Goele Jans

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

Maternal Micronutrient Deficiencies and Related Adverse Neonatal Outcomes after Bariatric Surgery: A Systematic Review

Pregnant and postpartum women with a history of bariatric surgery are at risk of micronutrient deficiencies as a result of the combination of physiologic changes related to pregnancy and iatrogenic postoperative alterations in the absorption and metabolism of crucial nutrients. This systematic review investigates micronutrient deficiencies and related adverse clinical outcomes in pregnant and postpartum women after bariatric surgery. A systematic approach involving critical appraisal was conducted independently by 2 researchers to examine deficiencies of phylloquinone, folate, iron, calcium, zinc, magnesium, iodide, copper, and vitamins A, D, and B-12 in pregnant and postpartum women after bariatric surgery, together with subsequent outcomes in the neonates. The search identified 29 relevant cases and 8 cohort studies. The quality of reporting among the case reports was weak according to the criteria based on the CARE (CAse REporting) guidelines as was that for the cohort studies based on the criteria from the Cohort Study Quality Assessment list of the Dutch Cochrane Center. The most common adverse neonatal outcomes related to maternal micronutrient deficiencies include visual complications (vitamin A), intracranial hemorrhage (phylloquinone), neurological and developmental impairment (vitamin B-12), and neural tube defects (folate). On the basis of the systematically collected information, we conclude that the evidence on micronutrient deficiencies in pregnant and postpartum women after bariatric surgery and subsequent adverse neonatal outcomes remains weak and inconclusive.

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.

Micronutrient levels and supplement intake in pregnancy after bariatric surgery: a prospective cohort study.

Background Studies report frequent micronutrient deficiencies after bariatric surgery, but less is known about micronutrient levels of pregnant women after bariatric surgery. Objective To prospectively evaluate micronutrient levels and supplement intake in pregnancy following bariatric surgery. Design A multicenter prospective cohort study including women with restrictive or malabsorptive types of bariatric surgery. Nutritional deficiencies, together with supplement intake, were screened during pregnancy. Results The total population included 18 women in the restrictive and 31 in the malabsorptive group. Most micronutrients were depleted and declined significantly during pregnancy. The proportion of women with low vitamin A and B-1 levels increased to respectively 58 and 17% at delivery (P = 0.005 and 0.002). The proportion of women with vitamin D deficiency decreased from 14% at trimester 1 to 6% at delivery (P = 0.030). Mild anemia was found in respectively 22 and 40% of the women at trimester 1 and delivery. In the first trimester, most women took a multivitamin (57.1%). In the second and third trimester, the majority took additional supplements (69.4 and 73.5%). No associations were found between supplement intake and micronutrient deficiencies. Conclusion Pregnant women with bariatric surgery show frequent low micronutrient levels. Supplementation partially normalizes low levels of micronutrients.

Obesity in pregnancy: Altered onset and progression of labour

BACKGROUND the incidence of obesity increases in all developed countries to frightful percentages, also in women of reproductive age. Maternal obesity is associated with important obstetrical complications; and this group also exhibits a higher incidence of prolonged pregnancies and labours. OBJECTIVE to review the literature on the pathophysiology of onset and progression of labour in obese woman and translate this knowledge into practical recommendations for clinical management. METHODS a literature review, in particular a critical summary of research, in order to determine associations, gaps or inconsistencies in this specific but limited body of research. FINDINGS the combination of a higher incidence of post-term childbirths and increased inadequate contraction pattern during the first stage of labour suggests an influence of obesity on myometrial activity. A pathophysiologic pathway for altered onset and progression of labour in obese pregnant women is proposed. CONCLUSIONS analysis of the literature shows that obesity is associated with an increased duration of pregnancy and prolonged duration of first stage of labour. IMPLICATIONS FOR PRACTICE an adapted clinical approach is suggested in these patients.

Vitamin K1 monitoring in pregnancies after bariatric surgery: a prospective cohort study.

