Jozien P. Holm

The Tulip classification of perinatal mortality: introduction and multidisciplinary inter-rater agreement

Objective  To introduce the pathophysiological Tulip classification system for underlying cause and mechanism of perinatal mortality based on clinical and pathological findings for the purpose of counselling and prevention.

Diverse placental pathologies as the main causes of fetal death.

OBJECTIVE: To estimate the occurrence of placental causes of fetal death in relation to different gestational ages and their clinical manifestations during pregnancy. METHODS: 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 &khgr;2 test. RESULTS: 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). CONCLUSION: Most fetal deaths were caused by a variety of placental pathologies. These were related to gestational age, and their clinical manifestations varied during pregnancy. LEVEL OF EVIDENCE: II

Reduction of high fetal loss rate by anticoagulant treatment during pregnancy in antithrombin, protein C or protein S deficient women

Hereditary thrombophilia is associated with an increased risk of fetal loss. Assuming that fetal loss is due to placental thrombosis, anticoagulant treatment might improve pregnancy outcome. In an observational family cohort study, we prospectively assessed the effects of anticoagulant drugs on fetal loss rates in women with hereditary deficiencies of antithrombin, protein C or protein S. The cohort contained 376 women (50 probands and 326 deficient or non‐deficient relatives). Probands were consecutive deficient patients with venous tromboembolism. Thromboprophylaxis during pregnancy was recommended in deficient women, irrespective of prior venous thromboembolism, and in non‐deficient women with prior venous thromboembolism. Outcome of first pregnancy was analysed in 55 eligible women. Of 37 deficient women, 26 (70%) received thromboprophylaxis during pregnancy, compared with three of 18 (17%) non‐deficient women. Fetal loss rates were 0% in deficient women with thromboprophylaxis versus 45% in deficient women without (P = 0·001) and 7% in non‐deficient women without thromboprophylaxis (P = 0·37). The adjusted relative risk of fetal loss in women who received thromboprophylaxis versus women who did not was 0·07 (95% confidence interval 0·001–0·7; P = 0·02). Our data suggest that anticoagulant treatment during pregnancy reduces the high fetal loss rate in women with hereditary deficiencies of antithrombin, protein C or protein S.

Subsequent pregnancy outcome after previous foetal death

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.

Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study

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.

Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study: Fetal loss and multiple thrombophilic defects

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.

Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects

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.