Placental histopathology in preeclampsia and outcome of the offspring

Preeclampsia (PE) is a major cause of maternal and fetal morbidity and mortality. The maternal symptoms are diverse and the neonates are often born premature and growth-restricted. Today the survival of premature infants has increased, but the neonatal complications including morbidity and long-term developmental deficits are still common. The etiology and pathophysiological mechanisms in PE are still not known, but it seems as if a central part of the pathogenesis is associated with an unsuccessful implantation of the placenta into the uterus. The only cure is to deliver the mother, which is often a difficult decision in regard to prematurity of the fetus, when the disease has begun early in pregnancy. In our first and second studies, we examined the placental pathology in relation to the maternal symptoms and severity of disease. The first study showed that there was a correlation between the severity of symptoms and the placental pathology. Further, the pathological picture was similar in mild and severe PE, but differed in relation to controls. To summarize, mild PE seems to be part of the PE spectrum, and not a normal physiological development of pregnancy, in contrast to what has previously been claimed. The second study showed that placental pathology differed in severe PE with and without HELLP syndrome (hemolysis, elevated liver enzymes and low platelets), which is a disease regarded as a PE subtype, although the clinical picture is different from classical PE. This indicates that other mechanisms might be involved in the HELLP syndrome. In the third and fourth studies, we examined the placental pathology in relation to perinatal, neonatal and childhood outcome. In the third study, we investigated the relation between placental pathology and perinatal and neonatal outcome in a cohort of PE patients and found that placental pathology was associated with adverse outcome. In the fourth study, in which we studied infants born extremely premature, we also found correlations between placental pathology and perinatal and neonatal outcome. In the fourth study, we also explored possible relations between placental pathology and neurologic and developmental outcome of the child at the age of 2.5 years. We found a significant association between placental infarction and cerebral palsy (CP), and tendencies between several pathological findings and developmental outcome. Overall, we have shown that the underlying pathologies in mild and severe PE probably are similar, whereas HELLP syndrome might have a different etiology. In addition, we have found associations between placental pathology and outcome of the offspring

Pregnancy-related maternal physiological adaptations and fetal chemical exposure

Prenatal life represents a susceptible window of development during which chemical exposures can permanently alter fetal development, leading to an increased likelihood of disease later in life. Therefore, it is essential to assess exposure in the fetus. However, direct assessment in human fetuses is challenging, so most research measures maternal exposure. Pregnancy induces a range of significant physiological changes in women that may affect chemical metabolism and responses. Moreover, placental function, fetal sex, and pregnancy complications may further modify these exposures. The purpose of this narrative review is to give an overview of major pregnancy-related physiological changes, including placental function and impacts of pregnancy complications, to summarize existing studies assessing chemical exposure in human fetal organs, and to discuss possible interactions between physiological changes and exposures. Our review reveals major knowledge gaps in factors affecting fetal chemical exposure, highlighting the need to develop more sophisticated tools for chemical health risk assessment in fetuses

Polyunsaturated Fatty Acids and Their Metabolites in Hyperemesis Gravidarum

Polyunsaturated fatty acids (PUFAs) have been studied in relation to pregnancy. However, there is limited knowledge on PUFAs and their metabolites in relation to hyperemesis gravidarum (HG), a pregnancy complication associated with nutritional deficiencies and excessive vomiting. In order to survey the field, a systematic review of the literature was performed, which also included nausea and vomiting of pregnancy (NVP) due to its close relationship with HG. In the very few published studies found, the main subjects of the research concerned free fatty acids (four records), lipid profiles (three records), and bioactive lipids (one article about prostaglandin E2 and one about endocannabinoids). The authors of these studies concluded that, although no cause-and-effect relationship can be established, HG is linked to increased sympathetic responsiveness, thermogenic activity and metabolic rate. In addition, NVP is linked to a metabolic perturbance (which lasts throughout pregnancy). The low number of retrieved records underlines the need for more research in the area of PUFAs and HG, especially with regard to the underlying mechanism for the detected effects, potentially involving growth differentiation factor 15 (GDF15) since evidence for GDF15 regulation of lipid metabolism and the role for GDF15 and its receptor in nausea and vomiting is emerging

“Navigating in a maze without a map“. Partners’ experiences of hyperemesis gravidarum- a qualitative study

