eTable 1. Clinical descriptive studies/case reports on growth and health outcomes of the consumption of plant-based milk alternatives (PBMA) in infancy, childhood, and adolescence.
| Source | Age at examination/ diagnosis | Type of nutrition (if reported) | Findings/diagnoses | Country, reason for use of PBMA, other relevant diagnoses (if reported) |
|---|---|---|---|---|
| Children < 2 years | ||||
| Mesa Medina et al. 2009 (17) | 1 month | Exclusive feeding with almond-based PBMA since birth | Failure to thrive/weight loss, dehydration, hypochloremic, hypokalemic metabolic alkalosis | Spain: Preterm birth (34 weeks of gestation), otherwise no diagnoses; after exclusion of other causes (vomiting, medication use, tubulopathy, cystic fibrosis), insufficient intake of sodium and chloride via the PBMA was considered the underlying cause |
| Fourreau et al. 2013(16) | 2.5 months | Feeding with various PBMA (chestnut, soy, hazelnut, almond, 6×110 mL) over 6 weeks | Failure to thrive, hypoalbuminemia. Hyponatremia (96 mmol/L), hypokalemia (1.5 mmol/L), respiratory acidosis | France: Hypoxic-ischemic encephalopathy following neonatal asphyxia, feeding via nasogastric tube, PBMA administered due to weight stagnation under tube feeding with infant formula; later, diagnosis of pneumonia and pneumococcal meningitis with fatal outcome |
| Gulledge et al. 2023 (12) | 4 months | Exclusively unsweetened almond-based PBMA with high calcium and low phosphate content (1900 mg calcium/L, 85 mg phosphate/L) over one month |
Weight loss/undernutrition (weight-for-length Z score: −2.46), recurring vomiting, restlessness, and lethargy, hypercalcemia with hypoparathyroidism, hypophosphatemia, and vitamin D deficiency (calcium 14.1 mg/dL, ionized calcium 2.34 mmol/L, phosphate 1.7 mg/dL, parathyroid hormone < 4 pg/ mL, 25-OH-vitamin D 21 ng/dL), bilateral nephrocal-cinosis | USA: The child had no underlying medical condition and was fed with PBMA due to a national shortage of infant formula. Fluid replacement and transition to standard infant formula led to satisfactory weight gain with normalization of the weight-for-length Z score (0.8). No electrolyte abnormalities were observed in the next month, and the nephrocalcinosis resolved within 6 months |
| Mesa Medina et al. 2009 (17) | 4 months | Exclusive feeding with almond-based PBMA since birth | Failure to thrive, dehydration, hypochloremic, hypokalemic metabolic alkalosis, hypothyroidism, myelinization disorders (optic neuritis, hearing loss) | Spain: No relevant prior medical conditions; after exclusion of other causes (vomiting, medication use, tubulopathy, cystic fibrosis), insufficient intake of sodium and chloride via the PBMA was considered the underlying cause |
| Liu et al. 2001 (29) |
4 months | Consumption of rice-based PBMA; duration unknown | Kwashiorkor | USA: Feeding with rice-based PBMA due to suspected cow’s milk intolerance |
| Diamanti et al. 2011 (28) | 4 months | Exclusive consumption of rice-based PBMA over one month | Kwashiorkor | Italy: Atopic dermatitis and vomiting; feeding with rice-based PBMA because the child refused hydrolyzed infant formula and rice-protein based hydrolyzed formula; cow’s milk allergy was diagnosed in two of the three children reported |
| Diamanti et al. 2011 (28) | 4 months | Exclusive consumption of rice-based PBMA over 2.5 months | Kwashiorkor | Italy: Feeding with rice-based PBMA because the family could not afford the hydrolyzed infant formula which had been recommended due to vomiting with regular infant formula; cow’s milk allergy was diagnosed in two of the three children reported |
| Diamanti et al. 2011 (28) | 4 months | Exclusive consumption of rice-based PBMA over 2 months | Kwashiorkor | Italy: Atopic dermatitis and diarrhea;feeding with rice-based PBMA because the child refused hydrolyzed infant formula and rice-protein based hydrolyzed formula; cow’s milk allergy was diagnosed in two of the three children reported |
| Le Louer et al. 2014(14) | 4.5 months | Exclusive consumption of rice-based PBMA over 2 months | Anemia (Hb 5.7 g/dL), kwashiorkor | France: Feeding with PBMA due to regurgitation, no relevant prior medical conditions |
