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.
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.
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.
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.
•PFASs were detected in maternal serum, placenta and fetal organs throughout pregnancy.•PFASs concentrations in fetal tissues were similar to placenta levels.•Fetal PFAS levels were highest in liver and lung and lowest in central nervous system.•PFOS, PFOA, and PFNA accumulated in placenta across gestation.•PFOA accumulated more in placentas with male fetuses compared to female fetuses.
Treatments for hyperemesis gravidarum: A systematic review Vinnars, Marie‐Therese; Forslund, Maria; Claesson, Ing‐Marie ...
Acta obstetricia et gynecologica Scandinavica,
January 2024, 2024-Jan, 2024-01-00, 20240101, 2024, Letnik:
103, Številka:
1
Journal Article
Recenzirano
Odprti dostop
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. s 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.
The certainty of evidence according to GRADE (The Grading of Recommendations Assessment, Development and Evaluation) was very low for all treatments of hyperemesis gravidarum except for acupressure in addition to standard care, which showed a possible moderate decrease in nausea and vomiting, with low certainty of evidence.
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.
•Fetal development is vulnerable to chemical exposures during pregnancy.•Human fetal organs face exposure to a mixture of industrial chemical residues.•Physiological changes in pregnancy can influence fetal chemical exposure.•Pregnancy complications are common, yet studies focus on “healthy women”.•In silico models offer potential for predicting fetal exposure to chemicals.
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.
Abundancy of CD4+ CD25++ adaptive T regulatory cells in endometriotic lesions could be responsible for impaired IFN gamma response and the observed downregulation of the cytotoxicity in endometriosis patients.
Problem
Pre‐eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to ...endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1‐3 in PE‐ and normal placenta.
Method of study
The cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1‐3 in PE placenta were assessed and compared to those in normal placenta using real‐time quantitative RT‐PCR.
Results
The cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta.
Conclusion
The destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor‐ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.
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.
•OCPs, PCBs, and PBDEs were detected in maternal serum, placenta, and fetal tissues.•All chemicals were found in fetuses even when not detected in maternal serum/placenta.•Tissue:serum ratios were higher in pregnancies with male fetuses and normal placenta.•Tissue:serum ratios differed by chemical type: OCP > PCB > PFAS.•Chemicals in maternal serum and placenta are not reliable proxies of fetal exposure.
Introduction
Previously, cerebral palsy has been associated with placental infarctions diagnosed macroscopically by midwifes. However, the risk of misclassification of infarctionsis is high without a ...histological verification. Therefore, the objective of this study was to study placental histopathology in relation to developmental outcome at 2.5 years corrected age in a population born extremely preterm.
Material and methods
A prospective cohort study was carried out at Karolinska University Hospital, Stockholm, Sweden on a population of 139 live born infants delivered <27 gestational weeks during 2004–2007. A senior perinatal pathologist, who was blinded to outcome data, evaluated all placental slides microscopically. Neuromotor and sensory functions of the children were evaluated. Bayley Scales of Infant and Toddler Development‐III (Bayley‐III) were used to assess development at corrected age 2.5 years. The outcome data were evaluated without reference to obstetrical and pathology data. The primary outcome measure was neurological and developmental status at 2.5 years of corrected age. This was measured as diagnosis of cerebral palsy, visual impairment, hearing impairment as well as performance on Bayley‐III scales evaluating cognitive, language and motor functions.
Results
Two out of seven children with placental infarction were diagnosed with cerebral palsy compared with one child of 51 without placental infarction (p = 0.036). For developmental outcome according to Bayley‐III at 2.5 years no statistically significant associations with placental pathology were found.
Conclusion
A possible association between placental infarction, verified by microscopic examination, and cerebral palsy has been identified in this extremely preterm population.
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 E
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.
•Partners experienced a stressful and demanding situation during their spouse’s illness.•Partners struggled to advocate for their spouses' care due to a lack of support from healthcare ...providers.•Experiencing HG strengthened their relationship but led to a reluctance to have more children.•It is essential for caregivers to recognise the partner's struggle and offer them support.
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.
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.
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.
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.
Introduction
Mothers at risk of preterm birth are treated with antenatal corticosteroids, which have advantageous effects for prematurely born infants. Accelerated villous maturation in the placenta ...is also associated with improved perinatal outcome. The primary aim of this study was to examine the association between antenatal corticosteroids and accelerated villous maturation. The secondary aim was to study associations with other placental pathologies.
Material and methods
A retrospective cohort study including 105 women who had (n = 75) or had not (n = 30) been treated with antenatal corticosteroids. The women gave birth between 22+0 and 26+6 weeks of gestation in Stockholm County between 1 April 2004 and 31 March 2007. A pathologist blinded to all clinical data except gestational age examined the placental slides to identify pathology parameters. The outcomes were correlated with antenatal corticosteroid treatment, and confounding factors were adjusted using logistic regression.
Results
Accelerated villous maturation was significantly higher in the group treated with corticosteroids (odds ratio 16, 95% CI 2.4–690, p = 0.0005). After adjustment for gestational age and preeclampsia, the difference remained significant (odds ratio 8.9, 95% CI 1.2–389, p = 0.021). No significant associations were found regarding the secondary outcome variables, after adjusting for possible confounders.
Conclusions
Antenatal corticosteroid treatment before preterm birth is associated with accelerated villous maturation. This could be one of the pathways by which corticosteroids are beneficial for preterm infants.
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