Johannes Erwich

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.

Severe hypotension and fetal death due to tocolysis with nifedipine.

A 23 year old woman of African origin was referred from a peripheral unit at 26 weeks and five days of gestation in her second pregnancy because of preterm labour. She had previously had an uncomplicated pregnancy. On admission, we continued the tocolytic therapy with atosiban and the administration of steroids to mature the fetal lungs, which had already been started in the referring hospital. The uterine contractions continued and indomethacin was combined with atosiban for 24 hours. Finally, the contractions ceased. Ultrasound investigation showed one fetus with no obvious abnormalities. The estimated fetal weight was 800 g (10th– 25th centile). The membranes were intact and there were no signs of infection: no fever and the urine sample and vaginal swab showed no abnormalities. On admission, her blood pressure was 115/75 mmHg and remained stable. After 48 hours, the atosiban was discontinued and 5 hours later the uterine contractions started again. On examination per vaginam the cervix was fully effaced and the os uterine was 3 cm dilated. Because of severe prematurity, tocolytic therapy was restarted with orally administered nifedipine as outlined in the following regimen: first dose nifedipine 10 mg tablet chewed, followed by three further doses of nifedipine 10 mg every 15 minutes, followed by nifedipine slow release 20 mg every 3 or 4 hours depending on uterine activity. After the second dose, fetal cardiotocography became difficult to interpret due to a poor quality record and the blood pressure dropped without symptoms to 73/30 mmHg. Ultrasound examination showed severe bradycardia soon followed by fetal death. Tocolytic therapy was discontinued and colloid infusion started and after 6 hours the blood pressure reached its normal level again. The next day, labour was induced with vaginally administered misoprostol. A stillborn girl of 780 g was born (10th–25th centile). No obvious abnormalities were seen, apart from a marginal insertion of the umbilical cord to the placenta. The placenta weighted 150 g. The umbilical cord showed two arteries and one vein. On histopathology, 20% placental infarction was reported. Permission for autopsy was not obtained.

Travel time from home to hospital and adverse perinatal outcomes in women at term in the Netherlands

Please cite this paper as: Ravelli A, Jager K, de Groot M, Erwich J, Rijninks‐van Driel G, Tromp M, Eskes M, Abu‐Hanna A, Mol B. Travel time from home to hospital and adverse perinatal outcomes in women at term in the Netherlands. BJOG 2011;118:457–465.

Hydrogen sulfide producing enzymes in pregnancy and preeclampsia

Preeclampsia, a human pregnancy specific disorder is characterized by an anti-angiogenic state. As hydrogen sulfide (H(2)S) has pro-angiogenic and anti-oxidative characteristics, we hypothesized that H(2)S levels could play a role in the pathogenesis of preeclampsia and studied the placental expression of the H(2)S-producing enzymes cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS). CBS and CSE protein are expressed in the fetal-placental endothelium and CBS only in Hofbauer cells. CBS mRNA expression is decreased (p = 0.002) in early-onset preeclampsia, while CSE mRNA is unchanged. Thus, down regulation of CBS during early-onset preeclampsia may result in less H(2)S-production and may aid in the anti-angiogenic state.

Altered expression of immune-associated genes in first-trimester human decidua of pregnancies later complicated with hypertension or foetal growth restriction

During pregnancy the maternal immune system has to coordinate uterine spiral-artery remodelling, trophoblast invasion, and acceptance of the semi-allogenic fetus simultaneously. As dysregulation of the immune system is associated with adverse pregnancy outcomes, we analysed first-trimester deciduas of pregnancies for immune parameters in later complicated pregnancies. Higher IL6 and macrophage mRNA expression, and lower ratios of regulatory macrophages were found in first-trimester deciduas of pregnancies later complicated with pregnancy-induced hypertension. Lower Gata3 (Th2) mRNA expression was found in deciduas of pregnancies with later foetal growth restriction. Our results suggest that adverse pregnancy outcomes are associated with immunological disturbances in first-trimester deciduas.

General movements in the first fourteen days of life in extremely low birth weight (ELBW) infants

OBJECTIVE To assess the quality of general movements (GMs) in the first fourteen days of life in relation to obstetric and postnatal risk factors and neurodevelopmental outcome in extremely low birth weight (ELBW) infants. STUDY DESIGN The GMs of nineteen infants were assessed on days 2, 4, 6, 10 and 14 with Prechtls method. Additionally, detailed GM assessment produced optimality scores (OSs). GMs and the OSs were related to obstetric and postnatal data and to neurodevelopmental outcome at 18 months. RESULTS GMs and OSs fluctuated substantially during the first fourteen days of life. Most infants had abnormal GMs, especially poor repertoire (PR) GMs. No relation was found between GMs and obstetric factors. Regarding postnatal factors, septicaemia correlated to hypokinesia (H) and artificial ventilation correlated to a lower OS. CONCLUSIONS Due to physiological disturbances the quality of GM in ELBW infants fluctuates substantially during the first fourteen days of life. Abnormal GMs, especially PR GMs, are mostly seen for the same reason. Septicaemia and artificial ventilation are associated with deterioration of the GMs (lower OSs), and in case of septicaemia also with hypokinesia.

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.

Making stillbirths visible: a systematic review of globally reported causes of stillbirth

Stillbirth is a global health problem. The World Health Organization (WHO) application of the International Classification of Diseases for perinatal mortality (ICD‐PM) aims to improve data on stillbirth to enable prevention.

Application of ICD-PM to preterm-related neonatal deaths in South Africa and United Kingdom

We explore preterm‐related neonatal deaths using the WHO application of the International Classification of Disease (ICD‐10) to deaths during the perinatal period: ICD‐PM as an informative case study, where ICD‐PM can improve data use to guide clinical practice and programmatic decision‐making.

Placental pathology is associated with illness severity in preterm infants in the first twenty-four hours after birth

BACKGROUND Placental pathology is associated with long-term neurological morbidity. Little is known about the association of placental pathology and illness severity directly after birth in preterm infants. OBJECTIVE To determine the association between placental pathology and illness severity in preterm infants during the first 24 h after birth. STUDY DESIGN Placentas of 40 preterm infants, born after singleton pregnancies (gestational age 25.4-31.7 weeks, birth weight 560-2250 g) were assessed for histopathology. Illness severity was measured using the Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE). A high SNAPPE reflects high illness severity. RESULTS Examination of the 40 placentas revealed: pathology consistent with maternal vascular underperfusion (MVU) (n=24), ascending intrauterine infection (AIUI) (n=17), villitis of unknown aetiology (VUE) (n=6), foetal thrombotic vasculopathy (FTV) (n=6), elevated nucleated red blood cells (NRBCs) (n=6), and chronic deciduitis (n=10). SNAPPE ranged from 1 to 53 (median 10). Infants with elevated NRBCs had a higher SNAPPE than infants without elevated NRBCs (median 30 vs. 10, p=0.014). The same was found for the presence of FTV (median 30 vs. 10, p=0.019). No relation existed between SNAPPE and the other placental pathologies. CONCLUSIONS Elevated NRBCs and FTV were associated with higher illness severity during the first 24 h after birth in preterm infants. Ascending intrauterine infection was not associated with high illness severity.