Publications by authors named "Sanne J Gordijn"

34 Publications

Abnormal Fetal Growth: Small for Gestational Age, Fetal Growth Restriction, Large for Gestational Age: Definitions and Epidemiology.

Obstet Gynecol Clin North Am 2021 Jun;48(2):267-279

Department of Obstetrics and Gynaecology, University Medical Center of Groningen, CB20, Hanzeplein 1, 9700RB Groningen, the Netherlands.

Abnormal fetal growth (growth restriction and overgrowth) is associated with perinatal morbidity, mortality, and lifelong risks to health. To describe abnormal growth, "small for gestational age" and "large for gestational age" are commonly used terms. However, both are statistical definitions of fetal size below or above a certain threshold related to a reference population, rather than referring to an abnormal condition. Fetuses can be constitutionally small or large and thus healthy, whereas fetuses with seemingly normal size can be growth restricted or overgrown. Although golden standards to detect abnormal growth are lacking, understanding of both pathologic conditions has improved significantly.
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http://dx.doi.org/10.1016/j.ogc.2021.02.002DOI Listing
June 2021

The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study.

BMC Pregnancy Childbirth 2021 Apr 9;21(1):285. Epub 2021 Apr 9.

Department of Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: Routine assessment in (near) term pregnancy is often inaccurate for the identification of fetuses who are mild to moderately compromised due to placental insufficiency and are at risk of adverse outcomes, especially when fetal size is seemingly within normal range for gestational age. Although biometric measurements and cardiotocography are frequently used, it is known that these techniques have low sensitivity and specificity. In clinical practice this diagnostic uncertainty results in considerable 'over treatment' of women with healthy fetuses whilst truly compromised fetuses remain unidentified. The CPR is the ratio of the umbilical artery pulsatility index over the middle cerebral artery pulsatility index. A low CPR reflects fetal redistribution and is thought to be indicative of placental insufficiency independent of actual fetal size, and a marker of adverse outcomes. Its utility as an indicator for delivery in women with reduced fetal movements (RFM) is unknown. The aim of this study is to assess whether expedited delivery of women with RFM identified as high risk on the basis of a low CPR improves neonatal outcomes. Secondary aims include childhood outcomes, maternal obstetric outcomes, and the predictive value of biomarkers for adverse outcomes.

Methods: International multicentre cluster randomised trial of women with singleton pregnancies with RFM at term, randomised to either an open or concealed arm. Only women with an estimated fetal weight ≥ 10th centile, a fetus in cephalic presentation and normal cardiotocograph are eligible and after informed consent the CPR will be measured. Expedited delivery is recommended in women with a low CPR in the open arm. Women in the concealed arm will not have their CPR results revealed and will receive routine clinical care. The intended sample size based on the primary outcome is 2160 patients. The primary outcome is a composite of: stillbirth, neonatal mortality, Apgar score < 7 at 5 min, cord pH < 7.10, emergency delivery for fetal distress, and severe neonatal morbidity.

Discussion: The CEPRA trial will identify whether the CPR is a good indicator for delivery in women with perceived reduced fetal movements.

Trial Registration: Dutch trial registry (NTR), trial NL7557 . Registered 25 February 2019.
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http://dx.doi.org/10.1186/s12884-021-03760-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034072PMC
April 2021

Systemic Oxidative Stress, Aging and the Risk of Cardiovascular Events in the General Female Population.

Front Cardiovasc Med 2021 9;8:630543. Epub 2021 Feb 9.

Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Menopause is associated with increased cardiovascular risk, in which oxidative stress plays a pivotal role. Systemic oxidative stress is reflected by decreased levels of free thiols (R-SH, sulfhydryl groups), which are key components of the extracellular antioxidant machinery. In this study, we investigated the relation between serum free thiols as marker of oxidative stress and the female cardiovascular phenotype, as well as potential associations with the risk of cardiovascular (CV) events in pre- and postmenopausal women from the general population. Female participants ( = 2,980) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study were included. Serum free thiol concentrations were analyzed for associations with demographic, clinical, biochemical, and gynecological parameters, as well as with menopausal status and, prospectively, with the risk of CV events. Postmenopausal women had significantly reduced levels of serum free thiols (4.8 ± 1.0 vs. 5.2 ± 1.0 μmol/g, < 0.001) compared to reproductive women. In multivariable analyses, serum free thiols were significantly associated with menopausal status (OR 0.70 [0.49-0.98], = 0.039), even when adjusted for potential confounding factors, except for age ( = 0.550). Prospectively, serum free thiols were significantly associated with the risk of CV events (HR 0.52 [0.27-0.97], = 0.040), even with covariate adjustment, although this disappeared when correcting for age. In this study, we revealed serum free thiols to be strongly associated with the female cardiovascular phenotype as well as with female risk of CV events, where the influence of age itself seemed to outweigh that of female menopause. Future studies are warranted to further unravel the clinical utility of serum free thiol levels in the context of female cardiovascular risk management.
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http://dx.doi.org/10.3389/fcvm.2021.630543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900172PMC
February 2021

Perinatal death in a term fetal growth restriction randomized controlled trial: the paradox of prior risk and consent.

Am J Obstet Gynecol MFM 2020 11 24;2(4):100239. Epub 2020 Sep 24.

Leiden University Medical Center, Leiden, the Netherlands.

Background: The disproportionate intrauterine growth intervention trial at term was an intention to treat analysis and compared labor induction with expectant monitoring in pregnancies complicated by fetal growth restriction at term and showed equivalence for neonatal outcomes.

Objective: To evaluate trial participation bias and to examine the generalizability of the results of an obstetrical randomized trial.

