Reference Values for Placental Weight and Placental:Fetal Weight Ratio in a Swedish Population.

INTRODUCTION: There is important clinical information from placental weight and its ratio to the fetal weight. The aim with this study was to establish reference values for the placental weight and the placental:fetal weight ratio for gestational weeks 13-43 in a Swedish population. MATERIALS AND METHODS: Cases were retrospectively collected from the database used at the Pathology Department at Karolinska University Hospital and information about the placental weight, fetal weight, and gestational age was retrieved. Conditions, which could affect the placental- or fetal weight were excluded. Thereafter percentile curves were calculated for the placental weight and the placental:fetal weight ratio for gestational weeks. RESULTS: A total of 730 cases were included and percentile curves for the placental weight for gestational week 13-43 and placental:fetal weight ratio for gestational week 18-43 are presented. CONCLUSIONS: Reference values for post fixation placental weight and its ratio to fetal weight for a Swedish population are presented. The reference values are lower than the current reference values used in our institution, and this will be of importance when interpreting findings after placental examination.

Missed abortion in the 11-21-week period: Fetal autopsy and placental histopathological analysis of 794 cases.

INTRODUCTION: Missed abortion (MA) is a type of miscarriage with multiple etiological factors that refers to fetal death with a failure of the retained intrauterine product of conception to be discharged spontaneously. Currently fetal death in missed abortion is categorized according to three main causes: Fetal, placental, and maternal factors. The aim of the current study was to contribute and increase knowledge in clinical practice of late first and second trimester MA (Gestational age: week 11 + 0 - week 20 + 6). MATERIAL AND METHODS: This retrospective case series study includes 794 cases of fetuses and matching placentas sent to the Section of Perinatal Pathology, Department of Pathology, Karolinska Hospital between 2003 and 2019 from five different gynecology departments in the Stockholm region, Sweden. RESULTS: The cases were divided into two groups according to gestational length; gestational week 11 + 0-14 + 6 (group A) and 15 + 0-20 + 6 (group B) respectively, and comparisons were made between groups. Fetal growth restriction and placental pathology were more common in late MA, but number of cases with malformation were higher in early MA. Cord pathology was seen in approximately 40 % of the cases and equally distributed in the gestational weeks included. DISCUSSION: Fetal growth restriction and placental pathology were more common in late second trimester MA. This might demonstrate an early placental dysfunction affecting fetal growth and may be associated to maternal comorbidity such as autoimmune disease and cardiovascular disease. It is advisable to investigate maternal factors more closely after late second trimester MA before a future pregnancy. The risk for recurrent MA is believed to be low in cases of significant cord pathology. CONCLUSION: Cord complications were over-represented in missed abortion suggesting a probable etiopathogenetic link to fetal demise in this condition.

Placental pathology in a large (Swedish) cohort of SARS-CoV-2 infected mothers.

INTRODUCTION: SARS-CoV-2 placentitis is associated with placental destruction and insufficiency and can affect perinatal outcome. The aim of the current study was to contribute with increased knowledge regarding placental histology in maternal SARS-CoV-2 infection during the pregnancy, as well as the correlation to the severity of maternal SARS-CoV-2 infection. MATERIAL AND METHODS: This retrospective observational study included 116 women who had a verified SARS-CoV-2 infection during pregnancy and gave birth between April 2020 and February 2022 in the Stockholm region, Sweden. Placental tissue was evaluated regarding several histopathological parameters, amongst them detection of the triad of characteristics of placental SARS-CoV-2 infection: chronic histiocytic intervillositis, fibrin deposition and villous trophoblast necrosis, and immunohistochemistry for ORF-3 protein expression was used for confirmation. Medical records were reviewed for maternal characteristics and neonatal outcome. RESULTS: SARS-CoV-2 placentitis was present in one-fifth of the examined placentas admitted to the institute due to maternal SARS-CoV-2 infection, out of which 86,4 % were delivered by acute caesarian section (ACS), all on fetal indication, and one pregnancy ended in stillbirth. Half of the cases without placentitis were delivered by ACS, out of which 50 % were on fetal indication. There was a clear tendency of a shorter time gap between confirmed maternal SARS-CoV-2 infection and delivery in the placentitis group. DISCUSSION: The presence of SARS-CoV-2 placentitis does not seem to correlate with maternal factors or the severity of infection. It does correlate with development of placental dysfunction of acute/subacute onset and is often manifested as reduced fetal movements.

