Preterm Birth International Collaborative Australasia Branch: Expert Consensus on Diagnosis and Treatment of Neonatal Lactose Intolerance (2025)

Abstract

This consensus aims to standardize the diagnosis and management of neonatal lactose intolerance (LI). A multidisciplinary working group was established under the auspices of the Preterm Birth International Collaborative (Australasia Branch). The development process included a comprehensive literature review of databases, which identified 61 publications. Recommendations were formulated using the Grading of Recommendations, Assessment, Development and Evaluation system for evidence evaluation. A modified Delphi method was used to achieve consensus. The consensus establishes that neonatal LI presents with nonspecific gastrointestinal symptoms, requiring stool assessment for diagnosis. Screening tests include fecal reducing sugar or urinary galactose tests, and the diagnosis is confirmed through elimination testing while excluding mimics. Treatment prioritizes lactase-supplemented breastfeeding; formula-fed infants receive lactase or reduced-lactose formulas. Probiotics with β-galactosidase activity can be used as an adjuvant therapy, and evidence-based lactase preparations are recommended, particularly for preterm infants. Treatment duration should be individualized, with a general minimum of 2 weeks; however, the routine use of lactose-free formula to prevent LI in preterm infants is not recommended. This consensus provides practical evidence-based guidance to standardize the diagnosis and management of neonatal LI, aiming to reduce variation in practice and improve patient outcomes. It emphasizes the importance of maintaining breastfeeding while incorporating lactase supplementation and highlights the need for further high-quality research, particularly randomized controlled trials, to refine diagnostic criteria and therapeutic strategies for preterm and very preterm infants. The recommendations are intended to support clinicians in making informed decisions while promoting family-centered care.

Keywords

diagnosis / lactose intolerance / lactose malabsorption / newborn / preterm / treatment

References

[1] R. Catanzaro, M. Sciuto, and F. Marotta, “Lactose Intolerance: An Update on Its Pathogenesis, Diagnosis, and Treatment,” Nutrition Research 89 (2021): 23–34.

[2] M. B. Heyman and N. Comm, “Lactose Intolerance in Infants, Children, and Adolescents,” Pediatrics 118, no. 3 (2006): 1279–1286.

[3] B. Misselwitz, M. Butter, K. Verbeke, and M. R. Fox, “Update on Lactose Malabsorption and Intolerance: Pathogenesis, Diagnosis and Clinical Management,” Gut 68, no. 11 (2019): 2080–2091.

[4] R.-J. Yu and Z. Zheng, “Exploration of Screening and Influencing Factors for Lactose Malabsorption and Lactose Intolerance in Early Newborns” [in Chinese], Chinese Journal of Neonatology no. 6 (2003): 244–246+286.

[5] Y. Ting, J. Yu and F. Ye, “Study on the Status and Risk Factors of Lactose Malabsorption and Intolerance in Newborns” [in Chinese], Maternal and Child Health Care of China 35, no. 14 (2020): 2638–2640.

[6] Y. Rao, H. Ye, D. Yu, et al., “The Study on the Incidence and Risk Factors of Lactase Deficiency in Newborns” [in Chinese], Chinese Journal of Neonatology 33, no. 2 (2018): 85–88.

[7] G. H. Guyatt, A. D. Oxman, R. Kunz, et al., “Going From Evidence to Recommendations,” BMJ 336, no. 7652 (2008): 1049–1051.

[8] F. Fassio, M. S. Facioni, and F. Guagnini, “Lactose Maldigestion, Malabsorption, and Intolerance: A Comprehensive Review With a Focus on Current Management and Future Perspectives,” Nutrients 10, no. 11 (2018): 1599.

[9] E. S. Yildirim, A. Aydin, T. Ince, Z. Varol, B. Ünal, and A. Demir, “Simethicone Medication Should Be Avoided in Infants Receiving Oral Lactase Treatment,” Children 11, no. 8 (2024): 1009.

