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Objective: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation.Design: Nationwide case series.Setting: All Dutch tertiary perinatal care centres.Population: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014.Methods: Women were identified through computerised hospital databases. Data were collected from medical records.Main Outcome Measures: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival).Results: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days.Conclusions: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling.Tweetable Abstract: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival. [ABSTRACT FROM AUTHOR]

Socioeconomic differences in health risk behaviours during pregnancy may be influenced by social relations. In this study, we aimed to investigate if social need fulfillment moderates the association between socioeconomic status (SES) and health risk behaviours (smoking and/or alcohol consumption) during pregnancy. We used baseline data from the Lifelines Cohort Study merged with data from the Lifelines Reproductive Origin of Adult Health and Disease (ROAHD) cohort. Education level was used to determine SES, categorized into low, middle, and high, with middle SES as the reference category. Social need fulfillment was taken as indicator for social relations and was measured with the validated Social Production Function Instrument for the Level of Well-being scale. The dependent variable was smoking and/or alcohol consumption during pregnancy. Univariable and multivariable logistic regression analysis was conducted to assess the association of SES and social need fulfillment with health risk behaviours and to test for effect modification. We included 1107 pregnant women. The results showed that women with a high SES had statistically significantly lower odds of health risk behaviours during pregnancy. The interaction effect between SES and social need fulfillment on health risk behaviours was not statistically significant, indicating that no moderation effect is present. The results indicate that social need fulfillment does not modify the effect of SES on health risk behaviours during pregnancy. However, in literature, social relations are identified as an important influence on health risk behaviours. More research is needed to identify which measure of social relations is the most relevant regarding the association with health risk behaviours., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Introduction: Refugees and their healthcare providers face numerous challenges in receiving and providing maternal and newborn care. Research exploring how these challenges are related to adverse perinatal and maternal outcomes is scarce. Therefore, this study aims to identify suboptimal factors in maternal and newborn care for asylum-seeking and refugee women and assess to what extent these factors may contribute to adverse pregnancy outcomes in the Netherlands., Methods: We conducted a retrospective analysis of national perinatal audit data from 2017 to 2019. Our analysis encompassed cases with adverse perinatal and maternal outcomes in women with a refugee background (n = 53). Suboptimal factors in care were identified and categorized according to Binder et al.'s Three Delays Model, and the extent to which they contributed to the adverse outcome was evaluated., Results: We identified 29 suboptimal factors, of which seven were related to care-seeking, six to the accessibility of services, and 16 to the quality of care. All 53 cases contained suboptimal factors, and in 67.9% of cases, at least one of these factors most likely or probably contributed to the adverse perinatal or maternal outcome., Conclusion: The number of suboptimal factors identified in this study and the extent to which they contributed to adverse perinatal and maternal outcomes among refugee women is alarming. The wide range of suboptimal factors identified provides considerable scope for improvement of maternal and newborn care for refugee populations. These findings also highlight the importance of including refugee women in perinatal audits as it is essential for healthcare providers to better understand the factors associated with adverse outcomes to improve the quality of care. Adjustments to improve care for refugees could include culturally sensitive education for healthcare providers, increased workforce diversity, minimizing the relocation of asylum seekers, and permanent reimbursement of professional interpreter costs., Competing Interests: The authors declare no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study., (Copyright: © 2024 Verschuuren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The rise of forced migration worldwide compels birth care systems and professionals to respond to the needs of women giving birth in these vulnerable situations. However, little is known about the perspective of midwifery professionals on providing perinatal care for forcibly displaced women. This study aimed to identify challenges and target areas for improvement of community midwifery care for asylum seekers (AS) and refugees with a residence permit (RRP) in the Netherlands., Methods: For this cross-sectional study, data were collected through a survey aimed at community care midwives who currently work or who have worked with AS and RRP. We evaluated challenges identified through an inductive thematic analysis of respondents' responses to open-ended questions. Quantitative data from close-ended questions were analyzed descriptively and included aspects related to the quality and organization of perinatal care for these groups., Results: Respondents generally considered care for AS and RRP to be of lower quality, or at best, equal quality compared to care for the Dutch population, while the workload for midwives caring for these groups was considered higher. The challenges identified were categorized into five main themes, including: 1) interdisciplinary collaboration; 2) communication with clients; 3) continuity of care; 4) psychosocial care; and 5) vulnerabilities among AS and RRP., Conclusions: Findings suggest that there is considerable opportunity for improvement in perinatal care for AS and RRP, while also providing direction for future research and interventions. Several concerns raised, especially the availability of professional interpreters and relocations of AS during pregnancy, require urgent consideration at legislative, policy, and practice levels., (© 2023 The Authors. Birth published by Wiley Periodicals LLC.)

