Project Description

Are high dose vitamin and mineral supplements safe and necessary to use for pregnant women post-bariatric surgery?

In this reference article, we inform you about the safety and need for nutritional supplementation for bariatric patients during pregnancy.
Use the categories on the left side of the page to scroll through the article sections.

Women request bariatric surgery more often than men – with the majority being of child bearing age1, 2, 3. The risk of maternal complications associated with obesity such as pre-eclampsia, gestational diabetes, macrosomia and premature birth is well known, and reduced risks following weight loss surgery (WLS) have been demonstrated1, 2. However, WLS has risks of its own, including nutrient deficits due to altered gut physiology (rerouting food away from its natural path) which reduces digestion and absorption of nutrients4. Energy, as well as micronutrient deficits are therefore an expected outcome, most commonly iron, calcium, fat soluble vitamins (A, D, E and K), folic acid, vitamin B12 and B15, 6.

Not only does WLS cause nutrient deficits, the majority of patients presenting for surgery appear to already have at least one vitamin or mineral deficiency preoperatively7. It is therefore not surprising that common practice is to recommend higher than normal doses of nutrients post WLS to prevent and/or manage these deficits. In Denmark for instance, the care of pregnant women post bariatric surgery follows national guidelines, recommending vitamin supplementation and close monitoring to ensure foetal growth and wellbeing8. Despite recommendations and guidelines, recent studies would suggest that the prevalence of micronutrient deficiencies post WLS have actually increased9, 10. Furthermore, some patients remain deficient despite supplementation11. For WLS-women who become pregnant, the risks are even greater.

During pregnancy the demand for micronutrients is greatly increased and maternal body stores and dietary intakes may be insufficient to meet demands12. In normal circumstances (non WLS), there appear to be some upregulation in absorption to compensate e.g. calcium and iron13, 14. However, in WLS patients the ability to upregulate may be considerably hindered due to altered gut physiology linked to surgeries15. Vitamins and minerals require e.g. enzymes, bile salts, acids and intrinsic factor for digestion and absorption, while WLS (such as biliopancreatic diversion (BPD)/and duodenal switch (BPD/ DS) and gastric bypass surgery) affects the production or utilisation of these, leading to major nutrient deficits.

The question arising then is, what level of supplementation is considered to be safe during pregnancy, post WLS?

Vitamin A

Vitamin A is a fat soluble vitamin (FSV) required for growth and development, for eye health, and is essential for the immune system of the mother, and her developing foetus2. Furthermore, retinoic acid, a derivative, acts like a hormone, regulating cell differentiation and embryonic development16. Vitamin A deficiency (VAD) may lead to blindness, and in young children to growth retardation. Having a low status during vulnerable periods, such as pregnancy, greatly increases the risk of developing health related problems17.

The digestion of vitamin A requires lipases (mainly pancreatic but also gastric), responsible for the majority of fat digestion. Surgeries which affect the production or utilisation of lipases (such as BPD/DS or Roux-en-Y gastric bypass (RYGB) hinder the digestion and uptake of fats and FSV18. Oxidative stress, maldigestion and malabsorption post-surgery, as well as dietary restrictions and liver failure (non-alcoholic hepatic steatosis), all contribute to the development of VAD in obese adults before and after RYGB2. Pereira et al. (2009) found that up to 53% of obese adults were vitamin A deficient 180 days post RYGB, despite daily supplementation of 5.000 IU (1.500 mg/1.500 μg) retinol palmitate19. De Vlieger et al. (2014) assessed 49 post bariatric pregnant women, with both restrictive and malabsorptive types of bariatric surgery 20. They found that 58% were vitamin A deficient at delivery, despite supplementation with 3 mg (3.000 μg) vitamin A in 73% of the women20. Cruz et al. (2017) found (in RYGB pregnant women), that serum concentrations of retinol tended to decrease during the trimesters, while requirements increase, especially in the last trimester 21. Shockingly, VAD affected 90% of the women and while 86,7% developed gestational night blindness, despite supplementation of 5.000 IU/day (1.500 μg/day) vitamin A21.

