Jamie Stang , PhD, MPH, RDN University of Minnesota School of Public Health

1. The Association Between Dietary Intake Before and During Pregnancy, Weight Status and Maternal-Fetal Outcomes: A Review of Evidence Jamie Stang, PhD, MPH, RDN University of Minnesota School of Public Health Division of Epidemiology and Community Health

2. Concepts to Cover • How does dietary intake before pregnancy affect maternal-fetal outcomes? • How does dietary intake during pregnancy affect maternal-fetal outcomes? • Does weight status prior to pregnancy affect maternal-fetal outcomes? • What is the relationship between gestational weight gain (GWG) and maternal-fetal outcomes?

3. Nutrition-Related Goals during Pregnancy • Optimize birthweight • Optimal weight gain and rate of gain • Optimal intake of macro- and micronutrients • Prevention of congenital anomalies • Manage or prevent complications, e.g. iron deficiency anemia, hypertension, gestational diabetes

4. Physiological Changes that Affect Nutrition Needs in Pregnancy • First half of pregnancy is anabolic for the mother • Second half of pregnancy is catabolic for mother and anabolic for fetus • CHO metabolism changes dramatically • 5% to 19% of pregnancies develop GDM • 5% to 10% of pregnancies experience a hypertensive disorder • 3% experience preeclampsia • 17% of women with gestational hypertension go on to develop preeclampsia • Cardiac output peaks earlier than plasma volume • 50% increase in blood volume but only 20% increase in RBCs = hemodilution • Pregnancy associated with increases in visceral fat stores and waist circumference • Abdominal fat increases during pregnancy • Non-subcutaneous abdominal fat increases 6-12 months postpartum

5. Energy/Nutrient Needs Change in Pregnancy • Kcals needs increase in response to increased metabolic rate, secondary to fetal growth rate • Increases in macronutrients also follow metabolic needs • Fluid needs increase to 3 liters • Changes in micronutrient needs related to changes in renal function and fetal demand • Weight gain recommendations and practices are somewhat controversial • Data suggest that current recommendations probably reduce risk of maternal-fetal complications • Weight loss in pregnancy not considered safe so pre-conception and postpartum weight status are important

6. P/B-24 Project • The Pregnancy and Birth to 24 Months (P/B-24) Project was initiated to examine diet-related topics of public health importance during pregnancy, infancy, and toddlerhood • Funded by USDA and DHHS (CDC) • Technical Expert Collaborative (TEC) subcommittee convened to examine relationships between dietary patterns prior to and during pregnancy and select maternal and fetal outcomes • Dietary patterns were examined, not individual nutrients, to inform foodprograms and policies Stoody, et al Am J ClinNutr2019;109(Suppl):685S–697S

7. Prenatal Nutrition and Birth Outcomes • Two systematic reviews assessed relationships between dietary patterns before and during pregnancy and • 1) gestational age at birth • 2) gestational age- and sex-specific birth weight • 9 databases searched from Jan 1980 to Jan 2017 • PubMed, Embase, and Cochrane • Two analysts independently screened articles using a priori inclusion and exclusion criteria • Data were extracted from articles • Risk of bias was assessed • Raghavan et al. Am J ClinNutr2019;109(Suppl):729S–756S

8. Prenatal Nutrition and Birth Outcomes • Data synthesized qualitatively • Conclusion statement was drafted for each question • Evidence supporting each conclusion was graded Of 9,103 studies identified: • 11 were included for gestational age outcome • 7 cohorts and 1 randomized controlled trial (RCT) • 21 were included for birth weight outcomes • 19 cohorts and 2 RCTs • Sample size ranged were generally small to adequate • 290 – 72,072 participants; avg= 3143

9. Dietary Guidelines for AmericansPregnancy Subcommittee TEC Report • “Evidence is insufficient to estimate the association between dietary patterns before pregnancy and gestational age at birth as well as the risk of preterm birth” • “Insufficient evidence exists to estimate the association between dietary patterns before pregnancy and birth weight outcomes. There are not enough studies available to answer this question”

10. Dietary Guidelines for Americans, Pregnancy Subcommittee Report • “Limited but consistent evidence suggests that certain dietary patterns during pregnancy are associated with a lower risk of preterm birth and spontaneous preterm birth. • These protective dietary patterns are higher in vegetables; fruits; whole grains; nuts, legumes, and seeds; and seafood (preterm birth, only) and lower in red and processed meats and fried foods. • “No conclusion can be drawn on the association between dietary patterns during pregnancy and birth weight outcomes. Although research is available, the ability to draw a conclusion is restricted by • inconsistency in study findings, inadequate adjustment of birth weight for gestational age and sex, and variation in study design, dietary assessment methodology, and adjustment of key confounding factors.”

