| 1. |
- Vogelezang, Suzanne, et al.
(författare)
-
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
|
|
| 2. |
- Abel, Marianne Hope, et al.
(författare)
-
Insufficient maternal iodine intake is associated with subfecundity, reduced foetal growth, and adverse pregnancy outcomes in the Norwegian Mother, Father and Child Cohort Study.
- 2020
-
Ingår i: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Severe iodine deficiency impacts fertility and reproductive outcomes. The potential effects of mild-to-moderate iodine deficiency are not well known. The aim of this study was to examine whether iodine intake was associated with subfecundity (i.e. >12months trying to get pregnant), foetal growth, and adverse pregnancy outcomes in a mild-to-moderately iodine-deficient population.We used the Norwegian Mother, Father and Child Cohort Study (MoBa) and included 78,318 pregnancies with data on iodine intake and pregnancy outcomes. Iodine intake was calculated using an extensive food frequency questionnaire in mid-pregnancy. In addition, urinary iodine concentration was available in a subsample of 2795 pregnancies. Associations were modelled continuously by multivariable regression controlling for a range of confounding factors.The median iodine intake from food was 121μg/day and the median urinary iodine was 69μg/L, confirming mild-to-moderate iodine deficiency. In non-users of iodine supplements (n=49,187), low iodine intake (<100-150μg/day) was associated with increased risk of preeclampsia (aOR=1.14 (95% CI 1.08, 1.22) at 75 vs. 100μg/day, p overall <0.001), preterm delivery before gestational week 37 (aOR=1.10 (1.04, 1.16) at 75 vs. 100μg/day, p overall=0.003), and reduced foetal growth (-0.08 SD (-0.10, -0.06) difference in birth weight z-score at 75 vs. 150μg/day, p overall <0.001), but not with early preterm delivery or intrauterine death. In planned pregnancies (n=56,416), having an iodine intake lower than ~100μg/day was associated with increased prevalence of subfecundity (aOR=1.05 (1.01, 1.09) at 75μg/day vs. 100μg/day, p overall=0.005). Long-term iodine supplement use (initiated before pregnancy) was associated with increased foetal growth (+0.05 SD (0.03, 0.07) on birth weight z-score, p<0.001) and reduced risk of preeclampsia (aOR 0.85 (0.74, 0.98), p=0.022), but not with the other adverse pregnancy outcomes. Urinary iodine concentration was not associated with any of the dichotomous outcomes, but positively associated with foetal growth (n=2795, p overall=0.017).This study shows that a low iodine intake was associated with restricted foetal growth and a higher prevalence of preeclampsia in these mild-to-moderately iodine-deficient women. Results also indicated increased risk of subfecundity and preterm delivery. Initiating iodine supplement use in pregnancy may be too late.
|
|
| 3. |
|
|
| 4. |
- Allvin, Kerstin, 1970, et al.
(författare)
-
Altered umbilical sex steroids in preterm infants born small for gestational age.
- 2020
-
Ingår i: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 33:24, s. 4164-4170
-
Tidskriftsartikel (refereegranskat)abstract
- Boys born small for gestational age (SGA) are at increased risk of testicular dysgenesis syndrome, and girls born SGA face the risk of polycystic ovary syndrome later in life. Our aim was to study whether neonates born SGA have an altered profile of steroid hormones at birth.A total of 168 singletons (99 boys, 69 girls) born at 32.0-36.9 gestational weeks were recruited to a population-based, university hospital, single-center study. Of these, 31 infants (17 boys, 14 girls) were born SGA. The concentrations of dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, cortisone, and cortisol were analyzed in umbilical cord serum with mass spectrometry.Girls born SGA had higher levels of androstenedione than girls born appropriate for gestational age (AGA) (4.0 versus 2.6nmol/L, p = 0.002). Boys born SGA had lower levels of estrone than boys born AGA (33822 versus 62471pmol/L, p = 0.038). Infants born SGA had lower levels of cortisone than infants born AGA, both in girls (340 versus 579nmol/L, p = 0.010) and in boys (308 versus 521nmol/L, p = 0.045). Furthermore, boys born SGA had a higher cortisol/cortisone ratio than boys born AGA (0.41 versus 0.25, p = 0.028). Gestational age correlated with DHEAS (boys r = 0.48, p = 0.000, girls r = 0.35, p = 0.013), and cortisol (boys r = 0.48, p = 0.000, girls r = 0.29, p = 0.039).In moderate-to-late preterm infants born SGA we observed a different steroid hormone profile in cord serum. Girls born SGA show increased levels of androstenedione and boys born SGA show decreased levels of estrone in cord serum, which could be related to placental aromatase deficiency in intrauterine growth restriction.