Study Design: We used data from participants and nonparticipants of a randomized controlled trial-the disproportionate intrauterine growth intervention trial at term (n=1116) -to perform a secondary analysis. This study compared induction of labor and expectant management in women with term growth restriction. Data were collected in the same manner for both groups. Baseline characteristics and neonatal and maternal outcomes were compared. The primary outcome was a composite measure of adverse neonatal outcome. Secondary outcomes were delivery by cesarean delivery and instrumental vaginal delivery; length of stay in the neonatal intensive care, neonatal ward, and the maternal hospital; and maternal morbidity.

Results: Nonparticipants were older, had a lower body mass index, had a higher level of education, smoked less, and preferred expectant management. The time between study inclusion and labor onset was shorter in participants than in nonparticipants. Notably, 4 perinatal deaths occurred among nonparticipants and none among participants. Among nonparticipants, there were more children born with a birthweight below the third centile. The nonparticipants who had expectant management were monitored less frequently than the participants in both the intervention and the expectant arm.

Conclusion: We found less favorable outcomes and more perinatal deaths in nonparticipants. Protocol-driven management, differences between participants and nonparticipants, or the fact that nonparticipants had a preference for expectant management might explain the findings.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100239DOI Listing
November 2020

Altered Levels of Decidual Immune Cell Subsets in Fetal Growth Restriction, Stillbirth, and Placental Pathology.

Front Immunol 2020 20;11:1898. Epub 2020 Aug 20.

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

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 ( = 250), SB ( = 64), and healthy pregnancies ( = 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 -test and Kruskal Wallis test with the Dunn's as test were used for statistical analysis. Numbers of CD68 macrophages were higher in FGR compared to healthy pregnancies ( < 0.001), accompanied by lower CD206/CD68 ratios ( < 0.01). In addition, in FGR higher numbers of FOXP3 Treg cells were seen ( < 0.01) with elevated FOXP3/CD3 ratios ( < 0.01). Similarly, in SB elevated FOXP3 Treg cells were found ( < 0.05) with a higher FOXP3+/CD3+ ratio ( < 0.01). Furthermore, a trend toward higher numbers of CD68 macrophages was found ( < 0.1) in SB. Numbers of CD3 and FOXP3 cells were higher in placentas with VUE compared to placentas without lesions ( < 0.01 and < 0.001), accompanied by higher FOXP3/CD3 ratios ( < 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.
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http://dx.doi.org/10.3389/fimmu.2020.01898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468421PMC
April 2021

A Core Outcome Set and minimum reporting set for intervention studies in growth restriction in the NEwbOrN: the COSNEON study.

Pediatr Res 2021 May 14;89(6):1380-1385. Epub 2020 Sep 14.

Department of Obstetrics and Gynaecology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands.

Background: Different interventions and treatments are available for growth-restricted newborns to improve neonatal and long-term outcomes. Lack of outcome standardization across trials of feeding interventions limits pooled analysis of intervention effects. This study aimed to develop a core outcome set (COS) and minimum reporting set (MRS) for this research field.

Methods: A scoping search identified relevant outcomes and baseline characteristics. These outcomes were presented to two stakeholder groups (lay experience and professional experts) in three rounds of online Delphi surveys. The professional experts were involved in the development of the MRS. All items were rated for their importance on a 5-point Likert scale and re-rated in subsequent rounds after presentation of the results at the group level. During a face-to-face consensus meeting the final COS and MRS were determined.

Results: Forty-seven of 53 experts (89%) who completed the first round completed all three survey rounds. After the consensus meeting, consensus was reached on 19 outcomes and 17 baseline characteristics.

Conclusions: A COS and MRS for feeding interventions in the newborn after growth restriction were developed. Use of these sets will promote uniform reporting of study characteristics and improve data synthesis and meta-analysis of multiple studies.

Impact: Both a COS and MRS for growth restriction in the newborn were developed. This study provides the first international combined health-care professional and patient consensus on outcomes and baseline characteristics for intervention and treatment studies in growth-restricted newborns. The use of COS and MRS results in the development of more uniform study protocols, thereby facilitating data synthesis/meta-analysis of multiple studies aiming to optimize treatment and interventions in growth restriction in the newborn.
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http://dx.doi.org/10.1038/s41390-020-01119-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163598PMC
May 2021

Investigating the current knowledge and needs concerning a follow-up for long-term cardiovascular risks in Dutch women with a preeclampsia history: a qualitative study.

BMC Pregnancy Childbirth 2020 Aug 24;20(1):486. Epub 2020 Aug 24.

Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Background: There is increasing evidence that a history of preeclampsia is an important risk factor for future cardiovascular events. Awareness of this risk could provide opportunities for identification of women at risk, with opportunities for prevention and / or early intervention. A standardized follow-up has not yet been implemented in the north of the Netherlands. The objective of this qualitative study was to explore the opinions and wishes among women and physicians about the follow-up for women with a history of preeclampsia.

Methods: Semi-structured interviews with 15 women and 14 physicians (5 obstetricians, 4 general practitioners, 3 vascular medicine specialists and 2 cardiologists) were performed and addressed topics about knowledge on CVR, current - and future follow-up. Women were approached through the HELLP foundation and their physicians. Physicians were approached by email. The interviews were recorded, typed and coded using ATLAS.ti software. A theoretical-driven thematic analysis was performed.

Results: Women had some knowledge about the association between preeclampsia and the increased CVR, but missed information from their health care providers. Specialists were aware of the association, but the information and advice they provided to their patients was minimal and inconsistent according to themselves. Whereas some general practitioners regarded their own knowledge as limited. There was a clear desire among women for a more extensive follow-up with specific attention to both emotional and physical consequences of preeclampsia. Physicians indicated that they preferred to see a follow up program concerning the CVR at the general practitioner as part of the already existent cardiovascular risk management (CVRM) program.

