Safety of supplementation during pregnancy

Are high dosed food supplements safe and necessary to use for pregnant women post-bariatric surgery?

Women request bariatric surgery more often than men – with the majority being of child bearing age^{1, 2, 3}. It is known that weight loss surgery (WLS) comes with risks, including micronutrient deficits, most commonly iron, calcium, fat soluble vitamins (A, D, E and K), folic acid, vitamin B12 and B1^{5, 6}. Since the majority of bariatric patients already have at least one vitamin or mineral deficiency preoperatively,⁷ it is not surprising that a high dosed food supplements are to be advised. The safety of supplementation during pregnancy for post-bariatric women, however, is often questioned.

In many countries, the care of pregnant women post bariatric surgery follows general guidelines, which include supplementation and close monitoring to ensure foetal growth and wellbeing⁸. Despite these guidelines, studies suggest that deficiencies post-WLS have actually increased^9-11. For WLS-women who become pregnant, the risks are even greater.

During pregnancy, the micronutrient demand is increased, resulting in insufficient dietary intake to meet demands¹². Under normal circumstances (non-WLS), absorption of some nutrients is increased to compensate these higher needs. For instance, this is the case for calcium and iron^{13, 14}. In WLS patients, however, the ability to increase absorption is hindered¹⁵, which further underscores the need of high-dosed supplementation. However, too high levels of certain nutrients, like vitamin A, may have a negative effect on foetal growth and health.

The question arising is, to what level can the safety of high-dosed supplementation be ensured during pregnancy, for women post-WLS, to reduce deficiency risk?

Vitamin A supplementation during pregnancy

Vitamin A is a fat-soluble vitamin, is required for growth and development, for eye health, and for the immune system of mother and foetus². Vitamin A deficiency 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. However, toxic levels of vitamin A have health risks as well. So, how to ensure safety in vitamin A supplementation during pregnancy?

Several bariatric procedures hinder the digestion and absorption of fat-soluble vitamins, like vitamin A. Oxidative stress, maldigestion and malabsorption post-surgery, as well as dietary restrictions and liver failure, all contribute to the development of vitamin A deficiencies before and after RYGB². Pereira et al. 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. assessed 49 post bariatric pregnant women. 58% were found to be vitamin A deficient at delivery, despite supplementation with 3 mg vitamin A in 73% of the women²⁰. Cruz et al. found, that, while requirements increase, serum concentrations of retinol tended to decrease during trimesters. Shockingly, 90% of the women were found deficient, despite supplementation of 5.000 IU/day (1.500 μg/day) vitamin A²¹.

Pregnancy post-WLS clearly increases the risk of vitamin A deficiency. Supplementation of between 1.500 – 3.000 μg/day is to be considered safe during pregnancy for women post RYGB and BPD^{20, 21}; and monitored for safety, 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 supplementation levels

Vitamin D deficiency during pregnancy 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. Reduced vitamin D levels are frequently observed in obese individuals, with a prevalence of around 84% in preoperative bariatric patients, and a presence of in 47% of post-bariatric pregnancies³. Vitamin D supplementation is essential during pregnancy to ensure safety, health and development of mother and child.

Post RYGB patients that received 50.000 IU of vitamin D per week (178 μg/day) in addition to the standard supplement of 800 IU (20 μg/day) dose per day, showed a reduction in vitamin D depletion up to 6 months after surgery²⁵. Another study advised a safety supplementation dose (not specified for pregnancy) of minimal 2.000 IU/day (125 μg/day) post RYGB²⁶. The ASMBS recommends 75 μg/day vitamin D for bariatric patients in general¹⁵. Depending on the surgical procedure doses will vary, but for RYGB, doses of up to 125 μg/day are advised²⁶. For BPD, the recommended dose is increased to 178 μg/day⁴. EFSA suggests a maximum level of 100 μg/day for all healthy adults (including pregnant and lactating women)^{27, 33}, but they did not take post-WLS women into account.

Folic acid and vitamin B12

Folic acid and vitamin B12 absorption are reduced after bariatric surgery. Therefore, supplementation is needed for all post-bariatric patients and is especially important for the safety of mother and child during pregnancy. Folic acid is normally recommended in higher doses for the first trimester for all women (400 μg/day), since deficiencies increase the risk of neural tube defects. Vitamin B12 deficiencies during pregnancy can cause neuropathy²⁹ and developmental delay in the neonate³⁰. De Vlieger et al. found the prevalence of vitamin B12 deficiency to be 48% in pregnant women post-bariatric surgery²⁰, whereas in another study, vitamin B12 and folate deficiencies were found in 53% and 16% of the cases respectively³⁰.

The exact requirements of B12 and folate differ per operation type. For BPD and RYGB, at least 350 μg/day is recommended for B12 (non-pregnant)^{4, 32}, and 600 μg/day of folic acid appears the recude deficiency risk post RYGB³². The ASMBS suggests between 350 – 500 μg/day for B12 and 800 – 1.000 μg/day folic acid¹⁵.

The safety of iron supplementation during pregnancy

Deficiency of a critical nutrient such as iron can lead to impaired cognitive function, due to its decisive role in brain development³⁵. A recent study 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.

A lowered iron absorption, together with a decreased intake of iron-rich products, impact the iron status of postoperative bariatric patients^15,32,38. In women after RYGB, the risks of maternal anemia and having a small for gestational age (SGA) baby, were increased. This has been linked to the malabsorption of nutrients such as iron³⁹. Alwan et al. reported that anaemia in the first half of pregnancy triples the risk of having an SGA baby⁴⁰.

The iron dose needed during pregnancy post-WLS is not well understood. An early study suggested iron requirements to be close to 1040 mg during pregnancy⁴², in healthy women. The World Health Organisation and the Food and Agricultural organisation (WHO/FAO) have proposed 840 mg, assuming sufficient iron storages (i.e. 500 mg available during the last two trimesters)⁴³. However, among post-WLS women, iron storages are often depleted, knowing that many WLS patients had deficits even prior to surgery⁴. The ASMBS suggest between 45-60 mg iron per day post RYGB, BPD/DS and SG – for men and women¹. However, Dogan et al. suggested that at least 100 mg/ day is needed to maintain iron status in females post RYGB³². Furthermore, the Obesity Management Task Force (2017) recommended doses of up to 200 mg/day⁶, particularly when deficits exist. A sensible approach would be to monitor status and adjust the dose according to needs. The last trimester is especially important, since iron status can be reduced and higher doses may be needed.

Conclusion

In pregnant women post WLS, vitamin and mineral dosages are both safe and necessary to ensure a healthy pregnancy. In fact, data 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 haemorrhage^1,6. Adequate nutritional assessment and supplementation, as well as monitoring of nutritional markers during pregnancy, are therefore essential to prevent adverse pregnancy outcomes^1,6. Finally, the ASMBS recommends preoperative screening to optimize postoperative outcomes and nutritional status¹⁵.

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