Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid

The development of immunoassays enables more sophisticated studies of the associations between protein concentrations and pregnancy outcomes, allowing early biomarker identification that can improve neonatal outcomes. The aim of this study was to explore associations between selected mid-trimester amniotic fluid proteins and (1) overall gestational duration and (2) spontaneous preterm delivery. A prospective cohort study, including women undergoing mid-trimester transabdominal genetic amniocentesis, was performed in Gothenburg, Sweden, 2008–2016 (n = 1072). A panel of 27 proteins related to inflammation was analyzed using Meso-Scale multiplex technology. Concentrations were adjusted for gestational age at sampling, experimental factors, year of sampling, and covariates (maternal age at sampling, parity (nulliparous/multiparous), smoking at first prenatal visit, and in vitro fertilization). Cox regression analysis of the entire cohort was performed to explore possible associations between protein concentrations and gestational duration. This was followed by Cox regression analysis censored at 259\ua0days or longer, to investigate whether associations were detectable in women with spontaneous preterm delivery (n = 47). Finally, linear regression models were performed to analyze associations between protein concentrations and gestational duration in women with spontaneous onset of labor at term (n = 784). HMG-1, IGFBP-1, IL-18, MIP-1α, MIP-1β, S100A8, and thrombospondin-1 were significantly associated with gestational duration at term, but not preterm. Increased concentrations of thrombospondin-1, MIP-1β, and S100A8, respectively, were significantly associated with decreased gestational duration after the Holm-Bonferroni correction in women with spontaneous onset of labor at term. This adds to the concept of a pregnancy clock, where our findings suggest that such a clock is also reflected in the amniotic fluid at early mid-trimester, but further research is needed to confirm this

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

Author summaryWhy was this study done? Maternal height, BMI, blood glucose, and blood pressure are associated with 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 underlying these observed associations are not clear. What did the researchers do and find? We dissected the relative contributions of maternal and fetal genetic effects using haplotype genetic score analysis in 10,734 mother-infant pairs of European ancestry. Genetically elevated maternal height is associated with longer gestational duration and larger birth size. In the fetus, alleles associated with adult height are positively associated with birth size. Alleles elevating blood pressure are associated with shorter gestational duration through a maternal effect and are associated with reduced fetal growth through a fetal genetic effect. Alleles that increase blood glucose in the mother are associated with increased birth weight, whereas risk alleles for type 2 diabetes in the fetus are associated with reduced birth weight. Alleles raising birth weight in fetus are associated with shorter gestational duration and higher maternal blood pressure during pregnancy. What do these findings mean? Maternal size and fetal growth are important factors in shaping the duration of gestation. Fetal growth is influenced by both maternal and fetal effects. Higher maternal BMI and glucose levels positively associate with birth weight through maternal effects. In the fetus, alleles associated with higher metabolic risks are negatively associated with birth weight. More rapid fetal growth is associated with shorter gestational duration and higher maternal blood pressure. These maternal and fetal genetic effects can largely explain the observed associations between maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes. Background 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. Methods and findings 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 x 10(-4)). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p<1 x 10(-17)). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p= 1.6 x 10(-4)). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p= 9.4 x 10(-3)), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p= 3.3 x 10(-2)andp= 4.5 x 10(-3), respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p= 4.7 x 10(-6)); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p= 2.2 x 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 x 10(-3)) and a stronger fetal effect (p= 1.3 x 10(-5)). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p= 1.8 x 10(-4)) and increased maternal systolic BP during pregnancy (p= 2.2 x 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. Conclusions 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.Peer reviewe

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P= 3.96 x 10(-14)). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.Peer reviewe

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P= 3.96 x 10(-14)). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality

