André Van Assche

Placental bed spiral arteries in the hypertensive disorders of pregnancy

Objective— The investigation of the histology of the placental bed spiral arteries in normal pregnancy and in pregnancies complicated by hypertension, with or without proteinura.

The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of analgesia during labor and on the incidence of instrumental deliveries.

In a double-blinded, randomized, prospective multi-center study of 695 women, we investigated whether epidural injection of sufentanil added to 0.125% bupivacaine with epinephrine (1:800,000) reduces the total amount of local anesthetic required, resulting in less motor blockade and reduced incidence of instrumental deliveries, and improves the quality of analgesia provided by this low concentration of local anesthetic without jeopardizing the safety of the baby. In addition, other potential benefits of sufentanil (such as decrease in the incidence of shivering) and side effects were examined. It was found that adding incremental doses of 10 micrograms sufentanil up to a maximum of 30 micrograms reduced the incidence of instrumental deliveries from 36 to 24% (P less than 0.01) and significantly improved quality and duration of analgesia without depressing the neurobehavioral status of the baby. No other benefits from adding sufentanil were found. The only side effect that occurred more frequently after sufentanil was pruritus. We conclude that epidural injection of 10-30 micrograms sufentanil added to 0.125% bupivacaine with epinephrine (1:800,000) improved the quality of analgesia during labor and reduced the incidence of instrumental deliveries without jeopardizing the safety of the baby.

“LUPUS” ANTICOAGULANT AND INHIBITION OF PROSTACYCLIN FORMATION IN PATIENTS WITH REPEATED ABORTION, INTRAUTERINE GROWTH RETARDATION AND INTRAUTERINE DEATH

We discovered a‘lupus’ anticoagulant in 2 out of 24 women with a history of repeated abortions, intrauterine growth retardation and intrauterine death of unknown origin. The‘lupus’ anticoagulant was detected by an abnormal dilute tissue thromboplastin assay (prothrombin time performed with dilute thromboplastin). The production of prostacyclin by fresh or exhausted rings of rat aorta was decreased by the plasma of one of these two patients with a‘lupus’ anticoagulant. In view of the increasing evidence for a physiological role of prostacyclin in pregnancy and fetal life, we suggest that an inhibition of prostacyclin production could compromise fetal outcome.

Tobacco smoking impairs the local immunosurveillance in the uterine cervix. An immunohistochemical study.

Previous reports have supported an association between tobacco smoking and cervical neoplasia. Our observations show an association between smoking and a reduction of the numerical densities of Langerhans cells and of helper/inducer T lymphocytes in the squamous epithelia of the transformation zone of the uterine cervix. This suggests a local impairment of cell-mediated immunity by smoking. This immunosuppressive effect could support the concept that smoking is an independent risk factor for cervical neoplasia.

Predictive value of increased plasma levels of fibronectin in gestational hypertension

Blood pressure, proteinuria, and plasma fibronectin and plasminogen activator inhibitor-1 levels were measured in 120 apparently healthy normotensive primigravid women during the first, second, and third trimesters of pregnancy and 2 days post partum. Thirty-two women developed hypertension (diastolic blood pressure ≥90 mm Hg) that in 17 women was associated with proteinuria (>0.3 gm/day). Fibronectin levels were 83% ± 22% of normal (mean ± SD) during the first trimester and 75% ± 20% at term in the healthy women but increased from 94% ± 36% to 187% ± 36% in the women who developed gestational hypertension (with or without proteinuria) ( p p 140%) were found in 31 of the 32 women with gestational hypertension with or without proteinuria and in 5 of the 88 healthy women (sensitivity 96%, specificity 94%). Fibronectin levels increased 3.6 ± 1.9 weeks earlier than the onset of hypertension and/or proteinuria. Increased levels of plasminogen activator inhibitor-1 at 25 to 32 weeks (≥280 ng/ml) were found in 16 of the 32 women who developed gestational hypertension with or without proteinuria and in 4 of the 88 healthy women (sensitivity 50%, specificity 95%). We conclude that increased fibronectin levels are the best predictor of gestational hypertension with or without proteinuria and that its level in plasma increases several weeks before the development of hypertension.