11. Dietary Patterns and Gestational Age Outcomes • ‘vegetable, fruit and white rice’; ‘prudent’; ‘traditional’; ‘seafood’, and ‘high protein/fruit’ dietary patterns showed 9% to 69% reduction in risk of PTB • 15% reduction in late PTB • 15% - 45% reduction in spontaneous PTB • 15% to 38% reduction in induced/iatrogenic PTB • Dietary patterns higher in red and processed meats and fried foods associated with greater risk • 53% to 55% overall increased risk of PTB • 18% to 92% increased risk of spontaneous PTB • 70% increased risk of induced PTB (70%)

12. Prenatal Nutrition and Maternal Outcomes • Systematic review examined the relationships between dietary patterns before and during pregnancy and • 1)Hypertensive disorders of pregnancy (HDP) • Included gestational hypertension, pre-eclampsia and chronic hypertension with super-imposed pre-eclampsia • 2) Gestational diabetes (GDM) • 9 databases searched from January 1980 to January 2017 • PubMed, Embase and Cochrane • Articles independently screened by two analysts using a priori inclusion and exclusion criteria Raghavan et al. Am J ClinNutr2019;109(Suppl):705S–728S.

13. Prenatal Nutrition and Maternal Outcomes • Relevant information was extracted for included articles • Risk of bias was assessed Of 9,103 studies identified: • 8 studies were included for HDP • 4 cohorts, 1 randomized controlled trial (RCT) • 11 studies included for GDM • 6 cohorts, 1 RCT • Sample sizes were too small to adequate • 12 – 15,254 participants ; avg = 3063

14. Dietary Patterns and Pregnancy Outcomes • “Limited evidence in healthy Caucasian women suggests that dietary patterns before and during pregnancy that are higher in vegetables, fruits, whole grains, nuts, legumes, fish, and vegetable oils and lower in meat and refined grains are associated with a reduced risk of hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension” • “Not all components of the assessed dietary patterns were associated with all hypertensive disorders. Evidence is insufficient to estimate the association between dietary patterns before pregnancy and risk of hypertensive disorders of pregnancy in minority women and those of lower socioeconomic status”

15. Prenatal Nutrition and HDP • 5 of the 8 studies showed an association between dietary patterns beforeand during pregnancy and risk of HDP • Dietary patterns higher in vegetables, fruits, whole grains, nuts, legumes, fish and vegetable oils reduced risk • High vegetable diet = 16% - 22% reduced risk of HDP • Mediterranean/New Nordic diets = 29% - 42% reduced risk of HDP • Higher intakes of meats, refined grains and processed foods were associated with increased risk • High processed food/Western diet = 21% increased risk • Non-adherence to Mediterranean diet = 41% increased risk

16. Prenatal Nutrition and GDM • “Limited but consistent evidence suggests that certain dietary patterns before pregnancy are associated with a reduced risk of gestational diabetes mellitus. • Evidence is insufficient to estimate the association between dietary patterns during pregnancy and risk of gestational diabetes mellitus.”

17. Prenatal Nutrition and GDM • Dietary patterns before pregnancy were associated with reduced risk of GDM in 8 of 11 studies • Insufficient evidence to examine dietary patterns during pregnancy and risk of GDM • Protective patterns prior to pregnancy were higher in vegetables, fruits, whole grains, nuts, legumes, fish and lower in red and processed meats • Mediterranean/DASH diets = 10% to 44% reduced risk of GDM • High red meat diet pattern = 20% to 55% increased risk of GDM • Western diet = 14% to 63% increased risk of GDM

18. Summary of P/B-24 TEC Subcommittee Findings • Healthy dietary patterns before pregnancy are associated with reduced risk of maternal complications, specifically HDP and GDM • Mediterranean, DASH, New Nordic, Prudent and similar dietary patterns • Unhealthy dietary patterns before pregnancy associated with increased risk of HDP and GDM • Western, processed food and other similar dietary patterns • Healthy dietary patterns during pregnancy associated with reduced risk of preterm birth and HDP but not infant birthweight or GDM risk • Unhealthy dietary patterns during pregnancy associated with increased risk of preterm birth and HDP

19. Obesity and Pregnancy Outcomes

20. OBESITY Conditions Associated with Obesity During PregnancyPregnancy Source: Adapted from Bray GA, 2003

21. Obesity and Pregnancy Outcomes • Women who enter pregnancy obese have more pregnancy complications and are increasedrisk for poor infant outcomes •  risk of miscarriage • 25% to 37% increased risk •  risk NTDs compared to normal weight women with same folate intakes and family history • Overweight = 35%  of congenital anomaly • Obese = 38%  of congenital anomaly •  risk for C-section delivery • Each BMI unit = 7%  in risk of C-section delivery •  risk for post delivery infection, excessive blood loss