Objective: A supportive environment for women with Hyperemesis Gravidarum is crucial but not always provided. There is a lack of research regarding Hyperemesis Gravidarum, its impact on the family, and the partner's perception of supporting their spouse. Thus, this study aims to explore partners’ experiences of Hyperemesis Gravidarum during their spousés pregnancy. Methods: Data were gathered through 13 individual, semi-structured, in-depth, digital interviews with partners of women who had experienced Hyperemesis Gravidarum and analysed with Qualitative Content Analysis. The partners were recruited through advertisement on a social media platform and were exclusively males, representing 8 of 21 Swedish regions. The mean age was 34, and they had, on average, 1 previous child. The mean time from the experience to the interview was 12 months. Findings: The main theme, “Navigating in a maze without a map”, explains partners’ situation as stressful and demanding when their spouse suffers from Hyperemesis Gravidarum, with insufficient support and guidance from healthcare providers. The analysis resulted in three themes: “Standing alone with a demanding responsibility”, “Being in a lottery when facing healthcare”, and “Climbing the mountain together.” The themes display challenges within everyday life and healthcare, as well as strained relations within the family. Conclusion: Partners experience a need to support their spouse in every aspect of daily life and advocate for adequate healthcare. Healthcare professionals must support and acknowledge the partners' struggles during the demanding situation with Hyperemesis Gravidarum

Treatments for hyperemesis gravidarum : a systematic review

Introduction: Hyperemesis gravidarum affects 0.3%–3% of pregnant women each year and is the leading cause of hospitalization in early pregnancy. Previous systematic reviews of available treatments have found a lack of consistent evidence, and few studies of high quality. Since 2016, no systematic review has been conducted and an up-to date review is requested. In a recent James Lind Alliance collaboration, it was clear that research on effective treatments is a high priority for both patients and clinicians. Material and methods: Searches without time limits were performed in the AMED, CINAHL, Cochrane Library, EMBASE, Medline, PsycINFO, and Scopus databases until June 26, 2023. Studies published before October 1, 2014 were identified from the review by O'Donnell et al., 2016. Selection criteria were randomized clinical trials and non-randomized studies of interventions comparing treatment of hyperemesis gravidarum with another treatment or placebo. Outcome variables included were: degree of nausea; vomiting; inability to tolerate oral fluids or food; hospital treatment; health-related quality of life, small-for-gestational-age infant; and preterm birth. Abstracts and full texts were screened, and risk of bias of the studies was assessed independently by two authors. Synthesis without meta-analysis was performed, and certainty of evidence was assessed using the GRADE approach. PROSPERO (CRD42022303150). Results: Twenty treatments were included in 25 studies with low or moderate risk of bias. The certainty of evidence was very low for all treatments except for acupressure in addition to standard care, which showed a possible moderate decrease in nausea and vomiting, with low certainty of evidence. Conclusions: Several scientific knowledge gaps were identified. Studies on treatments for hyperemesis gravidarum are few, and the certainty of evidence for different treatments is either low or very low. To establish more robust evidence, it is essential to use validated scoring systems, the recently established diagnostic criteria, clear descriptions and measurements of core outcomes and to perform larger studies

Enhanced local and systemic inflammatory cytokine mRNA expression in women with endometriosis evokes compensatory adaptive regulatory mRNA response that mediates immune suppression and impairs cytotoxicity

Problem: Endometriosis is a disease characterized by ectopic implantation of endometrium and impaired immune responses. To explore its pathogenic mechanisms, we studied the local and systemic cytokine mRNA profiles and their role in the immunity of patients with endometriosis and healthy controls. Method of Study: mRNA for eleven cytokines defining cytotoxic Th1, humoral Th2, regulatory Tr1/Th3, and inflammatory cytokine profiles was characterized locally in endometriotic tissue and endometrium, and systemically in PBMCs from women with endometriosis and healthy controls, using real‐time qRT‐PCR. In addition, immunohistochemical stainings with monoclonal antibodies were performed looking for T regulatory cells in endometriotic lesions. Results: We found a downregulation of mRNA for cytokines mediating cytotoxicity and antibody response and an upregulation of inflammatory and T‐regulatory cytokines in the endometriotic tissues and endometrium from the patients with endometriosis, suggesting enhanced local inflammation and priming of an adaptive regulatory response. Consistent with those findings, there was an abundancy of T regulatory cells in the endometriotic lesions. Conclusions: The ectopic implantation seen in endometriosis could be possible as a consequence of increased inflammation and priming of adaptive T regulatory cells, resulting in impaired cytotoxicity and enhanced immune suppression