[10] H. Ye, Y. X. Rao, C. Xu, D. Yu, and H. Ruan, “Investigation of Follow-Up for Lactase Deficiency and Physical Growth in Hospitalized Newborns” [in Chinese], Journal of Developmental Medicine(Electronic Version) 7, no. 2 (2019): 115–120, https://doi.org/10.3969/j.issn.2095-5340.2019.02.008.

[11] M. Porzi, K. J. Burton-Pimentel, B. Walther, and G. Vergères, “Development of Personalized Nutrition: Applications in Lactose Intolerance Diagnosis and Management,” Nutrients 13, no. 5 (2021): 1503.

[12] Y. Yang and C. Cai, “Progress in Neonatal Lactose Intolerance” [in Chinese], International Journal of Pediatrics 48, no. 7 (2021): 440–444.

[13] Z. L. Wang and Y. Shi, “Current Status and Prospect of Diagnosis and Treatment of Neonatal Lactose Intolerance” [in Chinese], Chongqing Medicine 53, no. 5 (2024): 641–650.

[14] X. Y. Zha, Y. Wang, P. Mao, et al., “Efficacy and Safety of Lactase Additive in Preterm Infants With Lactose Intolerance: A Prospective, Multi-Center, Randomized Controlled Trial” [in Chinese], Journal of Clinical Pediatrics 41, no. 1 (2023): 34–41.

[15] Z. Wang, L. Liu, C. Yu, et al., “Awareness About Neonatal Lactose Intolerance Among Chinese Neonatologists in Outpatient Settings: A Multi-Center Survey,” Children 11, no. 8 (2024): 1014.

[16] C. R. Tan-Dy and A. Ohlsson, “Lactase Treated Feeds to Promote Growth and Feeding Tolerance in Preterm Infants,” Cochrane Database of Systematic Reviews 2013, no. 3 (2013): Cd004591.

[17] F. J. Suchy, P. M. Brannon, T. O. Carpenter, et al., “NIH Consensus Development Conference Statement: Lactose Intolerance and Health,” NIH Consens State Sci Statements 27, no. 2 (2010): 1–27: PMID: 20186234.

[18] F. B. Yao, “Clinical Study on Infantile Lactose Intolerance” [in Chinese], Journal of Clinical Pediatrics 28, no. 5 (2010): 496–498.

[19] B. Xu and R.-Y. Ye, “Detection of Reducing Sugars in Stool Using Modified Benedict's Reagent Method” [in Chinese], Chinese Journal of Pediatrics, no. 1 (1994): 38.

[20] X. Cui, L. Wan, and M. Song, et al., “Clinical Significance of 135 Cases of Urine Galactose Detection in Neonate Diarrhea” [in Chinese], Chongqing Medicine 38, no. 24 (2009): 3135–3138.

[21] H. M. Su, Y. Jiang, Y. L. Hu, H. Yang, and T. J. Dong, “Lactose Intolerance in Neonates With Non-Infectious Diarrhea” [in Chinese], Chinese Journal of Contemporary Pediatrics 18, no. 4 (2016): 306–310.

[22] X. H. Zhang and F. Rao, “Clinical Application of Urine Galactose Determination in the Newborn Secondary Lactose Intolerance and the Related Adjunctivetherapy” [in Chinese], Chinese Journal of Child Health Care 16, no. 5 (2008): 563–564.

[23] F. Rao and X. H. Zhang, “Observation on Determination of Neonatal Diarrhea Complicated With Secondary Lactose Intolerance and Its Intervention Effect” [in Chinese], Chinese Nursing Research 23, no. 16 (2009): 1457–1458.

[24] A. Darma, K. R. Sumitro, J. Jo, and N. Sitorus, “Lactose Intolerance Versus Cow’s Milk Allergy in Infants: A Clinical Dilemma,” Nutrients 16, no. 3 (2024): 414.