It is clear that pregnancy post WLS increases the risk of vitamin A deficiency, while deficits have serious consequences for the mother and her developing foetus. In patients post BPD 2.145 μg/day of solubilized vitamin A was recommended to achieve normal serum levels4. While supplementation in the range of 10.000 IU (3.300 μg)/day for 4-8 weeks showed no risk of teratogenicity2, 22 (often a concern with vitamin A supplementation). The acceptable dose will therefore depend on the malabsorption level of the surgical procedure. Based on the above evidence, a starting dose of between 1.500 – 3.000 μg/day should be considered for pregnant women post RYGB and BPD20, 21; and monitored closely, especially in advanced pregnancy. This remains below the European Food Safety Association’s (EFSA) (2015) upper level (UL) of 3.000 μg RE/day for women of childbearing age and for pregnancy and lactation, which is based on the risk of hepatotoxicity and teratogenicity23.

Vitamin D

Vitamin D is an essential nutrient which can be synthesised in the skin by the action of sunlight on 7-dehydrocholesterol24. It is the name given to a group of fat soluble compounds that are essential for maintaining the mineral balance in the body. Furthermore, the active form of vitamin D in the blood, 1,25-dihydroxycholecalciferol (1,25-OH2-D) is considered to be a hormone. Maternal vitamin D deficiency (VDD) is associated with lower maternal weight gain, preeclampsia, gestational diabetes, caesarean delivery, reduced bone mineralization in the foetus, and increases risk of the development of type 1 diabetes, asthma, rhinitis and schizophrenia in childhood3. Absorption of vitamin D takes place in the upper part of the small intestine (ileum and jejunum) with the aid of bile salts, and is taken up by the lymphatic system (via chylomicrons) and stored in the liver24. Reduced vitamin D levels are frequently observed in obese individuals, with a prevalence of around 84% in preoperative bariatric patients, and a presence of VDD in 47% of post bariatric pregnancies3. Thus, post bariatric pregnancy can represent a high-risk situation for the development and exacerbation of VDD due to the malabsorption of lipids, the delay in the food mixing with pancreatic enzymes and bile salts, change in dietary patterns and poor compliance with supplementation3.

Post RYGB patients that received a safe and effective pharmacological dose of 50.000 IU/week (178 μg/day) in addition to the standard supplement 800 IU (20 μg/day) dose per day, showed greater reduction in vitamin D depletion up to 6 months after surgery, compared to the control group receiving standard supplementation25. While Goldner et al. (2009), recommended a minimum of 2.000 IU/day (125 μg/day) post RYGB (in non-pregnant)26. The American Society for Metabolic and Bariatric Surgery (ASMBS) (2017) recommends 75 μg/day vitamin D, but this is also for non-pregnant women15. Depending on the surgical procedure doses will vary, but for gastric bypass, doses of up to 125 μg/day are most likely needed26. For BPD, doses of 178 μg/day have been recommended 4. Although, EFSA suggests an UL of 100 μg/day for all healthy adults (including pregnant and lactating women)27, 33, they did not take post-WLS women into account, who are commonly deficient and often unable to absorb optimally25, 4.

Vitamin B12 and folate

Vitamin B12 is a cofactor for the enzymes methionine synthase and methylmalonyl CoA mutase28. These enzymes are also involved in the metabolic processes of folic acid and DNA synthesis. Deficiency of B12 affects these biosynthesis pathways leading to anaemia and neuropathy29. Moreover, maternal B12 deficiency can result in clinical neurological disease, and developmental delay in the neonate30. Folic acid deficiency leads to neural tube defects, and is normally recommended in higher doses for the first trimester of pregnancy in all women (400 μg/day). The digestion and absorption of B12 is divided into several phases. The first is the release of B12 from food, which requires acids and the enzyme pepsin29. This phase is impaired in individuals with reduced gastric secretions, such as in gastric bypass surgeries or sleeve gastrectomy (SG). The next phases are the binding of B12 by different binders in the stomach and the later degrading of these by pancreatic enzymes in the intestine; at which point B12 attaches to Intrinsic Factor (IF), and passes to the ileum where it is absorbed29. When any of these pathways are disrupted, such as reduced pancreatic sections post BPD surgery, or substantial lower levels of IF post gastric bypass, vitamin B12 and folic acid status is reduced. De Vlieger et al. (2014) found the prevalence of vitamin B12 deficiency to be 48% in pregnant women post-bariatric surgery20, whereas in a study with 39 pregnant women post RYGB, vitamin B12 and folate deficiency was found in 53% and 16% of the cases respectively30. Moreover these deficiencies appear to increase with time6. Yau et al. (2017) found 31% of women to be vitamin B12 deficient, particularly when in the first two years after surgery5. Folate deficiency, leading to neural tube defects post WLS has also been reported31.