Concentrations of perfluoroalkyl substances (PFASs) in human embryonic and fetal organs from first, second, and third trimester pregnancies

Background: The persistent environmental contaminants perfluoroalkyl substances (PFASs) have gained attention due to their potential adverse health effects, in particular following early life exposure. Information on human fetal exposure to PFASs is currently limited to one report on first trimester samples. There is no data available on PFAS concentrations in fetal organs throughout all three trimesters of pregnancy. Methods: We measured the concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorohexane sulfonic acid (PFHxS) in human embryos and fetuses with corresponding placentas and maternal serum samples derived from elective pregnancy terminations and cases of intrauterine fetal death. A total of 78 embryos and fetuses aged 7–42 gestational weeks were included and a total of 225 fetal organs covering liver, lung, heart, central nervous system (CNS), and adipose tissue were analyzed, together with 71 placentas and 63 maternal serum samples. PFAS concentrations were assayed by liquid chromatography/triple quadrupole mass spectrometry. Results: All evaluated PFASs were detected and quantified in maternal sera, placentas and embryos/fetuses. In maternal serum samples, PFOS was detected in highest concentrations, followed by PFOA > PFNA > PFDA = PFUnA = PFHxS. Similarly, PFOS was detected in highest concentrations in embryo/fetal tissues, followed by PFOA > PFNA = PFDA = PFUnA. PFHxS was detected in very few fetuses. In general, PFAS concentrations in embryo/fetal tissue (ng/g) were lower than maternal serum (ng/ml) but similar to placenta concentrations. The total PFAS burden (i.e. the sum of all PFASs) was highest in lung tissue in first trimester samples and in liver in second and third trimester samples. The burden was lowest in CNS samples irrespective of fetal age. The placenta:maternal serum ratios of PFOS, PFOA and PFNA increased across gestation suggesting bioaccumulation in the placenta. Further, we observed that the ratios were higher in pregnancies with male fetuses compared to female fetuses. Conclusions: Human fetuses were intrinsically exposed to a mixture of PFASs throughout gestation. The compounds were detected in all analyzed tissues, suggesting that PFASs reach and may affect many types of organs. Collectively, our results demonstrate that PFASs pass the placenta and deposit to embryo and fetal tissues, calling for risk assessment of gestational exposures

Mixtures of persistent organic pollutants are found in vital organs of late gestation human fetuses

Persistent organic pollutants (POPs) are industrial chemicals with long half-lives. Early life exposure to POPs has been associated with adverse effects. Fetal exposure is typically estimated based on concentrations in maternal serum or placenta and little is known on the actual fetal exposure. We measured the concentrations of nine organochlorine pesticides (OCPs), ten polychlorinated biphenyl (PCB) congeners, and polybrominated diphenyl ether (PBDE) congeners by gas chromatography – tandem mass spectrometry in maternal serum, placenta, and fetal tissues (adipose tissue, liver, heart, lung and brain) in 20 pregnancies that ended in stillbirth (gestational weeks 36–41). The data were combined with our earlier data on perfluoroalkyl substances (PFASs) in the same cohort (Mamsen et al. 2019). HCB, p,p’-DDE, PCB 138 and PCB 153 were quantified in all samples of maternal serum, placenta and fetal tissues. All 22 POPs were detected in all fetal adipose tissue samples, even in cases where they could not be detected in maternal serum or placenta. Tissue:serum ratios were significantly higher in later gestations, male fetuses, and pregnancies with normal placental function. OCPs showed the highest tissue:serum ratios and PFAS the lowest. The highest chemical burden was found in adipose tissue and lowest in the brain. Overall, all studied human fetuses were intrinsically exposed to mixtures of POPs. Tissue:serum ratios were significantly modified by gestational age, fetal sex and placental function. Importantly, more chemicals were detected in fetal tissues compared to maternal serum and placenta, implying that these proxy samples may provide a misleading picture of actual fetal exposures