Conclusion: Women and medical specialists consider it important to improve aftercare for women after a pregnancy complicated by preeclampsia. Introducing these women into the CVRM program at the general practitioner is regarded as a preferred first step. Further research is warranted to establish an evidence-based guideline for the follow-up of these women.
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http://dx.doi.org/10.1186/s12884-020-03179-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444252PMC
August 2020

Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19).

J Pathol 2020 07 10;251(3):228-248. Epub 2020 Jun 10.

Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Angiotensin-converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID-19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin-angiotensin-aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID-19 severity and progression, including age, sex, ethnicity, medication, and several co-morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2-expressing organs do not equally participate in COVID-19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID-19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS-CoV-2 infection is crucially important as it has major implications for understanding COVID-19 pathophysiology and the development of evidence-based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID-19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID-19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID-19 severity. In addition, we discuss the relevant pathological changes resulting from SARS-CoV-2 infection. Finally, we highlight a selection of potential treatment modalities for COVID-19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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http://dx.doi.org/10.1002/path.5471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276767PMC
July 2020

Systemic Oxidative Stress Is Increased in Postmenopausal Women and Independently Associates with Homocysteine Levels.

Int J Mol Sci 2020 Jan 2;21(1). Epub 2020 Jan 2.

Department of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 35, Al-Khoud 123, Muscat, Oman.

Oxidative stress plays a pivotal role in the pathogenesis of cardiovascular diseases (CVD). Postmenopausal women have an increased risk of developing CVD due to decreased estrogen availability, which is accompanied by increased oxidative stress. Serum free thiols (R-SH) provide a robust and powerful read-out of systemic oxidative stress. In this study, we aimed to establish serum levels of free thiols and explore associations between free thiols and demographic, clinical, and biochemical parameters related to obesity and the risk for developing CVD in both pre- and postmenopausal women. Serum free thiols were measured in a cohort consisting of healthy pre- ( = 223) and postmenopausal ( = 118) Omani women. Postmenopausal women had significantly lower levels of serum free thiols as compared to premenopausal women (762.9 ± 85.3 vs. 780 ± 80.9 μM, age-adjusted < 0.001). Women's age was positively associated with serum free thiol levels in premenopausal women (β = 0.36, = 0.002), whereas an inverse association was observed in postmenopausal women (β = -0.29, = 0.002). Homocysteine levels were significantly inversely associated with serum free thiol levels in both pre- (β = -0.19, = 0.005) and postmenopausal (β = -0.20, = 0.032) women, independent from known cardiovascular risk factors. In this study, we show that postmenopausal women are affected by increased systemic oxidative stress, which independently associates with homocysteine levels.
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http://dx.doi.org/10.3390/ijms21010314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982320PMC
January 2020

Postnatal Catch-Up Growth After Suspected Fetal Growth Restriction at Term.

Front Endocrinol (Lausanne) 2019 20;10:274. Epub 2019 Jun 20.

Department of Obstetrics, University Medical Centre Groningen, Groningen, Netherlands.

The aim of this study was to study growth patterns of children born after suspected fetal growth restriction (FGR) at term and to compare the effect of induction of labor (IoL) and expectant management (EM), also in relation to neurodevelopmental and behavioral outcome at age 2. We performed a 2 years' follow-up of growth of children included in the Disproportionate Intrauterine Growth Restriction Trial at Term (DIGITAT) study, a Randomized Controlled Trial (RCT) comparing IoL with EM in pregnancies with suspected FGR at term. We collected data on child growth until the age of 2 years. Standard deviation scores (SDSs) for height and weight were calculated at different ages. We assessed the effects of IoL compared with EM and the effects of a birth weight below or above the 3rd or 10th centile on catch-up growth. Target height SDSs were calculated using the height of both parents. We found a significant increase in SDS in the first 2 years. Children born after EM showed more catch-up growth in the first month [height: mean difference -0.7 (95% CI: 0.2; 1.3)] and weight [mean difference -0.5 (95% CI: 0.3; 0.7)]. Children born with a birth weight below the 3rd and 10th centiles showed more catch-up growth after 1 year [mean difference -0.8 SDS (95% CI: -1.1; -0.5)] and after 2 years [mean difference -0.7 SDS (95% CI: -1.2; -0.2)] as compared to children with a birth weight above the 3rd and 10th centiles. SDS at birth had the strongest effect on adverse neurodevelopmental outcome at 2 years of age. After FGR at term, postnatal catch-up growth is generally present and associated with the degree of FGR. Obstetric management in FGR influences postnatal growth. Longer-term follow-up is therefore needed and should be directed at growth and physical health. www.ClinicalTrials.gov, identifier SRCTN10363217.
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http://dx.doi.org/10.3389/fendo.2019.00274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598620PMC
June 2019

A Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints: the COSGROVE study.

Am J Obstet Gynecol 2019 10 29;221(4):339.e1-339.e10. Epub 2019 May 29.

Fetal Medicine Unit, St George's University and St George's University Hospitals NHS Foundation Trust, London, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom.

Background: Fetal growth restriction refers to a fetus that does not reach its genetically predetermined growth potential. It is well-recognized that growth-restricted fetuses are at increased risk of both short- and long-term adverse outcomes. Systematic evaluation of the evidence from clinical trials of fetal growth restriction is often difficult because of variation in the outcomes that are measured and reported. The development of core outcome sets for fetal growth restriction studies would enable future trials to measure similar meaningful outcomes.

