Identifying Optimal Diets for Glycemic Control during Pregnancy: A Network Meta-Analysis Vanessa Ha, PhD Student Supervisors: Drs. Sonia Anand and Russell de Souza

Complications of Gestational Diabetes Mellitus High blood pressure & pre-eclampsia Type 2 diabetes Mother Child Excessive Weight Gain Pre-term Birth Hypoglycemia Type 2 diabetes From: &

Diet and Gestational Diabetes Diet + Physical Activity Thangaratinam et al. BMJ 2012;344:e2088 Energy Restrictive Diet (-30%) Healthy & Energy Restrictive Diet A Review of Food Intake

Dietary Guidelines Energy intake for overweight or obese women may be restricted as long as the rate of weight gain is appropriate and provided ketosis is avoided [Grade D, Level 4]. It is generally recommended that total mixed carbohydrate comprise 40-45% of total energy or up to 50% of energy primarily from slowly released (low glycemic index) carbohydrate sources [Grade D, Level 4]. Accompanying a reduction in percentage of energy from carbohydrate, fat can comprise up to 40% of total energy intake during pregnancy [Grade D, Level 4] For obese women (BMI 30 kg/m2), a 30 –33% calorie restriction (to 25 kcal/kg actual weight per day) has been shown to reduce hyperglycemia and plasma triglycerides with no increase in ketonuria (2). Restriction of carbohydrates to 35–40% of calories has been shown to decrease maternal glucose levels and improve maternal and fetal outcomes (3). None for the Dietary Management of Glycemic Measures during Pregnancy

Dietary Guidelines None for the Dietary Management of Glycemic Measures during Pregnancy

Objectives To conduct a systematic review and network meta-analysis comparing the effects of various dietary patterns on glycaemic control (fasting blood glucose, fasting blood insulin, HbA1c, and HOMA- IR) in pregnant women.

CHOICE OF STUDY DESIGN: Traditional Pair-wise Meta-Analysis vs Network Meta-Analysis

Pair-wise Meta-Analysis Sievenpiper et al. Ann Int Med 2012; 156: 291.

Network Meta-Analysis  Extension of the pair-wise meta-analysis  Multiple pair-wise comparisons are made by including both direct and indirect evidence.  To rank different treatment to assess which is the “best.” Tianjing Li. Cochrane Comparing Multiple Interventions Methods Group Oxford Training event, March 2013.

Assumptions of Network Meta- Analysis 1.Homogeneity  Measure of variance between studies  Assumes that studies are “similar enough” to be pooled for analysis 2.Transitivity  Assumes that one can make an indirect comparison between treatment using a third treatment anchor  Assumes that the distribution of effect modifiers between comparisons are not systematically different 3.Consistency  Degree of agreement between direct and indirect evidence  If consistency holds, direct and indirect evidence can be pooled

STUDY METHODS

Literature Search MEDLINE (up to July ) EMBASE (up to July ) COCHRANE (up to July ) Manual search of references of included studies  Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version updated. The Cochrane Collaboration,  Reporting of results will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.  Hutton et al. Plos One 2014; 9 (3): e Protocol Database

Search Term Search Concept 1: Expectant Mothers Search Concept 2: Diet/Nutrient Intake Search Concept 3: Gestational Diabetes MeSH Terms -Pregnant Women -Prenatal Care -Maternal-Fetal Exchange -Diet (exp) -Diet Therapy (exp) -Food -Food Habits -Food Quality -Nutritional Status -Diabetes, Gestational (exp) -Blood Glucose -Hyperglycemia (exp) -Glucose Tolerance Test -Insulin Resistance (exp) -Hemoglobin A, Glycosylated -Fructosamine Joint MeSH Terms -Maternal Nutritional Physiological Phenomena (exp) Text Words -Pregnan* -Prenatal -Maternal -Expectant mother* -Diet OR Diets OR Dietary -Food* -Nutrition* -Nutrient* -Gestational diabetes -Blood glucose -Blood sugar -Glycaemic -Glycemic -Glycaemia -Glycemia -Hyperglycaemia* -Hyperglycemia* -Insulin -Glucose tolerance test -OGTT -Homostatic model assessment -HOMA-IR -Glycosylated haemoglobin* -Glycosylated hemoglobin* -Glycated haemoglobin* -Glycated hemoglobin* -HbA1c -Fructosamine -Impaired fasting glucose -Impaired glucose tolerance -Glucose intolerance -Hyperinsulin* -Dysglycaemia -Dysglycemia Eg. Medline

Entry Criteria Inclusion Criteria Exclusion Criteria  Pregnant Women with or without GDM  Randomized Trials  Dietary Interventions  Dietary Comparator or Standard of Care  Outcomes of interest: FBG, FBI, HbA1c, HOMA-IR  Follow-up duration ≥1 month  Non-pregnant participants  Non-Randomized Trials  Observational Studies  Non-Human Studies  Nutrient Supplemental Studies  No Adequate Comparator  No report on outcomes of interest  Acute studies <1 month No language restriction will be placed.

Data Extraction 2 independent reviewers (VH, TBD) Variables of Interest:  Study design (parallel or crossover)  Blinding (yes or no)  Sample size (n)  Sample characteristics (age, gender, BMI, pre-existing conditions)  Dietary Pattern  Comparator  Follow-up Duration  Macronutrient profile of the background diet  Mean±SD end values  P-values for differences between start and end values, and between treatments

Study Quality Assessment- Cochrane’s Risk of Bias Tool Low Risk of BiasHigh Risk of BiasUnclear Risk of Bias Random Sequence Generation Allocation Concealment Blinding of Participants and Personnel Incomplete Outcome Data Selective Reporting Other Sources of Bias Modified from: Higgins & Green. Cochrane handbook for systematic reviews of interventions version updated. The Cochrane Collaboration,  To assess if there are biases that would lead to under- or over estimation of the true intervention effect

Statistical Analysis Pooled Primary Outcomes Bayesian Fixed or Random Effects Model (Mean Difference with 95% Credible Intervals): 1.Fasting Blood Glucose 2.Fasting Blood Insulin 3.HbA1c 4.Homeostatic Assessment Model- Insulin Resistance (HOMA-IR) Heterogeneity Significance by Cochran’s Q-statistics with quantification by I 2 a priori Subgroups 1.Ethnicity (European, Asian, African, or Others) 2.Stage of Pregnancy (First, Second, or Third Trimester) 3.Gestational Diabetes Status (yes or no) 4.Pre-Pregnancy Body Weight Heterogeneity

Statistical Analysis Consistency Assessed using node-splitting method Ranking Markov Chain Monte Carlo Methods to generate probabilities of a given treatment as being the best Publication Bias 1.Visual inspection of funnel plots 2.Egger’s and Begg’s tests 3.Trim-and-Fill Method

GRADE Assessment  To assess the overall network meta-analysis confidence via: 1.Grading each pairwise network estimate 2.Grading the ranking  GRADE: 1.Study limitations 2.Indirectness 3.Inconsistency 4.Imprecision 5.Publication Bias

PRELIMINARY RESULTS

Consort Statement 4566 articles identified MEDLINE (up to July ) EMBASE (up to July ). 676 Cochrane Library (up to July ). Articles excluded based on title and/or abstract. Articles that will be reviewed in full. Articles that will be included in the network meta-analysis.

Next Steps TimeTask September 2014Database Search December 2014Literature Search February 2014Data Extraction and Entry April 2014Data Imputations July 2014Manuscript Draft October 2014Submit for Publication

Thank you!