|
|
| 5. |
- Barman, Malin, 1983, et al.
(författare)
-
Maternal dietary selenium intake is associated with increased gestational length and decreased risk of preterm delivery
- 2020
-
Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 123:2, s. 209-219
-
Tidskriftsartikel (refereegranskat)abstract
- The first positive genome-wide association study on gestational length and preterm delivery showed associations with a gene involved in the selenium metabolism. In this study we examine the associations between maternal intake of selenium and selenium status with gestational length and preterm delivery in 72,025 women with singleton live births from the population based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitativ food-frequency questionnaire answered in pregnancy week 22 was used to estimate selenium intake during the first half of pregnancy. Associations were analysed with adjusted linear and cox regressions. Selenium status was assessed in whole blood collected in gestational week 17 (n=2,637). Median dietary selenium intake was 53 (IQR: 44-62) μg/day, supplements provided additionally 50 (30-75) μg/day for supplement-users (n=23,409). Maternal dietary selenium intake was significantly associated with prolonged gestational length (β per SD=0.25, 95% CI=0.07-0.43) and decreased risk for preterm delivery (n=3,618, HR per SD=0.92, 95% CI=0.87-0.98). Neither selenium intake from supplements nor maternal blood selenium status was associated with gestational length or preterm delivery. Hence, this study showed that maternal dietary selenium intake, but not intake of selenium containing supplements, during the first half of pregnancy was significantly associated with decreased risk for preterm delivery. Further investigations, preferably in the form of a large RCT, are needed to elucidate the impact of selenium on pregnancy duration.
|
|
| 6. |
- Bergman, Lina, 1982, et al.
(författare)
-
Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study
- 2020
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
|
|
| 7. |
- Chen, Jing, et al.
(författare)
-
Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes: A mendelian-randomization and haplotype-based genetic score analysis in 10,734 mother-infant pairs.
- 2020
-
Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 17:8
-
Tidskriftsartikel (refereegranskat)abstract
- Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved.Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits.We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.
|
|
| 8. |
- Cobo, Teresa, et al.
(författare)
-
Risk factors for spontaneous preterm delivery.
- 2020
-
Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479. ; 150:1, s. 17-23
-
Tidskriftsartikel (refereegranskat)abstract
- There is a substantial variation in rates of preterm delivery between different parts of the world. The understanding of these variations, as well as the biological mechanisms behind spontaneous preterm delivery, is limited. Although the benefit of antenatal interventions has been shown to be limited, using well-known risk factors for spontaneous preterm delivery to select the correct pregnant women for targeted interventions is important from both a medical and caregiving perspective.To provide an introduction to a substantial research area dealing with risk factors of spontaneous preterm delivery.Risk factors in this review were classified as demographical, obstetrical, and gynecological and those related to the current pregnancy according to high-quality evidence of recent literature.An introduction to a substantial research area in maternal and fetal medicine was provided that might help clinicians to better understand the risk factors related to preterm delivery and select the correct pregnant women for targeted interventions.
|
|
| 9. |
- Gadsbøll, Kasper, et al.
(författare)
-
Current use of noninvasive prenatal testing in Europe, Australia and the USA: A graphical presentation.