[25] X. Zhang, Y. Jiang, Y. Zhang, et al., “Clinical Characteristics and Treatment of Infantile Lactose Intolerance and Evaluation of the Diagnostic Value of Fecal pH” [in Chinese], Chinese Journal of Applied Clinical Pediatrics 34, no. 19 (2019): 1467–1471.

[26] A. Anguita-Ruiz, C. M. Aguilera, and Á. Gil, “Genetics of Lactose Intolerance: An Updated Review and Online Interactive World Maps of Phenotype and Genotype Frequencies,” Nutrients 12, no. 9 (2020): 2689.

[27] N. Laforgia, G. Benedetti, T. Altavilla, et al., “Significance of Lactose Breath Test in the Newborn,” Minerva Pediatrica 47, no. 10 (1995): 433–436: PMID: 8569645.

[28] L. M. Nicholson, J. D. Mitchell, and J. M. Gupta, “Breath Hydrogen Excretion in Healthy Premature Infants,” Journal of Paediatrics and Child Health 28, no. 2 (1992): 176–179.

[29] R. G. Barr, J. Hanley, D. Kingsnorth Patterson, and J. Wooldridge, “Breath Hydrogen Excretion in Normal Newborn Infants in Response to Usual Feeding Patterns: Evidence for 'Functional Lactase Insufficiency' Beyond the First Month of Life,” Journal of Pediatrics 104, no. 4 (1984): 527–533, https://doi.org/10.1016/s0022-3476(84)80541-7.

[30] W. C. Maclean Jr and B. Fink, “Lactose Malabsorption by Premature Infants: Magnitude and Clinical Significance,” Journal of Pediatrics 97, no. 3 (1980): 383–388.

[31] Evidence-Based Medicine Group, “Clinical Guidelines for the Diagnosis and Treatment of Neonatal Necrotizing Enterocolitis (2020)” [in Chinese], Chinese Journal of Contemporary Pediatrics 23, no. 1 (2021): 1–11.

[32] J. Chen, C. M. Wan, S. T. Gong, et al., “Chinese Clinical Practice Guidelines for Acute Infectious Diarrhea in Children,” World Journal of Pediatrics 14, no. 5 (2018): 429–436.

[33] The Subspecialty Group of Gastroenterology, the Society of Pediatrics, Chinese Medical Association, The Editorial Board, Chinese Journal of PediatricsEditorial Board, Chinese Journal of Pediatrics, “Practice Guideline for Acute Infectious Diarrhea in Chinese Children” [in Chinese], Chinese Journal of Pediatrics 54, no. 7 (2016): 483–488.

[34] A. Guarino, A. Lo Vecchio, J. A. Dias, et al., “Universal Recommendations for the Management of Acute Diarrhea in Nonmalnourished Children,” Journal of Pediatric Gastroenterology and Nutrition 67, no. 5 (2018): 586–593.

[35] E. B. M. Group and N. Society, and Chinese Medical Doctor Association, “Clinical Guidelines for the Diagnosis and Treatment of Feeding Intolerance in Preterm Infants” [in Chinese], Chinese Journal of Contemporary Pediatrics 22, no. 10 (2020): 1047–1055.

[36] A. I. Coelho, G. T. Berry, and M. E. Rubio-Gozalbo, “Galactose Metabolism and Health,” Current Opinion in Clinical Nutrition and Metabolic Care 18, no. 4 (2015): 422–427.

[37] R. Leis, M. J. de Castro, C. de Lamas, R. Picáns, and M. L. Couce, “Effects of Prebiotic and Probiotic Supplementation on Lactase Deficiency and Lactose Intolerance: A Systematic Review of Controlled Trials,” Nutrients 12, no. 5 (2020): 1487.

[38] R. Francavilla, L. Calace, L. Brunetti, et al., “Faecal Microbiota and Gut Metabolic Profiles in Infants With Cow's-Milk Protein Allergy Before and After Lactose-Containing Diet,” Journal of Pediatric Gastroenterology and Nutrition 52 (2011): E89.

