Cause of stillbirth and pathophysiological pathways in mothers with overweight and obesity

PurposeObesity is independently associated with stillbirth, especially in early gestation and late-term gestation. Underlying pathophysiological mechanism causing fetal death is yet not clear. The purpose of this study was to determine the association between maternal body mass index and stillbirth and its importance in potential pathophysiological mechanisms of fetal death.MethodsIn a multicenter prospective cohort study from 2002 to 2008, 1.025 women with a fetal death > 20 weeks of gestation were studied. An extensive diagnostic workup was performed including maternal blood tests, coagulation tests, autopsy and placental examination. Cause of death was classified by a multidisciplinary panel. Odds ratios for each outcome stratified by gestational age were estimated for different maternal BMI classes (underweight BMI < 18.5; overweight BMI 25.0-29.9; obesity BMI > 30.0) compared with normal weight women (BMI 18.5–24.9) by using logistic regression and cause of death was studied.ResultsWe analysed 793 women. Obese women significantly more often had pre-existing hypertension, pregnancy induced hypertension or gestational diabetes. Early fetal death (< 37 weeks) in obese women is more often caused by placental bed pathology (OR 4.10, 95% CI 1.79–9.40, P 0.001), and term fetal death by developmental placental pathology (OR 1.93, 95% CI 1.01–3.71, P 0.05).ConclusionIn obese women there are at least 2 distinct underlying pathophysiological pathways causing fetal death. The underlying mechanisms of these pathways are uncertain and should be investigated in future

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

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 &lt; 0.001), accompanied by lower CD206+/CD68+ ratios (p &lt; 0.01). In addition, in FGR higher numbers of FOXP3+ Treg cells were seen (p &lt; 0.01) with elevated FOXP3+/CD3+ ratios (p &lt; 0.01). Similarly, in SB elevated FOXP3+ Treg cells were found (p &lt; 0.05) with a higher FOXP3+/CD3+ ratio (p &lt; 0.01). Furthermore, a trend toward higher numbers of CD68+ macrophages was found (p &lt; 0.1) in SB. Numbers of CD3+ and FOXP3+ cells were higher in placentas with VUE compared to placentas without lesions (p &lt; 0.01 and p &lt; 0.001), accompanied by higher FOXP3+/CD3+ ratios (p &lt; 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.</p

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

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

Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial

Contains fulltext : 87399.pdf (publisher's version ) (Open Access)BACKGROUND: In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-)effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. METHODS/DESIGN: We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cut-off level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation) or obstetric complication (low birth weight, preterm delivery or fetal death) in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. DISCUSSION: With this study we aim to provide insight into the balance of risks of undetected and detected Q fever during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov, protocol record NL30340.042.09

Neonatal Myocardial Infarction or Myocarditis?

We report a 29 week-gestation preterm infant who presented during his second week of life with cardiogenic shock. Clinical presentation and first diagnostics suggested myocardial infarction, but echocardiographic features during follow-up pointed to a diagnosis of enteroviral myocarditis. The child died of chronic heart failure at 9 months of age. Autopsy showed passed myocardial infarction. No signs for active myocarditis were found. We discuss the difficulties in differentiating between neonatal myocardial infarction and myocarditis. Recognizing enteroviral myocarditis as cause for cardiogenic shock is of importance because of the therapeutic options