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The mother, a 33-year-old G1P0, had been undergoing prenatal checkups at our hospital's obstetrics department due to monochorionic diamniotic twins. She was admitted to our obstetrics department at 31 weeks and 5 days of pregnancy due to threatened premature labor and underwent an emergency cesarean section at 32 weeks and 6 days of pregnancy. Her father was suspected to have primary lactose intolerance. The infant had a birth weight of 1688 g and Apgar score 8/9 (1 min/5 min). Enteral feeding was initiated on day 1 of life with 4 mL of milk per feeding. On day 2, feeding was discontinued due to feeding intolerance associated with patent ductus arteriosus. Enteral feeding was resumed on day 3. The volume of milk was gradually increased, and by day 8, the infant was transitioned to breast milk. On day 11, the volume of breast milk was increased to 32 mL per feeding, corresponding to a total fluid intake of 164 mL/kg/day. This feeding regimen was maintained thereafter. But diarrhea started on day 15, and watery stool was observed every time the diaper was changed (Figure 1). Abdominal distension was observed, but there was no fever, vomiting, or increase in gastric juice residue. A blood test (day 17) did not show an increased inflammatory reaction, and stool culture (day 20) showed only normal bacteria. The stool samples for antigens of rotavirus and norovirus were negative. No symptoms of illness were observed among parents or medical personnel. It was determined that there was no infection, including acute gastroenteritis. On day 21, lactose intolerance was suspected, and lactose-free hydrolyzed milk was started. Diarrhea disappeared 4 h after administration, and lactose intolerance was diagnosed. From then on, lactose-free hydrolyzed milk was consumed, and breast milk was prohibited. A breast milk challenge test (55 mL of breast milk 8 times a day) was performed on day 37, but no diarrhea was observed, so the baby was diagnosed with developmental lactose intolerance and discharged on day 43. The infant had a birth weight of 1266 g and Apgar score 8/9 (1 min/5 min). Enteral feeding was initiated with 3 mL per feeding on day 1 of life. On day 3, green gastric residuals were observed, leading to temporary fasting. Breast milk feeding was resumed on day 5. Gastric residuals of 2 mL per feeding were noted between days 6 and 7. From day 8, the volume of breast milk was gradually increased, reaching 16 mL per feeding by day 13, which was then maintained. Diarrhea was observed on day 15, similar to the first twin, so lactose intolerance was suspected on day 21, and hydrolyzed milk with lactose removed was started. Diarrhea disappeared a few hours after administration, and the same treatment as for the first twin was given thereafter. A breast milk challenge test was performed on day 50; no diarrhea was observed, and the baby was discharged on day 66. Lactose intolerance is a syndrome characterized by one or more of the following symptoms after lactose ingestion: abdominal pain, diarrhea, nausea, flatulence, and bloating.1 The diagnosis can be made by the improvement of symptoms after eliminating lactose. If lactose intolerance is observed in the neonatal period, it may be congenital or developmental. Congenital lactose intolerance is inherited as an autosomal recessive trait caused by a mutation in the structural gene for lactase (LCTgene). Infants experience intractable diarrhea immediately after ingesting lactose (breast milk, formula). Developmental lactose intolerance is a relative lactase deficiency in premature infants born at less than 34 weeks' gestation, and diarrhea is often not observed. In such cases, it is important to wait for a physiological increase in lactase activity. The key point of this report is that the improvement of developmental lactose intolerance occurred before a corrected age of 40 weeks. In previous case reports, the time to recovery for this disease was 2–6 months after birth,2 but it was suggested that, as in the present cases, it may occur before a corrected age of 40 weeks. Fetal lactase secretion begins at about 10 weeks of gestation, is 0%–30% of that of full-term at 28–34 weeks of gestation, and increases to 70% of that of full-term at 35–38 weeks of gestation.3 The time at which lactase activity increases in premature infants is thought to vary from case to case, but in the present cases, breastfeeding was resumed early by performing a breast milk tolerance test before a corrected age of 40 weeks. When a premature infant is diagnosed with lactose intolerance, it is necessary to differentiate between developmental lactose intolerance and congenital lactose intolerance. If a lactose tolerance test such as a breast milk tolerance test is positive after a corrected age of 40 weeks, it seems necessary to perform a repeated lactose tolerance test at intervals and a genetic test for congenital lactose intolerance. On the other hand, lactose tolerance testing in preterm infants may result in inaccurate diagnoses. In this test, a rise in blood glucose of less than 20 mg/dL or the presence of abdominal symptoms following lactose administration is considered a positive result, leading to a diagnosis of lactose intolerance. However, in preterm infants, the gastrointestinal system is immature, and monosaccharide absorption may be impaired even in the absence of lactase deficiency. As a result, glucose levels may not rise adequately after lactose administration, leading to false-positive results. Therefore, in preterm infants, the absence of abdominal symptoms combined with a blood glucose increase of less than 20 mg/dL may not be sufficient to diagnose lactose intolerance. Previous studies have reported that carbohydrate4 and monosaccharide5 absorption improves by 8–14 weeks of age in infants born after 30 weeks of gestation. Therefore, if initial lactose tolerance test yields no abdominal symptoms and a minimal rise in blood glucose, repeating the lactose tolerance test after 2–3 months may enhance diagnostic reliability. In the present case, the reason why neither infant exhibited diarrhea until 14 days of age, and why both developed symptoms on the same day, remains unclear. One possible explanation is that the increased volume of breast milk exceeded the infants' lactase activity, leading to insufficient lactose hydrolysis and subsequent gastrointestinal symptoms. Given the limited number of reports on developmental lactose intolerance in preterm infants, further accumulation of case data is warranted to better characterize this condition. Syunsuke Nagara wrote and edited the manuscript. Jiro Shinoda, Shungo Fujiki, Emi Tannaka, Shinji Usui, Miwa Kawashiri, Atsushi Yamagishi provided conceptual advice. All authors read and approved the final manuscript. Informed consent was obtained from the patient's parents for publication of this case report. The authors have no conflicts of interest to disclose. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.