A nationwide population-based cohort study of peripartum hysterectomy and arterial embolisation in Belgium: results from the Belgian Obstetric Surveillance System.

OBJECTIVES: To assess the prevalence of major obstetric haemorrhage managed with peripartum hysterectomy and/or interventional radiology (IR) in Belgium. To describe women characteristics, the circumstances in which the interventions took place, the management of the obstetric haemorrhage, the outcome and additional morbidity of these women. DESIGN: Nationwide population-based prospective cohort study. SETTING: Emergency obstetric care. Participation of 97% of maternities covering 98.6% of deliveries in Belgium. PARTICIPANTS: All women who underwent peripartum hysterectomy and/or IR procedures in Belgium between January 2012 and December 2013. RESULTS: We obtained data on 166 women who underwent peripartum hysterectomy (n=84) and/or IR procedures (n=102), corresponding to 1 in 3030 women undergoing a peripartum hysterectomy and another 1 in 3030 women being managed by IR, thereby preserving the uterus. Seventeen women underwent hysterectomy following IR and three women needed further IR despite hysterectomy. Abnormal placentation and/or uterine atony were the reported causes of haemorrhage in 83.7%. Abnormally invasive placenta was not detected antenatally in 34% of cases. The interventions were planned in 15 women. Three women were transferred antenatally and 17 women postnatally to a hospital with emergency IR service. Urgent peripartum hysterectomy was averted in 72% of the women who were transferred, with no significant difference in need for transfusion. IR procedures were able to stop the bleeding in 87.8% of the attempts. Disseminated intravascular coagulation secondary to major haemorrhage was reported in 32 women (19%). CONCLUSION: The prevalence in Belgium of major obstetric haemorrhage requiring peripartum hysterectomy and/or IR is estimated at 6.6 (95% CI 5.7 to 7.7) per 10 000 deliveries. Increased clinician awareness of the risk factors of abnormal placentation could further improve the management and outcome of major obstetric haemorrhage. A case-by-case in-depth analysis is necessary to reveal whether the hysterectomies and arterial embolisations performed in this study were appropriate or preventable.

Obstetric Admissions to the Intensive Care Unit in a Tertiary Hospital.

AIMS: A better understanding of the characteristics of obstetric patients admitted to an intensive care unit (ICU) could guide where the focus of obstetric training and awareness should be directed at to reduce further maternal mortality and morbidity. METHODS: We retrospectively assessed the charts of all women admitted during pregnancy or postpartum to a tertiary ICU over a 12-year period. We retrieved whether women were followed locally or referred from another hospital and whether the ICU admission was prophylactic or therapeutic. RESULTS: There were 190 admissions in 183 women. One-hundred and four admissions were in referred women and 86 in women cared for locally. Seventy-eight admissions (41.1%) were for direct obstetric causes (primarily postpartum hemorrhage (n = 14), hypertensive disorders of pregnancy (n = 12) and peripartum cardiomyopathy (n = 10)). Indirect obstetric admissions (n = 89; 46.8%) were primarily for cardiopathies (n = 35) and pulmonary diseases (n = 18). Among non-obstetric admissions, trauma (n = 6; 26.1%) and neurologic tumors (n = 6; 26.1%) were the most common. CONCLUSION: Pre-existing and acquired cardiopathies are the main reason for admission to an ICU in a developed country and have surpassed hypertensive disorders and hemorrhage. This should become a focus of obstetric care provider training.

Impact of childhood trauma on postpartum depression: a prospective study.

Studies on the impact of childhood trauma on postpartum depression show inconsistencies and methodological limitations. The present study examines the effect of childhood trauma on depression 12 and 24 weeks after childbirth, while controlling for history of depression, depression symptoms during pregnancy and type D personality. During the third trimester of pregnancy, 210 women completed self-report questionnaires assessing depression (current and/or past episodes), childhood trauma and type D personality, of whom 187 participated in the postpartum follow-up, with depression symptoms being reassessed at 12 and 24 weeks after delivery with three depression outcome measures. Eventually, 183 participants were retained for analysis. Results indicated no predictive value of childhood trauma on postpartum depression in the univariate analyses, nor after controlling for previous depression, depression symptoms during pregnancy and type D personality. However, past depression and depression symptoms during pregnancy did independently and convincingly predict postpartum depression, especially at 12 weeks and to a lesser extent at 24 weeks following childbirth. Overall, we found no significant association between childhood trauma and postpartum depression. Past depression and depression symptoms during pregnancy are more relevant factors to assess before childbirth.

