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Nino Berdzuli,1 Nino Lomia,1 Anne Cathrine Staff,1,2 Gunta Lazdane,3 Ekaterine Pestvenidze,1 Anne Flem Jacobsen1,2 1Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 2Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway; 3Department of Obstetrics and Gynaecology, Riga Stradins University, Riga, LatviaCorrespondence: Nino BerdzuliInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayTel +45 30354465Email nbniaber@gmail.comIntroduction: Quality of care is an important factor in reducing preventable maternal deaths, yet it is a significant challenge in many countries. Substandard and poor quality of care is the leading factor in two-thirds of maternal deaths in European countries. Our study investigated the deaths of all women of reproductive age in 2012 in Georgia. The aim was to define the underlying causes of maternal deaths and to identify the factors in women’s care which contributed to the fatal outcomes.Methods: A national Reproductive Age Mortality Survey was conducted in Georgia in 2014– 15. Data from multiple sources was triangulated to identify all deaths of women of reproductive age. This was followed by verbal autopsy diagnoses. Each case of early and late maternal death was investigated through interviews and medical record reviews at the last medical facility providing care for the deceased woman. A specialist panel reviewed and assigned underlying causes of death, assessed the management of each woman’s condition, and identified elements of suboptimal care.Results: We identified a total of 23 maternal deaths, including 15 (65%) early and eight (35%) late deaths. The maternal mortality ratio was 26.3 per 100 000 live births. The four leading causes of early maternal deaths were: sepsis, hemorrhage, embolism, and pregnancy-induced hypertension. Embolism and sepsis were the direct causes of the eight late maternal deaths. Cancer, tuberculosis, and postpartum suicide constituted the indirect causes of death. Improvements in care which would have made a difference to the outcomes were identified in 87% of early maternal deaths and 67% of late maternal deaths due to direct obstetric causes.Discussion: Delayed recognition and inappropriate management of maternal complications were common across almost all cases studied. The findings from Georgia highlight the conclusion that most maternal deaths were preventable and that improvement in obstetric care is urgently required.Keywords: maternal mortality, late maternal death, cause of death, quality of care, maternal death preventability

Nino Berdzuli,1 Nino Lomia,1 Anne Cathrine Staff,1,2 Maia Kereselidze,3 Gunta Lazdane,4 Anne Flem Jacobsen1,2 1Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 2Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway; 3Department of Medical Statistics, National Center for Diseases Control and Public Health, Tbilisi, Georgia; 4Riga Stradins University, Riga, LatviaCorrespondence: Nino Berdzuli; Anne Flem Jacobsen Tel +4530354465Email nbniaber@gmail.com; UXAFJA@ous-hf.noIntroduction: Accurate data on maternal mortality are essential for assessing progress towards Sustainable Development Goals (SDG).The aim of the study was to determine the incidence and causes of maternal deaths in Georgia, then explore the potential for improvement of quality of maternal health care. The study’s secondary aims were to identify the level of underreporting of maternal deaths in Georgian vital statistics over 1 year (2012) and to compare these results with previous data from 2006. The study findings allow to support the country in developing evidence-based policies and tracking progress towards meeting SDG targets.Methods: A national Reproductive Age Mortality Survey (RAMOS) was conducted in Georgia in 2014– 15. Multiple data sources were used to identify deaths of women aged 15– 49 years between January and December 2012. All deaths in women of reproductive age were investigated through verbal autopsy (VA) diagnoses. Deaths in women during pregnancy or one-year postpartum were further investigated by conducting interviews and medical record reviews at the last medical facility which provided health care for the woman during her fatal condition. A specialist panel reviewed these cases and assigned underlining causes of deaths.Results: We found that 98% of deaths among women of reproductive age were registered by Georgia’s civil registration and vital statistics system (CRVS). A total of 918 deaths met the study inclusion criteria. Thirty-six (4.1%) women died during pregnancy or within one-year postpartum. Among these 