| Le Louer et al. 2014(14) | 5 months | Exclusive consumption of chestnut- and almond-based PBMA over 1.5 months | Hypocalcemic seizures, kwashiorkor, anemia (Hb 8.5 g/dL), vitamin D deficiency | France: Feeding with PBMA due to gastroesophageal reflux and eczema, otherwise no relevant prior medical conditions |
| Houck et al. 2019 (23) | 5 months | Feeding with almond-based PBMA (270 mL every 4–5 hours, diluted 1:1 with water) and additional water (continuously over 3 weeks) |
Hyponatremic seizures (sodium 121 mmol/L) | USA: Feeding with PBMA due to gastroesophageal reflux in an otherwise healthy, full-term female infant with sickle cell trait |
| Imataka et al. 2004 (18) | 5 months | Consumption of soy-based PBMA over 4 months | Failure to thrive, rickets | Japan: Eczema, feeding with PBMA due to suspicion of cow’s milk allergy, no exposure to sunlight |
| Le Louer et al. 2014(14) | 6 months | Consumption of almond- and chestnut-based PBMA over 2 months | Failure to thrive, hypokalemia | France: Feeding with PBMA due to gastroesophageal reflux and diarrhea, otherwise no relevant prior medical conditions |
| Le Louer et al. 2014(14) | 6 months | Consumption of chestnut-based PBMA over 1.5 months | Failure to thrive | France: Feeding with PBMA due to parents’ beliefs; no relevant prior medical conditions |
| Novembre et al. 2003 (34) | 6 months | Consumption of rice-based PBMA (660 mL/day), with additional rice pudding, vegetable soup, and apple; duration unknown | Hypoproteinemia | Italy: Atopic dermatitis, feeding with PBMA on the recommmendation of a naturopathic physician |
| Doron et al. 2001 (21) | 6 months | Exclusive consumption of home-made almondbased PBMA over 3 months | Failure to thrive, anemia (Hb 7.7 g/dL), rickets, hypocalcemia | Israel: Feeding with PBMA because cow’s milk allergy was suspected due to diarrhea and vomiting |
| Le Louer et al. 2014(14) | 7 months | Consumption of rice-based PBMA over 6 months | Kwashiorkor, anemia (Hb 8.7 g/dL), hyponatremia | France: Consumption of PBMA because of eczema, otherwise no relevant prior medical conditions |
| Katz et al. 2005 (27) | 7 months | Feeding with rice-based PBMA over 5 months, with small amounts of complementary feeding and iron supplementation | Kwashiorkor, anemia | USA: Feeding with PBMA because various infant formulas, including an amino-acid-based formula, had not been tolerated since the age of 2 months |
| Kanaka et al. 1992 (20) | 7.5 months | Consumption of a home-made almond-based PBMA over 5 months, with small amounts of cereal and fruit | Failure to thrive, hypothyroidism with iodine deficiency, carnitine deficiency, osteopenia | Switzerland: Eczema, feeding with almond-based PBMA due to suspected cow’s milk allergy |
| Le Louer et al. 2014(14) | 8 months | Consumption of almond- and chestnut-based PBMA over 2 months | Failure to thrive, anemia (Hb 8.6 g/dL), hypoalbuminemia | France: Feeding with PBMA due to vomiting, no relevant prior medical conditions |
| Tierney et al. 2010 (30) | 8 months | Consumption of rice-based PBMA over 4 months, with small amounts of complementary feeding in the form of sweet potato and banana | Kwashiorkor | USA: Feeding with rice-based PBMA in a child whose mother suspected intolerance of the medically recommended extensively hydrolyzed formula |
| Doron et al. 2001 (21) | 8 months | Exclusive consumption of home-made almondbased PBMA over 3–4 months | Kwashiorkor | Israel: Status post surgical correction of vesicoureteral reflux and urethral valves; feeding with PBMA due to eczema (previous feeding with soy-based infant formula had brought no improvement) |
| Massa et al. 2001 (31) | 8 months | Consumption of rice-based PBMA over 4 months, with fruit and vegetables | Kwashiorkor | Belgium: Feeding with rice-based PBMA because of eczema, lack of improvement with hypoallergenic and soy-based infant formula |