Turning the pink cloud grey: dampening of positive affect predicts postpartum depressive symptoms.

OBJECTIVE: Maladaptive response styles to negative affect have been shown to be associated with prospective (postpartum) depression. Whether maladaptive styles to positive affect are also critically involved is understudied, even though anhedonia (a correlate of low positive affectivity) is a cardinal symptom of depression. The present study is the first to investigate the predictive value of cognitive response styles to both negative (depressive rumination) and positive affect (dampening) for postpartum depressive symptoms. METHODS: During the third trimester of pregnancy, 210 women completed self-report instruments assessing depression (symptom severity and current and/or past episodes) and scales gauging the presence of depressive rumination and dampening. Of these women, 187 were retained for postpartum follow-up, with depressive symptoms being reassessed at 12 (n=171) and 24 (n=176) weeks after delivery. RESULTS: Regression analyses showed that higher levels of dampening of positive affect during pregnancy predicted higher levels of depressive symptoms at 12 and 24 weeks postpartum, irrespective of initial symptom severity, past history of depression and levels of rumination to negative affect. Prepartum trait levels of rumination, however, did not predict postpartum symptomatology when controlled for baseline symptoms and history of major depressive episode(s). CONCLUSIONS: The results of this investigation suggest that the way women cognitively respond to positive affect contributes perhaps even more to the development of postpartum depression than maladaptive response styles to negative affect.

Analysis of Pregnancy Outcomes Using the New IADPSG Recommendation Compared with the Carpenter and Coustan Criteria in an Area with a Low Prevalence of Gestational Diabetes.

Aims. This paper aims to evaluate characteristics and pregnancy outcomes in women prior classified normal by Carpenter and Coustan criteria (old criteria) and now gestational diabetes (GDM) by the IADPSG criteria. Methods. Retrospective analysis of 6727 pregnancies is used. Using the old criteria, 222 had GDM (old GDM). Using the IADPSG criteria, 382 had GDM of which 160 had a normal glucose tolerance with the old criteria (new GDM). We compared the new GDM group with the old GDM group and women with normal glucose tolerance with both criteria (NGT group, 6345). Results. New GDM women were younger (31.6 ± 4.7 versus 33.3 ± 7.2 years, P = 0.010) than old GDM women. Caesarean section was performed in 30.5% of new GDM, in 32.4% of old GDM (P = 0.706), and in 23.3% of NGT women (P = 0.001). Large for gestational age occurred in 10.8% of new GDM, in 13.8% of old GDM (P = 0.473), and in 9.0% of NGT women (P = 0.099). Shoulder dystocia occurred in 3.9% of new GDM, in 3.2% of old GDM (P = 0.736), and in 1.4% of NGT women (P = 0.007). Conclusion. Using the IADPSG criteria, more women are identified as having GDM, and these women carry an increased risk for adverse gestational outcome compared to women without GDM.

PP082. Eclampsia in flanders: A comparative study between flanders, United Kingdom and The Netherlands.