BACKGROUND Neonatal intracranial bleedings and birth defects have been reported, possibly related to maternal vitamin K1 deficiency during pregnancy after bariatric surgery. The objective of this study was to investigate the effects of screening and supplementation on K1 serum levels in pregnant women with bariatric surgery, and to compare K1 levels and prothrombin time (PT %) in the first trimester with pregnant women without bariatric surgery. METHODS A prospective cohort study including 49 pregnant women with bariatric surgery. Nutritional deficiencies were prospectively screened. In case of observed low K1 serum levels, supplementation was provided. K1 serum levels and PT (%) during the first trimester were compared with a nonsurgical control group of 27 women. RESULTS During the first trimester, most women had low K1 serum levels (<0.8 nmol/l). Mean vitamin K1 levels were significantly lower in the surgical group compared to the nonsurgical control group (.44 versus .64 nmol/l; P = .016). PT (%) remained in the normal range, The surgery group showed a higher mean PT compared to the controls (111.3 versus 98.9%; P<.001) Mean K1 serum levels in the study group were higher during the third than during the first trimester (P = .014). PT (%) was significantly higher during the second and third than during the first trimester (P = .004). Most of the coagulation factors, including II, V, VII, IX, and X, remained within normal ranges. CONCLUSION Low circulating K1 appears to be common in pregnant women with and without bariatric surgery. Supplementation during pregnancy can restore vitamin K1 in women with bariatric surgery, potentially protecting the fetus and newborn against intracranial hemorrhage.

Internal Herniation in Pregnancy After Gastric Bypass: A Systematic Review

OBJECTIVE: To assess maternal and fetal outcomes of pregnancies complicated by internal herniation after Roux-en-Y gastric bypass. DATA SOURCES: Articles were identified through searches in online databases (ClinicalTrials.gov, MEDLINE, EMBASE, PubMed, and Google Scholar) from January 1980 to March 2015 for the following terms: [gastric bypass OR bariatric surgery] AND [pregnancy] AND [complication OR herniation OR obstruction]. Reference lists of relevant articles were hand-searched. Additionally, we searched our own hospitals obstetric database for cases of internal herniation after Roux-en-Y gastric bypass. METHODS OF STUDY SELECTION: Only articles in English and studies in humans were selected. Cases of internal herniation outside of pregnancy or internal herniation without a history of Roux-en-Y gastric bypass were excluded. Of 384 articles identified by the initial search, 22 were retained for further analysis. TABULATION, INTEGRATION, AND RESULTS: All retrieved articles were case reports or case series. There were no interventional studies. We retrieved 47 cases from the literature and five cases from our own database. The mean gestational age at diagnosis was 28.4±7.3 weeks. All women presented with abdominal pain. Nausea and vomiting were present in only 65%. Ultrasonography and laboratory results are usually noninformative, and computed tomography or magnetic resonance imaging confirmed the diagnosis in only 75% of cases. Nine of 52 women (17.3%) required bowel resections. There were two maternal deaths and three perinatal deaths, all in women treated later than 48 hours after onset of the symptoms. CONCLUSION: Internal herniation complicating pregnancy after Roux-en-Y gastric bypass typically presents with subtle signs in the third trimester of pregnancy. Timely recognition and early surgical intervention are associated with a reduced risk of bowel ischemia and maternal and fetal adverse outcomes.

Depression and Anxiety: Lack of Associations with an Inadequate Diet in a Sample of Pregnant Women with a History of Bariatric Surgery-a Multicenter Prospective Controlled Cohort Study

BackgroundAnxiety and depression levels are higher in obese compared to those in normal weight pregnant women. The aims of this study are to examine anxiety and depression in pregnancy following bariatric surgery and to compare with obese pregnant controls considering the dietary intake of polyunsaturated fatty acids (PUFA), folate, and vitamin B12.MethodsAnxiety (State-Trait Anxiety Inventory) and depression (Edinburgh Postnatal Depression Scale) were examined in the first (T1) and third (T3) pregnancy trimester in 54 women with bariatric surgery and 25 obese. T1 and T3 dietary intake of PUFA, folate, and vitamin B12 intake was assessed using a 3-day food record. Mixed models with a compound symmetry covariance structure and regression models were applied.ResultsAbout half of the women with surgery had high state and trait anxiety scores (≥ 40), which did not significantly change during pregnancy. Every 10-kg postoperative weight loss was associated with an increase in T1 state and trait anxiety with respectively 2.7 and 2.3 points. A smoking woman had a 8.6-point higher state anxiety score than a non-smoking woman in T1. In T3, every additional hour of sleep was associated with a decrease in trait anxiety score with 1.59 points. Anxiety and depression scores were not associated with and could not be explained by inadequate PUFAs, folate, and vitamin B12 intakes. Anxiety scores were higher following surgery than those in untreated obesity at both time points.ConclusionPregnancy following bariatric surgery induces high levels of anxiety that are not associated with an inadequate maternal diet.

