Svangerskapsdatering

SAMMENDRAG Svangerskapsdatering er et komplekst felt med mange aspekter. Minst tre svært forskjellige metoder for datering er i bruk: siste menstruasjon, ultralyd samt tidspunkt for fertilisering eller overføring av embryo ved in vitro-fertilisering. Bare innenfor ultralyddatering finnes en stor mengde forskjellige “formler” for datering. Jeg gir her en kort oversikt over de forskjellige tilnærmingene til svangerskapsdatering og viser noen av prinsippene bak populasjonsbasert ultralyddatering. ENGLISH ABSTRACT Pregnancy dating is a complex and multifaceted field. At least three very different methods for dating are commonly used: last menstrual period, ultrasound, and date of fertilization or embryo transfer during in vitro fertilization. Within ultrasound dating alone there is a wide range of different “formulas” for dating. I present a short overview over the different approaches to pregnancy dating and show some of the principles behind population-based ultrasound dating

A non linear parabolic equation with noise : a reduction method

In this paper we study a class of parabolic equations with a non-linear gradient term. The system is disturbed by white noise in time. We show that the solution of this problem can be represented as the Wick product between a normalized random variable of exponential form and the solution of a nonlinear parabolic equation. We allow random initial data which might be anticipating. A relation between the Wick product with a normalized exponential and translation is proved in order to establish our results

Maternal angiotensinogen (AGT) haplotypes, fetal renin (REN) haplotypes and risk of preeclampsia; estimation of gene-gene interaction from family-triad data

Background Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Although inconclusive, current evidence suggests that the renin-angiotensin system may be involved in hypertension. Therefore, our objective was to determine whether the genes for placental renin (REN) and maternal angiotensinogen (AGT) interact to influence the risk of preeclampsia. Methods Three haplotype-tagging SNPs (htSNPs) covering REN (rs5705, rs1464818, and rs3795575) and another three covering AGT (rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal AGT and fetal REN haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal AGT and fetal REN haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal AGT haplotype C-T-A and tested for an effect of fetal REN across these strata. Results We found evidence that mothers carrying the most frequent AGT haplotype, C-T-A, had a reduced risk of preeclampsia (RR of 0.4, 95% CI = 0.2-0.8 for heterozygotes and 0.6, 95% CI = 0.2-1.5 for homozygotes). Mothers homozygous for AGT haplotypes t-c-g and C-c-g appeared to have a higher risk, but only the former was statistically significant. We found only weak evidence of an overall effect of fetal REN haplotypes and no support for our hypothesis that an effect of REN depended on whether the mother carried the C-T-A haplotype of AGT (p = 0.33). Conclusion Our findings indicate that the mother's AGT haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal REN haplotypes.publishedVersio

Parent-of-origin-environment interactions in case-parent triads with or without independent controls

With case–parent triad data, one can frequently deduce parent of origin of the child's alleles. This allows a parent‐of‐origin (PoO) effect to be estimated as the ratio of relative risks associated with the alleles inherited from the mother and the father, respectively. A possible cause of PoO effects is DNA methylation, leading to genomic imprinting. Because environmental exposures may influence methylation patterns, gene–environment interaction studies should be extended to allow for interactions between PoO effects and environmental exposures (i.e., PoOxE). One should thus search for loci where the environmental exposure modifies the PoO effect. We have developed an extensive framework to analyze PoOxE effects in genome‐wide association studies (GWAS), based on complete or incomplete case–parent triads with or without independent control triads. The interaction approach is based on analyzing triads in each exposure stratum using maximum likelihood estimation in a log‐linear model. Interactions are then tested applying a Wald‐based posttest of parameters across strata. Our framework includes a complete setup for power calculations. We have implemented the models in the R software package Haplin. To illustrate our PoOxE test, we applied the new methodology to top hits from our previous GWAS, assessing whether smoking during the periconceptional period modifies PoO effects on cleft palate only.publishedVersio

A fast wavelet-based functional association analysis replicates several susceptibility loci for birth weight in a Norwegian population