Periprosthetic joint infection after total hip arthroplasty induces histological degeneration of the gluteus medius tendon.

Aims: A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient's quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. Methods: A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed. Results: Biopsy samples from the GMED from infected patients revealed a larger fibril diameter than control patients, as seen in the TEM (p < 0.001). Uninfected patients were slightly older and had their revisions performed significantly later than the infected patients. Histologically, samples from infected patients revealed significantly more vascularity (p < 0.001), the presence of glycosaminoglycans (p < 0.001), and a higher TDS (p = 0.003) than the control patients. The majority of patients had staphylococcal infections of various species. Conclusion: More histological degeneration in the GMED was found in patients undergoing THA revision surgery due to PJI than in patients undergoing THA revision surgery due to other reasons.

Spatial transcriptomics of human placentas reveal distinct RNA patterns associated with morphology and preeclampsia.

Spatial transcriptomics (ST) maps RNA level patterns within a tissue. This technology has not been previously applied to human placental tissue. We demonstrate analysis of human placental samples with ST. Unsupervised clustering revealed that distinct RNA patterns were found corresponding to different morphological structures. Additionally, when focusing upon terminal villi and hemoglobin associated structures, RNA levels differed between placentas from full term healthy pregnancies and those complicated by preeclampsia. The results from this study can provide a benchmark for future ST studies in placenta.

Al-Gazali Skeletal Dysplasia Constitutes the Lethal End of ADAMTSL2-Related Disorders.

Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

OBJECTIVE: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress. DESIGN: Retrospective, observational. SETTING: Nationwide. POPULATION: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden. METHODS: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells. MAIN OUTCOME MEASURES: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants. RESULTS: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission. CONCLUSIONS: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury.

CONTEXT.­: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. OBJECTIVE.­: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN.­: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. RESULTS.­: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. CONCLUSIONS.­: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

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.

Histological and ultrastructural degenerative findings in the gluteus medius tendon after hip arthroplasty.

BACKGROUND: Despite gluteus medius (GMED) tendinosis being relatively common, its presence in association with hip osteoarthritis (OA) or total hip arthroplasty (THA) is not well studied. It was hypothesized that more tendon degeneration would be found in patients with OA of the hip and in those that had undergone THA than that in a control group. METHODS: One hundred patients were included between 2016 and 2019 and were included into 4 groups; the patients were undergoing revision surgery in two groups and primary THA in the other two groups; 22 patients had previously undergone primary THA through a direct lateral approach (involving sectioning of the GMED tendon), 24 patients had previously undergone primary THA through a posterior approach (leaving the GMED tendon intact), 29 patients had primary hip OA, and 25 patients who suffered a femoral neck fracture served as controls. Biopsies from the GMED tendon were obtained at the time of the primary THA or the hip revision surgery. The tendon biopsies were examined ultrastructurally and histologically. RESULTS: Ultrastructurally, the direct lateral and posterior revision groups had statistically significantly more collagen fibrils with smaller diameters compared with the fracture and primary THA groups. Moreover, the direct lateral revision group had more collagen fibrils with smaller diameters compared with the posterior revision group. Histologically, the direct lateral revision group had a higher total degeneration score (TDS) compared with the primary hip OA group. CONCLUSIONS: The GMED tendon shows more ultrastructural degeneration in patients who undergo hip revision arthroplasty than in patients with primary OA of the hip and control patients, who had suffered a femoral neck fracture. Furthermore, patients who had previously undergone primary THA through a direct lateral approach revealed more histological GMED tendon degeneration than patients who suffer primary hip OA.

Maternal obesity and stillbirth at term; placental pathology-A case control study.

OBJECTIVE: The aim was to explore the potential role of the placenta for the risk of stillbirth at term in pregnancies of obese women. METHODS: This was a case-control study comparing placental findings from term stillbirths with placental findings from live born infants. Cases were singleton term stillbirths to normal weight or obese women, identified in the Stockholm stillbirth database, n = 264 and n = 87, respectively. Controls were term singletons born alive to normal weight or obese women, delivered between 2002-2005 and between 2018-2019. Placentas were compared between women with stillborn and live-born infants, using logistic regression analyses. RESULTS: A long and hyper coiled cord, cord thrombosis and velamentous cord insertion were stronger risk factors for stillbirth in obese women compared to normal weight women. When these variables were adjusted for in the logistic regression analysis, also adjusted for potential confounders, the odds ratio for stillbirth in obese women decreased from 1.89 (CI 1.24-2.89) to 1.63 (CI 1.04-2.56). CONCLUSION: Approximately one fourth of the effect of obesity on the risk of stillbirth in term pregnancies is explained by umbilical cord associated pathology.