Platelet activation and vascular damage in gestational hypertension

Increased plasma fibronectin levels are a highly sensitive and specific predictor of gestational hypertension. Of a total of 105 apparently healthy normotensive primigravid women seen at the outpatient clinic, 10 with increased plasma levels of fibronectin (mean +/- 2 SD), were compared with 14 controls. Parameters of early vascular damage (laminin, preprocollagen III), platelet activation (beta-thromboglobulin, platelet factor 4), and coagulation (thrombin-antithrombin III complexes, fibrinopeptide A) were measured at regular (weekly or monthly) intervals. Abnormal values of laminin (p less than 0.005) and fibronectin (p less than 0.0001) were found up to 4 weeks before the onset of clinical disease. Levels of beta-thromboglobulin (p less than 0.0001) were also elevated at least 4 weeks before the appearance of clinical symptoms. Our results show that increased levels of laminin, fibronectin, and platelet activation, as indicated by beta-thromboglobulin levels, are preclinical features of gestational hypertension and indicate that vascular damage has occurred. Fibrin formation would appear to occur later.

DALI: Vitamin D and lifestyle intervention for gestational diabetes mellitus (GDM) prevention: an European multicentre, randomised trial - study protocol

BackgroundGestational diabetes mellitus (GDM) is an increasing problem world-wide. Lifestyle interventions and/or vitamin D supplementation might help prevent GDM in some women.Methods/designPregnant women at risk of GDM (BMI≥29 (kg/m2)) from 9 European countries will be invited to participate and consent obtained before 19+6 weeks of gestation. After giving informed consent, women without GDM will be included (based on IADPSG criteria: fasting glucose<5.1mmol; 1 hour glucose <10.0 mmol; 2 hour glucose <8.5 mmol) and randomized to one of the 8 intervention arms using a 2×(2×2) factorial design: (1) healthy eating (HE), 2) physical activity (PA), 3) HE+PA, 4) control, 5) HE+PA+vitamin D, 6) HE+PA+placebo, 7) vitamin D alone, 8) placebo alone), pre-stratified for each site. In total, 880 women will be included with 110 women allocated to each arm. Between entry and 35 weeks of gestation, women allocated to a lifestyle intervention will receive 5 face-to-face, and 4 telephone coaching sessions, based on the principles of motivational interviewing. The lifestyle intervention includes a discussion about the risks of GDM, a weight gain target <5kg and either 7 healthy eating ‘messages’ and/or 5 physical activity ‘messages’ depending on randomization. Fidelity is monitored by the use of a personal digital assistance (PDA) system. Participants randomized to the vitamin D intervention receive either 1600 IU vitamin D or placebo for daily intake until delivery. Data is collected at baseline measurement, at 24–28 weeks, 35–37 weeks of gestation and after delivery. Primary outcome measures are gestational weight gain, fasting glucose and insulin sensitivity, with a range of obstetric secondary outcome measures including birth weight.DiscussionDALI is a unique Europe-wide randomised controlled trial, which will gain insight into preventive measures against the development of GDM in overweight and obese women.Trial registrationISRCTN70595832

Effect of physical activity and/or healthy eating on GDM risk: The DALI Lifestyle Study