Problem: Women with a previous uncomplicated pregnancy have lower risks of immune-associated pregnancy disorders in a subsequent pregnancy. This could indicate a different maternal immune response in multigravid women compared to primigravid women. In a previous study, we showed persistent higher memory T cell proportions with higher CD69 expression after uncomplicated pregnancies. To our knowledge no studies have reported on immune cells in general, and immune memory cells and macrophages specifically in multigravid and primigravid women., Method of Study: T cells and macrophages were isolated from term decidua parietalis and decidua basalis tissue from healthy primigravid women (n = 12) and multigravid women (n = 12). Using flow cytometry, different T cell populations including memory T cells and macrophages were analyzed. To analyze whether a different immune phenotype is already present in early pregnancy, decidual tissue from uncomplicated ongoing pregnancies between 9 and 12 weeks of gestation from multigravida and primigravid women was investigated using qRT-PCR., Results: Nearly all T cell subsets analyzed in the decidua parietalis had significantly higher CD69 + proportions in multigravid women compared to primigravid women. A higher proportion of decidual (CD50 - ) M2-like macrophages was found in the decidua parietalis in multigravid women compared to primigravid women. In first trimester decidual tissue higher FOXP3 mRNA expression was found in multigravid women compared to primigravid women., Conclusions: This study shows that decidual tissue from multigravid women has a more activated and immunoregulatory phenotype compared to decidual tissue from primigravid women in early pregnancy and at term which could suggest a more balanced immune adaptation towards pregnancy after earlier uncomplicated pregnancies., (© 2022 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

The electronic cigarette (e-cigarette) became commercially available around 2004, yet the characteristics of pregnant women who use these devices and their effects on maternal and infant health remain largely unknown. This study aimed to investigate maternal characteristics and pregnancy outcomes according to maternal smoking status. We conducted a cross-sectional study of Dutch women with reported pregnancies between February 2019 and May 2022, using an online questionnaire to collect data on smoking status and demographic, lifestyle, pregnancy, and infant characteristics. Smoking status is compared among non-smokers, tobacco cigarette users, e-cigarette users, and dual users (tobacco and e-cigarette). We report descriptive statistics and calculate differences in smoking status between women with the chi-square or Fisher (Freeman-Halton) test. Of the 1937 included women, 88.1% were non-smokers, 10.8% were tobacco cigarette users, 0.5% were e-cigarette users, and 0.6% were dual users. Compared with tobacco users, e-cigarette users more often reported higher education, having a partner, primiparity, and miscarriages. Notably, women who used e-cigarettes more often had small infants for gestational age. Despite including few women in the e-cigarette subgroup, these exploratory results indicate the need for more research to examine the impact of e-cigarettes on pregnancy outcomes.