Re: Vitamin D and gestational diabetes mellitus: a systematic review based on data free of Hawthorne effect

Sir, We have read with utmost interest the recently published systematic review and meta-analysis of Zhang et al. on the relationship between vitamin D and gestational diabetes mellitus (GDM). The authors have performed a comprehensive review including 87 observational studies and 25 randomised controlled trials addressing the relationship between vitamin D and glucose homeostasis during pregnancy. The meta-analysis on observational studies confirmed that gravidas with low blood vitamin D have a higher risk of GDM (odds ratio 1.85) linked to higher fasting plasma glucose and Homeostatic Model Assessment of Insulin Resistance index (HOMA-IR). The crucial point in clinical practice is to know if vitamin D supplementation in addition to recommended dietary allowances is able to prevent GDM. The authors have performed a meta-analysis on randomised controlled trials showing that vitamin D supplementation elevates the concentrations of 25-OHD in blood, and reduces fasting insulin, fasting plasma glucose and HOMA-IR, as well as having favourable effects on glutathione, C-reactive protein and total and high-density lipoprotein cholesterol. However, after pooling the data from four trials including 968 pregnant women, it was unclear whether vitamin D supplementationwas effective inGDM prevention (relative risk 0.718, 95% CI 0.392–1.314, I = 0% [I is in fact 37]). The authors identified that omitting the study of Hossain et al. rendered the comparison significant (Table 1 in Zhang et al, P = 0.008). In the study of Hossain et al. the outcome reported was not incident GDM but an abnormal glucose challenge test. Although it is intriguing that the rate of abnormal glucose challenge tests was higher albeit not significantly in the intervention group, our point is that this study should not be pooled together with studies where the outcome is GDM. We have performed the meta-analysis of the remaining three studies including 793 pregnant women and the result is relative risk 0.53, 95% CI 0.33–0.85, I = 0%, P = 0.009 (Figure 1). Common features of these three studies are that the participants’ average vitamin D concentration at baseline was < 50 nmol/l and that vitamin D doses in the intervention arm were high ( 3500 iu/day, 5000 iu/ day, up to 3400 iu/day), including doses higher than the Institute of Medicine’s tolerable upper intake level. Hence, as to external validity, these results would only apply to pregnant women with low vitamin D receiving high daily doses of the vitamin. Furthermore, in one of the trials, women in the control arm did not receive any supplement. Notably, the magnitude of the risk of GDM with low vitamin D (odds ratio 1.85) and the protection afforded by supplementation (relative risk 0.53) are of a similar magnitude and opposite direction. On the basis of these additional considerations, we conclude that ‘highdose vitamin D supplementation during pregnancy halves the rate of GDM in pregnant women with baseline vitamin D for less than 50 nmol/l’.&

A pilot study on the impact of maternal diet and preconception body mass index on breast milk macronutrient composition

Materials and methods A cross-sectional study was conducted at the maternity units of the University Hospital of Leuven, Belgium. Postpartum women, who delivered a term (≥37 weeks of gestation), did not smoke, were normoglycaemic and who were not on predefined medication, were invited to participate. Participants completed a 24 dietary recall and donated a breast milk sample of 1.5-2cl at day 4 post-delivery. The samples were collected during the first feeding in the morning by use of a vacuum pump. Each sample was analyzed for macronutrients (carbohydrates, protein, fats) and energy with the MIRIS Human Milk Analyzer. The prepregnancy weight and length were assessed from the online medical patient file to calculate the pre-pregnancy BMI. Further baseline characteristics included maternal age, ethnicity and parity. Pregnancy outcomes included delivery mode, the use of combined spinal epidural, gestational age, birth weight and gender of the baby.