The requirements of B12 and folate will depend on the surgical procedure. For BPD and RYGB at least 350 μg/day has been recommended for B12 (non-pregnant)4, 32, and 600 μg/day folic acid appeared to maintain status post RYGB32. The ASMBS suggest between 350 – 500 μg/day for B12 and 800 – 1.000 μg/day folic acid15. EFSA did not set an upper limit for B12 and suggest 1000 μg/day as UL for Folic acid (see Table 1)33. During pregnancy blood levels should be monitored closely, especially if pregnancy occurs after an extended period post-WLS.

Table 1: Micronutrient supplementation for post-WLS pregnancy

Recommendations after WLS EFSA Upper Limit Dosage in WLS Optimum Dosage in WLS Forte
Vitamin A 1500-3000 μg/day20, 21 3000 μg/day23 800 μg 600 μg
Vitamin D3 75-178 μg/day4, 15, 26 100 μg/day27,33 75 μg 75 μg
Vitamin B12 350-500 μg/day4, 15, 32 No upper limits set 100 μg 350 μg
Iron 45-60 mg/day15 No upper limits set 28 μg 70 μg
Folic Acid 600-1000 μg/day15, 32 1000 μg/day33 500 μg 600 μg

Iron

Iron is an essential nutrient, playing a fundamental role in many functions of the body, including: oxygen transport, production of ATP (the main energy storage and transfer molecule in the cell), DNA synthesis, mitochondrial function, and protection of cells from oxidative damage34. Deficiency of a critical nutrient such as iron can lead to impaired cognitive function, due to its decisive role in brain development35. In a recent study Yusrawati and colleagues (2018), found that maternal iron deficiency in late pregnancy had an indirect impact on neurotrophic factors in the foetal hippocampus, which plays an important role in the development of learning, memory, and behaviour36. Evidence suggests that iron supplementation improved attention, concentration and IQ in children37.

Iron is absorbed by an active saturable process primarily in the duodenum38. Surgeries which exclude the duodenum from the absorptive tract, such as RYGB, reduce the major site of iron absorption1. Furthermore, post WLS intakes of iron-rich foods are often reduced while use of proton-pump inhibitors (in first months post-surgery) further impacts iron status15, 32. In women with a history of RYGB surgery, the risk of maternal anaemia and having a small for gestational age baby (SGA) was increased. This has been shown to be linked to the malabsorption of nutrients, such as iron, rather than altered gestational weight gain39. Furthermore, Alwan et al. (2015) reported that anaemia in the first half of pregnancy triples the risk of having a SGA baby40. It has also been noted that WLS patients showed higher latent iron binding capacity, which may be associated with the malabsorption of iron 1; as well as reduced haemoglobin (HB) levels during pregnancy, compared to the period preceding the pregnancy. This has recently been described by Kotkiewicz et al. (2015) where HB values below the normal range may be an indication of iron deficiency41. It is clear therefore, that pregnancy post WLS increases the risk of iron deficiency, due to increased demands while the capacity to upregulate absorption is hindered.

The iron dose needed during pregnancy post WLS is not well understood. Halberg (1988) suggested iron requirements to be close to 1040 mg during pregnancy42, in healthy women. While the World Health Organisation and the Food and Agricultural organisation (WHO/FAO) proposed 840 mg, assuming sufficient iron stores (i.e. stores of 500 mg available during the last two trimesters)43, also in non-pregnant women. However, in this population iron stores are often deplete, in fact many WLS patients had deficits even prior to surgery4. The ASMBS (2017)15, suggest between 45-60 mg/day post RYGB, BPD/DS and SG – for men and women (see table 1). However, Dogan et al. (2014) suggested that at least 100 mg/ day was needed to maintain iron status in females post RYGB32. Furthermore, the Obesity Management Task Force (2017) recommended doses of up to 200 mg/day 6, particularly when deficits exist. EFSA did not set upper limits for iron. A sensible approach would be to monitor status and adjust the dose according to needs. The last trimester is especially important to consider, since status can be reduced and higher doses may be needed.