| Lemale et al. 2018(15) | 8.8 ± 3.8 months (mean ± SD) n = 34 children | Almond-based PBMA (n = 15), chestnut-based PBMA (n = 4), rice-based PBMA (n = 4), soy-based PBMA (n = 1); 29% of the infants received milk from animals other than cows over a mean 3.7 ± 2.5 months (mean ± SD) | Impairment of longitudinal growth and body weight (n = 28), asthenia (n = 22), scaly erythema (n = 14), status epilepticus (n = 10), anemia with Hb < 10 g/L (n = 12, including n = 5 with Hb < 6 g/dL), hyponatremia with mean sodium 126 mmol/L (96–134 mmol/L) (n = 8, including n = 1 death with sodium 96 mmol/L following consumption of chestnut-based PBMA), severe vitamin D deficiency (< 7 μg/mL, n = 6), edema (n = 6), hypocalcemic seizures (n = 2), metabolic alkalosis (n = 1), spontaneous leg fracture with bone demineralization (n = 1); hospitalization in 19/34 cases | France: The reasons for consumption of PBMA were cow’s milk intolerance (n = 15), minor digestive problems (n = 11), and cutaneous symptoms (n = 8) |
| Fourreau et al. 2013(16) | 9 months | Feeding with rice-based PBMA over 2 months | Kwashiorkor | France: Atopic dermatitis; feeding with rice-based PBMA because of ■difficulties” in weaning off breast milk and because the mother suspected cow’s milk allergy |
| Le Louer et al. 2014(14) | 10 months | Consumption of almond- and rice-based PBMA over 3 months | Failure to thrive, anemia (Hb 9.2 g/dL), hypoalbuminemia | France: Consumption of PBMA, because the child refused to drink milk from a bottle; no relevant prior medical conditions |
| Vitoria et al. 2016 (33) | 11 months | Consumption of an almond-based PBMA (680 g/day) with added almond flour, sesame powder, rice malt, and cereal porridge over 8.5 months | Failure to thrive, scurvy, osteopenia and pathological fracture with vitamin D deficiency | Spain: Feeding with almond-based PBMA with additives on a physician’s recommendation in eczema |
| Mori et al. 2015 (25) | Unknown (first year of life) | Consumption of rice-based PBMA since age 6 months, for first 2 months with additional consumption of fruit, rice, poultry, and vegetable broth, all subsequently refused by the child | Kwashiorkor, anemia (5.7 g/dL) | Italy: Atopic dermatitis; feeding with PBMA on the recommendation of a naturopathic physician |
| Keller et al. 2012 (26) | 12 months | Consumption of rice-based PBMA with rolled oats and fruit over 5 months | Kwashiorkor | USA: Feeding with rice-based PBMA because vomiting and diarrhea occurred with cow’s milk nutrition, and goat’s milk and soy-based PBMA led to worsening of existing eczema |
| Fourreau et al. 2013(16) | 13 months | Feeding with almond-based PBMA (840 mL/day) over 3 weeks, very small amounts of additional complementary feeding | Hypochloremic, hypokalemic alkalosis | France: Congenital myopathy, tracheostoma placement, feeding partially via nasogastric tube, transition from follow-up formula to PBMA due to feeding difficulties |
| Fourreau et al. 2013(16) | 14 months | Consumption of rice-based PBMA (ca. 300 mL/day) over 2 months; previously the child had been breastfed fully for 5 months and partially for 12 months; as for complementary feeding, the child had recently started receiving fruit, vegetables, and meat, but no milk (products); the mother had had a varied diet, but had eaten little meat during pregnancy | Iron- and vitamin B12-deficiency anemia | France: No prior medical conditions; consumption of PBMA because of parents’ beliefs |
| Salama et al. 2024 (24) | 14 months | Almost exclusive consumption of ca. 1300 mL/day almond-based PBMA with high calcium and low phosphate content (1900 mg calcium/L, 85 mg phosphate/L) over 2 months |
Dehydration with hypercalcemia (14.6 mg/dL) and hypophosphatemia (phosphate 1.6 mg/dL) | USA: Status post liver transplantation at age 7 months due to biliary atresia, immunosuppression with mycophenolate and tacrolimus; consumption of PBMA due to suspected cow’s milk allergy and difficulties with solid food intake; after fluid substitution and transition to infant formula, normalization of electrolytes within 6 days; a parathyroid hormone-related cause of hypercalcemia was excluded due to absent urinary phosphate excretion; 2 months later, diagnosis of T-cell posttransplant lymphoproliferative disorder with fatal outcome |
| Le Louer et al. 2014(14) | 14 months | Consumption of almond- and chestnut-based PBMA for 11 months | Failure to thrive, hypokalemia (2.8 mmol/L), hypocalcemia, vitamin D deficiency | France: consumption of PBMA because of infantile colic; otherwise no relevant prior medical conditions |