- 2020
-
Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 99:6, s. 722-730
-
Tidskriftsartikel (refereegranskat)abstract
- Noninvasive prenatal testing (NIPT), using cell-free fetal DNA, has increasingly been adopted as a screening tool for fetal aneuploidies. Several studies have discussed benefits and limitations of NIPT compared to both ultrasound and invasive procedures, but in spite of some shortcomings NIPT has become extensively used within the last five years. This study aims to describe the current use of NIPT in Europe, Australia and the USA.We conducted a survey to describe the current use of NIPT. Colleagues filled in a simple email-based questionnaire on NIPT in their own country, providing information on: 1) Access to NIPT, 2) NIPT's chromosomal coverage, 3) financial coverage of NIPT for the patient and 4) the proportion of women using NIPT in pregnancy. Some data are best clinical estimates, due to a lack of national data.In Europe, 14 countries have adopted NIPT into a national policy/program. Two countries (Belgium and the Netherlands) offer NIPT for all pregnant women, whereas most other European countries have implemented NIPT as an offer for higher risk women after first trimester screening. In Australia, either Combined First Trimester Screening (cFTS) or NIPT are used as primary prenatal screening tests. In the USA, there are no national consensus policies on the use of NIPT, however, NIPT is widely implemented. In most European countries offering NIPT, the proportion of women using NIPT is well below 25%. In the Netherlands, Austria, Italy, Spain and most Australian and American States, 25-50% of women have NIPT performed and only in Belgium it is above 75%. In most countries NIPT reports on trisomy 13, 18 and 21, and often also on sex chromosome aneuploidies. Only in Belgium, the Netherlands, Lithuania, Greece, Cyprus and Italy is NIPT offered predominantly as a genome-wide test (including some microdeletions or a whole genome coverage).NIPT has been widely adopted throughout Europe, Australia and the USA, but only some countries/states have a national policy on the use of NIPT. The variation in NIPT utilization is considerable.
|
|
| 10. |
- Golubinskaya, Veronika, 1974, et al.
(författare)
-
Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants
- 2020
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm infants exposed to chorioamnionitis and with a fetal inflammatory response are at risk for neonatal morbidity and adverse outcome. Alarmins S100A8, S100A9, and S100A12 are expressed by myeloid cells and have been associated with inflammatory activation and monocyte modulation. Aim: To study S100A alarmin expression in cord blood monocytes from term healthy and preterm infants and relate results to clinical findings, inflammatory biomarkers and alarmin protein levels, as well as pathways identified by differentially regulated monocyte genes. Methods: Cord blood CD14+ monocytes were isolated from healthy term (n = 10) and preterm infants (<30 weeks gestational age, n = 33) by MACS technology. Monocyte RNA was sequenced and gene expression was analyzed by Principal Component Analysis and hierarchical clustering. Pathways were identified by Ingenuity Pathway Analysis. Inflammatory proteins were measured by Multiplex ELISA, and plasma S100A proteins by mass spectrometry. Histological chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) were diagnosed by placenta histological examination. Results: S100A8, S100A9, and S100A12 gene expression was significantly increased and with a wider range in preterm vs. term infants. High S100A8 and S100A9 gene expression (n = 17) within the preterm group was strongly associated with spontaneous onset of delivery, HCA, FIRS and elevated inflammatory proteins in cord blood, while low expression (n = 16) was associated with impaired fetal growth and physician-initiated delivery. S100A8 and S100A9 protein levels were significantly lower in preterm vs. term infants, but within the preterm group high S100A gene expression, spontaneous onset of labor, HCA and FIRS were associated with elevated protein levels. One thousand nine hundred genes were differentially expressed in preterm infants with high vs. low S100A alarmin expression. Analysis of 124 genes differentially expressed in S100A high as well as FIRS and HCA groups identified 18 common pathways and S100A alarmins represented major hubs in network analyses. Conclusion: High expression of S100A alarmins in cord blood monocytes identifies a distinct clinical risk group of preterm infants exposed to chorioamnionitis and with a fetal inflammatory response. Gene and pathway analyses suggest that high S100A alarmin expression also affects monocyte function. The connection with monocyte phenotype and inflammation-stimulated S100A expression in other cell types (e.g., neutrophils) warrants further investigation.
|
|