Context Lifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results. Objective The aim of the present study was to compare the effectiveness of 3 lifestyle interventions [healthy eating (HE), physical activity (PA), and both HE and PA (HE+PA)] with usual care (UC) in reducing GDM risk. Design The present study was a multicenter randomized controlled trial conducted from 2012 to 2014 [the DALI (vitamin D and lifestyle intervention for GDM prevention) lifestyle study]. Setting The study occurred at antenatal clinics across 11 centers in 9 European countries. Patients Consecutive pregnant women at <20 weeks of gestation with a body mass index (BMI) of ≥29 kg/m2 and without GDM using the International Association of Diabetes and Pregnancy Study Group criteria (n = 436). For the intervention, women were randomized, stratified by site, to UC, HE, PA, or HE+PA. The women received 5 face-to-face and ≤4 telephone coaching sessions using the principles of motivational interviewing. A gestational weight gain (GWG) <5 kg was targeted. The coaches received standardized training and an intervention toolkit tailored to their culture and language. Main Outcome Measures The endpoints were the GWG at 35 to 37 weeks and the fasting glucose and insulin sensitivity [homeostasis model assessment insulin resistance (HOMA-IR)] at 24 to 28 weeks. Results We randomized 108 women to HE+PA, 113 to HE, 110 to PA, and 105 to UC. In the HE+PA group, but not HE or PA alone, women achieved substantially less GWG than did the controls (UC) by 35 to 37 weeks (-2.02; 95% confidence interval, -3.58 to -0.46 kg). Despite this reduction, no improvements were seen in fasting or postload glucose levels, insulin concentrations, or HOMA-IR. The birthweights and large and small for gestational age rates were similar. Conclusions The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycemia. Thus, lifestyle changes alone are unlikely to prevent GDM among women with a BMI of ≥29 kg/m2.

Maternal obesity in Europe: where do we stand and how to move forward?: A scientific paper commissioned by the European Board and College of Obstetrics and Gynaecology (EBCOG)

Paralleling the global epidemic of obesity figures in the general population, the incidence of maternal obesity (BMI>30kg/m(2) at the start of pregnancy) has been rising over the last world. While most European countries do not systematically report obesity figures in their pregnant population, the prevalence of maternal obesity varies from 7 to 25% and seems strongly related to social and educational inequalities. Obesity during pregnancy represents an important preventable risk factor for adverse pregnancy outcomes and is associated with negative long-term health outcomes for both mothers and offspring. These effects are often aggravated by the high incidence of abnormal glucose tolerance and excessive gestational weight gain found in this group. The main controversies around the management of the obese pregnant women are related to (1) the value of repeated weighing during pregnancy, (2) the optimal gestational weight gain to advise and the lifestyle messages to deliver in order to achieve this, (3) the optimal strategy and timing of screening for gestational diabetes (GDM) and (4) the optimal timing and mode of delivery. These controversies are reviewed in this review, with the exception of screening for gestational diabetes that is discussed extensively elsewhere in this issue (Benhalima et al.). An agenda for research is proposed with the hope that it will catch the attention of policy-makers and funders and ultimately lead to the development of European-wide evidence-based guidelines for clinicians.

IADPSG and WHO 2013 Gestational Diabetes Mellitus Criteria Identify Obese Women With Marked Insulin Resistance in Early Pregnancy

Implementation of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and the World Health Organization 2013 (WHO 2013) recommendations leads to an increased prevalence of gestational diabetes mellitus (GDM) due to more stringent criteria and early screening of women at high risk for diabetes in pregnancy (DIP) (1,2). IADPSG members now recommend that their GDM criteria should not be used in early pregnancy but have not provided alternative criteria (3). We have compared the characteristics of overweight/obese women early in pregnancy, with and without GDM using the new criteria, to assess whether those testing positive are metabolically distinct. Pregnant women with a BMI ≥29.0 kg/m2 underwent a 75-g oral glucose tolerance test in early pregnancy as part of enrollment into the DALI (Vitamin D And Lifestyle Intervention for GDM prevention) pilot and lifestyle Pan-European multicenter trials (4). GDM and DIP were diagnosed using WHO 2013 criteria. A high rate of GDM (237/1,035 or 22.9%: DIP 0.5%; total hyperglycemia in early pregnancy 23.4%) was found at a …