Objective: The purpose of this study was to develop core outcome sets for trials of prevention or treatment of fetal growth restriction.

Study Design: This was a Delphi consensus study. A comprehensive literature review was conducted to identify outcomes that were reported in studies of prevention or treatment of fetal growth restriction. All outcomes were presented for prioritization to key stakeholders (135 healthcare providers, 68 researchers/academics, and 35 members of the public) in 3 rounds of online Delphi surveys. A priori consensus criteria were used to reach agreement on the final outcomes for inclusion in the core outcome set at a face-to-face meeting with 5 healthcare providers, 5 researchers/academics, and 6 maternity service users.

Results: In total, 22 outcomes were included in the final core outcome set. These outcomes were grouped under 4 domains: maternal (n=4), fetal (n=1), neonatal (n=12), and childhood (n=5).

Conclusion: The Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints study identified a large number of potentially relevant outcomes and then reached consensus on those factors that, as a minimum, should be measured and reported in all future trials of prevention or treatment of fetal growth restriction. This will enable future trials to measure similar meaningful outcomes and to ensure that findings from different studies can be compared and combined.
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http://dx.doi.org/10.1016/j.ajog.2019.05.039DOI Listing
October 2019

More Maternal Vascular Malperfusion and Chorioamnionitis in Placentas After Expectant Management vs. Immediate Delivery in Fetal Growth Restriction at (Near) Term: A Further Analysis of the DIGITAT Trial.

Front Endocrinol (Lausanne) 2019 24;10:238. Epub 2019 Apr 24.

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Management of late fetal growth restriction (FGR) is limited to adequate fetal monitoring and optimal timing of delivery. The (DIGITAT) trial compared induction of labor with expectant management in pregnancies at (near) term complicated by suspected FGR. Findings of the DIGITAT trial were that expectant monitoring prolonged pregnancy for 10 days and increased birth weight with only 130 grams. This resulted in more infants born below the 2.3rd percentile compared to induction of labor, respectively, 12.5% in induction of labor and 30.6% in expectant monitoring group. The main placental lesions associated with FGR are maternal vascular malperfusion, fetal vascular malperfusion, and villitis of unknown etiology. We investigated whether placentas of pregnancies complicated with FGR in the expectant monitoring group reveal more and more severe pathology due to pregnancy prolongation. The DIGITAT trial was a multicenter, randomized controlled trial with suspected FGR beyond 36 + 0 weeks. We now analyzed all available cases ( = 191) for placental pathology. The macroscopic details were collected and histological slides were recorded and classified by a single perinatal pathologist, blinded for pregnancy details and outcome. The different placental lesions were scored based on the latest international criteria for placental lesions as defined in the Amsterdam Placental Workshop Group Consensus Statement. The presence of maternal vascular malperfusion and chorioamnionitis were higher in the expectant management group ( < 0.05 and < 0.01, respectively). No differences in placental weight and maturation of the placenta between the induction of labor and the expectant management group were seen. Fetal vascular malperfusion, villitis of unknown etiology and nucleated red blood cell count did not differ between the groups. Expectant management of late FGR is associated with increased maternal vascular malperfusion and chorioamnionitis. This may have implications for fetal and neonatal outcome, such as programming in the developing child influencing health outcomes later in life.
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http://dx.doi.org/10.3389/fendo.2019.00238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499154PMC
April 2019

Computerized fetal cardiotocography analysis in early preterm fetal growth restriction - a quantitative comparison of two applications.

J Perinat Med 2019 May;47(4):439-447

Department of Obstetrics, Amsterdam University Medical CenterAmsterdam, The Netherlands.

Background We developed an open-source software for the computerized analysis of antenatal fetal cardiotocography (CTG) without limitation of duration of the registration, enabling batch processing and adaptation to any digital storage system. Methods STVcalc was developed based on literature about the FetalCare system (Huntleigh Healthcare Ltd, Cardiff, UK). For comparison with FetalCare, we selected the CTGs of all women who delivered in 2011 a small-for-gestational-age (SGA) fetus between 24 and 31 weeks by cesarean section (CS) for fetal distress, or had fetal death, before labor onset. Results In 471 CTGs from 39 women, the agreement was 99% for a short-term variation (STV) cut-off of 2.6 ms below 29 weeks and 3.0 ms thereafter, and 95% for 3.5 and 4.0 ms, respectively. In 18 (4%) cases, the proportional difference in STV between FetalCare and STVcalc was more than 10%. Conclusion As only slight differences were observed between the proposed feature-rich application and the FetalCare system, it can be considered valuable for clinical practice and research purposes.
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http://dx.doi.org/10.1515/jpm-2018-0412DOI Listing
May 2019

Reactive Species Interactome Alterations in Oocyte Donation Pregnancies in the Absence and Presence of Pre-Eclampsia.

Int J Mol Sci 2019 03 6;20(5). Epub 2019 Mar 6.

Department of Obstetrics and Gynaecology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.

In pregnancy, maternal physiology is subject to considerable adaptations, including alterations in cardiovascular and metabolic function as well as development of immunological tolerance towards the fetus. In an oocyte donation pregnancy, the fetus is fully allogeneic towards the mother, since it carries both oocyte donor antigens and paternal antigens. Therefore, oocyte donation pregnancies result in an immunologically challenging pregnancy, which is reflected by a higher-than-normal risk to develop pre-eclampsia. Based on the allogeneic conditions in oocyte donation pregnancies, we hypothesized that this situation may translate into alterations in concentration of stable readouts of constituents of the reactive species interactome (RSI) compared to normal pregnancies, especially serum free thiols, nitric oxide (NO) and hydrogen sulfide (H₂S) related metabolites. Indeed, total free thiol levels and nitrite (NO₂) concentrations were significantly lower whereas protein-bound NO and sulfate (SO₄) concentrations were significantly higher in both oocyte donation and naturally conceived pregnancies complicated by pre-eclampsia. The increased concentrations of nitrite observed in uncomplicated oocyte donation pregnancies suggest that endothelial NO production is compensatorily enhanced to lower vascular tone. More research is warranted on the role of the RSI and bioenergetic status in uncomplicated oocyte donation pregnancies and oocyte donation pregnancies complicated by pre-eclampsia.
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http://dx.doi.org/10.3390/ijms20051150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429516PMC
March 2019

The Possible Role of Placental Morphometry in the Detection of Fetal Growth Restriction.