36 deaths, 23 (63.8%) were maternal deaths, 15 early (either during pregnancy or 42 days postpartum) and eight late (43– 365 days postpartum) deaths (65.2% vs 34.8%). The remaining 13 of 36 deaths were coincidental deaths. Fourteen maternal deaths were reported by official statistics and nine deaths were not included in these statistics. Thus, the underreporting rate was 39%. Direct obstetric causes accounted for 73.9% (n=17) of maternal deaths, whereas 26.1% (n=6) were indirect. The leading causes of direct maternal deaths were infection (21.7%), hemorrhage (17.4%), pulmonary embolism (13.0%), and pregnancy-induced hypertension (8.7%). The RAMOS study calculated a maternal mortality ratio (early maternal deaths) of 26.3 per 100,000 live births compared with the official figure of 22.8 per 100,000 live births.Discussions: Registration of early maternal deaths significantly improved since last survey in 2008, while indirect and late maternal deaths continue to be unrecognized, as reflected in official Georgian statistics. The difference between RAMOS study findings and officially reported maternal mortality rates is minimal, showing improvements in detection of maternal deaths by the national maternal mortality surveillance system. The greatest number of direct obstetric deaths occur in the first week postpartum, which likely reflects deficiencies in quality of care.Keywords: maternal mortality, maternal death, incidence, causes, underreporting of maternal deaths, verbal autopsy, reproductive age mortality study

Objective: To develop a chart for risk of small-for-gestational-age (SGA) at birth depending on deviations in symphysis-fundus (SF) height values for gestational age during pregnancy weeks 24-42.Design: Registry-based population cohort study.Setting: Antenatal clinics, Västra Götaland County, Sweden, 2005-2010.Population: The study included 42 018 women with ultrasound-dated singleton pregnancies who delivered at Sahlgrenska University Hospital. Data (including 282 713 SF height measurements) were extracted from the hospital's computerised obstetric database.Methods: Linear and binary regression analyses were used to derive prediction models with deviations in birthweight (BW) and SF height by gestational age as dependent and independent variables, respectively. Receiver operating characteristic curves were generated to evaluate the predictive value of the model in detecting SGA.Main Outcome Measures: Birthweight and small-for-gestational-age.Results: Symphysis-fundus height accounted for 3% of individual BW variance at 24 weeks, increasing gradually to 20% at 40 weeks. Maternal factors explained an additional 10 percentage points of BW variance. Receiver operating characteristic curves confirmed that SF height was a stronger SGA predictor in late than in early pregnancy. Using an SGA relative risk cut-off limit of ≥2-fold, the overall sensitivity was 50% and the overall specificity 80%. Only the most recent SF measurement was useful in predicting BW deviation; previous measurements added nothing to the predictive value.Conclusions: The ability of SF measurements to detect SGA status at birth increases with gestational age. Only the most recent SF measurement has predictive value; a static or falling pattern of SF values did not increase SGA likelihood.Tweetable Abstract: New SF curves predict SGA best in late pregnancy; only the most recent SF measurement has predictive value. [ABSTRACT FROM AUTHOR]

Preeclampsia is associated with increased risk of cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP), a precursor of the atrial natriuretic peptide, is a biomarker for cardiovascular disease. We obtained plasma from 184 pregnant women in gestational weeks 24 to 42 (normotensive pregnancies: n=77, preeclampsia: n=107), from 25 of these women at 5 to 8 years after index pregnancy (normotensive pregnancies: n=11, preeclampsia: n=14), and from 49 normotensive, nonpregnant women and analyzed them by immunoassay for MR-proANP. To investigate potential sources, placental and decidual atrial natriuretic peptide mRNA expression levels were analyzed by quantitative real-time PCR in 21 normotensive and 23 preeclamptic pregnancies, as well as in human heart and kidney samples. For further confirmation, we measured circulating MR-proANP and performed expression studies in a transgenic rat model for preeclampsia. MR-proANP was significantly elevated in maternal plasma in preeclampsia compared with normotensive pregnancies (135 versus 56 pmol/L; P<0.001). However, 5 to 8 years after pregnancy, there was no difference (formerly preeclamptic women versus formerly normotensive in pregnancy: 53 versus 49 pmol/L; P=0.5). Our preeclamptic rat model confirmed the acute MR-proANP differences between preeclamptic and normotensive pregnancies (10.9±1.9 versus 4.3±0.3 pmol/L; P=0.05). Atrial natriuretic peptide expression was high in the heart but negligible in the uteroplacental unit in both normotensive humans and rats, whereas expression in maternal and fetal hearts in the preeclamptic rats was significantly increased, compared with controls. MR-proANP is a serviceable biomarker in preeclampsia, both in humans and a rat model, probably reflecting cardiovascular hemodynamic stress. