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Background: The World Health Organization (WHO) adopted more stringent diagnostic criteria for GDM in 2013, to improve pregnancy outcomes. However, there is no global consensus on these new diagnostic criteria, because of limited evidence. The objective of the study was to evaluate maternal characteristics and pregnancy outcomes in two cohorts in the Netherlands applying different diagnostic criteria for GDM i.e. WHO-2013 and WHO-1999. Methods: A multicenter retrospective study involving singleton GDM pregnancies in two regions, between 2011 and 2016. Women were diagnosed according to the WHO-2013 criteria in the Deventer region (WHO-2013-cohort) and according to the WHO-1999 criteria in the Groningen region (WHO-1999-cohort). After GDM diagnosis, all women were treated equally based on the national guideline. Maternal characteristics and pregnancy outcomes were compared between the two groups. Results: In total 1386 women with GDM were included in the study. Women in the WHO-2013-cohort were older and had a higher pre-gestational body mass index. They were diagnosed earlier (24.9 [IQR 23.3–29.0] versus 27.7 [IQR 25.9–30.7] weeks, p = 90th percentile, corrected for sex, ethnicity, parity, and gestational age) was lower in the WHO-2013- cohort, but not statistical significant (16.5% versus 18.5%, p = 0.379). There were no differences between the cohorts regarding stillbirth, birth trauma, low Apgar score, and preeclampsia. Conclusions: Using the new WHO-2013 criteria resulted in an earlier GDM diagnosis, less women needed insulin treatment and more spontaneous deliveries occurred when compared to the cohort diagnosed with WHO-1999 criteria. No differences were found in adverse pregnancy outcomes.

Aims/hypothesis Detection and management of gestational diabetes mellitus (GDM) are crucial to reduce the risk of pregnancy-related complications for both mother and child. In 2013, the WHO adopted new diagnostic criteria for GDM to improve pregnancy outcomes. However, the evidence supporting these criteria is limited. Consequently, these new criteria have not yet been endorsed in the Netherlands. The aim of this study was to determine the impact of these criteria on the number of GDM diagnoses and pregnancy outcomes. Methods Data were available from 10,642 women who underwent a 75 g OGTT because of risk factors or signs suggestive of GDM. Women were treated if diagnosed with GDM according to the WHO 1999 criteria. Data on pregnancy outcomes were obtained from extensive chart reviews from 4,431 women and were compared between women with normal glucose tolerance (NGT) and women classified into the following groups: (1) GDM according to WHO 1999 criteria; (2) GDM according to WHO 2013 criteria; (3) GDM according to WHO 2013 fasting glucose threshold, but not WHO 1999 criteria; and (4) GDM according to WHO 1999 2 h plasma glucose threshold (2HG), but not WHO 2013 criteria. Results Applying the new WHO 2013 criteria would have increased the number of diagnoses by 45% (32% vs 22%) in this population of women at higher risk for GDM. In comparison with women with NGT, women classified as having GDM based only on the WHO 2013 threshold for fasting glucose, who were not treated for GDM, were more likely to have been obese (46.1% vs 28.1%, p

Perinatal death (PD) is a devastating obstetric complication. Determination of cause of death helps in understanding why and how it occurs, and it is an indispensable aid to parents wanting to understand why their baby died and to determine the recurrence risk and management in subsequent pregnancy. Consequently, a perinatal death requires adequate diagnostic investigation. An important first step in the analysis of PD is to identify the case circumstances, including relevant details regarding maternal history, obstetric history and current pregnancy (complications are evaluated and recorded). In the next step, placental examination is suggested in all cases, together with molecular cytogenetic evaluation and fetal autopsy. Investigation for fetal maternal hemorrhage by Kleihauer is also recommended as standard. In cases where parents do not consent to autopsy, alternative approaches such as minimally invasive postmortem examination, postmortem magnetic resonance imaging, and fetal photographs are good alternatives. After all investigations have been performed it is important to combine findings from the clinical review and investigations together, to identify the most probable cause of death and counsel the parents regarding their loss. (C) 2017 Elsevier Ltd. All rights reserved.