Front Physiol 2018 8;9:1884. Epub 2019 Jan 8.

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Fetal growth restriction (FGR) is often the result of placental insufficiency and is characterized by insufficient transplacental transport of nutrients and oxygen. The main underlying entities of placental insufficiency, the pathophysiologic mechanism, can broadly be divided into impairments in blood flow and exchange capacity over the syncytiovascular membranes of the fetal placenta villi. Fetal growth restriction is not synonymous with small for gestational age and techniques to distinguish between both are needed. Placental insufficiency has significant associations with adverse pregnancy outcomes (perinatal mortality and morbidity). Even in apparently healthy survivors, altered fetal programming may lead to long-term neurodevelopmental and metabolic effects. Although the concept of fetal growth restriction is well appreciated in contemporary obstetrics, the appropriate detection of FGR remains an issue in clinical practice. Several approaches have aimed to improve detection, e.g., uniform definition of FGR, use of Doppler ultrasound profiles and use of growth trajectories by ultrasound fetal biometry. However, the role of placental morphometry (placental dimensions/shape and weight) deserves further exploration. This review article covers the clinical relevance of placental morphometry during pregnancy and at birth to help recognize fetuses who are growth restricted. The assessment has wide intra- and interindividual variability with various consequences. Previous studies have shown that a small placental surface area and low placental weight are associated with a slower growth of the fetus. Parameters such as placental surface area, placental volume and placental weight in relation to birth weight can help to identify FGR. In the future, a model including sophisticated antenatal placental morphometry may prove to be a clinically useful method for screening or diagnosing growth restricted fetuses, in order to provide optimal monitoring.
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http://dx.doi.org/10.3389/fphys.2018.01884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331677PMC
January 2019

Study protocol: developing, disseminating, and implementing a core outcome set for selective fetal growth restriction in monochorionic twin pregnancies.

Trials 2019 Jan 9;20(1):35. Epub 2019 Jan 9.

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: Selective fetal growth restriction in monochorionic twin pregnancies is associated with an increased risk of perinatal mortality and morbidity and represents a clinical dilemma. Interventions include expectant management with early preterm delivery if there are signs of fetal compromise, selective termination of the compromised twin, fetoscopic laser coagulation of the communicating placental vessels or termination of the whole pregnancy. Previous studies evaluating interventions have reported many different outcomes and outcome measures. Such variation makes comparing, contrasting, and combining results challenging, limiting ongoing research on this uncommon condition to inform clinical practice. We aim to produce, disseminate, and implement a core outcome set for selective fetal growth restriction research in monochorionic twin pregnancies.

Methods: An international steering group, including professionals, researchers, and lay experts, has been established to oversee the development of this core outcome set. The methods have been guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. Potential core outcomes will be developed by undertaking a systematic review of studies evaluating interventions for selective fetal growth restriction in monochorionic twin pregnancies. Potential core outcomes will be entered into a three-round Delphi survey and key stakeholders including clinical professionals, researchers, and lay experts will be invited to participate. Repeated reflection and rescoring of individual outcomes should encourage group and individual stakeholder convergence towards consensus outcomes which will be entered into a modified Nominal Group Technique to finalize the core outcome set. Once core outcomes have been agreed, we will establish standardized definitions and recommend high-quality measurement instruments for each outcome.

Discussion: The development, dissemination, and implementation of a core outcome set for selective fetal growth restriction should ensure that future research protocols select, collect, and report outcomes and outcome measures in a standardized manner. Data synthesis will be possible on a broad level and rigorous implementation should advance the quality of research studies and their effective use in order to guide clinical practice, improve patient care, maternal, short-term perinatal outcomes, and long-term neurodevelopmental outcomes.

Trial Registration: Core Outcome Measures in Effectiveness Trials (COMET) registration number: 998. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42018092697 . 18th April 2018.
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http://dx.doi.org/10.1186/s13063-018-3153-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327411PMC
January 2019

Point.

Am J Obstet Gynecol 2019 01 10;220(1):74-82. Epub 2018 Oct 10.

Department of Obstetrics & Gynaecology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.

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http://dx.doi.org/10.1016/j.ajog.2018.10.007DOI Listing
January 2019

Screening performance of consensus definition of fetal growth restriction inappropriately evaluated.

Lancet Child Adolesc Health 2018 09;2(9):e22

Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.

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http://dx.doi.org/10.1016/S2352-4642(18)30243-8DOI Listing
September 2018

Development of a core outcome set for immunomodulation in pregnancy (COSIMPREG): a protocol for a systematic review and Delphi study.

BMJ Open 2018 08 5;8(8):e021619. Epub 2018 Aug 5.

Department of Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Introduction: To establish pregnancy, the maternal immune system must adapt to tolerate the semiallogenic fetus. Less than optimal adaptation of the maternal immune system during (early) pregnancy is implicated in several complications of pregnancy. The development of effective immune modulation interventions as preventive or therapeutic strategies for pregnancy complications holds promise. Several studies sought to evaluate the safety and effectiveness of various approaches. However, a limitation is the high variability in clinical and immune outcomes that are reported. We, therefore, aim to develop a core outcome set for application to studies of immune modulation in pregnancy (COSIMPREG).