Conclusion

In pregnant women post WLS, higher than normal doses of vitamins and some minerals, are both safe and necessary to ensure a healthy pregnancy. In fact, data would suggest that these women are particularly at risk of nutritional deficiencies, leading to maternal anaemia, neural tube defects, microphthalmia, Wernicke’s encephalopathy and foetal cerebral haemorrhage1, 6. Adequate nutritional assessment and supplementation, as well as monitoring of nutritional markers during pregnancy, is therefore essential to prevent adverse pregnancy outcomes1, 6. Finally, the American Society of Metabolic and Bariatric Surgery (ASMBS) recommends that optimizing postoperative outcomes and nutritional status, begins with preoperative screening15.

References:
1. Gimenes JC, Ferreira Nicoletti C, Augusta de Souza M et al. Pregnancy after Roux-en-Y gastric bypass: Nutritional and Biochemical aspects. Obesity Surgery 2017;27: 1815 – 1821 2. Chagas CB, Saunders C, Pereira S et al. Vitamin A Deficiency in Pregnancy: Perspectives after Bariatric Surgery. Obesity Surgery 2013; 23: 249 – 254
3. Medeiros M, Saunders C, Chagas CB et al. Vitamin D deficiency in pregnancy after bariatric surgery. Obesity Surgery 2013;23: 1679-1684
4. Homan J, Schijns W, Edo O et al. Treatment of Vitamin and Mineral Deficiencies After Biliopancreatic Diversion With or Without Duodenal Switch: a Major Challenge. Obesity Surgery 2018; 28:234–241
5. Yau P, Parikh M, Saunders JK et al. Pregnancy after bariatric surgery: the effect of time-to-conception on pregnancy outcomes. Surgery for Obesity and related diseases 2017; (13) 1899 – 1907
6. Busetto L, Dicker D, Azran C et al. Practical recommendations of the Obesity Management Task Force of the European Association for the Study of obesity for the post Bariatric Surgery Medical Management. Obesity Facts 2017;(10): 597 – 632
7. Gehrer S, Kern B, Peters T et al. Fewer nutrient deficiencies after laparoscopic sleeve gastrectomy(LSG)than after laparoscopic Roux-Y-gastric bypass(LRYGB):a prospective study. Obesity Surgery 2010; 20(4):447–53.
8. Renault K, Andersen LLT, Damm P et al. Gravide som er bariatrisk opererede. Sandbjerg 2017 [Pregnant women who have had bariatric surgery}. Dansk Selskab for Obstetrik og Gynækologi. 2017.
9. Gudzune KA, Huizinga MM,Chang HY et al. Screening and diagnosis of micronutrient deficiencies before and after bariatric surgery. Obesity Surgery 2013;23(10):1581–9.
10. Peterson LA, Cheskin LJ, Furtado M, et al. Malnutrition in bariatric surgery candidates: multiple micronutrient deficiencies prior to surgery. Obesity Surgery 2016;26(4):833–8.
11. Lee. C. Bariatric surgery https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Diabetes_Guide/547015/all/Bariatric_Surgery
12. Wheeler S. Symposium on ‘Translation of research in nutrition II: the bed’ Assessment and interpretation of micronutrient status during pregnancy. Proceedings of the Nutrition Society 2008; 67, 437–450
13. European Food Safety (EFSA). Scientific Opinion on Dietary Reference Values for iron. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). EFSA Journal 2015;13(10):4254
14. Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr. 2000;72(1 Suppl):257S-264S. Review.
15. Parrott J, Frank L, Rabena R et al American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update: Micronutrients. Surgery for Obesity and Related Diseases 2017; 00–00
16. Biesalski HK. Bioavailability of vitamin A. EJCN 1997. Suppl. 1, S71-75
17. World Health Organization (WHO) – Global prevalence of Vitamin A deficiency in populations at risk from 1995-2005. WHO global database. 2016
18. Winkler FK, D’Arcy A, Hunziker W. “Structure of human pancreatic lipase”. Nature 1990. 343 (6260): 771–774.
19. Pereira S, Saboya C, Chaves G et al. Class III obesity and its relationship with the nutritional status of vitamin A in pre and post-operative gastric bypass. Obesity Surgery 2009; 19: 738 – 744
20. De vlieger R, Guelinckx I, Jans G et al. Micronutrient levels and supplement intake in pregnancy after bariatric surgery: A prospective cohort study. PLOS ONE 2014; 9 (12)