ContextThyroid dysfunction is thought to be associated with stillbirth. Therefore, thyroid function is often recommended in the diagnostic investigations for stillbirth.ObjectiveWe aimed to evaluate the added value of thyroid function testing in the diagnostic investigations for stillbirth.Design and patientsA nationwide multicentre prospective cohort study in 1025 women who suffered stillbirth >20 weeks of gestation performed between 2002 and 2008. In each woman, an extensive diagnostic work-up was performed, including placental examination and autopsy. TSH and FT4 values below the 25th percentile or above the 975th percentile according local laboratory reference values were regarded as abnormal. Women with a history of thyroid disease were evaluated separately.Main outcome measuresThyroid function abnormalities in women with stillbirth.ResultsOf 1025 included women, 21 had a history of thyroid disease (2%). In the 875 with TSH and FT4 results and no history of thyroid disease, 10% had hypothyroxinemia, 46% subclinical hypothyroidism, 16% overt hypothyroidism and 15% subclinical hyperthyroidism. Women with a subclinical hyperthyroidism more often had a foetal death caused by foetal hydrops: 23% vs 29% (adjusted OR 103, 95% CI 25-42).ConclusionsWomen with a stillbirth had a slightly higher prevalence of overt hypothyroidism, subclinical hypothyroidism and hypothyroxinaemia compared to previous studies on thyroid dysfunction in pregnant women. Given the absence of a strong associations with the cause of stillbirth, and no demonstrated beneficial effects of treating thyroid dysfunction in these women, routine screening after stillbirth is not justified.

Background Each year, about 5.3 million babies die in the perinatal period. Understanding of causes of death is critical for prevention, yet there is no globally acceptable classification system. Instead, many disparate systems have been developed and used. We aimed to identify all systems used or created between 2009 and 2014, with their key features, including extent of alignment with the International Classification of Diseases (ICD) and variation in features by region, to inform the World Health Organization’s development of a new global approach to classifying perinatal deaths. Methods A systematic literature review (CINAHL, EMBASE, Medline, Global Health, and PubMed) identified published and unpublished studies and national reports describing new classification systems or modifications of existing systems for causes of perinatal death, or that used or tested such systems, between 2009 and 2014. Studies reporting ICD use only were excluded. Data were independently double-extracted (except from non-English publications). Subgroup analyses explored variation by extent and region. Results Eighty-one systems were identified as new, modifications of existing systems, or having been used between 2009 and 2014, with an average of ten systems created/modified each year. Systems had widely varying characteristics: (i) comprehensiveness (40 systems classified both stillbirths and neonatal deaths); (ii) extent of use (systems were created in 28 countries and used in 40; 17 were created for national use; 27 were widely used); (iii) accessibility (three systems available in e-format); (iv) underlying cause of death (64 systems required a single cause of death); (v) reliability (10 systems tested for reliability, with overall Kappa scores ranging from .35–.93); and (vi) ICD alignment (17 systems used ICD codes). Regional databases were not searched, so system numbers may be underestimated. Some non-differential misclassification of systems was possible. Conclusions The plethora of systems in use, and continuing system development, hamper international efforts to improve understanding of causes of death. Recognition of the features of currently used systems, combined with a better understanding of the drivers of continued system creation, may help the development of a truly effective global system. Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-1071-0) contains supplementary material, which is available to authorized users.

Background: To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment-diet-only versus additional insulin therapy-were based on the 2010 national Dutch guidelines.Methods: Retrospective study of the electronic medical files of 820 singleton GDM pregnancies treated between January 2011 and September 2014 in a university and non-university hospital. Pregnancy outcomes were compared between regular care treatment regimens diet-only versus additional insulin therapy- and pregnancy outcomes of the Northern region of the Netherlands served as a reference population.Results: A total of 460 women (56 %) met glycaemic control on diet-only and 360 women (44 %) required additional insulin therapy. Between the groups, there were no differences in perinatal complications (mortality, birth trauma, hyperbilirubinaemia, hypoglycaemia), small for gestational age, large for gestational age (LGA), neonate weighing > 4200 g, neonate weighing >= 4500 g, Apgar score Conclusions: Neonatal and obstetric outcomes were comparable either with diet-only or additional insulin therapy. However, compared with the general obstetric population, the incidence of LGA neonates was significantly increased in this GDM cohort.

