Prevalence and patterns of micronutrient deficiency and anaemia in pregnancy following bariatric surgery

High rates of iron-related deficiencies and anaemia were reported during pregnancy following bariatric surgery. Anaemia was common during pregnancy after bariatric surgery, with reported prevalence ranging from 61%^{(Reference Amaral-Moreira, Redezuk, Pereira, Borovac-Pinheiro and Rehder26)} to 73%^{(Reference Chagas, Saunders, Pereira, Silva, Saboya and Ramalho27)}. In the two studies that reported anaemia patterns, more than half of the affected women had microcytic-hypochromic anaemia^{(Reference Amaral-Moreira, Redezuk, Pereira, Borovac-Pinheiro and Rehder26,Reference Ben-Porat, Elazary, Sherf-Dagan, Weiss, Levin and Rottenstreich28)} , and the majority (71%) had iron deficiency^{(Reference Amaral-Moreira, Redezuk, Pereira, Borovac-Pinheiro and Rehder26)}. Evidence on anaemia risk in women with and without bariatric surgery remains inconsistent^{(Reference Garretto, Kim, Quadro, Rhodas, Pimentel and Crnosija29,Reference Hammeken, Betsagoo, Jensen, Sørensen and Overgaard30)} . In contrast, studies comparing pregnancies before and after bariatric surgery found lower anaemia rates after surgery^{(Reference Hazan, Shimonov, Goldstein and Dayan31,Reference Gadgil, Chang, Richards, Gudzune, Huizinga and Clark32)} .

While megaloblastic anaemia was not reported during pregnancy following bariatric surgery, vitamin B12 deficiency was frequently observed across studies. Vitamin B12 deficiency varied widely^{(Reference Bebber, Rizzolli, Casagrande, Rodrigues, Padoin and Mottin33–Reference Mead, Sakkatos, Sakellaropoulos, Adonakis, Alexandrides and Kalfarentzos36)}, and some comparative evidence suggested higher deficiency rates or greater need for B12 injections among pregnant women after bariatric surgery^{(Reference Gadgil, Chang, Richards, Gudzune, Huizinga and Clark32,Reference Mansoori, Bataineh, Momani and Ali37)} . Vitamin D deficiency or insufficiency was common despite supplementation^{(Reference Bretón, Velasco, Cuerda, Motilla, Serrano and Morales34,Reference Heusschen, Berendsen, van Bon, van Laar, Krabbendam and Hazebroek35,Reference Hazart, Le Guennec and Accoceberry38–Reference Medeiros, Matos, Pereira, Saboya and Ramalho42)} , although comparative findings were mixed^{(Reference Gadgil, Chang, Richards, Gudzune, Huizinga and Clark32,Reference Mansoori, Bataineh, Momani and Ali37)} .

Vitamin A status, assessed by measuring serum retinol and β-carotene, was evaluated in several studies. Vitamin A deficiency was particularly evident following a Roux-en-Y gastric bypass (RYGB)^{(Reference Cruz, Matos, Da Cruz, Pereira, Saboya and Ramalho43,Reference Chagas, Saunders and Pereira44)} and was sometimes associated with clinical symptoms such as night blindness^{(Reference Chagas, Saunders and Pereira44)}. Comparative results between women with prior bariatric surgery and control were limited and mixed^{(Reference Garretto, Kim, Quadro, Rhodas, Pimentel and Crnosija29,Reference Machado, Pereira, Saboya, Saunders and Ramalho45)} . Other deficiencies, including zinc, selenium, thiamine, vitamin C, vitamin B6, vitamin E, vitamin K1, and magnesium, were assessed less frequently but reported in some studies. Detailed prevalence estimates and study-level findings are provided in supplementary Table 2.

Determinants of micronutrient deficiencies and anaemia in pregnancy after bariatric surgery