22. Obesity and Gestational Hypertensive Disorders • Hypertension is among top 3 causes of maternal mortality • 10% of women 18-44 years old have hypertension • 15% among 35-44 year old females • Rates of hypertension have nearly doubled in 2 decades • Racial and ethnic disparities in hypertension among women • 19% among non-Hispanic black women • 9% among non-Hispanic white women • 8% among other racial/ethnic groups Schummers et al. ObstetGyncecol 2015; Lo et al. CurrOpinObstetGynceol 2013; Robbins et al. MMWR 2014

23. Obesity and Gestational Hypertensive Disorders • Risks for hypertension and pre-eclampsia in pregnancy follow pre-pregnancy weight trends • Women who are overweight or obese at conception are at more than 6 times the risk (OR = 6.31, CI: 4.30 – 9.26) • Risk increases incrementally with class of obesity • Obese women 3 to 8 times more likely to develop pre-eclampsia • 10% prevalence among women with class I obesity • 12.8% prevalence among women with class II obesity • 16.3% prevalence among women with class III obesity • 3.4% prevalence among normal weight women Schummers et al ObstetGynecol 2015; Bautista-Castano et al PLoS One 2013; Gaillard et al Obesity 2013; El-Chaar et al. J ObstetGynaecol Can 2013

24. Obesity and Gestational Diabetes • Women obese at conception are up to 6 times more likely to develop GDM than normal weight women • Risk increases incrementally with class of obesity • 9.7% prevalence with class I obesity • 13.7% prevalence with class II obesity • 16.6% prevalence with class III obesity • 6.1% prevalence among ideal weight women • Women who experience GDM are 13 times more likely to develop type 2 diabetes later in life • More than half will experience GDM in subsequent pregnancies Schummers et al ObstetGynecol 2015; Bautista-Castano et al PLoS One 2013; Gaillard et al Obesity 2013; El-Chaar et al. J ObstetGynaecol Can 2013

25. Obesity, Gestational Hypertension, Gestational Diabetes and Long-Term Health Outcomes of Women • Gestational hypertension and gestational diabetes are strong co-morbid contributors to long-term health among women • Gestational hypertension and pre-eclampsia both double risk of a woman developing type 2 diabetes within 17 years of pregnancy • Women who develop both gestational diabetes and hypertension or pre-eclampsia are at 13 to 18-times higher risk for developing type 2 diabetes later in life • Insulin resistance is an underlying physiological condition in gestational hypertension, pre-eclampsia and gestational diabetes • Women with either pre-eclampsia or hypertension but without GDM have been shown to be at 3 times the risk of developing type 2 diabetes within 1-4 years after delivery suggesting that insulin resistance persists in some women Feig et al 2013; Engeland et al Eur J Epidem 2011; Schummers et al ObstetGynecol 2015; Bautista-Castano et al PLoS One 2013; Gaillard et al Obesity 2013; El-Chaar et al. J ObstetGynaecol Can 2013

26. Obesity and Delivery • Women who are obese prior to pregnancy are twice as likely to require induction of labor • 4 times the risk of induced labor secondary to hypertension • Up to 11 times the risk for induction secondary to pre-eclampsia or GDM • C-section delivery twice as common among obese compared to ideal weight women • 26.5% prevalence among ideal weight women • 38.2% among class I obese women • 43.1% among class II obese women • 49.7% among class III obese women • Postpartum hemorrhage is doubled among primiparous obese women Fyfe et al BMC Preg Childbirth 2012; ACOGComm Opinion 548 2013;

27. Prepregnancy Weight and Birth Defects • Overweight and obesity prior to pregnancy is an independent risk factor for some birth defects • NTDs (esp spina bifida) • Cardiac defects • Hypospadia • Omphalocele • Anorectal atresia and limb reduction (obesity only) • Underweight prior to pregnancy is a risk for defects • cleft lip and palate • Overweight Prior to pregnancy protective factor for one specific birth defect • gastroschisis

28. Omphalocele

29. Gestational Weight Gain and Maternal-Fetal Health Outcomes

30. Obesity and Gestational Weight Gain NAS Inst of Medicine 2009

31. Fewer than 1 in 4 obese pregnant women gains within the IOM-recommended range Deputy et al. Ob Gyn2015

32. Obesity and Gestational Weight Gain NAS IOM 2009

33. Gestational diabetes (GDM) MacDonald et al. Epidemiology 2017 2.0 1.5 Adjusted odds ratio (95% CI) 1.0 Grade 1 obese n = 179 cases Grade 2 obese n = 129 cases Grade 3 obese n = 96 cases

34. Grade 2 obesity:Multiple, competing outcomes of varying severity IOM-recommended range Cesarean delivery LGA birth Infant death Preterm SGA birth 9.9 -4.0 1.8 37 21 21 -8.2 37 9.9 1.8 -4.0 Equivalent total weight gain at 40 weeks, kg Equivalent total weight gain at 40 weeks, kg Bodnar et al. Epidemiology 2016 Bodnar et al. Obesity 2016