Comparing maternal and neonatal outcomes after conventional cesarean section (CS) versus a "natural" or "skin-to-skin" cesarean section (SSCS).Retrospective cohort of women who underwent a SSCS (01-2013 until 12-2013) compared to conventional CS (08-2011 to 08-2012). CS before 37 weeks, under general anesthesia and in case of fetal distress were excluded. Main outcome measures were maternal blood loss, post-operative infection and admission; neonatal infection and admission; procedural outcomes.We analyzed 285 (44%) women in the SSCS-group and 365 (56%) in the conventional CS-group. There were no significant differences in surgical site infection (2.1% versus 1.6%; RR 1.1; 95%CI 0.64-2.0), or other maternal outcomes. Fewer neonates born after SSCS were admitted to the pediatric ward (9.5% versus 18%; RR 0.58; 95%CI 0.41-0.80) and fewer neonates had a suspected neonatal infection (2.0% versus 7.3%; RR 0.40; 95%CI 0.19-0.83). No differences were observed for other outcomes. Mean operation time was 4m42s longer in the SSCS-group compared to the conventional CS-group (58m versus 53m; 95%CI 2m44s-6m40s). Mean recovery time was 14m46s shorter (114m versus 129m; 95%CI 3m20s-26m).Adverse maternal and neonatal outcomes were not increased after skin-to-skin cesarean compared to conventional cesarean delivery.

Please cite this paper as: Korteweg F, Folkeringa N, Brouwer J, Erwich J, Holm J, van der Meer J, Veeger N. Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study. BJOG 2012;119:422–430. Objective To assess the absolute risk of fetal loss associated with hereditary deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), and the contribution of additional thrombophilic defects to this risk. Design A retrospective family cohort study. Setting A tertiary referral teaching hospital. Population Women from families with hereditary deficiencies of AT, PC and PS, and their non-deficient relatives. Methods We assessed the absolute risk of fetal loss, comparing deficient women with non-deficient female relatives. Main outcome measures Early, late and total fetal loss rates; odds ratios of fetal loss. Results We evaluated 289 women, who had 860 pregnancies. The total fetal loss rates were 23% (AT deficient), 26% (PC deficient), 11% (type-I PS deficient) and 15% (type-III PS deficient), compared with 11, 18, 12 and 13% in non-deficient women, respectively. Odds ratios were 2.3 (95% CI 0.9–6.1), 2.1 (95% CI 0.9–4.7), 0.7 (95% CI 0.2–1.8) and 1.1 (95% CI 0.6–2.0), none of which reached statistical significance. Differences were mainly the result of higher late fetal loss rates in women deficient in AT (OR 11.3, 95% CI 3.0–42.0) and PC (OR 4.7, 95% CI 1.3–17.4). The concomitance of factor-V Leiden and prothrombin G20210A was observed in 19% of women, and did not increase the risk of fetal loss. Conclusions Although absolute risks of fetal loss were high, odds ratios of total fetal loss were not statistically significant in deficient versus non-deficient women. However the higher absolute risks appeared to reflect higher late fetal loss rates as opposed to early fetal loss rates. An additional effect of concomitance of factor-V Leiden and prothrombin G20210A was not demonstrated, which may result from the exclusion of women at highest risk of venous thromboembolism, or from the small numbers sampled in the study.