| Katz et al. 2005 (27) | 14 months | Feeding with rice-based PBMA for 6 months as well as vegetables and meat (the consumption of solid food had decreased in the weeks preceding diagnosis) | Kwashiorkor, anemia | USA: Feeding with PBMA because various infant formulas were not tolerated after weaning at the age of 8 months |
| Barreto-Chang et al. 2010 (22) | 16 months | Consumption of rice-based PBMA for 3 months; the child was partially breastfed up to the age of 1 year and received a varied diet of complementary foods (fruit, vegetables, soups, clear chicken broth—but no milk[products]) from the age of 5 months | Failure to thrive with weight loss, vitamin D deficiency rickets | USA (California): Child of Hispanic origin; eczema, several episodes of upper respiratory tract infection and bronchiolitis in first year of life; enriched soy-based PBMA was recommended by a physician due to suspected cow’s milk allergy but was not tolerated by the child, so rice-based PBMA was fed |
| Le Louer et al. 2014(14) | 16.5 months | Consumption of almond- and hazelnut-based PBMA over 7 months | Vitamin D and calcium deficiency with fracture of left leg following minimal trauma | France: Asthma, consumption of PBMA because of parents’ beliefs |
| Keller et al. 2012 (26) | 17 months | Consumption of rice-based PBMA, chick peas, lentils, and olives over 5 months | Kwashiorkor, anemia (Hb 7 g/dL) | USA: Consumption of PBMA in a child with pre-existing eczema and positive skin prick test for several foods, including cow’s milk |
| Kuhl et al. 2004 (32) | 17 months | Consumption of 950 mL rice-based PBMA daily together with two dessert spoons of baby food or solid food (no meat) for 4 months | Kwashiorkor, anemia (Hb 7.8 g/dL), delayed bone age (7.5 months) | USA: Consumption of PBMA due to atopic dermatitis and multiple food allergies (including cow’s milk) |
| Carvalho et al. 2001 (19) | 17 months | Consumption of soy-based PBMA (ca. 900 mL/day) for 7 months, together with a varied but completely vegan diet with no animal products; no data on supplements | Failure to thrive, rickets | USA: Child with dark skin pigmentation and limited exposure to sunlight, vegan feeding including soy-based PBMA because of parents’ beliefs |
| Keller et al. 2012 (26) | 19 months | Consumption of rice-based PBMA as well as rice, potatoes, and carrots over 7 months | Kwashiorkor, subsequently tibial fracture with osteopenia | USA: Consumption of PBMA in eczema and positive skin prick test for several foods, including cow’s milk (the child refused hydrolyzed formula) |
| Carvalho et al. 2001 (19) | 22 months | Consumption of rice-based PBMA (ca. 1.5 L/day) over 9 months; very little other food | Kwashiorkor, anemia | USA: Eczema, consumption of rice-based PBMA because the parents suspected cow’s milk intolerance |
| Children ≥ 2 years | ||||
| Martini et al. 2018 (35) | 5 years | Oat-based PBMA (> 2 years) | Failure to thrive, severe vitamin-A deficiency with irreversible vision loss, anemia | Italy: Severely restricted diet consisting mainly of oat-based PBMA in a conflict-rich mother-child relationship with little external support |
| Ellis and Lieb 2015 (36) | 3, 9 and 10 years (n = 3) | 700 to 1000 ml almond-based PBMA/day each (duration of consumption 2 years for one of the children, not reported for the others) | Dysuria (n = 3), colicky abdominal or costovertebral pain (n = 2), intermittent macrohematuria (n = 2), persisting microhematuria (n = 3), 24-hour hyperoxaluria (n = 3), detection of calcium oxalate crystals in urine (n = 2), bilateral kidney stones and ureteral stone (n = 1) | USA: PBMA were consumed due to lactose intolerance, and, in one of the children, to improve tics in Tourette syndrome; two of the children had a family history of kidney stones in first-degree relatives |
| Infante and Tormo 2000 (37) | 2 bis 14 years (n = 4 children) | Soy-based PBMA (> 2 years), together with occasional consumption of dairy products | Low bone mineral density (measured by dual-energy X-ray absorptiometry at level of L2–L4) in range of osteopenia to osteoporosis (T score −2 to −3) | Spain: Consumption of PBMA due to lactose intolerance (n = 2) or hypercholesterolemia (n = 2) |
Hb, Hemoglobin; PBMA, plant-based milk alternatives; SD, standard deviation