INTRODUCTION: Eclampsia fulfills the European criteria of "uncommon medical conditions". OBJECTIVES: To describe eclampsia in Flanders and compare the results with data of United Kingdom Obstetric Surveillance System (UKOSS) and a similar study in the Netherlands. Methods Between January and December 2012 each maternity hospital in Flanders was contacted monthly to learn whether a case of eclampsia had occurred. For each reported case an extensive questionnaire was completed. The obtained data were analyzed using the IBM-SPSSvs20 and BMJ-CIA programs. RESULTS: Over 95% of all maternity hospitals in Flanders participated. In 2012, 16 eclampsia cases were reported (incidence 2.3/10,000). Data of 14/16 cases could be used for analysis. No maternal or perinatal death occurred. In 71.4% (10/14;95%CI:45.4-88.3%) the gestational age at time of delivery was <37 weeks; in 28.6% (4/14;95%CI:11.7-54.6%) the insult occurred after the delivery; 50.00% (7/14;95%CI:26.8-73.2%) of the patients was primigravida and 28.6% (4/14;95%CI:11.7-54.6%) was negroid. Data presented in the table below summarize the findings of the last medical examination preceding the insult (n=13, insufficient data in 1 case). CONCLUSIONS: The incidence of eclampsia in Flanders is comparable to that of the UK (2.7/10,000) and is 2.7 times smaller than that of the Netherlands (6.2/10.000). Proteinuria was not tested in 9. In 5 of 14 no clear alert sign was seen at the last observation compared to 10.8% and 21% in Ndl and UK.

Physiologic variations of serum tumor markers in gynecological malignancies during pregnancy: a systematic review.

BACKGROUND: Recent insights provide support for the treatment of cancer during pregnancy, a coincidence that poses both mother and fetus at risk. Our aim was to critically review studies on the physiologic variations during pregnancy, the most common tumor markers used in diagnosis and follow-up of gynecological cancers. METHODS: We conducted a systematic review of six tumor markers during normal pregnancy: carbohydrate antigen (CA) 15-3 (breast cancer); squamous cell carcinoma antigen (cervical cancer); and CA 125, anti-Müllerian hormone, inhibin B and lactate dehydrogenase (ovarian cancer). RESULTS: For CA 15-3, 3.3% to 20.0% of all measurements were above the cut-off (maximum 56 U/mL in the third trimester). Squamous cell carcinoma antigen values were above cut-off in 3.1% and 10.5% of the measurements (maximum 4.3 µg/L in the third trimester). Up to 35% of CA 125 levels were above cut-off: levels were highest in the first trimester, with a maximum value up to 550 U/mL. Inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels were not elevated in maternal serum during normal pregnancy. CONCLUSION: During normal pregnancy, tumor markers including CA 15.3, squamous cell carcinoma antigen and CA 125 can be elevated; inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels remain below normal cut-off values. Knowledge of physiological variations during pregnancy can be clinically important when managing gynecological cancers in pregnant patients.

Endovascular trophoblast and preeclampsia: A reassessment.

Since the earliest report on impaired spiral artery remodelling in preeclamptic human pregnancies, numerous studies have been devoted to possible mechanisms of impaired trophoblast invasion. A better knowledge of early uteroplacental blood flow has provided a physiological context for the processes of spiral artery invasion and associated remodelling, revealing a closely timed relationship between increasing flow and early steps in vascular remodelling. Concerning the impaired trophoblast invasion in preeclampsia, it has also to be considered that impaired invasion not only concerns invasion depth per se, but also the extension of this deep invasion from the central towards the more lateral spiral arteries of the placental bed. Since also in preeclampsia the very central spiral arteries may be normally invaded, the existence of such spatial gradient provides a further dimension to the problem. A practical consequence is that frequently used rodent models, which show invasion of two or three spiral arteries only, may be less useful for studying this particular aspect of the disease. Amongst non-human primates, baboons and rhesus monkeys are 'shallow invaders', and only in some of the great apes deep trophoblast invasion and associated spiral artery remodelling occurs. A better knowledge of the evolutionary history of deep invasion and its possible selective benefit might ultimately improve our understanding of failed deep invasion and impaired spiral artery remodelling in preeclampsia.

A randomized controlled trial of misoprostol and sulprostone to end pregnancy after fetal death.

