| 1. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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| 2. |
- Liu, Xueping, et al.
(författare)
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Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- 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 × 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.
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| 3. |
- Laisk, Triin, et al.
(författare)
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The genetic architecture of sporadic and multiple consecutive miscarriage.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.
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| 4. |
- Cobo, Teresa, et al.
(författare)
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A prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes: analyses of multiple proteins in the amniotic fluid.
- 2012
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Ingår i: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the best prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes (PPROM) using selected candidate proteins in the amniotic fluid (AF). Material and methods: Prospective cohort study. Twenty-six AF proteins were assayed by a multiple immunoassay from 107 women with membranes rupture from 23+0 to 36+6 weeks. The Czech Republic policy is active management, and the majority of women were delivered within 72 h after the rupture of membranes, except for women with PPROM <28+0 weeks who were managed conservatively. The best predictive models to diagnose histological chorioamnionitis and funisitis were calculated by logistic regression depending on the gestational age (GA) at membrane rupture. Results: Both IL-6 and a combination of IL-10, and migration inhibiting factor (MIF) were the best predictive models of histological chorioamnionitis and funisitis, respectively, with sensitivity, specificity, positive and negative predictive values and positive likelihood ratio (LR+) of 62, 83, 37, 93 and 3.6 and of 63, 91, 53, 94 and 7.0, respectively. Depending on whether GA at membrane rupture was <32 or ≥ 32 weeks, IL-10, alone or in combination with MIF and triggering receptor expressed on myeloid cells-1, was the strongest inflammatory biomarker for funisitis (LR+10.6 and 36.6, respectively). Conclusion: Regardless of the GA at membrane rupture, IL-6 from the AF was the best predictor of histological chorioamnionitis. Amniotic fluid IL-10 was notably accurate in the prediction of funisitis.
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| 5. |
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| 6. |
- Cobo, Teresa, et al.
(författare)
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Intra-amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture.
- 2012
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349.
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To predict microbial invasion of the amniotic cavity (MIAC) and spontaneous preterm delivery within seven days using a panel of selected proteins from amniotic fluid in a Swedish population of preterm prelabor membrane rupture (PPROM). Design. Prospective cohort study. Setting. Evaluation of intra-amniotic inflammation in preterm premature rupture of membranes. Population. Sixty-six pregnant women with preterm prelabor membrane rupture at 22(+0-) 33(+6) weeks' gestational age. Methods. Twenty-seven amniotic fluid proteins were assayed by a multiple immunoassay. Main outcome measures. The intra-amniotic inflammatory response was evaluated according to the presence of MIAC and the risk of spontaneous preterm delivery within seven days. A prediction model was constructed using logistic regression. Results. The overall rates of MIAC and spontaneous preterm delivery within seven days were 20% and 50%, respectively. There was a higher inflammatory response in women with MIAC than without. Earlier gestational age at delivery and lower birthweight were observed in the presence of microbial invasion of the amniotic cavity. Amniotic fluid Interleukin (IL)-6 and IL-10 were the best predictors of MIAC in terms of sensitivity (69%), specificity (81%), positive predictive value (47%), negative predictive value (91%) and positive likelihood ratio of 3.6. There were no differences in intra-amniotic inflammatory response according to the risk of spontaneous preterm delivery within seven days. Conclusion. Amniotic fluid IL-6 and IL-10 are the best inflammatory biomarkers to predict MIAC in women with PPROM. Intra-amniotic inflammation does not predict the occurrence of spontaneous preterm delivery within seven days of PPROM.
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| 7. |
- Hallingström, Maria, et al.