35. Preterm birth at <37 weeks Grade 3 obese (n=4701 cases) ~21 kg at 40 weeks Grade 2 obese (n=4701 cases) Grade 1 obese (n=12,881 cases) 35 kg Bodnar et al. Epidemiology 2016

36. Preventing Excessive Gestational Weight Gain • 2 intervention groups = Physical Activity (PA) and Physical Activity + Diet (PA+D) plus control group • Counseled by dietitian to walking at least 11,000 steps/day • PA+D group also counseled by dietitian every 2 weeks regarding a 1,200 – 1,675 kcal Mediterranean-type diet (based on trimester) • Gestational weight gain significantly lower in both intervention groups compared to the control group • More women in intervention groups gained within IOM guidelines • 55% in PA+D group • 49% in PA • 37% of women in the control group • Gestational weight gain reduced by an additional 1.38 kg among those who used a pedometer • Women in the PA+D group had a lower rate of emergency cesarean deliveries compared to the other groups

37. Preventing Excessive Gestational Weight Gain • 100 women were randomized to counseling or control group • n=57 intervention group, n=43 control group • Lifestyle counseling • Balanced diet of 40% CHO, 30% protein, 30% fat • 20-30 mins physical activity 3-5 times/week • Intervention group gained significantly less than controls • 28.7 lb compared with 35.6 lb • 61% of intervention group gained within IOM guidelines • 49% of controls gained with IOM guidelines

38. Prevention of Excessive Gestational Weight Gain • 50 obese Danish women (n=23 intervention, n=27 control) • Intervention included • Ten, 1-hour consultations with dietitian • Balanced diet with energy restriction based on individual estimated requirements plus fetal growth allowance • (30% fat, 15% to 20% protein, 50% to 55% CHO) • Total weight gain was reduced significantly • Intervention group gained 6.6 kg • Control group gained 13.3 kg • Weekly weight gain from enrollment to 36 weeks gestation was significantly reduced • 0.18 kg/week in intervention group • 0.26 kg/week in control group • Intervention group had significantly lower weight at 4 weeks post-partum.

39. Prevention of Excessive Gestational Weight Gain • 124 pregnant overweight or obese women • Intervention n=63 and control n=61 • Intervention included nutrition and mental health education • 5-minute nutrition consultation prior to each prenatal visit • Weight self-monitoring • Psychology evaluation and treatment • Increased intake of water, fresh fruits & vegetables, home-cooked meals • Reduction in carbonated beverages, juices, convenience foods, fast foods • Intervention group gained 7 kg, control group gained 13.8kg

40. Prevention of Excessive GWG: Results of Dietary Interventions • Intervention studies focused on dietary counseling had 3.36 kg reduction in GWG • Effective interventions included at least 6 weeks of educational classes or counseling that focused on behavioral change strategies to improve dietary intake • Reductions on poor maternal outcomes noted • 33% reduction in risk of preeclampsia • 70% reduction in risk of gestational hypertension • 32% reduction in risk of preterm birth • 48% reduction in risk for gestational diabetes • No significant increases in poor infant outcomes • Infants were 0.07 kg lighter • 27% reduction in the risk for LGA • 69% reduction in shoulder dystocia were observed • No effects on low birthweight or SGA

41. 2020-2025 Dietary Guidelines for Americans • Questions specific to pregnancy are included as systematic review topics • What is the relationship between dietary patterns consumed during pregnancy and risk of gestational diabetes? • What is the relationship between dietary patterns consumed during pregnancy and risk of hypertensive disorders during pregnancy? • What is the relationship between dietary patterns consumed during pregnancy and gestational age at birth? • What is the relationship between dietary patterns consumed during pregnancy and birth weight standardized for gestational age and sex? • What is the relationship between dietary patterns consumed during pregnancy and gestational weight gain? • What is the relationship between dietary patterns consumed during pregnancy and micronutrient status?

42. What is the relationship between specific nutrients from supplements and/or fortified foods consumed before and during pregnancy and lactation and micronutrient status? • What is the relationship between specific nutrients from supplements and/or fortified foods consumed before and during pregnancy and lactation and risk of gestational diabetes? • What is the relationship between specific nutrients from supplements and/or fortified foods consumed before and during pregnancy and lactation and risk of hypertensive disorders during pregnancy? • What is the relationship between specific nutrients from supplements and/or fortified foods consumed before and during pregnancy and lactation and human milk composition and quantity? • What is the relationship between specific nutrients from supplements and/or fortified foods consumed before and during pregnancy and lactation and developmental milestones, including neurocognitive development? • What is the relationship between maternal diet during pregnancy and lactation and risk of infant and child food allergies and atopic allergic diseases?