Background: The high prevalence of smoking pregnant women in Dutch areas with lower socioeconomic status and the consecutively harmful exposure to tobacco to both mother and child, depicted a high need for a novel intervention. According to other studies, the utilisation of financial incentives appeared to be a promising method for smoking cessation in pregnant women. Therefore, the aim of this study was to investigate the feasibility of implementing contingent financial incentives as smoking cessation support for pregnant women in the Netherlands., Methods: Feasibility study consisting of four developmental phases: (1) acceptability of Dutch population regarding financial-incentive-intervention by conducting an online questionnaire, (2) composing a pilot study utilising the financial-incentive-intervention in clinical practice, (3) execution of the composed pilot study and (4) evaluation of the executed pilot study utilising a mixed-methods approach. A financial-incentive-intervention, given in a contingent financial scheme (during five consequential appointments, respectively €25/€50/€100/€150/€250), if smoking abstinence was proven by the amount of cotinine in the urine of the pregnant women measured utilising a urine dipstick test. The public acceptability for the financial-incentive-intervention was assessed using 5-Likert scales. The number of pregnant women able to abstain from smoking during the pilot study and utilising the financial-incentive-intervention in clinical practice were used to assess the prosperity and practicality of the pilot study respectively. The pilot study was evaluated using a mixed-methods approach., Results: In total, 55.1% of the Dutch population sample (n = 328) found a financial incentive inappropriate for smoking cessation in pregnant women, while the healthcare professionals and pilot study participants thought the financial-incentive-intervention to be a helpful approach. Eleven vouchers were given during the pilot study, and one woman completed all test points and tested negative for cotinine at the end of the pilot study., Conclusion: Although the financial-incentive-intervention appeared to be a promising approach for smoking cessation in pregnant women, the acceptability of the Dutch population and the number of pregnant women able to abstain smoking during this pilot study was low. Despite the limited study population, this study proved the concept of this financial-incentive-intervention to be feasible for implementation in the Netherlands., Trial Registration: Not applicable since this is a feasibility study prior to a trial., (© 2022. The Author(s).)

Introduction: Human error plays a vital role in diagnostic errors in the emergency department. A thorough analysis of these human errors, using information-rich reports of serious adverse events (SAEs), could help to better study and understand the causes of these errors and formulate more specific recommendations., Methods: We studied 23 SAE reports of diagnostic events in emergency departments of Dutch general hospitals and identified human errors. Two researchers independently applied the Safer Dx Instrument, Diagnostic Error Evaluation and Research Taxonomy, and the Model of Unsafe acts to analyze reports., Results: Twenty-one reports contained a diagnostic error, in which we identified 73 human errors, which were mainly based on intended actions (n = 69) and could be classified as mistakes (n = 56) or violations (n = 13). Most human errors occurred during the assessment and testing phase of the diagnostic process., Discussion: The combination of different instruments and information-rich SAE reports allowed for a deeper understanding of the mechanisms underlying diagnostic error. Results indicated that errors occurred most often during the assessment and the testing phase of the diagnostic process. Most often, the errors could be classified as mistakes and violations, both intended actions. These types of errors are in need of different recommendations for improvement, as mistakes are often knowledge based, whereas violations often happen because of work and time pressure. These analyses provided valuable insights for more overarching recommendations to improve diagnostic safety and would be recommended to use in future research and analysis of (serious) adverse events., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Placental pathology and pregnancy complications are associated with unfavorable regulation of the maternal immune system. Although much research has been performed towards the role of immune cells like macrophages and T cells in this context, little is known about the presence and function of mast cells (MC). MC can be sub classified in tryptase-positive (MC T ) and tryptase- and chymase-positive (MC TC ). This study investigates the presence of MC in the decidua of pregnancies complicated by fetal growth restriction (FGR) and stillbirth (SB)., Methods: Placental tissue from FGR (n = 250), SB (n = 64) and healthy pregnancies (n = 42) was included. Histopathological lesions were classified according to the Amsterdam Placental Workshop Group criteria. Tissue sections were stained for tryptase and chymase. Decidual MC were counted manually, and the results were expressed as number of cells/mm 2 decidual tissue., Results: A significant lower median number of MC TC was found in the decidua of FGR (0.40 per mm 2 ; p < 0.001) and SB (0.51 per mm 2 ; p < 0.05) compared to healthy controls (1.04 per mm 2 ). No difference in MC T number (1.19 per mm 2 , 1.88 per mm 2 and 1.37 per mm 2 respectively) was seen between the groups. There was no difference in number of MC T and MC TC between placental pathological lesions., Discussion: Our findings suggest a shift in decidual MC balance towards MC T in pregnancy complications. No difference in numbers of MC subtypes was found to be related to histopathologic lesions., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Women who smoke during pregnancy make less use of prenatal care; the relation of smoking behavior with the use of other forms of maternal healthcare is unknown. The objective of this study is to investigate the association between women's smoking behavior and their use of healthcare during pregnancy, birth and six weeks postpartum., Methods: We analyzed data from the Dutch Midwifery Case Registration System (VeCaS), period 2012-2019. We included women with a known smoking status, singleton pregnancies, and who had their first appointment before 24 weeks of gestation with the primary care midwife. We compared three groups: non-smokers, early stoppers (stopped smoking in the first trimester), and late- or non-stoppers (stopped smoking after the first trimester or continued smoking). Descriptive statistics were used to report maternal healthcare utilization (during pregnancy, birth and six weeks postpartum), statistical differences between the groups were calculated with Kruskal-Wallis tests. Multivariable logistic regression was conducted to assess the association between smoking behavior and referrals to primary, secondary or tertiary care., Results: We included 41 088 pregnant women. The groups differed significantly on maternal healthcare utilization. The late- or non-stoppers initiated prenatal care later and had less face-to-face consultations with primary care midwives during pregnancy. Compared to the non-smokers, the early- and late- or non-stoppers were statistically signficiantly more likely to be referred to the obstetrician during pregnancy and birth. Postpartum, the early- and late- or non-stoppers were statistically signficantly less likely to be referred to the obstetrician compared to the non-smokers., Conclusions: Although the early- and late- or non-stoppers initiated prenatal care later than the non-smokers, they did receive adequate prenatal care (according to the recommendations). The results suggest that not smoking during pregnancy may decrease the likelihood of referral to secondary or tertiary care. The large population of smokers being referred during pregnancy underlines the important role of the collaboration between healthcare professionals in primary and secondary or tertiary care. They need to be more aware of the importance of smoking as a medical and as a non-medical risk factor., (© 2022. The Author(s).)