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to assess changes in placenta growth factor and soluble fms-like tyrosine kinase-1 as predictors of preeclampsia. Study Design: Nested case-control study of 154 preeclampsia cases delivered preterm and 190 delivered at term, and 392 controls. Results: Comparing the lowest and highest quartile of placenta growth factor increase from first to second trimester, the odds for preterm preeclampsia was 13.8 (95% CI, 4.4-43.2) higher for women with the lowest increase. Compared with controls, women with preterm preeclampsia had lower soluble fms-like tyrosine kinase-1 in the first, but higher in second trimester. Comparing highest and lowest quartile of increase, the odds for preterm preeclampsia was 9.2 (95% CI 3.4-25.0) higher for women with highest increase. Low placenta growth factor and high soluble fms-like tyrosine kinase-1 increase combined yielded extremely high relative risk of preterm preeclampsia (odds ratio, 35.3, 95% CI, 7.6-164.2), compared with the combination of high (placenta growth factor) and low (soluble fms-like tyrosine kinase-1) increase. Conclusion: Low placenta growth factor and high soluble fms-like tyrosine kinase-1 increase from first to second trimester are strong predictors of preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia and diabetic pregnancies share pathophysiological features suggested to influence epigenetic changes during foetal life with importance for later development and metabolic and cardiovascular diseases. Aim: Our objective was to study the myocardium in offspring after pregnancy complications. Methods: Forty-five children (age 5-8 years) delivered from pregnancies complicated by preeclampsia (n = 25), diabetes mellitus type 1 (n = 8) or gestational diabetes mellitus (n = 12) were included. Fifteen children from uneventful pregnancies served as controls. Myocardial functions of right and left ventricle were examined by conventional Doppler and tissue Doppler imaging (TDI). Results: No major differences were found in the myocardial function between offspring of pregnancy complications and control group. However, the preeclampsia group had smaller hearts, increased heart rate and increased late diastolic velocity (A'-wave) at mitral valve attachments shown by both pulsed wave and colour TDI compared to the control and diabetic groups together (p ≤ 0.01). Conclusion: Children born after preeclampsia may show effects of a negative impact on the heart already at the age of 5 to 8 years. The numbers of examined children were, however, limited. [ABSTRACT FROM AUTHOR]

Purpose: Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing premature cardiovascular disease (CVD). The mechanisms behind this are not fully understood, but microvascular alterations have been documented in retinal arterioles and venules. The aim of this study was to use non-invasive retinal imaging to investigate the structural and functional properties of arterioles, venules and capillaries in this patient group., Methods: We examined 27 women with previous HDP and 23 controls at 3 years postpartum. The retinal microvasculature was assessed by vessel calibre measurements, retinal oximetry and optical coherence tomography angiography. Differences were analysed using non-parametric tests and multiple regression analyses, adjusted for age and body mass index., Results: Median arteriolar oxygen saturation (SaO 2 ; 94.2% vs. 93.0%), venular oxygen saturation (SvO 2 ; 60.1% vs. 62.4%) and arteriovenous saturation difference (AV-difference; 32.8% vs. 32.3%) were similar across groups. Capillary vessel density (VD; 46.2% vs. 46.3%), skeletonised VD (VSD; 21.3 vs. 21.1 mm/mm 2 ) and vessel diameter index (21.65 vs. 21.86) were also comparable. In the HDP group, mean arterial pressure (MAP) was positively correlated with AV-difference (R 2  = 0.209) and negatively correlated with arteriolar diameter (CRAE; r 2  = 0.382)., Conclusions: Structural microvascular alterations appear not