Objective. To compare effectiveness, side effects, and patients' perception of vaginal misoprostol versus intravenous sulprostone for ending pregnancy after fetal death between 14 and 42 weeks gestation. Method. Multicenter randomized controlled trial, using block randomization, central allocation, and prior power analysis. Outcome measures. Induction-delivery interval, gastrointestinal side effects, use of analgesia, pain perception, pyrexia, placental retention, hemorrhage, and women's opinions. Results. Of 176 women aimed for, 143 were randomized over 7 years, of whom 4 were excluded. There was no difference in delivery within 24 and 36 hours: 91.4% and 97.1% with misoprostol (n = 70) versus 85.5% and 92.8% with sulprostone (n = 69). There was no difference in either gastrointestinal side effects, as reported by the women and their caregivers, use of analgesia, women's pain perception, blood loss or placental retention. Hyperthermia >/=38 degrees C was more common with misoprostol (24.3%) than with sulprostone (11.6%; difference: +12.7%; 95% CI: +1.2% to +25.3%) and related to the total dose used. Acceptability of both induction methods was similar except for freedom of movement, which was substantially in favor of misoprostol (lack of freedom reported with misoprostol in 34.3% versus 63.8% with sulprostone; difference: -29.5%; 95% CI: -13.6% to -45.4%). Conclusions. Misoprostol and sulprostone are similarly effective with little difference in side effects except for hyperthermia, related to the dose of misoprostol used, and women's reported lack of mobility with intravenous sulprostone. Effectiveness of both methods increased with gestational age.

Trends in preterm births in Flanders, Belgium, from 1991 to 2002.

Changes in the preterm birth rate have been attributed predominantly to increases in multiple pregnancies, associated with advanced maternal age and assisted reproduction, and to obstetric intervention. We examined their contribution to the frequencies of preterm (<37 weeks), very preterm (<32 weeks) and severely preterm (<28 weeks) birth among 700 383 singleton and twin births in Flanders from 1991 to 2002. We examined changes across four 3-year periods (triennia) with confidence interval [CI] analysis and yearly incremental rates using linear and logistic regression analyses. Over the 12 years, twin pregnancies increased from 1.5% to 2.0%, averaging 1.6% [95% CI 1.54, 1.66] in 1991-93 and 1.9% [95% CI 1.81, 1.94] in 2000-02 (P < 0.001). The proportion of women aged 35 years or more increased from 6.8% [95% CI 6.69, 6.92] in 1991-93 to 11.3% [95% CI 11.2, 11.5] in 2000-02 (P < 0.001) and those aged under 20 from 1.9% [95% CI 1.81, 1.93] to 2.3% [95% CI 2.26, 2.41] (P < 0.001). Assisted reproduction increased from 2.6% [95% CI 2.48, 2.62] to 4.2% [95% CI 4.11, 4.30] (P < 0.001) and obstetric intervention to end pregnancy from 36.2% [95% CI 36.0, 36.4] to 40.3% [95% CI 40.1, 40.6] (P < 0.001). These increases related to an annual increase of 0.23% in the preterm birth rate from 5.5% [95% CI 5.4, 5.6] in 1991-93 to 7.2% [95% CI 7.1, 7.3] in 2000-02 (P < 0.001). The proportions of very and severely preterm births also increased by nearly a third, but their contribution to the total preterm birth rate remained stable at 15% and 5%, respectively. Odds ratios for the increases per year were 1.035 [95% CI 1.032, 1.038] for preterm birth, 1.024 [95% CI 1.018, 1.031] for very preterm and 1.028 [95% CI 1.017, 1.040] for severely preterm births after adjusting for other changes in the population. Overall, the data show, first, marked increases in the frequency of known contributors to the preterm birth rate, including twin pregnancies, advanced maternal age, assisted reproduction and obstetric intervention. Second, the preterm birth rate further increased significantly within subgroups of women with one or more of these characteristics. Third, the preterm birth rate also rose, from 4.4% [95% CI 4.2, 4.5] in 1991-93 to 5.6% [95% CI 5.5, 5.8] in 2000-02 (P < 0.001), in women with none of these contributing factors. This indicates that changes in the frequency of these known predictors are insufficient to explain the steady increase in preterm, very preterm and severely preterm births over more than a decade.

Gynecologic cancers in pregnancy: guidelines of an international consensus meeting.