[39] I. Antonowicz and E. Lebenthal, “Developmental Pattern of Small Intestinal Enterokinase and Disaccharidase Activities in the Human Fetus,” Gastroenterology 72, no. 6 (1977): 1299–1303: PMID: 558125.

[40] D. Micic, V. L. Rao, and D. T. Rubin, “Clinical Approach to Lactose Intolerance,” JAMA 322, no. 16 (2019): 1600–1601.

[41] H. D. Erasmus, H. M. Ludwig-Auser, P. G. Paterson, D. Sun, and K. Sankaran, “Enhanced Weight Gain in Preterm Infants Receiving Lactase-Treated Feeds: A Randomized, Double-Blind, Controlled Trial,” Journal of Pediatrics 141, no. 4 (2002): 532–537.

[42] Y. Chen, Y. Zhu, C. Chen, et al., “Multi-Center Study on Efficacy and Safety of Lactase Drops in the Treatment of Lactose Intolerance in Premature Infants” [in Chinese], Chinese Journal of Hospital Drug Evaluation and Analysis 22, no. 12 (2022): 1488–1495.

[43] Y. Cao, Z. H. Li, S.-P. Han, et al., “Expert Consensus on Breast Milk Utilization in the Neonatal Intensive Care Unit (NICU)” [in Chinese], Chinese Journal of Evidence Based Pediatrics 16, no. 3 (2021): 171–178.

[44] Yangtze River Delta Immunization Integration Working Group, Chinese Medical Association Infectious Diseases Branch Children′s Infection and Hepatology Group, M. Zeng, and X. D. Sun, “Expert Consensus on the Prevention, Diagnosis and Treatment of Rotavirus Gastroenteritis (RVGE) in Children” [in Chinese], Chinese Journal of Preventive Medicine 54, no. 4 (2020): 392–405, https://doi.org/10.3760/cma.j.cn112150-20200102-00003.

[45] Nutritional Committee of Neonatology Branch of Chinese Medical Doctor Association, Preterm Committee of Neonatology Branch of Chinese Medical Doctor Association, Editorial Committee of Chinese Journal of Contemporary PediatricsPreterm Committee of Neonatology Branch of Chinese Medical Doctor AssociationEditorial Committee of Chinese Journal of Contemporary Pediatrics, “Expert Consensus on Enteral Nutrition Management of Preterm Infants” [in Chinese], Chinese Journal of Contemporary Pediatrics 26, no. 6 (2024): 541–552.

[46] L. Wang, Y. W. Wang, J. T. Tan, et al., “Efficacy and Safety of Lactase Additive in Preterm Infants With Lactose Intolerance: A Prospective Randomized Controlled Trial” [in Chinese], Chinese Journal of Contemporary Pediatrics 23, no. 7 (2021): 671–676.

[47] Y.-F. Sun, Z.-L. Sun, and J.-H. Lai, “Impact of Early Implementation of Lactose-Free Formula Feeding on Lactose Intolerance in Preterm Low Birth Weight Infants” [in Chinese], Clinical Medicine 38, no. 3 (2018): 91–93.

[48] A. Kozłowska-Jalowska, A. Stróżyk, A. Horvath, and H. Szajewska, “Effect of Lactase Supplementation on Infant Colic: Systematic Review of Randomized Controlled Trials,” Journal of Pediatric Gastroenterology and Nutrition 78, no. 5 (2024): 1009–1016.

[49] R. Nocerino, G. De Marco, L. Cosenza, et al., “Efficacy of a New Partially Hydrolyzed Whey Formula on Infant Colic: A Randomized Controlled Trial,” Digestive and Liver Disease 44 (2012): S272: PUI: L71690799.

[50] I. Xinias, A. Mavroudi, M. Pampouka, et al., “Lactose Free Partially Hydrolised Milk Formula Improves Infantile Colic,” Allergy: European Journal of Allergy and Clinical Immunology 64 (2009): 372.