to be key biomarkers for CVD risk after HDP as early as 3 years postpartum in otherwise healthy women. Further studies are needed to evaluate whether such changes occur later in life. MAP was associated with AV-difference only in the HDP group, suggesting specific mechanisms affecting functional microvascular properties in these women., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objective: To describe intrapartum fetal monitoring methods used in all births in Norway in 2019-2020, assess adherence to national guidelines, investigate variation by women's risk status, and explore associations influencing monitoring practices., Methods: A nationwide population-based study. We collected data about all pregnancies with a gestational age ≥ 22 weeks during 2019-2020 from the Medical Birth Registry of Norway. We used descriptive analyses, stratified for risk status, to examine fetal monitoring methods used in all deliveries. Univariable and multivariable logistic regression models were used to determine factors associated with monitoring with cardiotocography (CTG) in low-risk, straightforward births., Results: In total, 14 285 (14%) deliveries were monitored with only intermittent auscultation (IA), 46214 (46%) with only CTG, and 33417 (34%) with IA and CTG combined. Four percent (2 067/50 533) of women with risk factors were monitored with IA only. Half (10589/21 282) of the low-risk women with straightforward births were monitored with CTG. Maternal and fetal characteristics, size of the birth unit and regional practices influenced use of CTG monitoring in this group., Conclusions: Most births are monitored with CTG only, or combined with IA. Half the women with low-risk pregnancies and straightforward births were monitored with CTG although national guidelines recommending IA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit., Design: Individual participant data meta-analysis., Data Sources: Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset., Eligibility Criteria for Selecting Studies: Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model., Results: The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R 2 ) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making., Conclusions: The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required., Trial Registration: PROSPERO CRD42019135045., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research Health Technology Assessment UK programme for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Smoking in pregnancy has detrimental effects on infant respiratory health, while the effects of other nicotine-containing products on infant lung function are unclear. We aimed to explore if smokeless tobacco such as snus used in pregnancy increased the risk of lower lung function in infancy and if the associations differed by sex., Methods: From the Scandinavian population-based Preventing Atopic Dermatitis and ALLergies in Children birth cohort, we included 1163 infants with available tidal flow-volume measurements at 3 months of age and maternal self-reported use of nicotine-containing products in pregnancy. The risk of a ratio of time to peak tidal expiratory flow to total expiratory time <25th percentile by any nicotine exposure, snus exclusively and cigarette smoking with or without other nicotine-containing products was explored by regression analyses adjusting for maternal age, education and asthma., Results: Overall 120 out of 1163 (10.3%) infants were exposed to any nicotine in utero , 71 out of 120 by snus exclusively and 49 out of 120 by smoking, with six also exposed to snus. By pregnancy week 6, 85.8% of mothers reported stopping nicotine use. The risk of lower lung function was higher in children exposed in utero to nicotine-containing products with an odds ratio (OR) of 1.63 (95% confidence interval (CI) 1.02-2.59) with a similar tendency for snus exclusively (OR 1.55, 95% CI 0.88-2.71) and smoking (OR 1.79, 0.84-3.84). Effect estimates were similar after adjusting for covariates. No differences of the effect by sex were observed., Conclusion: Our study suggests that in utero exposure to not only cigarettes, but also snus, may negatively affect infant lung function., Competing Interests: Conflict of interest: K.E.S. Bains reports support for the present manuscript from The PreventADALL study was supported by sponsors to the institutions listed in the financial disclosures outlined in the manuscript. Salary for the PhD project of K.E.S. Bains was provided by Xtrastiftelsen and Klosterstiftelsen. Conflict of interest: E.M. Rehbinder reports receiving personal fees from honoraria for lectures from Sanofi Genzyme, Leo Pharma, NAAF, PEF and Abbvie, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