BACKGROUND: Gynecologic cancer during pregnancy is a special challenge because cancer or its treatment may affect not only the pregnant women in general but directly involve the reproductive tract and fetus. Currently, there are no guidelines on how to deal with this special coincidence. METHODS: An international consensus meeting on staging and treatment of gynecological malignancies during pregnancy was organised including a systematic literature search, and interpretation followed by a physical meeting of all participants with intensive discussion. In the absence of large trials and randomized studies, recommendations were based on available literature data and personal experience thus representing a low but best achievable level of evidence. FINDINGS: Randomized trials and prospective studies on cancer treatment during pregnancy are lacking. Gynecological cancer during pregnancy is a demanding problem, and multidisciplinary expertise should be available. Counseling both parents on the maternal prognosis and fetal risk is needed. When there is a firm desire to continue the pregnancy, gynecological cancer can be treated in selected cases. The staging and treatment should follow the standard approach as much as possible. Guidelines for safe pelvic surgery during pregnancy are presented. Mainly in cervical and ovarian cancer, chemotherapy and an alternative surgical approach need to be considered. Administration of chemotherapy during the second or third trimester may probably not increase the incidence of congenital malformations. Until now, the long-term outcome of children in utero exposed to oncological treatment modalities is poorly documented, but preterm birth on its own is associated with cognitive impairment. Delivery should be postponed preferably until after a gestational age of 35 weeks. INTERPRETATION: Further research including international registries for gynecologic cancer in pregnancy is urgently needed. The gathering of both available literature and personal experience allowed only suggesting models for treatment of gynecologic cancer in pregnancy.

Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study.

OBJECTIVE: To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations. DESIGN: Prospective cohort study. SETTING: 28 hospitals in the Netherlands and Belgium. PARTICIPANTS: 1920 consecutive women treated with tocolytics for threatened preterm labour. MAIN OUTCOME MEASURES: Maternal adverse events (those suspected of being causally related to treatment were considered adverse drug reactions) leading to cessation of treatment. RESULTS: An independent panel evaluated the recorded adverse events, without knowledge of the type of tocolytic used. Of the 1920 women treated with tocolytics, 1327 received a single course of treatment (69.1%), 282 sequential courses (14.7%), and 311 combined courses (16.2%). Adverse drug reactions were categorised as serious or mild in 14 cases each. The overall incidence of serious adverse drug reaction was 0.7%. Compared with atosiban, the relative risk of an adverse drug reaction for single treatment with a beta adrenoceptor agonist was 22.0 (95% confidence interval 3.6 to 138.0) and for single treatment with a calcium antagonist was 12 (1.9 to 69). Multiple drug tocolysis led to five serious adverse drug reactions (1.6%). Multiple gestation, preterm rupture of membranes, and comorbidity were not independent risk factors for adverse drug reactions. CONCLUSIONS: The use of beta adrenoceptor agonists or multiple tocolytics for preventing preterm birth is associated with a high incidence of serious adverse drug reactions. Indometacin and atosiban were the only drugs not associated with serious adverse drug reactions. A direct comparison of the effectiveness of nifedipine and atosiban in postponing preterm delivery is needed.

Neonatal transient respiratory depression after maternal urapidil infusion for hypertension.

Urapidil is a potent antihypertensive drug that has been in clinical use for more than 20 years. It has been proven to be an effective and well-tolerated antihypertensive drug during pregnancy, but clinical experiences with urapidil have been described in only a limited number of studies. There have also been only limited observations on the (side-)effects of urapidil on the neonate. We describe here a case of postnatal transient respiratory depression following maternal administration of urapidil. We suggest that the fetal and neonatal effects of more recently implemented antihypertensive drugs, such as urapidil, should be included in a prospective evaluation of antihypertensive treatment of women during pregnancy. Infants of mothers who received urapidil should be carefully watched in the immediate postnatal phase as urapidil may still exert some significant effects on the neonate.

Fetal cerebral hemorrhage caused by vitamin K deficiency after complicated bariatric surgery.