[51] S. A. Abrams, I. J. Griffin, and P. M. Davila, “Calcium and Zinc Absorption From Lactose-Containing and Lactose-Free Infant Formulas,” American Journal of Clinical Nutrition 76, no. 2 (2002): 442–446.

[52] R. J. Shulman, R. J. Schanler, C. Lau, M. Heitkemper, C. N. Ou, and E. Smith, “Early Feeding, Feeding Tolerance, and Lactase Activity in Preterm Infants,” Jornal de Pediatria 133, no. 5 (1998): 645–649.

[53] R. J. Shulman, W. W. Wong, and E. O. Smith, “Influence of Changes in Lactase Activity and Small-Intestinal Mucosal Growth on Lactose Digestion and Absorption in Preterm Infants,” American Journal of Clinical Nutrition 81, no. 2 (2005): 472–479.

[54] X. Y. Li, C. Y. Zhang, L. H. An, et al., “Impact of Feeding Regimens on Nutritional Status and Clinical Outcomes in Preterm Infants With Lactose Intolerance” [in Chinese], Anhui Medical Journal 41, no. 11 (2020): 1278–1281.

[55] C. L. Kien, J. Kepner, K. A. Grotjohn, M. M. Gilbert, and R. E. McClead, “Efficient Assimilation of Lactose Carbon in Premature Infants,” Journal of Pediatric Gastroenterology and Nutrition 15, no. 3 (1992): 253–259.

[56] J. Spolidoro, T. Oliveira, E. Dallo, et al., “Use of Lactase Enzyme for Control of Diarrhea in Patients Breast Fed With Short Bowel Syndrome,” supplement, Transplantation 105, no. 7S1 (2021): S68.

[57] C. H. Lifschitz, E. O. Smith, and C. Garza, “Delayed Complete Functional Lactase Sufficiency in Breast-Fed Infants,” Journal of Pediatric Gastroenterology and Nutrition 2, no. 3 (1983): 478–482.

[58] A. Shaukat, M. D. Levitt, B. C. Taylor, et al., “Systematic Review: Effective Management Strategies for Lactose Intolerance,” Annals of Internal Medicine 152, no. 12 (2010): 797–803.

[59] L. T. Weaver, M. F. Laker, and R. Nelson, “Neonatal Intestinal Lactase Activity,” Archives of Disease in Childhood 61, no. 9 (1986): 896–899.

[60] Nutritional Committee of Neonatology Branch of Chinese Medical Doctor Association, Preterm Committee of Neonatology Branch of Chinese Medical Doctor Association, Editorial Committee of Chinese Journal of Contemporary Pediatrics, “Expert Consensus on Enteral Nutrition Management for Preterm Infants in Special Situations” [in Chinese], Chinese Journal of Contemporary Pediatrics 26, no. 7 (2024): 665–676.

[61] S. J. Oak and R. Jha, “The Effects of Probiotics in Lactose Intolerance: A Systematic Review,” Critical Reviews in Food Science and Nutrition 59, no. 11 (2019): 1675–1683.

[62] X.-S. Xiang and J.-H. Han, “Expert Consensus on Evidence-Based Milk Consumption for Lactose Intolerance” [in Chinese], Journal of Hygiene Research 53, no. 5 (2024): 689–693.

[63] Neonatology Group, Pediatric Branch of Chinese Medical Association; National Clinical Research Center for Child Health and Disorders (Chongqing); Editorial Board of Chinese Journal of Neonatology, “Expert Consensus on Diagnosis and Treatment of Neonatal Lactose Intolerance” [in Chinese], Chinese Journal of Neonatology (Chinese & English Edition) 40, no. 9 (2025): 513–521.

RIGHTS & PERMISSIONS

2026 The Author(s). Pediatric Discovery published by John Wiley & Sons Australia, Ltd on behalf of Children's Hospital of Chongqing Medical University.