In this review, we summarize how an increasingly stressed and aging placenta contributes to the maternal clinical signs of preeclampsia, a potentially lethal pregnancy complication. The pathophysiology of preeclampsia has been conceptualized in the two-stage model. Originally, highlighting the importance of poor placentation for early-onset preeclampsia, the revised two-stage model explains late-onset preeclampsia as well, which is often preceded by normal placentation. We discuss how cellular senescence in the placenta may fit with the framework of the revised two-stage model of preeclampsia pathophysiology and summarize potential cellular and molecular mechanisms, including effects on placental and maternal endothelial function. Cellular senescence may occur in response to inflammatory processes and oxidative, mitochondrial, or endoplasmic reticulum stress and chronic stress induce accelerated, premature placental senescence. In preeclampsia, both circulating and tissue-based senescence markers are present. We suggest that aspirin prophylaxis, commonly recommended from the first trimester onward for women at risk of preeclampsia, may affect placentation and possibly mechanisms of placental senescence, thus attenuating the risk of preeclampsia developing clinically. We propose that biomarkers of placental dysfunction and senescence may contribute to altered preventive strategies, including discontinuation of aspirin at week 24-28 depending on placenta-associated biomarker risk stratification., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Introduction: Knowledge on prevalence and association of human papillomavirus (HPV) in third trimester placentae and adverse pregnancy outcomes is limited. We investigated the prevalence of placental HPV at delivery, explored urine HPV characteristics associated with placental HPV and whether placental HPV increased the risk adverse pregnancy outcomes., Methods: Pregnant women were enrolled in the Scandinavian PreventADALL mother-child cohort study at midgestation. Human papillomavirus genotyping was performed on placental biopsies collected at delivery (n = 587) and first-void urine at midgestation and delivery (n = 556). Maternal characteristics were collected by questionnaires at gestational week 18 and 34. Adverse pregnancy outcomes were registered from chart data including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. Uni- and multivariable regression models were used to investigate associations., Results: Placental HPV was detected in 18/587 (3 %). Twenty-eight genotypes were identified among the 214/556 (38 %) with midgestational urine HPV. Seventeen of the 18 women with placental HPV were midgestational HPV positive with 89 % genotype concordance. Midgestational high-risk-(HR)-HPV and high viral loads of Any- or HR-HPV were associated with placental HPV. Persisting HPV infection from midgestation to delivery was not associated with placental HPV. Adverse pregnancy outcomes were seen in 2/556 (0.4 %) of women with placental HPV., Discussion: In this general cohort of pregnant women, the prevalence of placental HPV was 3 %, and midgestational urinary HPV 38 %. High HPV viral load increased the risk for placental HPV infections. We observed no increased risk for adverse pregnancy outcomes in women with placental HPV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In the general population randomized controlled trial PreventADALL, frequent emollient bath additives from 2 weeks of age did not prevent atopic dermatitis, while the effect on skin barrier function throughout infancy is not established., Objectives: The primary aim of this exploratory substudy was to assess the effect of mineral-based oil baths on transepidermal water loss (TEWL) and dry skin through infancy, and secondarily to explore if filaggrin (FLG) mutations modified the effect., Methods: Overall, 2153 infants were included and randomized to either the 'Skin intervention' (SI) group (n = 995) (oil bath 4 times weekly from 2 weeks through 8 months) or 'No skin intervention' (NSI) group (n = 1158), with TEWL measurements at 3, 6 and/or 12 months of age. Information on FLG mutation status was available for 1683 of these infants. Effects of the skin intervention on TEWL and dry skin through infancy were assessed by mixed-effects regression modelling. Background characteristics and protocol adherence were collected from electronic questionnaires, birth records and weekly diaries., Results: The TEWL (95% confidence