Introduction: Gestational diabetes mellitus (GDM) is a common disorder of pregnancy with health risks for mother and child during pregnancy, delivery and further lifetime, possibly leading to type 2 diabetes mellitus (T2DM). Current treatment is focused on reducing hyperglycaemia, by dietary and lifestyle intervention and, if glycaemic targets are not reached, insulin. Metformin is an oral blood glucose lowering drug and considered safe during pregnancy. It improves insulin sensitivity and has shown advantages, specifically regarding pregnancy-related outcomes and patient satisfaction, compared with insulin therapy. However, the role of metformin in addition to usual care is inconclusive and long-term outcome of metformin exposure in utero are lacking. The primary aim of this study is to investigate the early addition of metformin on pregnancy and long-term outcomes in GDM., Methods and Analysis: The Pregnancy Outcomes: Effects of Metformin study is a multicentre, open-label, randomised, controlled trial. Participants include women with GDM, between 16 and 32 weeks of gestation, who are randomised to either usual care or metformin added to usual care, with insulin rescue in both groups. Metformin is given up to 1 year after delivery. The study consists of three phases (A-C): A-until 6 weeks after delivery; B-until 1 year after delivery; C-observational study until 20 years after delivery. During phase A, the primary outcome is a composite score consisting of: (1) pregnancy-related hypertension, (2) large for gestational age neonate, (3) preterm delivery, (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia, (8) neonatal intensive care admission. During phase B and C the primary outcome is the incidence of T2DM and (weight) development in mother and child., Ethics and Dissemination: The study was approved by the Central Committee on Research Involving Human Subjects in the Netherlands. Results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT02947503., Competing Interests: Competing interests: KH received a lecture fee and travel grant from Novo Nordisk. All other authors declare they have no competing interests related to this study., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the health risks of smoking, some women continue during pregnancy. Professional smoking cessation support has shown to be effective in increasing the proportion of pregnant women who quit smoking. However, few women actually make use of professional support., Aim: To investigate the needs of women and their partners for professional smoking cessation support during pregnancy., Methods: Semi-structured interviews were held with pregnant women and women who recently gave birth who smoked or quit smoking during pregnancy, and their partners, living in the north of the Netherlands. Recruitment was done via Facebook, LinkedIn, food banks, baby stores and healthcare professionals. The interviews were recorded, transcribed and thematically analysed., Results: 28 interviews were conducted, 23 with pregnant women and women who recently gave birth, and five with partners of the women. The following themes were identified: 1) understanding women's needs, 2) responsibility without criticism, and 3) women and their social network. These themes reflect that women need support from an involved and understanding healthcare professional, who holds women responsible for smoking cessation but refrains from criticism. Women also prefer involvement of their social network in the professional support., Conclusion: For tailored support, the Dutch guideline for professional smoking cessation support may need some adaptations. The adaptations and recommendations, e.g. to involve women and their partners in the development of guidelines, might also be valuable for other countries. Women prefer healthcare professionals to address smoking cessation in a neutral way and to respect their autonomy in the decision to stop smoking., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants., Competing Interests: The work of MH, FD, LF, FN, MS, MV, SO, and FV has been funded by the European Union via the Horizon 2020: Future Emerging Topics call FET Open, grant EU863087, project PLS, https://cordis.europa.eu/project/id/863087. MH, MV, and SO are shareholders in Juno Perinatal Healthcare BV, Netherlands. AP is Chair of Scientific Advisory Board of Concord Neonatal BV, for which he receives no compensation, https://concordneonatal.com. He also consults for Fisher and Paykel Healthcare and receives compensation https://www.fphcare.com/en-gb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van der Hout-van der Jagt, Verweij, Andriessen, de Boode, Bos, Delbressine, Eggink, Erwich, Feijs, Groenendaal, Kramer, Lely, Loop, Neukamp, Onland, Oudijk, te Pas, Reiss, Schoberer, Scholten, Spaanderman, van der Ven, Vermeulen, van de Vosse and Oei.)

