Pre-eclampsia, Soluble fms-like Tyrosine Kinase 1, and the Risk of Reduced Thyroid Function: Nested Case-Control and Population Based Study

Objective: To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy. Design: Nested case-control study during pregnancy and population based follow-up study after pregnancy. Setting: Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous women in the United States during 1992-5, and a Norwegian population based study (Nord-Trondelag Health Study or HUNT-2) during 1995-7 with linkage to the medical birth registry of Norway. Participants: All 141 women (cases) in the Calcium for Pre-eclampsia Prevention trial with serum measurements before 21 weeks’ gestation (baseline) and after onset of pre-eclampsia (before delivery), 141 normotensive controls with serum measurements at similar gestational ages, and 7121 women in the Nord-Trondelag Health Study whose first birth had occurred in 1967 or later and in whom serum levels of thyroid stimulating hormone had been subsequently measured. Main outcome measures: Thyroid function tests and human chorionic gonadotrophin and soluble fms-like tyrosine kinase 1 concentrations in the Calcium for Pre-eclampsia Prevention cohort and odds ratios for levels of thyroid stimulating hormone above the reference range, according to pre-eclampsia status in singleton pregnancies before the Nord-Trondelag Health Study. Results: In predelivery specimens of the Calcium for Pre-eclampsia Prevention cohort after the onset of pre-eclampsia, thyroid stimulating hormone levels increased 2.42 times above baseline compared with a 1.48 times increase in controls. The ratio of the predelivery to baseline ratio of cases to that of the controls was 1.64 (95% confidence interval 1.29 to 2.08). Free triiodothyronine decreased more in the women with pre-eclampsia than in the controls (case ratio to control ratio 0.96, 95% confidence interval 0.92 to 0.99). The predelivery specimens but not baseline samples from women with pre-eclampsia were significantly more likely than those from controls to have concentrations of thyroid stimulating hormone above the reference range (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4). Both in women who developed pre-eclampsia and in normotensive controls the increase in thyroid stimulating hormone concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1 (P for trend 0.002 and 3.5 mIU/l). In particular, they were more likely to have high concentrations of thyroid stimulating hormone without thyroid peroxidase antibodies (adjusted odds ratio 2.6, 95% confidence interval 1.3 to 5.0), suggesting hypothyroid function in the absence of an autoimmune process. This association was especially strong (5.8, 1.3 to 25.5) if pre-eclampsia had occurred in both the first and the second pregnancies. Conclusion: Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later years

Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study

Objective To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy

Does Pregnancy Alter Life Course Lipid Trajectories?:Evidence from the HUNT Study in Norway

We examined the association between pregnancy and life-course lipid trajectories. Linked data from the Nord-Trøndelag Health Study and the Medical Birth Registry of Norway yielded 19,987 parous and 1,625 nulliparous women. Using mixed-effects spline models, we estimated differences in nonfasting lipid levels from before to after first birth in parous women and between parous and nulliparous women. HDL cholesterol (HDL-C) dropped by −4.2 mg/dl (95% CI: −5.0, −3.3) from before to after first birth in adjusted models, a 7% change, and the total cholesterol (TC) to HDL-C ratio increased by 0.18 (95% CI: 0.11, 0.25), with no change in non-HDL-C or triglycerides. Changes in HDL-C and the TC/HDL-C ratio associated with pregnancy persisted for decades, leading to altered life-course lipid trajectories. For example, parous women had a lower HDL-C than nulliparous women at the age of 50 years (−1.4 mg/dl; 95% CI: −2.3, −0.4). Adverse changes in lipids were greatest after first birth, with small changes after subsequent births, and were larger in women who did not breastfeed. Findings suggest that pregnancy is associated with long-lasting adverse changes in HDL-C, potentially setting parous women on a more atherogenic trajectory than prior to pregnancy

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis : the CARTA consortium

Peer reviewe

Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers

Peer reviewe

Heavier smoking may lead to a relative increase in waist circumference : evidence for causal relationship from a Mendelian iandomisation meta-analysis. The CARTA consortium

Objectives: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes. Participants: 148 731 current, former and neversmokers of European ancestry aged >= 16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). Primary outcome measures: Waist and hip circumferences, and waist-hip ratio. Results: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% Cl -0.57% to - 0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% Cl - 0.42% to -0.19), -0.08% (-0.19% to 0.03%) and - 0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele. Conclusions: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.Peer reviewe

Does regular exercise during pregnancy influence lumbopelvic pain? A randomized controlled trial

Objective. To study lumbopelvic pain in women randomized to a regular exercise program during pregnancy in comparison to women receiving standard antenatal care. Design. A two-armed, two-center, randomized controlled trial. Setting. St Olavs Hospital, Trondheim University Hospital and Stavanger University Hospital. Population. A total of 855 pregnant women were randomized to intervention or control groups. Methods. The intervention was a 12 week exercise program, including aerobic and strengthening exercises, conducted between 20 and 36 weeks of pregnancy. One weekly group session was led by physiotherapists, and home exercises were encouraged twice a week. The control group received standard antenatal care. Main outcome measures. Self-reports of lumbopelvic pain and sick leave due to lumbopelvic pain. The data were analysed according to the intention-to-treat principle. Results. There were no significant differences between groups of women reporting lumbopelvic pain at 36 weeks (74 vs. 75%, p=0.76). The proportion of women on sick leave due to lumbopelvic pain was lower in the intervention group (22% vs 31%, p=0.01). Conclusions. Exercise during pregnancy does not influence the prevalence of lumbopelvic pain, but women offered a regular exercise course seem to handle the disorder better

Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study.

Close to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings.Study population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses.Compared with a sibling born in week 37-41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population.Preterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings

A prospective study of screening for hypertensive disorders of pregnancy at 11-13 weeks in a Scandinavian population

ObjectiveTo investigate the prediction of preeclampsia and gestational hypertension using maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at gestational weeks 11-13 in a Scandinavian population with a medium to high prior risk for developing hypertensive disorders of pregnancy. DesignProspective screening study. SettingNational Center for Fetal Medicine, Trondheim, Norway. Population579 women who were nulliparous or had a previous history of preeclampsia or gestational hypertension. MethodsWomen were examined between 11(+0) and 13(+6)weeks, with interviews for maternal characteristics and measurements of MAP, UtAPI, PAPP-A and PlGF. The tests were evaluated separately and in combined models with receiver operating characteristics (ROC) curves. Main outcome measuresPrediction of preeclampsia, severe preeclampsia and gestational hypertension. ResultsThe best model for severe preeclampsia (MAP+UtAPI+PlGF+PAPP-A) achieved an area under the ROC curve of 0.866 [95% confidence interval (95% CI) 0.756-0.976]. The best models for preeclampsia (MAP+UtAPI+age) achieved 0.738 (0.634-0.841), gestational hypertension (MAP) 0.820 (0.727-0.913) and hypertensive disorders in pregnancy overall (MAP+PlGF+age) 0.783 (0.709-0.856). Using the best model we could identify 61.5% (95% CI 31.6-86.1) of severe preeclampsia, 38.5% (95% CI 20.2-59.4) of preeclampsia and 42.9% (95% CI 21.8-66) of gestational hypertension at a fixed 10% false-positive rate. ConclusionsMaternal characteristics, MAP, UtAPI, PAPP-A and PlGF showed limited value as screening tests. Further research on biochemical and biophysical tests and algorithms combining these parameters is needed before first trimester screening for hypertensive disorders of pregnancy is included in antenatal care in Scandinavia