Is obesity in pregnancy associated with signs of chronic fetal hypoxia?

INTRODUCTION: The prevalence of obesity in pregnancy is increasing worldwide. Maternal obesity increases risks of severe fetal and neonatal complications. The underlying pathophysiological mechanisms are unclear. One possible contributing factor could be chronic fetal hypoxia. The aim of this study was to compare placentas from women with and without obesity with respect to placental lesions, which could reflect compensatory mechanisms in response to chronic fetal hypoxia as well as lesions possibly leading to chronic fetal hypoxia. In addition, levels of erythropoietin in cord blood were compared between offspring of lean and obese women. MATERIAL AND METHODS: This cohort study included 180 women with uneventful, full-term, singleton pregnancies, out of which 91 lean women had a body mass index (BMI) of 18.5-24.9 kg/m2 and 89 women had obesity (BMI ≥30 kg/m2 ). Women were recruited at Södersjukhuset between 16 October 2018 and 2 December 2019. Placentas were investigated by two senior perinatal pathologists, who were blinded for maternal BMI. Cord blood was analyzed for levels of erythropoietin. RESULTS: Levels of erythropoietin in cord blood increased with maternal BMI (P = .01, ß = 0.97, 95% CI 0.27-1.68). There was no difference between placentas of obese and lean women in number of placental lesions reflecting chronic fetal hypoxia or in lesions that could possibly lead to chronic fetal hypoxia. CONCLUSIONS: This study of term and uneventful pregnancies demonstrated a positive association between maternal obesity and concentrations of erythropoietin in cord blood at birth. This finding supports the hypothesis of chronic fetal hypoxia as a risk factor for complications in the pregnancies of obese women. There were no differences in lesions associated with hypoxia between placentas of obese and lean women.

Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome.

The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann-like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. We identified essential loss-of-function variants in IL6ST (a homozygous nonsense variant and a homozygous intronic splice variant with exon skipping). Functional tests showed absent cellular responses to GP130-dependent cytokines including IL-6, IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF). Genetic reconstitution of GP130 by lentiviral transduction in patient-derived cells reversed the signaling defect. This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development.

Epigenetic Modifications in Placenta are Associated with the Child's Sensitization to Allergens.

Prenatal environmental exposures are considered to contribute to the development of allergic sensitization by epigenetic mechanisms. The role of histone acetylation in the placenta has not been examined yet. We hypothesized that placental histone acetylation at the promoter regions of allergy-related immune regulatory genes is associated with the development of sensitization to allergens in the child. Histones H3 and H4 acetylation at the promoter regions of 6 selected allergy-related immune regulatory genes was assessed by a chromatin immunoprecipitation assay in 173 term placentas collected in the prospective birth-cohort ALADDIN. The development of IgE sensitization to allergens in the children was followed from 6 months up to 5 years of age. We discovered significant associations of histone acetylation levels with decreased risk of allergic sensitization in 3 genes. Decreased risk of sensitization to food allergens was associated with higher H3 acetylation levels in placentas at the IFNG and SH2B3 genes, and for H4 acetylation in HDAC4. Higher HDAC4 H4 acetylation levels were also associated with a decreased risk of sensitization to aeroallergens. In conclusion, our results suggest that acetylation of histones in placenta has a potential to predict the development of sensitization to allergens in children.

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.

Identification of putative pathogenic single nucleotide variants (SNVs) in genes associated with heart disease in 290 cases of stillbirth.