Methods And Analysis: We will use a stepwise approach to develop a COSIMPREG. First, we will perform a systematic review to identify reported outcomes. For this review, Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. Second, we will use the Delphi method to develop a preliminary COSIMPREG. In three rounds, the outcomes of the systematic review will be scored. A panel comprising experts from relevant disciplines and diverse geographical locations will be assembled until a sufficient quality of the panel is reached. We will use predefined decision rules for outcomes. After each round outcomes, including scores, will be returned to the panel for further refinement. The outcomes not excluded after the third round will be taken to a consensus meeting. In this meeting, experts from all relevant disciplines will discuss and finalise the COSIMPREG.

Ethics And Dissemination: For this study ethical approval is not required. The systematic review will be published in an appropriate open access reproductive immunology journal. Once the COSIMPREG is finalised, it will be published in an open access reproductive immunology journal, and disseminated at appropriate international meetings, as well as through relevant research and scientific societies. Experts involved in the Delphi study will be asked to give informed consent.
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http://dx.doi.org/10.1136/bmjopen-2018-021619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078247PMC
August 2018

Lower mRNA Expression in First-Trimester Decidual Tissue from Uncomplicated Term Pregnancies with a Male Fetus.

J Immunol Res 2018 29;2018:1950879. Epub 2018 May 29.

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, Netherlands.

Pregnancies with a male fetus are associated with higher risks of pregnancy complications through maladaptation of the maternal immune system. The pathophysiology of this phenomenon is unknown. A possible pathway could be a fetal sex-dependent maternal immune response, since males have a Y chromosome encoding specific allogenic proteins, possibly contributing to a different response and higher complication risks. To analyze whether fetal sex affects mRNA expression of maternal immune genes in early pregnancy, real-time PCR quantification was performed in the decidual tissue from primigravid pregnancies ( = 20) between 10 and 12 weeks with uncomplicated term outcomes. Early-pregnancy decidual mRNA expression of the regulatory T-cell marker, , was sixfold lower ( < 0.01) in pregnancies with a male fetus compared to pregnancies with a female fetus. Additionally, mRNA expression of was sixfold ( < 0.05) lower in pregnancies with a male fetus. The present data imply maternal immunologic differences between pregnancies with male and female fetuses which could be involved in different pregnancy pathophysiologic outcomes. Moreover, this study indicates that researchers in reproductive immunology should always consider fetal sex bias.
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http://dx.doi.org/10.1155/2018/1950879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996436PMC
November 2018

Oxidative stress in placental pathology.

Placenta 2018 09 16;69:153-161. Epub 2018 Mar 16.

Department of Pathology and Medical Biology, Pathology Section, University of Groningen, University Medical Center Groningen, The Netherlands.

The most important function of the placenta is the exchange of nutrients and oxygen between a mother and her fetus. To establish a healthy functioning placenta, placentation needs to occur with adequate remodelling of spiral arteries by extravillous trophoblasts. When this process is impaired, the resulting suboptimal and inadequate placenta function results in the manifestation of pregnancy complications. Impaired placenta function can cause preeclampsia and leads to fetal growth restriction due to hypoxia. Presence of hypoxia leads to oxidative stress due to an imbalance between reactive oxygen species and antioxidants, thereby causing damage to proteins, lipids and DNA. In the placenta, signs of morphological adaptation in response to hypoxia can be found. Different placental lesions like maternal or fetal vascular malperfusion or chronic villitis lead to a decreased exchange of oxygen between the mother and the fetus. Clinically, several biomarkers indicative for oxidative stress, e.g. malondialdehyde and reduced levels of free thiols are found. This review aims to give an overview of the causes and (potential) role of placental oxidative stress in the development of placental parenchymal pathology and its clinical consequences. Also, therapeutic options aiming at prevention or treatment of hypoxia of the placenta and fetus are described.
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http://dx.doi.org/10.1016/j.placenta.2018.03.003DOI Listing
September 2018

Consensus Based Definition of Growth Restriction in the Newborn.

J Pediatr 2018 05 28;196:71-76.e1. Epub 2018 Feb 28.

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Objective: To develop a consensus definition of growth restriction in the newborn that can be used clinically to identify newborn infants at risk and in research to harmonize reporting and definition in the current absence of a gold standard.

Study Design: An international panel of pediatric leaders in the field of neonatal growth were invited to participate in an electronic Delphi procedure using standardized methods and predefined consensus rules. Responses were fed back at group-level and the list of participants was provided. Nonresponders were excluded from subsequent rounds. In the first round, variables were scored on a 5-point Likert scale; in subsequent rounds, inclusion of variables and cut-offs were determined with a 70% level of agreement. In the final round participants selected the ultimate algorithm.

Results: In total, 57 experts participated in the first round; 79% completed the procedure. Consensus was reached on the following definition: birth weight less than the third percentile, or 3 out of the following: birth weight <10th percentile; head circumference <10th percentile; length <10th percentile; prenatal diagnosis of fetal growth restriction; and maternal pregnancy information.

Conclusions: Consensus was reached on a definition for growth restriction in the newborn. This definition recognizes that infants with birth weights <10th percentile may not be growth restricted and that infants with birth weights >10th percentile can be growth restricted. This definition can be adopted in clinical practice and in clinical trials to better focus on newborns at risk, and is complementary to the previously determined definition of fetal growth restriction.
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http://dx.doi.org/10.1016/j.jpeds.2017.12.059DOI Listing
May 2018

Adaptation of the WHO maternal near miss tool for use in sub-Saharan Africa: an International Delphi study.