OBJECTIVE: We sought to evaluate the contribution of different diagnostic tests for determining cause of fetal death. Our goal was to propose a workup guideline.STUDY DESIGN: In a multicenter prospective cohort study from 2002 through 2008, for 1025 couples with fetal death >= 20 weeks' gestation, an extensive nonselective diagnostic workup was performed. A panel classified cause and determined contribution of diagnostics for allocating cause.RESULTS: A Kleihauer-Betke, autopsy, placental examination, and cytogenetic analysis were abnormal in 11.9% (95% confidence interval [CI], 9.8-14.2), 51.5% (95% CI, 47.4-55.2), 89.2% (95% CI, 87.2-91.1), and 11.9% (95% CI, 8.7-15.7), respectively. The most valuable tests for determination of cause were placental examination (95.7%; 95% CI, 94.2-96.8), autopsy (72.6%; 95% CI, 69.2-75.9), and cytogenetic analysis (29.0%; 95% CI, 24.4-34.0).CONCLUSION: Autopsy, placental examination, cytogenetic analysis, and testing for fetal maternal hemorrhage are basic tests for workup after fetal death. Based on the results of these tests or on specific clinical characteristics, further sequential testing is indicated.

OBJECTIVE: To estimate whether parental thrombophilic defects after fetal death, either acquired or inherited, were more prevalent than in the normal population and to estimate associations between these thrombophilic defects and different fetal death causes.METHODS: In a multicenter, prospective cohort study of 750 fetal deaths, we tested couples for antithrombin, protein C, total and free protein S, and von Willebrand factor (vWF) plasma levels. Mothers' values were compared with reference values in gestational age-matched healthy pregnant women, and fathers were compared with healthy men. Prevalence of factor V Leiden, prothrombin G20210A mutation, and lupus anticoagulant were compared with the normal population. A panel classified death cause.RESULTS: More women with fetal death had decreased antithrombin (16.8%, P CONCLUSION: Except for vWF and paternal free protein S, acquired and inherited thrombophilic defects were not more prevalent after fetal death. Routine thrombophilia testing after fetal death is not advised.

Different classification systems for the cause of intra-uterine fetal death (IUFD) are used internationally. About two thirds of these deaths are reported as unexplained and placental causes are often not addressed. Differences between systems could have consequences for the validity of vital statistics, for targeting preventive strategies and for counselling parents on recurrence risks. Our objective was to compare use of the Tulip classification with other currently used classification systems for causes of IUFD. We selected the extended Wigglesworth classification, modified Aberdeen and the classifications by Hey, Hovatta, de Galan-Roosen and Morrison. We also selected the ReCoDe system for relevant conditions, comparable to contributing factors in the Tulip classification. Panel classification for 485 IUFD cases in the different systems was performed by assessors after individual investigation of structured patient information. Distribution of cases into cause of death groups for the different systems varied, most of all for the placental and unknown groups. Systems with a high percentage of cases with an unknown cause of death and death groups consisting of clinical manifestations only are not discriminatory. Our largest cause of death group was placental pathology and classification systems without placental cause of death groups or minimal subdivision of this group are not useful in modern perinatal audit as loss of information occurs. The most frequent contributing factor was growth restriction. This illustrates the vital role of the placenta in determination of optimal fetal development. In the Tulip classification, mother, fetus and placenta are addressed together. The system has a clear defined subclassification of the placenta group, a low percentage of unknown causes and is easily applied by a multidisciplinary team. A useful classification aids future research into placental causes of IUFD. (c) 2007 Published by Elsevier Ltd.

Objective: A history of foetal death is a risk factor for complications and foetal death in subsequent pregnancies as most previous risk factors remain present and an underlying cause of death may recur. The purpose of this study was to evaluate subsequent pregnancy outcome after foetal death and to compare cases of recurrent foetal death.Study design: A retrospective cohort study in a tertiary referral centre. All women with a stillbirth beyond 16 weeks of gestation between January 1999 and December 2004 (n = 193) were identified. After providing informed consent, the medical records of 163 women were reviewed until August 2006 in terms of clinical, medical, obstetric and paediatric data of the pregnancy after the index pregnancy that resulted in foetal death. The cause of death for reported cases of foetal death and recurrent foetal death were classified by a multidisciplinary team according to the Tulip classification.Results: Recurrent foetal death occurred in 11 cases, and various causes were identified. The cause of death was explained in seven cases. An association was found between the index foetal death and subsequent foetal death in some cases, especially in early gestation.Conclusions: This study illustrates the importance of classifying the cause of recurrent foetal death and contributing risk factors using the same classification system. This provides more insight into the pathophysiological pathways leading to foetal death, and enables meaningful comparisons to be made in recurrent foetal death. This is required before preventive strategies can be instituted and implemented to reduce the risk of foetal death. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