Several factors were examined as potential determinants of micronutrient deficiencies and anaemia during pregnancy after bariatric surgery, including the type of bariatric procedure, the interval between surgery and conception, gestational weight gain, pre-pregnancy BMI, and the type of supplementation administered. Overall, malabsorptive or combined procedures, particularly RYGB, were more often associated with lower micronutrient levels and a higher prevalence of deficiencies than restrictive procedures^{(Reference Bechensteen, Sithiravel and Strom-Roum46–Reference Watanabe, Seki and Haruta49)}, although this pattern was not consistent across all nutrients or studies^{(Reference Amaral-Moreira, Redezuk, Pereira, Borovac-Pinheiro and Rehder26,Reference Bretón, Velasco, Cuerda, Motilla, Serrano and Morales34,Reference Mansoori, Bataineh, Momani and Ali37,Reference Hazart, Le Guennec and Accoceberry38,Reference Ducarme, Planche, Abet, Desroys du Roure and Ducet-Boiffard50)} . The evidence regarding the association between pre-pregnancy BMI or gestational weight gain and vitamin D and vitamin A-related markers were inconsistent across studies^{(Reference Cruz, de Matos, da Cruz, Pereira, Saboya and Ramalho41–Reference Chagas, Saunders and Pereira44,Reference Cruz, de Matos, da Cruz, Pereira, Saboya and Ramalho51)} , whereas no significant association was observed for anaemia^{(Reference Amaral-Moreira, Redezuk, Pereira, Borovac-Pinheiro and Rehder26,Reference Bretón, Velasco, Cuerda, Motilla, Serrano and Morales34,Reference Stentebjerg, Andersen, Renault, Støving and Jensen52)} or other micronutrient deficiencies^{(Reference Bretón, Velasco, Cuerda, Motilla, Serrano and Morales34,Reference Gascoin, Gerard, Sallé, Becouarn, Rouleau and Sentilhes53)} .

The evidence showed that the timing of conception after bariatric surgery was not associated with micronutrient status, except for iron-related outcomes after RYGB. Four studies found that women who conceived at least four years^{(Reference Nomura, Dias, Igai, Paiva and Zugaib54,Reference Walter, Dolzan, Areias, Bergmann, Rizzolli and Mottin55)} or at least 18 months after RYGB^{(Reference Stentebjerg, Andersen, Renault, Støving and Jensen52,Reference Crusell, Nilas, Svare and Lauenborg56)} had a higher risk of iron deficiency or iron-deficiency anaemia compared to those who conceived earlier. Additionally, the late-conception groups required intravenous iron or blood transfusion more frequently than early-conception groups^{(Reference Stentebjerg, Andersen, Renault, Støving and Jensen52,Reference Nomura, Dias, Igai, Paiva and Zugaib54,Reference Walter, Dolzan, Areias, Bergmann, Rizzolli and Mottin55)} . However, this pattern was not observed in all studies, with some reporting no association between surgery-to-conception interval and anaemia^{(Reference Amaral-Moreira, Redezuk, Pereira, Borovac-Pinheiro and Rehder26,Reference Günakan, Buluş and Tohma57)} or other micronutrient deficiencies^{(Reference Garretto, Kim, Quadro, Rhodas, Pimentel and Crnosija29,Reference Mansoori, Bataineh, Momani and Ali37,Reference Devlieger, Guelinckx, Jans, Voets, Vanholsbeke and Vansant48,Reference Crusell, Nilas, Svare and Lauenborg56–Reference Yau, Parikh, Saunders, Chui, Zablocki and Welcome58)} . This finding requires further investigation and should be interpreted in the context of obstetric guidance recommending delayed conception for 12–24 months after bariatric surgery^{(Reference Ostrowska, Lech, Stefańska, Jastrzębska-Mierzyńska and Smarkusz59)}. Limited evidence suggested that specialised weight-loss surgery multivitamins may be associated with better micronutrient status during pregnancy after bariatric surgery, including higher haemoglobin, ferritin, and vitamin D levels compared with standard supplements^{(Reference Heusschen, Berendsen, van Bon, van Laar, Krabbendam and Hazebroek35,Reference Snoek, van de Woestijne, Willemsen, Klaassen, Galjaard and Laven60)} .

Pregnancy-related trends in micronutrient and haematological markers after bariatric surgery

Consistent declines in haemoglobin levels during pregnancy were reported, particularly in the second and third trimesters, a pattern that may partly reflect normal physiological haemodilution during pregnancy. Haemoglobin concentrations during pregnancy were often significantly lower than pre-pregnancy levels^{(Reference Bretón, Velasco, Cuerda, Motilla, Serrano and Morales34,Reference Gimenes, Nicoletti, de Souza Pinhel, de Oliveira, Salgado Júnior and Marchini61)} or pre-operative levels^{(Reference Snoek, van de Woestijne, Willemsen, Klaassen, Galjaard and Laven60,Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62)} . Additionally, haemoglobin levels may decrease significantly from the first trimester to subsequent trimesters in pregnancies following bariatric surgery^{(Reference Mead, Sakkatos, Sakellaropoulos, Adonakis, Alexandrides and Kalfarentzos36,Reference Hazart, Le Guennec and Accoceberry38,Reference Devlieger, Guelinckx, Jans, Voets, Vanholsbeke and Vansant48)} . In contrast, findings regarding ferritin levels were less consistent, with evidence of decline in some cases^{(Reference Bretón, Velasco, Cuerda, Motilla, Serrano and Morales34,Reference Devlieger, Guelinckx, Jans, Voets, Vanholsbeke and Vansant48)} and no significant change^{(Reference Snoek, van de Woestijne, Willemsen, Klaassen, Galjaard and Laven60–Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62)} in others.