interval) was on average 0.42 g m-2 h-1 (0.13-0.70, P = 0.004) higher in the SI group compared with the NSI group through the first year of life, with significantly higher levels at 3 months [8.6 (8.3-9.0) vs. 7.6 (7.3-7.9)], but similar at 6 and 12 months. Dry skin was observed significantly more often in the NSI group compared with the SI group at 3 months (59% vs. 51%) and at 6 months of age (63% vs. 53%), while at 12 months of age, the difference was no longer significant. At 3 months, the TEWL of FLG mutation carriers was similar to the TEWL in the SI group. No interaction between SI and FLG mutation was found in the first year of life., Conclusions: Infants given frequent oil baths from 2 weeks of age had reduced skin barrier function through infancy compared with controls, largely attributed to higher TEWL at 3 months of age, while the skin at 3 and 6 months appeared less dry in infants subjected to the skin intervention., Competing Interests: Conflicts of interest E.M.R. has received honoraria for lectures from Leo Pharma, Novartis, Norwegian Asthma and Allergy Association, Norwegian Psoriasis and Eczema Association, and Sanofi Genzyme. K.C.L.C. reports that her institution has received an honorarium from Thermo Fisher Scientific for symposium presentation. C.M.J. has received honoraria for lectures from the Norwegian Medical Association outside the submitted work and M.L. reports personal fees from MSD. All other authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Cardiovascular disease (CVD) is globally the leading cause of death and disability. Sex-specific causes of female CVD are under-investigated. Pregnancy remains an underinvestigated sex-specific stress test for future CVD and a hitherto missed opportunity to initiate prevention of CVD at a young age. Population-based studies show a strong association between female CVD and hypertensive disorders of pregnancy. This association is also present after other pregnancy complications that are associated with placental dysfunction, including fetal growth restriction, preterm delivery and gestational diabetes mellitus. Few women are, however, offered systematic cardio-preventive follow-up after such pregnancy complications. These women typically seek help from the health system at first clinical symptom of CVD, which may be decades later. By this time, morbidity is established and years of preventive opportunities have been missed out. Early identification of modifiable risk factors starting postpartum followed by systematic preventive measures could improve maternal cardiovascular health trajectories, promoting healthier societies. In this non-systematic review we briefly summarize the epidemiological associations and pathophysiological hypotheses for the associations. We summarize current clinical follow-up strategies, including some proposed by international and national guidelines as well as user support groups. We address modifiable factors that may be underexploited in the postpartum period, including breastfeeding and blood pressure management. We suggest a way forward and discuss the remaining knowledge gaps and barriers for securing the best evidence-based follow-up, relative to available resources after a hypertensive pregnancy complication in order to prevent or delay onset of premature CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Age-related gut bacterial changes during infancy have been widely studied, but it remains still unknown how these changes are associated with immune cell composition. This study's aim was to explore if the temporal development of gut bacteria during infancy prospectively affects immune cell composition. Faecal bacteria and short-chain fatty acids were analysed from 67 PreventADALL study participants at four timepoints (birth to 12 months) using reduced metagenome sequencing and gas chromatography. Immune cell frequencies were assessed using mass cytometry in whole blood samples at 12 months. The infants clustered into four groups based on immune cell composition: clusters 1 and 2 showed a high relative abundance of naïve cells, cluster 3 exhibited increased abundance of classical- and non-classical monocytes and clusters 3 and 4 had elevated neutrophil levels. At all age groups, we did observe significant associations between the gut microbiota and immune cell clusters; however, these were generally from low abundant species. Only at 6 months of age we observed significant associations between abundant (>8%) species and immune cell clusters. Bifidobacterium adolescentis and Porphyromonadaceae are associated with cluster 1, while Bacteroides fragilis and Bifidobacterium longum are associated with clusters 3 and 4 respectively. These species have been linked to T-cell polarization and maturation. No significant correlations were found between short-chain fatty acids and immune cell composition. Our findings suggest that abundant gut bacteria at 6 months may influence immune cell frequencies at 12 months, highlighting the potential role of gut microbiota in shaping later immune cell composition., (© 2023 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