To estimate success rates for cytogenetic analysis in different tissues after intrauterine fetal death, and study selection criteria and value of cytogenetic testing in determining cause of death.Cytogenetic analyses and the value of this test in determining cause by a multidisciplinary panel were studied in 750 fetal deaths. Morphologic abnormalities, small for gestational age (SGA), advanced maternal age (older than 35 years) and maceration were studied as selection criteria.Chromosomal abnormalities were observed in 13% of fetal deaths. Cytogenetic success rates were significantly higher for invasive testing (85%) than for postpartum tissue analysis (28%, P.001). There were more abnormal chromosomes (38%) in fetal deaths with morphologic abnormalities than in those without (5%, P.001). This was not observed for SGA (16% compared with 9.2%, P=.22) or for advanced maternal age (16.7% compared with 12.0%, P=.37). The posterior probability of a chromosomal abnormality in the absence of morphologic abnormalities was still 4.6%. Cytogenetic analysis was successful in 35% of severely macerated fetuses. We do not advise using these selection criteria, because the failure rate was high on postpartum tissues. Cytogenetic analysis was valuable in determining the cause in 19% of the fetal deaths.Parents should be counseled on aspects of cytogenetic analysis after fetal death. We advise performing nonselective invasive testing after fetal death and before labor for all fetal deaths.

Please cite this paper as: Korteweg F, Folkeringa N, Brouwer J, Erwich J, Holm J, van der Meer J, Veeger N. Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study. BJOG 2012;119:422–430. Objective To assess the absolute risk of fetal loss associated with hereditary deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), and the contribution of additional thrombophilic defects to this risk. Design A retrospective family cohort study. Setting A tertiary referral teaching hospital. Population Women from families with hereditary deficiencies of AT, PC and PS, and their non-deficient relatives. Methods We assessed the absolute risk of fetal loss, comparing deficient women with non-deficient female relatives. Main outcome measures Early, late and total fetal loss rates; odds ratios of fetal loss. Results We evaluated 289 women, who had 860 pregnancies. The total fetal loss rates were 23% (AT deficient), 26% (PC deficient), 11% (type-I PS deficient) and 15% (type-III PS deficient), compared with 11, 18, 12 and 13% in non-deficient women, respectively. Odds ratios were 2.3 (95% CI 0.9–6.1), 2.1 (95% CI 0.9–4.7), 0.7 (95% CI 0.2–1.8) and 1.1 (95% CI 0.6–2.0), none of which reached statistical significance. Differences were mainly the result of higher late fetal loss rates in women deficient in AT (OR 11.3, 95% CI 3.0–42.0) and PC (OR 4.7, 95% CI 1.3–17.4). The concomitance of factor-V Leiden and prothrombin G20210A was observed in 19% of women, and did not increase the risk of fetal loss. Conclusions Although absolute risks of fetal loss were high, odds ratios of total fetal loss were not statistically significant in deficient versus non-deficient women. However the higher absolute risks appeared to reflect higher late fetal loss rates as opposed to early fetal loss rates. An additional effect of concomitance of factor-V Leiden and prothrombin G20210A was not demonstrated, which may result from the exclusion of women at highest risk of venous thromboembolism, or from the small numbers sampled in the study.