Background: A history of stillbirth is a risk factor for recurrent fetal death in a subsequent pregnancy. Reported risks of recurrent fetal death are often not stratified by gestational age. In subsequent pregnancies increased rates of medical interventions are reported without evidence of perinatal benefit. The aim of this study was to estimate gestational-age specific risks of recurrent stillbirth and to evaluate the effect of obstetrical management on perinatal outcome after previous stillbirth., Methods: A retrospective cohort study in the Netherlands was designed that included 252.827 women with two consecutive singleton pregnancies (1 st and 2 nd delivery) between 1999 and 2007. Data was obtained from the national Perinatal Registry and analyzed for pregnancy outcomes. Fetal deaths associated with a congenital anomaly were excluded. The primary outcome was the occurrence of stillbirth in the second pregnancy stratified by gestational age. Secondary outcome was the influence of obstetrical management on perinatal outcome in a subsequent pregnancy., Results: Of 252.827 first pregnancies, 2.058 pregnancies ended in a stillbirth (8.1 per 1000). After adjusting for confounding factors, women with a prior stillbirth have a two-fold higher risk of recurrence (aOR 1.96, 95% CI 1.07-3.60) compared to women with a live birth in their first pregnancy. The highest risk of recurrence occurred in the group of women with a stillbirth in early gestation between 22 and 28 weeks of gestation (a OR 2.25, 95% CI 0.62-8.15), while after 32 weeks the risk decreased. The risk of neonatal death after 34 weeks of gestation is higher in women with a history of stillbirth (aOR 6.48, 95% CI 2.61-16.1) and the risk of neonatal death increases with expectant obstetric management (aOR 10.0, 95% CI 2.43-41.1)., Conclusions: A history of stillbirth remains an important risk for recurrent stillbirth especially in early gestation (22-28 weeks). Women with a previous stillbirth should be counselled for elective induction in the subsequent pregnancy at 37-38 weeks of gestation to decrease the risk of perinatal death., (© 2021. The Author(s).)

Background: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies., Methods: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015-2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies., Results: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015-2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39)., Conclusion: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome., (© 2021. The Author(s).)