Background: Largely unexplored, we investigated if lower lung function, impaired skin barrier function by transepidermal water loss (TEWL), eczema, and filaggrin (FLG) mutations in infancy were associated with asthma in early childhood., Methods: From the factorially designed randomized controlled intervention study PreventADALL, we evaluated 1337/2394 children from all randomization groups with information on asthma at age 3 years, and at age 3 months either lung function, TEWL, eczema, and/or FLG mutations. Lower lung function was defined as the time to peak tidal expiratory flow to expiratory time (t PTEF /t E ) <0.25, and skin barrier impairment as a high TEWL >9.50 g/m 2 /h. Eczema was clinically observed, and DNA genotyped for FLG mutations. Asthma was defined as asthma-like symptoms (≥3 episodes of bronchial obstruction) between age 2-3 years as well as a history of doctor-diagnosed asthma and/or asthma medication use. Associations were analyzed in logistic regression models, presented with adjusted ORs (aOR) and 95% confidence intervals (CI)., Results: Lower lung function and skin barrier impairment were associated with asthma in general; aOR (95% CI) 5.4 (2.1, 13.7) and 1.6 (1.1, 2.5), while eczema and FLG mutations were associated with asthma in children with atopic dermatitis or allergic sensitization only. Stratifying for sex, the risk of asthma was only increased in boys with lower lung function; aOR (95% CI) 7.7 (2.5, 23.6), and in girls with FLG mutations; aOR (95% CI) 3.5 (1.5, 8.2)., Conclusion: Lower lung function and impaired skin barrier function in infancy may increase the risk of asthma at age 3 years., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Fetal microchimerism (FMc) arises when fetal cells enter maternal circulation, potentially persisting for decades. Increased FMc is associated with fetal growth restriction, preeclampsia, and anti-angiogenic shift in placenta-associated proteins in diabetic and normotensive term pregnancies. The two-stage model of preeclampsia postulates that placental dysfunction causes such shift in placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLt-1), triggering maternal vascular inflammation and endothelial dysfunction. We investigated whether anti-angiogenic shift, fetal sex, fetal growth restriction, and severe maternal hypertension correlate with FMc in hypertensive disorders of pregnancy with new-onset features (n = 125). Maternal blood was drawn pre-delivery at > 25 weeks' gestation. FMc was detected by quantitative polymerase chain reaction targeting paternally inherited unique fetal alleles. PlGF and sFlt-1 were measured by immunoassay. We estimated odds ratios (ORs) by logistic regression and detection rate ratios (DRRs) by negative binomial regression. PlGF correlated negatively with FMc quantity (DRR = 0.2, p = 0.005) and female fetal sex correlated positively with FMc prevalence (OR = 5.0, p < 0.001) and quantity (DRR = 4.5, p < 0.001). Fetal growth restriction no longer correlated with increased FMc quantity after adjustment for correlates of placental dysfunction (DRR = 1.5, p = 0.272), whereas severe hypertension remained correlated with both FMc measures (OR = 5.5, p = 0.006; DRR = 6.3, p = 0.001). Our findings suggest that increased FMc is independently associated with both stages of the two-stage preeclampsia model. The association with female fetal sex has implications for microchimerism detection methodology. Future studies should target both male and female-origin FMc and focus on clarifying which placental mechanisms impact fetal cell transfer and how FMc impacts the maternal vasculature., Competing Interests: Declaration of Competing Interest Angiogenic protein reagents (sFlt-1 and PlGF) were donated in-kind to Anne Cathrine Staff by Roche Diagnostics. Some of the microchimerism data have been generated at Chimerocyte Inc., at which Sami B Kanaan is founder. The data were generated in a blinded fashion and Chimerocyte had no role in the final interpretation of the data. The remaining authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)