Venous thromboembolism (VTE)during pregnancy is still an important cause of maternal morbidity and mortality in the Western world. The risk VTE in pregnant women is five times higher than in non-pregnant women of the same age. This risk is increased by thrombophilic defects. In a family cohort study we assessed the risk of VTE during pregnancy/puerperium and the contribution of concomitant thrombophilic defects in women with hereditary antithrombin, protein C or protein S deficiencies. Women were recruited from a previous large family cohort study, which was designed to estimate the risk of VTE in first degree relatives from probands with documented VTE and a deficiency of antithrombin, protein C or protein S. Probands were excluded from analysis. Blood samples of female relatives were tested on the index deficiencies and prothrombin G20210A, factor V Leiden, hyperhomocysteinemia and increased levels of VIII:C, IX:C and XI:C. Observation time was defined as the fertile period (from age 15–45 years), or until the first VTE, or until end of study period. The cohort contained 222 female relatives, of whom 101 women were deficient and 121 non-deficient. The absolute risk of venous thromboembolism in deficient women was 1.76 per 100 person-years versus 0.19 per 100 person-years in non-deficient women (Relative Risk (RR) 9.2; 95% CI 3.8–26.7). Concomitance of none, one and more than one thrombophilic defect increased the risk in deficient (1.55, 2.14 and 2.92 per 100 person-years, respectively) and non-deficient women (0.16, 0.09 and 0.54 per 100 person -years, respectively). Annual incidences (AI) were lower in ever pregnant than never pregnant deficient women, 1.37 per 100 person-years versus 2.96 per 100 person-years (RR 0.5; 95% CI 0.2–0.99)(Table). These were 0.09 per 100 person-years versus 0.70 per 100 person-years in non-deficient women (RR 0.1; 95% CI 0.02–0.9). In ever pregnant deficient women 71% of VTE episodes were pregnancy related. A majority (75%) of never pregnant deficient women revealed VTE associated with oral contraceptives. Women with hereditary antithrombin, protein C or protein S deficiencies are at high risk of VTE. Concomitance of other thrombophilic defects increased this risk. In fertile women most episodes of VTE are associated with either pregnancy or oral contraceptives. Deficient Non-deficient Ever pregnant (n=54) Never Pregnant (n=47) Ever pregnant (n=79) Never pregnant (n=42) Women with VTE, n 17 12 2 3 Observation period, yr 1241 405 2169 430 AI, % (95% CI) 1.37 (0.80–2.19) 2.96 (1.53–5.18) 0.09 (0.01–0.33) 0.70 (0.14–2.04) RR (95% CI) 0.5 (0.2–0.99) P=0.05 0.1 (0.02–0.9) P=0.04 Pregnancy related VTE, n (%) 12 (71) 0 1 (50) 0 Oral contraceptive related VTE, n (%) 2 (12) 9 (75) 0 3 (100)

To estimate the occurrence of placental causes of fetal death in relation to different gestational ages and their clinical manifestations during pregnancy.In a prospective cohort study conducted from 2002 to 2006, we studied 750 couples with singleton intrauterine fetal death after 20 weeks of gestation. Cause of death was classified according to the Dutch Tulip cause of death classification for perinatal mortality. Differences between groups for categorical data were evaluated by the Fisher exact test or chi test.The main causes were placental pathology (64.9%), congenital anomaly (5.3%), infection (1.9%), other (4.8%), and unknown (23.1%). The contribution of causes differed over gestational age periods. At lower gestational age, placental and unknown were the most dominant causes of death (34.8% and 41.7%, respectively); at higher gestational age, the relative importance of an unknown cause decreased and a placental cause increased (16.5% and 77.6%) (P.001). Placental bed pathology was observed in 33.6% of all fetal deaths, with the highest occurrence between 24 0/7 and 31 6/7 weeks and a strong decline after 32 weeks. In contrast, contribution of developmental placental pathology (17.6%) increased after 32 weeks of gestation (P.001), as did umbilical cord complications (5.2%) and combined placental pathology (5.4%). Solitary placental parenchyma pathology was less frequent (3.1%). Hypertension-related disease was observed in 16.1% (95% confidence interval [CI] 13.6-19.0) of the cohort, small for gestational age fetuses in 37.9% (95% CI 34.1-41.7), and diabetes-related disease in 4.1% (95% CI 2.8-5.8).Most fetal deaths were caused by a variety of placental pathologies. These were related to gestational age, and their clinical manifestations varied during pregnancy.II.