The incidence of stillbirth in Sweden has essentially remained constant since the 1980's, and despite thorough investigation, many cases remain unexplained. It has been suggested that a proportion of stillbirth cases is caused by heart disease, mainly channelopathies. The aim of this study was to analyze DNA from 290 stillbirth cases without chromosomal abnormalities for pathogenic single nucleotide variants (SNVs) in 70 genes associated with cardiac channelopathies and cardiomyopathies. The HaloPlex Target Enrichment System (Agilent Technologies) was utilized to prepare sequencing libraries which were sequenced on the Illumina NextSeq platform. We found that 12.1% of the 290 investigated stillbirth cases had one (n = 31) or two (n = 4) variants with evidence supporting pathogenicity, i.e. loss-of-function variants (nonsense, frameshift, splice site substitutions), evidence from functional studies, or previous identification of the variants in affected individuals. Regarding identified putative pathogenic variants in genes associated with channelopathies, the prevalence was significantly higher in the stillbirth cohort (n = 23, 7.93%) than the corresponding prevalence of the same variants in the non-Finnish European population of the Exome Aggregation Consortium (2.70%, p<0.001) and SweGen, (2.30%, p<0.001). Our results give further support to the hypothesis that cardiac channelopathies might contribute to stillbirth. Screening for pathogenic SNVs in genes associated with heart disease might be a valuable complement for stillbirth cases where today's conventional investigation does not reveal the underlying cause of fetal demise.

Genetic Analysis of Copy Number Variation in Large Chorangiomas.

INTRODUCTION: Chorangioma (CA) is the most common nontrophoblastic, vascular tumor-like lesion of the placenta with a reported incidence of 0.5% to 1% in all examined placentas. The underlying molecular mechanisms of CAs are still poorly elucidated, and a systematic investigation of the genetic background of CAs has not previously been done. MATERIALS AND METHODS: Tissue biopsies from 8 large (>40 mm) histologically confirmed CAs and 8 unaffected matched placenta controls, along with standard control DNA samples were analyzed for large genomic deletions and duplications using array comparative genomic hybridization (array-CGH) method. RESULTS: Array-CGH analysis revealed no rare or novel copy number variants in the CA samples compared with either standard control DNA or unaffected placenta DNA from the same individual. DISCUSSION: In this study, a systematic genetic investigation of 8 large CAs failed to demonstrate any large-scale pathogenic genetic changes. This lack of association might support a nongenetic, nontumorous origin of these lesions; however, additional genetic studies focusing on smaller genomic alterations are required to fully assess any possible genetic contribution.

Placental inflammation, lifestyle, maternal and early child sensitisation to allergens - the assessment of lifestyle and allergic disease during infancy birth cohort.

AIM: To investigate (i) whether maternal sensitisation to allergens, and lifestyle can influence the risk of acute and chronic inflammation of the placenta, in the forms of chorioamnionitis and villitis, respectively, and (ii) whether these placental inflammations are associated with the outcome of sensitisation for the child during preschool age. METHODS: Placentas from term uncomplicated pregnancies (n = 275) in the assessment of lifestyle and allergic disease during infancy study were analysed for the presence of acute chorioamnionitis and chronic villitis. Stepwise logistic regression was performed to estimate the relative risk of placental inflammation in relation to maternal allergic sensitisation and lifestyle, and the association between placental inflammation and sensitisation of the child up to five years of age. RESULTS: Parity and delivery at home were independently associated with chorioamnionitis, home delivery only with the low grade. Maternal allergic sensitisation was associated with increased risk of villitis in the bivariable model, however, not in the multivariable model. No significant associations were detected between placental inflammation and the outcome of sensitisation to allergens at five years of age. CONCLUSION: Our data do not support the hypothesis that the increased risk for sensitisation of a child when the mother is allergic is mediated via placental inflammation.

Testing strategies to reduce morbidity and mortality from Lynch syndrome.

OBJECTIVE: Lynch syndrome (LS) has an autosomal dominant inheritance pattern and is associated with increased risk for colorectal cancer (CRC) and other cancers. Various strategies are used to identify patients at risk and offer surveillance and preventive programs, the cost effectiveness of which is much dependent on the prevalence of LS in a population. Universal testing (UT) is proposed as an effective measure, targeting all newly diagnosed CRC patients under a certain age. MATERIALS AND METHODS: LS cases were identified in a cohort of 572 consecutive CRC patients. Immunohistochemistry was performed in 539 cases, using antibodies against mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. Microsatellite instability and gene mutation screening were performed in 57 cases. RESULTS: In total 11 pathogenic variants were detected, identifying LS in 1.9% of new CRC cases. Comparing the results with current clinical methods, 2 pathogenic variants were found with Amsterdam criteria and 9 when using either Bethesda guidelines or our institution's prior clinical criteria. Pathogenic variants in MSH6 were the most common in our series. We also found different outcomes using different age cut offs. CONCLUSION: Our study demonstrates that UT of tumors before age on onset at 75 years would most likely be cost-efficient and essentially equivalent to applying the Bethesda guidelines or our institution's prior clinical criteria on all new CRC.