Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role

Controversies in implementing non-invasive prenatal testing in a public antenatal care program

Women's autonomy and an inclusive society for all individuals are highly valued in Norway. The Norwegian Biotechnology Act changed in 2020 allowing first-trimester screening and cell-free DNA for common trisomies to all pregnant women. However, implementing non-invasive prenatal testing (NIPT) in a public antenatal care program is difficult, because many patients, politicians, and medical professionals do not consider trisomy 21 a severe medical disease. Screening for trisomies at an early gestation might inevitably lead to an increase in pregnancy terminations and making cost–benefit calculations is ethically challenging. Moreover, offering NIPT to all pregnant women is debatable because of the lower prevalence of fetal trisomies in younger women. Therefore, appropriate genetic pre-test counseling is essential. Furthermore, organizing the service between private institutions and public hospitals poses another debate and challenges both quality and equal access to health services for women across the country.publishedVersio

Cardiopulmonary Collapse during Labour

Cardiopulmonary collapse during labour is a catastrophic event caused by various medical, surgical and obstetrical conditions. It is an emergency that threatens the life of the mother and her unborn child. We present a case of a pregnant woman who suffered from preeclampsia and underwent induction of labour. Severe lung edema occurred early in labour that caused cardiopulmonary collapse. Advanced heart-lung resuscitation was established immediately and continued until an emergency cesarean section was performed few minutes later. The outcome was favourable for both mother and child. We further discuss some aspects of the pathophysiology and appropriate treatment of cardiorespiratory arrest during labour, which involves the coordinated action of the obstetric, pediatric and surgical ward personnel

Obstetric and psychological characteristics of women choosing epidural analgesia during labour: A cohort study

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Laeverin Protein Expression in Normal and Preeclamptic Placentas using Tissue Microarray Analysis

This is the peer reviewed version of the following article: Nystad, M., Sitras, V.S., Nordbakken, C., Pedersen, M.I. & Acharya, G. (2018). Laeverin Protein Expression in Normal and Preeclamptic Placentas using Tissue Microarray Analysis. Acta Obstetricia et Gynecologica Scandinavica, 97(5), 536-544, which has been published in final form at https://doi.org/10.1111/aogs.13304. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Introduction - Laeverin is a placenta‐specific protein that is normally expressed in the plasma membrane of human trophoblasts. In previous studies, we showed higher expression levels of laeverin gene in preeclamptic compared with normal placentas and found that laeverin protein was ectopically expressed in the cytoplasm of the preeclamptic placentas. Our objective was to investigate laeverin protein expression in normal and preeclamptic placentas combining immunohistochemistry and immunofluorescence. Material and methods - Tissue microarray analysis of 72 placentas, obtained from 33 preeclamptic and 39 uncomplicated pregnancies, was performed. Laeverin was labeled with a specific antibody for immunohistochemistry and immunofluorescence studies. Results - Immunohistochemistry showed that laeverin was expressed in syncytiotrophoblasts, cytotrophoblasts and extravillous trophoblasts in all placentas examined. In preeclamptic placentas (n = 33) compared with normal placentas (n = 39), laeverin was expressed in the cell membrane in 21 (64%) vs. 21 (54%) samples (p = 0.726), in the cytoplasm in 3 (9%) vs. 2 (5%) samples (p = 0.795) and in both the cytoplasm and membrane in 9 (27%) vs. 16 (41%) samples (p = 0.0522). All placental samples that showed cytoplasmic expression of laeverin were obtained from women who delivered before 34 weeks of gestation (early‐onset preeclampsia). Further, immunofluorescence studies showed laeverin expression in the cytoplasm of six preeclamptic (three early‐onset and three late‐onset) and one normal placenta but did not reveal any simultaneous cell membrane and cytoplasmic expression of laeverin. Conclusion - Laeverin is expressed in all trophoblast cell types of normal and preeclamptic placentas. Expression pattern of laeverin in trophoblast cells is heterogeneous and not necessarily membrane‐bound

Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes

Introduction The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. Material and Methods Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000–2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. Results A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). Conclusions The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.publishedVersio

Placental Protein 13 (PP13) – a placental immunoregulatory galectin protecting pregnancy

Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure d

Platelet alloimmunization is associated with low grade chronic histiocytic intervillositis - A new link to a rare placental lesion?

Introduction - Maternal alloimmunization against human platelet antigen (HPA)-1a has been implied to mediate both reduced birth weight and chronic placental inflammation. Fetal growth restriction is associated with different types of chronic inflammation in the placenta, mainly chronic histiocytic intervillositis and chronic villitis. The aim of this prospective study was to do a systematic examination of placentas from HPA-1a alloimmunized pregnancies, with focus on the histopathological and immunohistochemical diagnosis of variants of chronic inflammation. Material and methods - In a Polish-Norwegian study, 48 placentas were examined. The histopathology of placentas from 27 HPA-1a immunized women was compared with 21 placentas from non-immunized HPA-1a negative women (controls). In the group of alloimmunized women, ten received antenatal intravenous immunoglobulin G (IVIg). Tissue sections from formalin fixed paraffin embedded placental tissue were stained with hematoxylin and eosin and microscopically examined with focus on various types of chronic placental inflammations. Results - Chronic histiocytic intervillositis was observed in 40.7% of placentas from HPA-1a alloimmunized pregnancies, compared to none in the control group (p = 0.001). Chronic villitis of unknown etiology was more frequently found in the alloimmunized group, however this difference was not statistically significant. Maternal administration of IVIg did not seem to protect against chronic inflammatory lesions. Discussion - Placentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis

Differences in Gene Expression between First and Third Trimester Human Placenta: A Microarray Study

BACKGROUND: The human placenta is a rapidly developing organ that undergoes structural and functional changes throughout the pregnancy. Our objectives were to investigate the differences in global gene expression profile, the expression of imprinted genes and the effect of smoking in first and third trimester normal human placentas. MATERIALS AND METHODS: Placental samples were collected from 21 women with uncomplicated pregnancies delivered at term and 16 healthy women undergoing termination of pregnancy at 9-12 weeks gestation. Placental gene expression profile was evaluated by Human Genome Survey Microarray v.2.0 (Applied Biosystems) and real-time polymerase chain reaction. RESULTS: Almost 25% of the genes spotted on the array (n = 7519) were differentially expressed between first and third trimester placentas. Genes regulating biological processes involved in cell proliferation, cell differentiation and angiogenesis were up-regulated in the first trimester; whereas cell surface receptor mediated signal transduction, G-protein mediated signalling, ion transport, neuronal activities and chemosensory perception were up-regulated in the third trimester. Pathway analysis showed that brain and placenta might share common developmental routes. Principal component analysis based on the expression of 17 imprinted genes showed a clear separation of first and third trimester placentas, indicating that epigenetic modifications occur throughout pregnancy. In smokers, a set of genes encoding oxidoreductases were differentially expressed in both trimesters. CONCLUSIONS: Differences in global gene expression profile between first and third trimester human placenta reflect temporal changes in placental structure and function. Epigenetic rearrangements in the human placenta seem to occur across gestation, indicating the importance of environmental influence in the developing feto-placental unit