BACKGROUND: Restrictive bariatric surgery decreases obesity-related morbidity and mortality. With the widespread use of these interventions, an increasing number of women who have undergone bariatric surgery become pregnant. CASE: A women, pregnant 2 years after laparoscopic gastric banding, presented with prolonged vomiting due to slippage of the gastic band resulting in gastric outlet obstruction. Parenteral feeding was initiated for 3 weeks until the patient was delivered because of a nonreassuring fetal heart rate pattern. A postnatal diagnosis of an extensive intracranial fetal hemorrhage due to maternal vitamin K deficiency was made. CONCLUSION: Although restrictive bariatric surgery is generally considered safe, we want to warn of possible severely adverse outcomes related to the intervention. In case of food intolerance, early vitamin substitution is indicated.

Fetal-maternal conflict, trophoblast invasion, preeclampsia, and the red queen.

The much publicized conflict hypothesis for understanding fetal-maternal interaction during pregnancy often invokes a 'battle' metaphor, rather than a well orchestrated interplay occurring as a series of well controlled moves and counter-moves as happens in a game of chess. Such stepwise interaction is particularly obvious in the spiral artery remodelling process, and it would be interesting to trace the history of the successive steps in histological adaptation throughout primate phylogeny. The restricted invasion observed in a few species on a 'lower' evolutionary scale suggests a tendency of progressive deeper invasion during primate evolution. Unfortunately, our knowledge of invasive processes in the placental bed in nonhuman primates is highly inadequate. A paradigm underscoring the stepwise interaction between mother and fetus may be provided by the Red Queen hypothesis, which is a useful model to explain co-evolutionary processes between different species. The apparent association between preeclampsia and restricted endovascular trophoblast invasion, combined with the absence of the disease in primate species showing shallow invasion, suggests that preeclampsia may result from a failure in one or more interactive steps necessary for deeper invasion. Evidence for a genetic component invokes the puzzling question as to why "preeclampsia genes" are not eliminated from human populations. As in other fields of medicine, a proper understanding of Darwinian selection processes may throw some light on the causes of preeclampsia.

Successful conservative treatment of endocervical adenocarcinoma stage Ib1 diagnosed early in pregnancy.

Traditionally when cervical cancer is diagnosed during the first trimester of pregnancy, oncological treatment is given priority despite the pregnant state. A 32-year-old primigravida was diagnosed with invasive endocervical adenocarcinoma stage Ib1 at 8 weeks' gestation. As the patient wanted to preserve the pregnancy, an amputation of the anterior cervix and retroperitoneal pelvic lymphadenectomy were performed. Based on favourable prognostic markers, we decided to maintain the pregnancy with careful cytological and histological follow-up. The patient gave birth at term to a healthy boy, and 18 months after the delivery there is no evidence of recurrent disease. In the absence of poor prognostic markers, we decided to adopt a conservative approach for cervical adenocarcinoma in a pregnant patient at 8 weeks' gestation.

Urachal carcinoma during pregnancy.

We report a case of Stage T4aN2M0 urachal carcinoma that was diagnosed early in pregnancy. Because positive pelvic lymph nodes and uterine involvement were present, surgical resection, including hysterectomy with termination of the pregnancy, and postoperative radiotherapy were performed. The treatment options, which largely depend on the duration of the pregnancy, the tumor stage, and the patient's desire to continue the pregnancy, are discussed.

In vivo analysis of trophoblast cell invasion in the human.

In vivo analysis of trophoblast cell invasion is highly dependent on histological techniques, which are amply described in standard textbooks. The emphasis of this chapter therefore lies on material collection and interpretation of tissue sections, rather than on histological techniques per se. Proper identification of vascular structures on placental bed histological sections is important, the more because invading trophoblastic cells induce significant structural changes in uterine blood vessels, which may be disturbed in complicated pregnancies. Guidelines for distinguishing several vascular structures are provided, and different approaches for qualitative and quantitative assessment of spiral artery changes are discussed. The purpose of such studies is not only to obtain a better insight into mechanisms of trophoblast invasion and associated maternal tissue changes, but also to understand placental bed defects in various pregnancy complications.