21. Cruz S, Matos A, Pereira da Cruz S et al. Relationship between the Nutritional Status of Vitamin A per Trimester of Pregnancy with Maternal Anthropometry and Anemia after Roux-en-Y Gastric Bypass. Nutrients 2017, 9, 989.
22. IVAGG (International Vitamin A Consultative Group). IVACG Statement. Safe Doses of Vitamin A during Pregnancy & Lactation. 1998
23. European Food Safety Association (EFSA) -(Panel on Dietetic Products, Nutrition and Allergies). Scientific Opinion on the dietary reference values for vitamin A. EFSA Journal 2015;13(3):4028
24. Van den Berg, H. Bioavailability of vitamin D. EJCN 1997. Suppl. 1, S76-79
25. Carlin A, Rao D, Yager K et al. Treatment of vitamin D depletion after Roux-en-Y gastric bypass: a randomized prospective clinical trial. Surgery for Obesity and Related Diseases 2009; 5(4): 444-449
26. Goldner WS, Stoner JA, Lyden E, et al. Finding the optimal dose of vitamin D following Roux-en-Y gastric bypass: a prospective, randomized pilot clinical trial. Obesity Surgery 2009;19:173–179.
27. European Food Safety Association (EFSA) (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2012. Scientific Opinion on the Tolerable Upper Intake Level of vitamin D. EFSA Journal 2012;10(7):2813, 45 pp.
28. Chanarin I. The Megaloblastic Anaemias, 2nd Ed. Blackwell Scientific Publications. Oxford.
29. Scott JM. Bioavailability of B12. EJCN 1997. Suppl. 1, S49-53
30. Jans G, Matthys C, Bogaerts A et al. Adverse neonatal outcomes after bariatric surgery: A systematic review. Advances in nutrition 2015 (6): 420 – 429
31. Haddow JE, Hill LE, Kloza EM et al. Neural tube defects after gastric bypass. Lancet 1986;1 (8493):1330
32. Dogan K, Aarts EO, Koehestanie P et al. Optimization of Vitamin Suppletion After Roux-En-Y Gastric Bypass Surgery Can Lower Postoperative Deficiencies. A Randomized Controlled Trial. Medicine 2014. Volume 93, Number 25.
33. European Food Safety Association (EFSA) (Panel on Dietetic Products, Nutrition and Allergies). Scientific Opinion – summary table of Tolerable Upper Intake Levels – version 3 – 2017 http://www.efsa.europa.eu/sites/default/files/assets/UL_Summary_tables.pdf
34. Atamna H, Walter PB, Ames BN. The role of heme and iron-sulfur clusters in mitochondrial biogenesis, maintenance, and decay with age. Arch Biochem Biophys 2002;397:345– 53.
35. Perignon M, Fiorentino M, Kuong K, et al. Stunting, Poor Iron Status and Parasite Infection Are Significant Risk Factors for Lower Cognitive Performance in Cambodian School- Aged Children. PLOS ONE November 2014 | Volume 9 | Issue 11
36. Yusrawati, Rina G, Indrawati LN et al. Differences in brain-derived neurotrophic factor between neonates born to mothers with normal and low ferritin. Asia Pac J Clin Nutr. 2018;27(2):389-392.
37 . Falkingham M, Abdelhamid A, Curtis P et al. The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis. Nutrition Journal 2010; 9:4: 2-14
38. Charlton RW & Bothwell TH. Iron absorption. Ann Rev Med 1983; 34:55-68
39. Hammeken LH, Betsagoo R ,Jensen AN et al. Nutrient deficiency and obstetrical outcome in pregnant women following Roux-en-Y gastric bypass: A retrospective Danish cohort study with a matched comparison group. European Journal of Obstetric & Gynecology and Reproductive Biology 2017; (216) 56-60
40. Alwan NA, Cade JE, McArdle HJ, et al. Maternal iron status in early pregnancy and birth outcomes: insights from the Baby’s Vascular health and Iron in Pregnancy study. Br J Nutr 2015;113(June (121)):1985–92.
41. Kotkiewics A, Donaldson K, Dye C, et al. Anemia and the need for intravenous Iron infusion after Roux-en-Y gastric bypass. Clin Med insights Blood Disord 2015;8
42. Hallberg L. Iron balance in pregnancy. In: Vitamins and minerals in pregnancy and lactation. 2431 Nestlé Nutrition Workshop Series, n°16. Ed Berger H. 1988 Raven Press, New York, USA, 115-127.
43. World Health Organization (WHO) and Food and Agricultural Organization (FAO) of the United Nations. Vitamin and mineral requirements in Human Nutrition. 2nd Ed. 2004

Stay up to date with the latest scientific news!

Sign up now for the FitForMe Research newsletter.