Folate and vitamin B12 showed different patterns during pregnancy following bariatric surgery. Folate levels generally increased during pregnancy compared with pre-pregnancy^{(Reference Bretón, Velasco, Cuerda, Motilla, Serrano and Morales34)} or pre-operative levels^{(Reference Mead, Sakkatos, Sakellaropoulos, Adonakis, Alexandrides and Kalfarentzos36,Reference Snoek, van de Woestijne, Willemsen, Klaassen, Galjaard and Laven60,Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62)} . In contrast, findings regarding vitamin B12 levels were inconsistent, with evidence of decline in later pregnancy in some cases^{(Reference Bretón, Velasco, Cuerda, Motilla, Serrano and Morales34,Reference Snoek, van de Woestijne, Willemsen, Klaassen, Galjaard and Laven60)} and stability in others^{(Reference Gimenes, Nicoletti, de Souza Pinhel, de Oliveira, Salgado Júnior and Marchini61,Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62)} .

Trends in vitamin D and calcium levels during pregnancy after bariatric surgery were inconsistent. Calcium levels either declined during pregnancy compared with pre-operative levels^{(Reference Snoek, van de Woestijne, Willemsen, Klaassen, Galjaard and Laven60)} or non-pregnant post-bariatric controls^{(Reference Cruz, de Matos, da Cruz, Pereira, Saboya and Ramalho51)}, or remained stable across pregnancy in other studies^{(Reference Mead, Sakkatos, Sakellaropoulos, Adonakis, Alexandrides and Kalfarentzos36,Reference Gimenes, Nicoletti, de Souza Pinhel, de Oliveira, Salgado Júnior and Marchini61)} . Similarly, vitamin D levels showed no consistent pattern, with evidence of stability during pregnancy^{(Reference Devlieger, Guelinckx, Jans, Voets, Vanholsbeke and Vansant48,Reference Snoek, van de Woestijne, Willemsen, Klaassen, Galjaard and Laven60)} , a late-pregnancy decline^{(Reference Medeiros, Matos, Pereira, Saboya and Ramalho42)}, or higher levels than non-pregnant post-bariatric controls^{(Reference Cruz, de Matos, da Cruz, Pereira, Saboya and Ramalho51)}. Vitamin A concentrations tended to decline during pregnancy after bariatric surgery^{(Reference Devlieger, Guelinckx, Jans, Voets, Vanholsbeke and Vansant48,Reference da Cruz, Matos, Pereira, Saboya, da Cruz and Ramalho63)} . These changes were associated with a higher prevalence of vitamin A deficiency and more frequent night blindness among pregnant individuals than non-pregnant controls^{(Reference da Cruz, Matos, Pereira, Saboya, da Cruz and Ramalho63)}.

Energy and macronutrient intake during pregnancy after bariatric surgery

Energy and macronutrient intake were assessed in relation to pregnancy recommendations, comparisons with women without bariatric surgery, and changes over time from the pre-operative to pregnancy. Mean energy intake during pregnancy after bariatric surgery was reported as lower^{(Reference Araki, Shani Levi, Abutbul Vered, Solt and Rozen64)} or similar^{(Reference Gagnon, Carreau, Plante, Savard, Lemieux and Weisnagel65)} compared to women without bariatric surgery. When compared with pregnancy recommendations, intake was reported as below requirements in some cases^{(Reference Guthrie, Lee and Kothari66)} and within acceptable ranges in others^{(Reference Dias, de Souza Fazio, de Oliveira, Nomura, Faintuch and Zugaib67)}. Changes in energy intake over time also showed no clear pattern^{(Reference Gimenes, Nicoletti, de Souza Pinhel, de Oliveira, Salgado Júnior and Marchini61,Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62)} .