(författare)
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The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery
- 2020
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Ingår i: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 33:4, s. 583-592
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to explore inflammatory response and identify early potential biomarkers in mid-trimester amniotic fluid associated with subsequent spontaneous preterm delivery (PTD). Methods: A cohort study was performed at Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, between 2008 and 2010. Amniotic fluid was collected from consecutive women undergoing mid-trimester transabdominal genetic amniocentesis at 14–19 gestational weeks. Clinical data and delivery outcome variables were obtained from medical records. The analysis included 19 women with spontaneous PTD and 118 women who delivered at term. A panel of 26 candidate proteins was analyzed using Luminex xMAP technology. Candidate protein concentrations were analyzed with ANCOVA and adjusted for plate effects. Results: The median gestational age at delivery was 35 + 3 weeks in women with spontaneous PTD and 40 + 0 weeks in women who delivered at term. Nominally significantly lower amniotic fluid levels of adiponectin (PTD: median 130,695 pg/mL (IQR 71,852–199,414) vs term: median 185,329 pg/mL (IQR (135,815–290,532)), granulocyte-macrophage colony stimulating factor (PTD: median 137 pg/mL (IQR 74–156) vs term: median 176 pg/mL (IQR 111–262)), and macrophage migration inhibitory factor (PTD: median 3025 pg/mL (IQR 1885–3891) vs term: median 3400 pg/mL (IQR 2181–5231)) were observed in the spontaneous PTD group, compared with the term delivery group, after adjusting for plate effects. No significant differences remained after Bonferroni correction for multiple comparisons. Conclusions: Our results are important in the process of determining the etiology behind spontaneous PTD but due to the non-significance after Bonferroni correction, the results should be interpreted with caution. Further analyses of larger sample size will be required to determine whether these results are cogent and to examine whether microbial invasion of the amniotic cavity or intra-amniotic inflammation occurs in asymptomatic women in the mid-trimester with subsequent spontaneous PTD.
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| 8. |
- Hellgren, Gunnel, 1961, et al.
(författare)
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Proliferative Retinopathy Is Associated with Impaired Increase in BDNF and RANTES Expression Levels after Preterm Birth.
- 2010
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 98:4, s. 409-418
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Tidskriftsartikel (refereegranskat)abstract
- Background: Extremely preterm delivery is, amongst other complications, associated with retinopathy of prematurity (ROP). Untreated, ROP can progress to visual impairment and blindness due to an overgrowth of new vessels in the retina and vitreous cavity. Objective: The aim of this study was to identify cytokine markers within the first weeks of life that could be used to predict the risk for development of ROP later in life. Methods: Serum levels of 27 different cytokines in infants born at gestational weeks 23-30 were analyzed using a multiplex immunoassay method and compared between infants who did not develop ROP and infants who later developed proliferative ROP. In addition, mRNA levels of brain-derived neurotrophic factor (BDNF) in retinas from mice exposed to hyperoxia were analyzed using quantitative real-time PCR. Results: At birth, serum levels of IL-5 were higher in infants with no ROP compared to infants with proliferative ROP. 10-14 days after birth, serum levels of BDNF and RANTES were lower in infants who later developed proliferative ROP compared to infants who did not develop ROP. Furthermore, mRNA expression levels of BDNF in retinas from mice exposed to hyperoxia were significantly lower at postnatal day 15 compared to retinas from mice in room air. Conclusions: These results indicate that BDNF and RANTES may be important factors in the selective vulnerability of ROP development in preterm infants.
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| 9. |
- Kacerovsky, Marian, et al.
(författare)
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Intraamniotic inflammatory response to bacteria: analysis of multiple amniotic fluid proteins in women with preterm prelabor rupture of membranes.
- 2012
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Ingår i: The Journal of Maternal-Fetal and Neonatal Medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To analyse whether intraamniotic inflammation in response to bacteria is different below and above gestational age 32 weeks in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). Methods: A prospective study was performed, and 115 women with singleton pregnancies complicated by PPROM at gestational ages between 24(0/7) and 36(6/7) weeks were included in the study. Transabdominal amniocenteses were performed. Amniotic fluid was analysed using polymerase chain reactions for genital mycoplasmas and cultured for aerobic and anaerobic bacteria. The concentrations of 26 proteins in the amniotic fluid were determined simultaneously using multiplex technology. Results: Bacteria were found in the amniotic fluid of 43% (49/115) of the women. The women were stratified into two subgroups according to gestational age 32 weeks. The amniotic fluid levels of four (interleukin-6, interleukin-10, CC chemokine ligands 2, and 3) and one specific (CC chemokine ligands 2) proteins were higher in women with the presence of bacteria in the amniotic fluid below and above 32 gestational weeks, respectively. Conclusions: An intraamniotic inflammatory response to bacteria in pregnancies complicated by PPROM seems to be different below and above 32 weeks of gestation.
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| 10. |
- Viklund, Felicia, et al.
(författare)
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Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid
- 2020
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7205 .- 1933-7191. ; 27:12, s. 2146-2157
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Tidskriftsartikel (refereegranskat)abstract
- 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 days 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.
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