 women from the Generation R Study; a prospective population-based cohort, we measured lipid levels (total cholesterol, triglycerides and high-density lipoprotein cholesterol [HDL-c]), and low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated in early pregnancy (median 13.2 weeks, 90% range [10.5 to 17.1]) and six years after pregnancy (median 6.5 years, 90% range [6.2 to 7.8]). MS was assessed six years after pregnancy according to the NCEP/ATP3 criteria. We also examined the influence of pregnancy complications on these associations. RESULTS: Gestational lipid levels were positively associated with corresponding lipid levels six years after pregnancy, independent of pregnancy complications. Six years after pregnancy the prevalence of MS was 10.0%; the prevalence was higher for women with a previous placental syndrome (13.5%). Gestational triglycerides and remnant cholesterol in the highest quartile and HDL-c in the lowest quartile were associated with the highest risk for future MS, independent of smoking and body mass index. CONCLUSIONS: Gestational lipid levels provide an insight in the future cardiovascular risk profile of women in later life. Monitoring and lifestyle intervention could be indicated in women with an unfavorable gestational lipid profile to optimize timely cardiovascular risk prevention.

Maternal lipid profile in early pregnancy is associated with foetal growth and the risk of a child born large-for-gestational age: a population-based prospective cohort study : Maternal lipid profile in early pregnancy and foetal growth.

BACKGROUND: Lipids such as cholesterol and triglycerides play an important role in both maternal and foetal energy metabolism. Little is known about maternal lipid levels in pregnancy and their effect on foetal growth. The aim of this study was to assess maternal lipid levels, foetal growth and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA). METHODS: We included 5702 women from the Generation R Study, a prospective population-based cohort. Maternal lipid levels (total cholesterol, triglycerides and high-density lipoprotein cholesterol [HDL-c]) were measured in early pregnancy (median 13.4 weeks, 90% range [10.5 to 17.2]). Low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated. Foetal growth was measured repeatedly by ultrasound. Information on birth anthropometrics was retrieved from medical records. A birth weight below the 10th percentile was defined as SGA and above the 90th percentile as LGA. RESULTS: Maternal triglyceride and remnant cholesterol levels were associated with increased foetal head circumference and abdominal circumference growth rates. Triglycerides and remnant cholesterol were positively associated with the risk of LGA (odds ratio [OR] 1.11, 95% confidence interval [CI] [1.01 to 1.22] and OR 1.11, 95% CI [1.01 to 1.23], respectively). These associations were independent of maternal pre-pregnancy body mass index, but not maternal glucose levels. We observed no association between maternal lipids in early pregnancy and SGA. CONCLUSIONS: Our study suggests a novel association of early pregnancy triglyceride and remnant cholesterol levels with foetal growth, patterns of foetal growth and the risk of LGA. Future studies are warranted to explore clinical implication possibilities.

Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis.

BACKGROUND: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placenta-mediated complications could exist. OBJECTIVE: To determine the association of fetal sex with multiple maternal pregnancy complications. SEARCH STRATEGY: Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies. SELECTION CRITERIA: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies. DATA COLLECTION AND ANALYSES: Data were extracted by 2 independent reviewers using a predesigned data collection form. MAIN RESULTS: From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition. CONCLUSION: This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus. FUNDING: None.

Maternal cardiovascular adaptation to twin pregnancy: a population-based prospective cohort study.

BACKGROUND: In women with singleton pregnancies, maternal adaptation is considered a stress test for later life cardiovascular disease. The aim of this study was to assess maternal adaptation in women with twin pregnancies compared to women carrying singletons during and after pregnancy. METHODS: This was a population based prospective cohort study of 91 women with twin pregnancies and 8107 women carrying singletons. The association of twin pregnancy and maternal adaptation was examined using regression analyses. In pregnancy, we measured soluble fms-like tyrosine kinase-1 (sFLT-1), placental growth (PGF) factor, systolic (SBP) and diastolic blood pressure (DBP), and the occurrence of pre-eclampsia (PE). After pregnancy, measurements were obtained on SBP and DBP, cardiac function, retinal calibres, intima media thickness and distensibility of the common carotid artery. RESULTS: sFLT-1 and PGF concentrations were higher in early (13.4 weeks) and mid-pregnancy (20.4 weeks) in women with twin pregnancies compared to women with singleton pregnancies. Women with twin pregnancies had a different DBP pattern in pregnancy. Women with twin pregnancies were more likely to have PE (odds ratio 3.63; 95% CI [1.76 to 7.48]). Six and ten years after pregnancy, no differences in maternal adaptation were observed. CONCLUSIONS: Women with twin pregnancies show an altered adaptation during pregnancy compared to women with singleton pregnancies. This is associated with a substantially increased incidence of PE, but does not lead to persistent altered maternal adaptation years after pregnancy.