Protein intake generally met or exceeded pregnancy recommendations after bariatric surgery^{(Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62,Reference Guthrie, Lee and Kothari66–Reference Guelinckx, Devlieger, Donceel, Bel, Pauwels and Bogaerts68)} . However, total fat and saturated fat intake exceeded recommended levels during pregnancy after bariatric surgery^{(Reference Gagnon, Carreau, Plante, Savard, Lemieux and Weisnagel65,Reference Guthrie, Lee and Kothari66,Reference Guelinckx, Devlieger, Donceel, Bel, Pauwels and Bogaerts68)} . Fat quality was also suboptimal, with excessive saturated fat intake and inadequate mono- and polyunsaturated fat intake reported in both post-bariatric pregnancies and controls with obesity. In late pregnancy, polyunsaturated fat intake, including omega-3 and omega-6, was lower among women with prior bariatric surgery than among controls^{(Reference Jans, Matthys, Bogaerts, Ameye, Delaere and Roelens69)}. Carbohydrate intake tended to be low during pregnancy after bariatric surgery, with intake reported below recommended levels in some cases^{(Reference Guthrie, Lee and Kothari66,Reference Guelinckx, Devlieger, Donceel, Bel, Pauwels and Bogaerts68)} and lower than in women without bariatric surgery in comparative evidence^{(Reference Gagnon, Carreau, Plante, Savard, Lemieux and Weisnagel65)}. Longitudinal evidence was limited to one study, which reported a decline in carbohydrate intake in the second trimester followed by partial recovery in the third trimester^{(Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62)}. Fibre intake was also substantially inadequate during pregnancy after bariatric surgery, with intake reported below recommendations^{(Reference Guthrie, Lee and Kothari66,Reference Guelinckx, Devlieger, Donceel, Bel, Pauwels and Bogaerts68)} and lower than in women without bariatric surgery in comparative evidence^{(Reference Gagnon, Carreau, Plante, Savard, Lemieux and Weisnagel65)}. Limited evidence comparing different bariatric procedures showed no clear differences in macronutrient intake by surgery type^{(Reference Coupaye, Legardeur, Sami, Calabrese, Mandelbrot and Ledoux47,Reference Guthrie, Lee and Kothari66)} .

Micronutrient intake during pregnancy after bariatric surgery

Dietary micronutrient intake was assessed in relation to pregnancy recommendations, comparisons with women without bariatric surgery, and changes over time from the pre-operative to pregnancy. Dietary intake of calcium^{(Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62,Reference Guthrie, Lee and Kothari66,Reference Guelinckx, Devlieger, Donceel, Bel, Pauwels and Bogaerts68)} , zinc^{(Reference Guthrie, Lee and Kothari66)}, vitamin A^{(Reference Guthrie, Lee and Kothari66)}, vitamin B12^{(Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62,Reference Guthrie, Lee and Kothari66)} , iron^{(Reference Guthrie, Lee and Kothari66)}, and folate^{(Reference Guthrie, Lee and Kothari66)} was below the recommended levels for pregnancy following bariatric surgery. However, iron^{(Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62,Reference Guelinckx, Devlieger, Donceel, Bel, Pauwels and Bogaerts68)} and folate^{(Reference Faintuch, Dias, De Souza Fazio, De Oliveira, Nomura and Zugaib62)} intake met or exceeded recommendations in others. Importantly, in one study, when supplementation was included, the median intake of all micronutrients met or exceeded the recommended levels^{(Reference Guthrie, Lee and Kothari66)}.

Comparative analyses between women with and without bariatric surgery showed mixed results. Overall dietary micronutrient intake was similar between groups^{(Reference Garretto, Kim, Quadro, Rhodas, Pimentel and Crnosija29,Reference Gagnon, Carreau, Plante, Savard, Lemieux and Weisnagel65)} , and inadequate folate, vitamin B12^{(Reference Jans, Matthys, Bogaerts, Ameye, Delaere and Roelens69)}, or vitamin A intake^{(Reference Garretto, Kim, Quadro, Rhodas, Pimentel and Crnosija29)} was reported in both post-bariatric and control cohorts. However, total iron and calcium intake appeared higher among women with prior bariatric surgery when supplementation was included^{(Reference Araki, Shani Levi, Abutbul Vered, Solt and Rozen64)}.

Longitudinal and subgroup analyses provided limited and mixed evidence on factors influencing micronutrient intake. Micronutrient intake did not show significant changes over time^{(Reference Gimenes, Nicoletti, de Souza Pinhel, de Oliveira, Salgado Júnior and Marchini61)} or by surgery-to-conception interval^{(Reference Guthrie, Lee and Kothari66)}. However, malabsorptive procedures were associated with lower folate, vitamin A, and vitamin E intake, while greater dietitian contact was associated with higher vitamin A and vitamin B12 intake from diet and supplements^{(Reference Guthrie, Lee and Kothari66)}.