BMC Pregnancy Childbirth 2017 12 29;17(1):445. Epub 2017 Dec 29.

Department of Obstetrics and Gynaecology (CB20), University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9700 RB, Groningen, Netherlands.

Background: Assessments of maternal near miss (MNM) are increasingly used in addition to those of maternal mortality measures. The World Health Organization (WHO) has introduced an MNM tool in 2009, but this tool was previously found to be of limited applicability in several low-resource settings. The aim of this study was to identify adaptations to enhance applicability of the WHO MNM tool in sub-Saharan Africa.

Methods: Using a Delphi consensus methodology, existing MNM tools were rated for applicability in sub-Saharan Africa over a series of three rounds. Maternal health experts from sub-Saharan Africa or with considerable knowledge of the context first rated importance of WHO MNM parameters using Likert scales, and were asked to suggest additional parameters. This was followed by two confirmation rounds. Parameters accepted by at least 70% of the panel members were accepted for use in the region.

Results: Of 58 experts who participated from study onset, 47 (81%) completed all three rounds. Out of the 25 WHO MNM parameters, all 11 clinical, four out of eight laboratory, and four out of six management-based parameters were accepted, while six parameters (PaO2/FiO2 < 200 mmHg, bilirubin >100 μmol/l or >6.0 mg/dl, pH <7.1, lactate >5 μmol/l, dialysis for acute renal failure and use of continuous vasoactive drugs) were deemed to not be applicable. An additional eight parameters (uterine rupture, sepsis/severe systemic infection, eclampsia, laparotomy other than caesarean section, pulmonary edema, severe malaria, severe complications of abortions and severe pre-eclampsia with ICU admission) were suggested for inclusion into an adapted sub-Saharan African MNM tool.

Conclusions: All WHO clinical criteria were accepted for use in the region. Only few of the laboratory- and management based were rated applicable. This study brought forward important suggestions for adaptations in the WHO MNM criteria to enhance its applicability in sub-Saharan Africa and possibly other low-resource settings.
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http://dx.doi.org/10.1186/s12884-017-1640-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747119PMC
December 2017

In Reply.

Arch Pathol Lab Med 2017 02;141(2):185

3   Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

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http://dx.doi.org/10.5858/arpa.2016-0455-LEDOI Listing
February 2017

Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement.

Arch Pathol Lab Med 2016 Jul 25;140(7):698-713. Epub 2016 May 25.

From SA Pathology, Women's and Children's Hospital, University of Adelaide, North Adelaide, Australia (Dr Khong); the Department of Pathology, National Maternity Hospital, Dublin, Ireland (Drs Mooney and Kelehan); the Department of Pathology, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel (Dr Ariel); the Department of Pathology, Kennemer Gasthuis, Haarlem, the Netherlands (Dr Balmus); the Department of Pathology, Boston Children's Hospital, and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (Dr Boyd); the Departments of Pathology and Laboratory Medicine, and Pediatrics, University of Calgary, Calgary, Alberta, Canada (Dr Brundler); the Maternal & Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom (Ms Derricott); the Department of Pathology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (Dr Evans); the Department of Pathology, University of Alabama at Birmingham, (Dr Faye-Petersen); the Department of Pathology, Rotunda Hospital, Dublin, Ireland (Dr Gillan); the Institute of Human Development, Faculty of Medical and Human Sciences.

Context: -The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories.

Objective: -To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community.

Data Sources: -Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible.

Conclusions: -The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous maturation, patterns of ascending intrauterine infection, and villitis of unknown etiology were agreed upon. Topics requiring further discussion were highlighted. Ongoing developments in our understanding of the pathology of the placenta, scientific bases of the maternofetoplacental triad, and evolution of the clinical significance of defined lesions may necessitate further refinements of these consensus guidelines. The proposed structure will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.
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http://dx.doi.org/10.5858/arpa.2015-0225-CCDOI Listing
July 2016

Classification of substandard factors in perinatal care: development and multidisciplinary inter-rater agreement of the Groningen-system.

BMC Pregnancy Childbirth 2015 Sep 11;15:215. Epub 2015 Sep 11.

Department of Obstetrics and Gynaecology, University Medical Centre, University of Groningen, PO BOX 30.001, CB20 9700 RB, Groningen, The Netherlands.

Background: Perinatal audit is an established method for improving the quality of perinatal care. In audit meetings substandard factors (SSF) are identified in cases of perinatal mortality and morbidity. To our knowledge there is no classification system specifically designed for the classification of substandard factors. Such a classification may help to standardise allocation of substandard factors to categories. This will help to prioritise, guide and implement actions in quality improvement programs.

Methods: A classification system of 284 substandard factors (SSF) identified in perinatal audit meetings between 2007 and 2011 was drawn up using the WHO Conceptual Framework for the International Classification for Patient Safety as a starting point. Discussions were held on inter-rater disagreements, inclusion of items, format and organisation and definitions of the main- and subcategories. A guideline was developed. An independent multidisciplinary group tested the classification. Independent of inter-rater agreement the allocations to categories were counted. For the counts in the subcategories one and two, we used the allocations in the main category as reference. The chance corrected agreement between classifiers was tested with Cohen's kappa statistic.