Background: Stillbirth, the death of a baby before birth, is associated with significant psychological and social consequences that can be mitigated by respectful and supportive bereavement care. The absence of high-level evidence to support the broad scope of perinatal bereavement practices means that offering a range of options identified as valued by parents has become an important indicator of care quality. This study aimed to describe bereavement care practices offered to parents across different high-income and middle-income countries., Methods: An online survey of parents of stillborn babies was conducted between December 2014 and February 2015. Frequencies of nine practices were compared between high-income and middle-income countries. Differences in proportions of reported practices and their associated odds ratios were calculated to compare high-income and middle-income countries., Results: Over three thousand parents (3041) with a self-reported stillbirth in the preceding five years from 40 countries responded. Fifteen countries had atleast 40 responses. Significant differences in the prevalence of offering nine bereavement care practices were reported by women in high-income countries (HICs) compared with women in middle-income countries (MICs). All nine practices were reported to occur significantly more frequently by women in HICs, including opportunity to see and hold their baby (OR = 4.8, 95% CI 4.0-5.9). The widespread occurrence of all nine practices was reported only for The Netherlands., Conclusions: Bereavement care after stillbirth varies between countries. Future research should look at why these differences occur, their impact on parents, and whether differences should be addressed, particularly how to support effective communication, decision-making, and follow-up care., (© 2021 Wiley Periodicals LLC.)

Objectives: Maternal report of reduced fetal movements (RFM) is a means of identifying fetal compromise in pregnancy. In live births RFM is associated with altered placental structure and function. Here, we explored associations between RFM, pregnancy characteristics, and the presence of placental abnormalities and fetal growth restriction (FGR) in cases of stillbirth., Methods: A retrospective cohort study was carried out in a single UK tertiary maternity unit. Cases were divided into three groups: 109 women reporting RFM, 33 women with absent fetal movements (AFM) and 159 who did not report RFM before the diagnosis of stillbirth. Univariate and multivariate logistic regression was used to determine associations between RFM/AFM, pregnancy characteristics, placental insufficiency and the classification of the stillbirth., Results: AFM or RFM were reported prior to diagnosis of stillbirth in 142 (47.2%) of cases. Pregnancies with RFM prior to diagnosis of stillbirth were independently associated with placental insufficiency (Odds Ratio (OR) 2.79, 95% Confidence Interval (CI) 1.84, 5.04) and were less frequently associated with maternal proteinuria (OR 0.16, 95% CI 0.07, 0.62) and previous pregnancy loss <24 weeks (OR 0.20, 95% CI 0.07, 0.70). When combined, AFM and RFM were less frequently reported in twin pregnancies ending in stillbirth and in intrapartum stillbirths., Conclusions: The association between RFM and placental insufficiency was confirmed in cases of stillbirth. This provides further evidence that RFM is a symptom of placental insufficiency. Therefore, investigation after RFM should aim to identify placental dysfunction., (© 2021 Madeleine ter Kuile et al., published by De Gruyter, Berlin/Boston.)