Improving automatic processing of wildlife sound recordings

Acoustic monitoring of wildlife is emerging as a promising tool for animal conservation and research. Large amounts of natural sound recordings are routinely produced, but current use of this data is limited by lack of automatic analysis tools to process it efficiently. This thesis presents new methods for better detection of sound events, noise removal or robustness, and a framework for evaluating such improvements. Statistical and computational theory is used to support the generality of these tools, and also extended with results applicable outside of bioacoustics. In the first study included in the thesis, we set out to establish a metric for bioacoustic population surveys that could be used to evaluate various design or analysis choices. Currently, a variety of metrics is used, such as the F1 score or area under the curve for call detection. Using a combination of theoretical arguments and data examples, we show that rankings produced by these metrics depend on unobserved parameters, and do not necessarily correspond to overall survey performance in terms of ecological aims. These issues are avoided if the designs are ranked by the precision of spatial capture-recapture estimates. This framework covers a variety of practically important survey designs, and thus provides a single metric for general method evaluation. The next study turns to the question of event detection. Both in acoustics and other fields, various problems feature series with temporary changes in a parameter. Estimating the onset and offset times of such events – changepoint detection – can be achieved in a principled and efficient way, but only if the background is stable, which is rare in practice. We build a two-type changepoint detector that is robust to nuisance dynamics, and demonstrate its use on different types of real data. The detector assumes that nuisance and signals events have different length, which allows distinguishing them even if the same parameter is affected. As part of this, we develop a faster algorithm for fixed-background changepoint detection, and analyse its properties in the case of changing mean of a Gaussian series. The above changepoint detector is applied to acoustic events in the third paper of this thesis. We propose to combine it with a wavelet packet decomposition, thus producing a robust detector of frequency-specific energy increases. The theoretical analysis from Study II is extended to discuss the properties of this method. We test it on acoustic surveys using the evaluation framework developed in Study I, and observe consistently higher efficiency compared to other energy detectors. In a public challenge of household sound analysis, it was combined with a simple classifier to reach comparable performance to deep learning models with much less training data. Study IV concerns wind and other transient broadband noises. They interfere with sound analysis, and their rapid dynamics counter most existing noise removal methods. We develop a short-term estimator of broadband noise level, based on polynomial models of wavelet packet spectrum. Two uses for the estimator are demonstrated: adjusting the detector from Study III to further reduce false alarms and improve survey efficiency, and restoring denoised sound by wavelet shrinkage. Various design choices are discussed, such as a robust alternative for noise estimation in rich soundscapes.</p

Data from: AviaNZ: a future-proofed program for annotation and recognition of animal sounds in long-time field recordings

The routine collection of long‐time acoustic recordings of animals in the field presents new challenges in data analysis. While many terabytes of data are collected annually, effective use of this noisy, highly variable data require skilled humans to manually identify calls. While computer programs to automatically analyse these recordings are becoming available, it is important that they are user‐friendly and easy‐to‐use, so that everybody – citizen scientists, wildlife managers, researchers – can take advantage of them, and that they keep the human in the loop so analyses carried out this year are comparable both to manual call counts from the past, and more accurate automated analyses performed in the future. We present the AviaNZ program, which is designed to achieve these goals: the software includes methods for simple, rapid manual annotation of recordings, denoising and segmentation methods, and a training procedure by which the user can prepare their own filters to automatically recognize individual species. The software can run in batch mode, automatically processing folders of field recordings, and then present the outputs to enable the quick and easy review of the results. Finally, the outputs are presented in a variety of spreadsheets to enable different statistical analyses to be performed. We describe the various workflows of manually and semi‐automatically processing sound files, annotating them to train automatic filters, using those filters in batch mode, and how the software facilitates rapid evaluation of the automated analysis. A demonstration of the software, comparing manual and automatic detection of calls of the little spotted kiwi Apteryx owenii is given. It shows that while the automatic detection does produce false positives, human correction of these is far faster than manual review of the whole sound file. AviaNZ is a freely available open‐source standalone program. Our experience shows that it can be used by anybody quickly and easily. However, for experienced users it is easily customizable and extendable. By enabling everybody involved with acoustic bird recording to quickly and easily analyse their own data, while future‐proofing it by keeping the human in the loop, we are enabling acoustic field recordings to meet their potential