Results: The classification consists of 9 main categories with one or two subcategories. The main categories are (1) Equipment and Materials, (2) Medication, (3) Additional tests/ investigations, (4) Transportation , (5) Documentation, (6) Communication, (7) Medical practice, (8) Other and (9) non classifiable. Of 3663 allocations by 13 classifiers 1452 SSF's were allocated (40%) to 'medical practice' and 1247 (34%) to 'documentation'. 118 (3%) times SSF's were not classifiable, mainly due to unclear phrasing of the SSF. The chance corrected agreement of 284 substandard factors in the main category was 0.68 (95% CI 0.66-0.70) and 0.57 (95% CI 0.54-0.59) for the CDG and the IGD respectively.

Conclusions: Classifying substandard factors has given insight into problem area's in perinatal care and can give direction to medical, political and financial quality improvement measures. The Groningen-system has well defined categories and subcategories and the guidelines and examples are clear. The multidisciplinary inter-rater agreement is moderate to good. Improvement of the phrasing of the substandard factors is expected to improve inter-rater agreement.
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http://dx.doi.org/10.1186/s12884-015-0638-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567791PMC
September 2015

Making stillbirths count, making numbers talk - issues in data collection for stillbirths.

BMC Pregnancy Childbirth 2009 Dec 17;9:58. Epub 2009 Dec 17.

Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway.

Background: Stillbirths need to count. They constitute the majority of the world's perinatal deaths and yet, they are largely invisible. Simply counting stillbirths is only the first step in analysis and prevention. From a public health perspective, there is a need for information on timing and circumstances of death, associated conditions and underlying causes, and availability and quality of care. This information will guide efforts to prevent stillbirths and improve quality of care.

Discussion: In this report, we assess how different definitions and limits in registration affect data capture, and we discuss the specific challenges of stillbirth registration, with emphasis on implementation. We identify what data need to be captured, we suggest a dataset to cover core needs in registration and analysis of the different categories of stillbirths with causes and quality indicators, and we illustrate the experience in stillbirth registration from different cultural settings. Finally, we point out gaps that need attention in the International Classification of Diseases and review the qualities of alternative systems that have been tested in low- and middle-income settings.

Summary: Obtaining high-quality data will require consistent definitions for stillbirths, systematic population-based registration, better tools for surveys and verbal autopsies, capacity building and training in procedures to identify causes of death, locally adapted quality indicators, improved classification systems, and effective registration and reporting systems.
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http://dx.doi.org/10.1186/1471-2393-9-58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805601PMC
December 2009

Causes of death and associated conditions (Codac): a utilitarian approach to the classification of perinatal deaths.

BMC Pregnancy Childbirth 2009 Jun 10;9:22. Epub 2009 Jun 10.

Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Nydalen, Oslo, Norway.

A carefully classified dataset of perinatal mortality will retain the most significant information on the causes of death. Such information is needed for health care policy development, surveillance and international comparisons, clinical services and research. For comparability purposes, we propose a classification system that could serve all these needs, and be applicable in both developing and developed countries. It is developed to adhere to basic concepts of underlying cause in the International Classification of Diseases (ICD), although gaps in ICD prevent classification of perinatal deaths solely on existing ICD codes.We tested the Causes of Death and Associated Conditions (Codac) classification for perinatal deaths in seven populations, including two developing country settings. We identified areas of potential improvements in the ability to retain existing information, ease of use and inter-rater agreement. After revisions to address these issues we propose Version II of Codac with detailed coding instructions.The ten main categories of Codac consist of three key contributors to global perinatal mortality (intrapartum events, infections and congenital anomalies), two crucial aspects of perinatal mortality (unknown causes of death and termination of pregnancy), a clear distinction of conditions relevant only to the neonatal period and the remaining conditions are arranged in the four anatomical compartments (fetal, cord, placental and maternal).For more detail there are 94 subcategories, further specified in 577 categories in the full version. Codac is designed to accommodate both the main cause of death as well as two associated conditions. We suggest reporting not only the main cause of death, but also the associated relevant conditions so that scenarios of combined conditions and events are captured.The appropriately applied Codac system promises to better manage information on causes of perinatal deaths, the conditions associated with them, and the most common clinical scenarios for future study and comparisons.
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http://dx.doi.org/10.1186/1471-2393-9-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706222PMC
June 2009

A multilayered approach for the analysis of perinatal mortality using different classification systems.

Eur J Obstet Gynecol Reprod Biol 2009 Jun 9;144(2):99-104. Epub 2009 Mar 9.

Department of Obstetrics and Gynaecology, University Medical Centre Groningen, University of Groningen, The Netherlands.

Many classification systems for perinatal mortality are available, all with their own strengths and weaknesses: none of them has been universally accepted. We present a systematic multilayered approach for the analysis of perinatal mortality based on information related to the moment of death, the conditions associated with death and the underlying cause of death, using a combination of representatives of existing classification systems. We compared the existing classification systems regarding their definition of the perinatal period, level of complexity, inclusion of maternal, foetal and/or placental factors and whether they focus at a clinical or pathological viewpoint. Furthermore, we allocated the classification systems to one of three categories: 'when', 'what' or 'why', dependent on whether the allocation of the individual cases of perinatal mortality is based on the moment of death ('when'), the clinical conditions associated with death ('what'), or the underlying cause of death ('why'). A multilayered approach for the analysis and classification of perinatal mortality is possible by using combinations of existing systems; for example the Wigglesworth or Nordic Baltic ('when'), ReCoDe ('what') and Tulip ('why') classification systems. This approach is useful not only for in depth analysis of perinatal mortality in the developed world but also for analysis of perinatal mortality in the developing countries, where resources to investigate death are often limited.
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http://dx.doi.org/10.1016/j.ejogrb.2009.01.012DOI Listing
June 2009

[Appendicitis during pregnancy].

Ned Tijdschr Geneeskd 2009 Jan;153(1-2):20-4

Universitair Medisch Centrum Groningen, Groningen.

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January 2009