The preconception period has been recognized as one of the earliest sensitive windows for human development. Maternal dietary intake during this period may influence the oocyte quality, as well as placenta and early embryonic development during the first trimester of pregnancy. Previous studies have found associations between macronutrient intake during preconception and pregnancy outcomes. However, as food products consist of multiple macro- and micronutrients, it is difficult to relate this to dietary intake behavior. Therefore, the aim of this study was to investigate the association between intake of specific food groups during the preconception period with birth weight, using data from the Perined-Lifelines linked birth cohort. The Perined-Lifelines birth cohort consists of women who delivered a live-born infant at term after being enrolled in a large population-based cohort study (The Lifelines Cohort). Information on birth outcome was obtained by linkage to the Dutch perinatal registry (Perined). In total, we included 1698 women with data available on birth weight of the offspring and reliable detailed information on dietary intake using a semi-quantitative food frequency questionnaire obtained before pregnancy. Based on the 2015 Dutch Dietary Guidelines and recent literature 22 food groups were formulated. Birth weight was converted into gestational age-adjusted z-scores. Multivariable linear regression was performed, adjusted for intake of other food groups and covariates (maternal BMI, maternal age, smoking, alcohol, education level, urbanization level, parity, sex of newborn, ethnicity). Linear regression analysis, adjusted for covariates and intake of energy (in kcal) (adjusted z score [95% CI], P) showed that intake of food groups "artificially sweetened products" and "vegetables" was associated with increased birth weight (resp. ( β = 0.001 [95% CI 0.000 to 0.001, p = 0.002]), ( β = 0.002 [95% CI 0.000 to 0.003, p = 0.03])). Intake of food group "eggs" was associated with decreased birth weight ( β = -0.093 [95% CI -0.174 to -0.013, p = 0.02]). Intake in food groups was expressed in 10 g per 1000 kcal to be able to draw conclusions on clinical relevance given the bigger portion size of the food groups. In particular, preconception intake of "artificially sweetened products" was shown to be associated with increased birth weight. Artificial sweeteners were introduced into our diets with the intention to reduce caloric intake and normalize blood glucose levels, without compromising on the preference for sweet food products. Our findings highlight the need to better understand how artificial sweeteners may affect the metabolism of the mother and her offspring already from preconception onwards.

Immune cells are critically involved in placental development and functioning, and inadequate regulation of the maternal immune system is associated with placental pathology and pregnancy complications. This study aimed to explore numbers of decidual immune cells in pregnancies complicated with fetal growth restriction (FGR) and stillbirth (SB), and in placentas with histopathological lesions: maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), delayed villous maturation (DVM), chorioamnionitis (CA), and villitis of unknown etiology (VUE). Placental tissue from FGR ( n = 250), SB ( n = 64), and healthy pregnancies ( n = 42) was included. Histopathological lesions were classified according to criteria developed by the Amsterdam Placental Workshop Group. Tissue slides were stained for CD68 (macrophages), CD206 (M2-like macrophages), CD3 (T cells), FOXP3 [regulatory T (Treg) cells], and CD56 [natural killer (NK) cells]. Cell numbers were analyzed in the decidua basalis using computerized morphometry. The Mann-Whitney U -test and Kruskal Wallis test with the Dunn's as post-hoc test were used for statistical analysis. Numbers of CD68 + macrophages were higher in FGR compared to healthy pregnancies ( p < 0.001), accompanied by lower CD206 + /CD68 + ratios ( p < 0.01). In addition, in FGR higher numbers of FOXP3 + Treg cells were seen ( p < 0.01) with elevated FOXP3 + /CD3 + ratios ( p < 0.01). Similarly, in SB elevated FOXP3 + Treg cells were found ( p < 0.05) with a higher FOXP3+/CD3+ ratio ( p < 0.01). Furthermore, a trend toward higher numbers of CD68 + macrophages was found ( p < 0.1) in SB. Numbers of CD3 + and FOXP3 + cells were higher in placentas with VUE compared to placentas without lesions ( p < 0.01 and p < 0.001), accompanied by higher FOXP3 + /CD3 + ratios ( p < 0.01). Elevated numbers of macrophages with a lower M2/total macrophage ratio in FGR suggest a role for a macrophage surplus in its pathogenesis and could specifically indicate involvement of inflammatory macrophages. Higher numbers of FOXP3 + Treg cells with higher Treg/total T cell ratios in VUE may be associated with impaired maternal-fetal tolerance and a compensatory response of Treg cells. The abundant presence of placental lesions in the FGR and SB cohorts might explain the increase of Treg/total T cell ratios in these groups. More functionality studies of the observed altered immune cell subsets are needed., (Copyright © 2020 Bezemer, Schoots, Timmer, Scherjon, Erwich, van Goor, Gordijn and Prins.)