Background Birth weight (BW) is one of the most widely studied anthropometric traits in humans because of its role in various adult-onset diseases. The number of loci associated with BW has increased dramatically since the advent of whole-genome screening approaches such as genome-wide association studies (GWASes) and meta-analyses of GWASes (GWAMAs). To further contribute to elucidating the genetic architecture of BW, we analyzed a genotyped Norwegian dataset with information on child’s BW (N=9,063) using a slightly modified version of a wavelet-based method by Shim and Stephens (2015) called WaveQTL. Results WaveQTL uses wavelet regression for regional testing and offers a more flexible functional modeling framework compared to conventional GWAS methods. To further improve WaveQTL, we added a novel feature termed “zooming strategy” to enhance the detection of associations in typically small regions. The modified WaveQTL replicated five out of the 133 loci previously identified by the largest GWAMA of BW to date by Warrington et al. (2019), even though our sample size was 26 times smaller than that study and 18 times smaller than the second largest GWAMA of BW by Horikoshi et al. (2016). In addition, the modified WaveQTL performed better in regions of high LD between SNPs. Conclusions This study is the first adaptation of the original WaveQTL method to the analysis of genome-wide genotypic data. Our results highlight the utility of the modified WaveQTL as a complementary tool for identifying loci that might escape detection by conventional genome-wide screening methods due to power issues. An attractive application of the modified WaveQTL would be to select traits from various public GWAS repositories to investigate whether they might benefit from a second analysis.publishedVersio

Estimation of fetal weight in pregnancies past term

Introduction: The aim of the study was to investigate the accuracy of estimating fetal weight with ultrasound in pregnancies past term, using the eSnurra algorithm. Material and methods: In all, 419 women with pregnancy length of 290 days, attending a specialist consultation at Stavanger University Hospital, Norway, were included in a prospective observational study. Fetal weight was estimated using biparietal diameter (BPD) and abdominal circumference (AC). The algorithm implemented in an electronic calculation (eSnurra) was used to compute estimated fetal weight (EFW). Results were compared with birthweight (BW). Results: The mean interval between the ultrasound examination and birth was 2 days (SD 1.4). The median difference between BW and EFW was −6 g (CI −40 to +25 g) and the median percentage error was –0.1% (95% CI −1.0 to 0.6%). The median absolute difference was 190 g (95% CI 170–207 g). The BW was within 10% of EFW in 83% (95% CI 79–87%) of cases and within 15% of EFW in 94% (95% CI 92–96%) of cases. Limits of agreement (95%) were from −553 g to +556 g. Using 5% false‐positive rates, the sensitivity in detecting macrosomic and small for gestational age fetuses was 54% (95% CI 35–72%) and 49% (95% CI 35–63%), respectively. Conclusion: The accuracy of fetal weight estimation was good. Clinicians should be aware of limitations related to prediction at the upper and lower end, and the importance of choosing appropriate cut‐off levels.publishedVersio

Identity, Resilience and Power in Self-Determination Conflicts

Sem resumo disponível

Candidate gene analysis of spontaneous preterm delivery: New insights from re-analysis of a case-control study using case-parent triads and control-mother dyads

Background: Spontaneous preterm delivery (PTD) has a multifactorial etiology with evidence of a genetic contribution to its pathogenesis. A number of candidate gene case-control studies have been performed on spontaneous PTD, but the results have been inconsistent, and do not fully assess the role of how two genotypes can impact outcome. To elucidate this latter point we re-analyzed data from a previously published case-control candidate gene study, using a case-parent triad design and a hybrid design combining case-parent triads and control-mother dyads. These methods offer a robust approach to genetic association studies for PTD compared to traditional case-control designs. Methods: The study participants were obtained from the Norwegian Mother and Child Cohort Study (MoBa). A total of 196 case triads and 211 control dyads were selected for the analysis. A case-parent triad design as well as a hybrid design was used to analyze 1,326 SNPs from 159 candidate genes. We compared our results to those from a previous case-control study on the same samples. Haplotypes were analyzed using a sliding window of three SNPs and a pathway analysis was performed to gain biological insight into the pathophysiology of preterm delivery. Results: The most consistent significant fetal gene across all analyses was COL5A2. The functionally similar COL5A1 was significant when combining fetal and maternal genotypes. PON1 was significant with analytical approaches for single locus association of fetal genes alone, but was possibly confounded by maternal effects. Focal adhesion (hsa04510), Cell Communication (hsa01430) and ECM receptor interaction (hsa04512) were the most constant significant pathways. Conclusion: This study suggests a fetal association of COL5A2 and a combined fetal-maternal association of COL5A1 with spontaneous PTD. In addition, the pathway analysis implied interactions of genes affecting cell communication and extracellular matrix.publishedVersio