Is maternal lipid profile in early pregnancy associated with pregnancy complications and blood pressure in pregnancy and long term postpartum?

BACKGROUND: An atherogenic lipid profile is a risk factor for the initiation and progression of atherosclerosis. This ultimately leads to cardiovascular disease. Women with a history of hypertensive disorders of pregnancy are at increased risk of sustained hypertension and cardiovascular disease later in life. Currently it is unclear whether dyslipidemia during pregnancy contributes to these risks. OBJECTIVE: The objective of the study was to determine the associations between early pregnancy maternal lipid profile, hypertensive disorders of pregnancy, and blood pressure during and years after pregnancy. STUDY DESIGN: We included 5690 women from the Generation R Study, an ongoing population-based prospective birth cohort. Two hundred eighteen women (3.8%) developed gestational hypertension and 139 (2.4%) preeclampsia. A maternal lipid profile consisting of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, remnant cholesterol, and non-high-density lipoprotein cholesterol was determined in early pregnancy (median, 13.4 weeks of gestation). Systolic and diastolic blood pressures were measured in early, mid-, and late pregnancy and 6 and 9 years after pregnancy. RESULTS: Triglycerides and remnant cholesterol in early pregnancy were positively associated with preeclampsia. Maternal lipid levels in early pregnancy were not associated with gestational hypertension. Total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and especially triglycerides and remnant cholesterol were positively associated with blood pressure in pregnancy and 6 and 9 years after pregnancy. Triglycerides and remnant cholesterol are positively associated with sustained hypertension 6 and 9 years after pregnancy. CONCLUSION: An atherogenic lipid profile in early pregnancy reflecting impaired triglyceride-rich lipoprotein metabolism is independently associated with preeclampsia and blood pressure throughout pregnancy but also with sustained hypertension long term postpartum. Lipid levels in early pregnancy may help to identify women at risk for future hypertension and perhaps also women at risk for future cardiovascular disease.

Electroejaculation as a method of fertility preservation in boys diagnosed with cancer: a single-center experience and review of the literature.

OBJECTIVE: To evaluate the feasibility of electroejaculation to perform semen cryopreservation in pubertal boys before gonadotoxic therapy and to review the literature on this topic. DESIGN: Retrospective cohort study and review of the literature. SETTING: Academic children's hospital. PATIENT(S): Boys diagnosed with cancer to whom sperm cryopreservation was offered before the start of gonadotoxic therapy. INTERVENTION(S): We studied the outcome of electroejaculation, including patient characteristics, hormone levels, and pretreatment semen parameters. MAIN OUTCOME MEASURE(S): Semen cryopreservation. RESULT(S): Pretreatment semen samples were obtained by masturbation in 106/114 boys with cancer, of which 78/106 were adequate for preservation. Electroejaculation was offered to 11 boys, of which three of 11 samples appeared adequate for preservation. Reviewing all reported electroejaculation cases in children with cancer in the literature, 13/29 (45%) cases were successful. Testosterone levels were higher in patients with successful sperm yield obtained by electroejaculation (median, 8.3 nmol/L [5.2-42.4] in successful harvests, vs. median 1.7 nmol/L [0.01-17.9] in unsuccessful harvests). CONCLUSION(S): Semen cryopreservation should be offered to all pubertal boys diagnosed with cancer. If masturbation fails, electroejaculation can be considered as a useful option for semen cryopreservation and leads to adequate material for cryopreservation in about half of the cases.