We reported earlier that an anti-inflammatory small peptide receptor-formyl peptide receptor-2 (FPR2) was significantly decreased in placentas from third trimester pregnancies complicated with fetal growth restriction (FGR), compared to placentas from uncomplicated control pregnancies, suggesting FPR2 may play a role in the development of FGR. The aim of this study is to investigate whether the actions of FPR2 alters placental growth process in humans. Accordingly, using small-for-gestation age (SGA) as a proxy for FGR, we hypothesize that FPR2 expression is decreased in first-trimester placentas of women who later manifest FGR, and contributes to aberrant trophoblast function and the development of FGR. Chorionic villus sampling (CVS) tissues were collected at 10-12 weeks gestation in 70 patients with singleton fetuses; surplus tissue was used. Real-time PCR and immunoassays were performed to quantitate FPR2 gene and protein expression. Silencing of FPR2 was performed in two independent, trophoblast-derived cell lines, HTR-8/ SVneo and JEG-3 to investigate the functional consequences of FPR2 gene downregulation. FPR2 mRNA relative to 18S rRNA was significantly decreased in placentae from SGA-pregnancies ( n = 28) compared with controls ( n = 52) ( p < 0.0001). Placental FPR2 protein was significantly decreased in SGA compared with control ( n = 10 in each group, p < 0.05). Proliferative, migratory and invasive potential of the human placental-derived cell lines, HTR-8/ SVneo and JEG-3 were significantly reduced in siFPR2 treated cells compared with siCONT control groups. Down-stream signaling molecules, STAT5B and SOCS3 were identified as target genes of FPR2 action in the trophoblast-derived cell lines and in SGA and control chorionic villous tissues. FPR2 is a novel regulator of key molecular pathways and functions in placental development, and its decreased expression in women destined to develop FGR reinforces a placental origin of SGA/FGR, and that it contributes to causing the development of SGA/FGR.

Patient safety incidents have strong personal and professional impact on the health care professionals involved. Following such an incident, many of them experience long-term negative emotions and impaired professional functioning. For this reason, in 2016 Shapiro argued for the provision of peer support directly after an incident. Five Dutch University Medical Centres formed a partnership that same year to set up a Peer Support program. A descriptive evaluation of their experience shows that Peer Support is widely provided, fulfils an apparent need, is highly valued by colleagues who received it, and noticeably contributes to an open culture. The Peer Support program helps the upset professionals to continue to function in their role and to contribute to quality improvement after the incident. The benefits of Peer Support are clearly noticeable, but difficult to quantify. Therefore, we suggest that Peer Support should be assessed by the new, more qualitative evaluation of health care benefits, so hospital boards will support continuation of the program.

Creatine is a metabolite involved in cellular energy homeostasis. In this study, we examined placental creatine content, and expression of the enzymes required for creatine synthesis, transport and the creatine kinase reaction, in pregnancies complicated by low birthweight. We studied first trimester chorionic villus biopsies (CVBs) of small for gestational age (SGA) and appropriately grown infants (AGA), along with third trimester placental samples from fetal growth restricted (FGR) and healthy gestation-matched controls. Placental creatine and creatine precursor (guanidinoacetate-GAA) levels were measured. Maternal and cord serum from control and FGR pregnancies were also analyzed for creatine concentration. mRNA expression of the creatine transporter (SLC6A8); synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT); mitochondrial (mtCK) and cytosolic (BBCK) creatine kinases; and amino acid transporters (SLC7A1 & SLC7A2) was assessed in both CVBs and placental samples. Protein levels of AGAT (arginine:glycine aminotransferase), GAMT, mtCK and BBCK were also measured in placental samples. Key findings; total creatine content of the third trimester FGR placentae was 43% higher than controls. The increased creatine content of placental tissue was not reflected in maternal or fetal serum from FGR pregnancies. Tissue concentrations of GAA were lower in the third trimester FGR placentae compared to controls, with lower GATM and GAMT mRNA expression also observed. No differences in the mRNA expression of GATM, GAMT or SLC6A8 were observed between CVBs from SGA and AGA pregnancies. These results suggest placental creatine metabolism in FGR pregnancies is altered in late gestation. The relevance of these changes on placental bioenergetics should be the focus of future investigations., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)