Patient Presentation
A 5-year-old female came to clinic with a fever for 2-3 days with rhinorrhea but no cough. Her fever was up to 101.2F and was responsive to antipyretics. She was tired, but was playing and generally acting normal, except for eating slight less. She was drinking and urinating well. A variety of community viruses and streptococcal sore throat were circulating.

The past medical history and family history was non-contributory. The review of systems was negative for cough, emesis or nausea, diarrhea, changes in urine or stool. There were no rashes.

The pertinent physical exam showed a tired appearing female who was very conversant and interactive. Her vital signs showed a pulse of 78/minute, blood pressure of 94/68, respiratory rate of 18 per minute, temperature of 37.4C and pulse oximeter of 98% on room air. HEENT showed some clear rhinorrhea, slightly thickened tympanic membranes without erythema or bulging, her tonsils were 2+ bilaterally and her throat had no erythema. Her heart was regular rate and rhythm with a grade II/V musical systolic murmur best at lower left sternal border. Lungs were clear. She didn’t like her abdomen examined but her liver seemed to be slightly enlarged, but no other obvious masses or splenomegaly. There was no costovertebral angle or suprapubic tenderness. She had 1 anterior cervical node that was 1 cm and a few other shotty nodes. She also had a few shotty inguinal nodes. There were no other lymph nodes palpated on her head, supraclavicular, axillary, epitrochlear or popliteal areas. She had no skin rashes, but her skin overall had a distinctly grayer appearance. She had extremely pale oral and conjunctival mucosa, conjunctiva, and very pale palms.

The diagnosis of of a clinically significant anemia and a differential diagnosis consistent with it was made. The laboratory evaluation of a complete metabolic profile showed slightly elevated AST and ALT, but normal uric acid and lactate dehydrogenase. Her complete blood count was significant for a hemoglobin of 4.1 g/dL, hematocrit of 14%, white blood cell count of 3.5 x 1000/mm² and platelets of 210 x 1000/mm². The general pediatrician remembered that < 5 g/dL usually needed to be transfused in addition to this patient needing further evaluation for the cause of the severe anemia. The hematologist agreed and the patient was admitted. The differential and blood smear came back as probable leukemia which was later confirmed. The patient received red blood cell transfusions, antibiotics potential infectious diseases and was discharged after workup and induction chemotherapy.

Discussion
While modern science, especially in pharmaceuticals, has made tremendous therapies available, blood and blood products continue to be a “…finite and limited resource that must be used wisely….” Blood banking and transfusion guidelines and procedures continue to maintain and improve a safe system for blood product use, which has made significant improvements in patient mortality and morbidity.

As with any treatment there are potential risks and blood products carry some unique ones as they are biological agents. Some potential risks of transfusion include:

• Hemolytic reactions, acute and delayed
• Infection
• Electrolyte problems
• Cardiovascular overload
• Acute lung injury

Transfusion related risks can be reduced by using blood products that have leukoreduction (decreasing the numbers of residual leukocytes if the end product is not leukocytes), irradiation (kills residual potentially viable leukocytes and infectious organisms), and washing (removes plasma proteins and additives such as glycerol), ABO blood group antigen matching, and volume reduction.
These are important, but probably more important is transfusion stewardship where systems of care can help to reduce the need for transfusions. Some of these include:

• Use of guidelines for indications for transfusion
• Performing the minimal phlebotomy needed for clinical care including not initiating or discontinuation of “routine” tests, and asking how will the test results assist in clinical care before ordering them
• Using smaller phlebotomy tubes (i.e. neonatal collection tubes) so less blood is needed to perform the test
• Using point of care testing devices
• Delayed cord clamping at birth
• Removal of sampling lines early
• Iron supplementation if appropriate
• Use of surgical interventions such as cell salvage or antifibrinolytics

Learning Point

• Red blood cells
  • Goal is to correct the anemia to provide hemostability and adequate oxygen carrying capacity and tissue perfusion.
  • Main indications:
    • Acute or chronic anemia
    • Hemoglobin variant complication prevention
    • Bleeding/Hemorrhage – if hemodynamically unstable then multiple blood products are recommended including red blood cells, plasma and platelets
  • Transfusion for anemia centers mainly on 3 questions:
    • Is the child hemodynamically stable? If not, then transfusion should be considered based on clinical judgement
    • Are there special circumstances to consider such as patient is a neonate, has oncological disease or congenital heart disease, etc.?
    • What is the hemoglobin?
      • < 5 g/dL transfusion is recommended
      • 5-7 g/dL transfusion may be recommended based on clinical judgement
      • > 7 g/dL and hemodynamically unstable – may be recommended based on clinical judgement
      • > 7 g/dL and hemodynamically stable – generally transfusion is not recommended but will depend on clinical scenario and clinical judgement
    • Amount to transfuse is often 10-15 ml/kg/transfusion, but will depend on clinical scenario.
• Platelets
  • Goal is to stop or prevent bleeding
  • Main indications
    • Bleeding/hemorrhage
    • Risk for bleeding such as procedures
    • Congenital platelet abnormalities
  • Generally transfused when platelet count is < 10 x 10⁹g/dL, but this may differ significantly depending on the clinical scenario such as oncology patients or those with a high risk of intracranial hemorrhage using higher platelet counts as a threshold.
  • Amount to transfuse is often 10-15 ml/kg/transfusion, but will depend on clinical scenario.
• Other blood products
  • Plasma
    • Main indications
    • Bleeding/hemorrhage
    • Coagulation profile correction
  • Granulocyte transfusions
    • Main indication is severe or prolonged neutropenia
  • Cryoprecipitate
    • Main indications
      • Fibrinogen replacement
      • Also used as source of Factor XIII, Factor VIII and von Willebrand factor before pharmacological factor concentrates

Questions for Further Discussion
1. What is the differential diagnosis of anemia? A review can be found here
2. How does acute leukemia present? A review can be found here
3. What are the clotting factors? A review can be found here

Related Cases

Disease: Blood Transfusion and Donation | Anemia | Leukemia, Childhood

Symptom/Presentation: Anemia | Fatigue | Fever and Fever of Unknown Origin

Specialty: Hematology | Oncology

Age: School Ager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Blood Transfusion , Anemia and Leukemia.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Valentine SL, Bembea MM, Muzynski JA, et al. Consensus recommendations for RBC transfusion practice in critically ill children from the pediatric critical care transfusion and anemia expertise initiative. Pediatr Crit Care Med 2018:19(9):884-98.

Maw G, Furyk C. Pediatric Massive Transfusion: A Systematic Review. Pediatric Emergency Care. 2018;34(8):594. doi:10.1097/PEC.0000000000001570

Nellis ME, Goel R, Karam O. Transfusion Management in Pediatric Oncology Patients. Hematology/Oncology Clinics of North America. 2019;33(5):903-913. doi:10.1016/j.hoc.2019.05.011

Mo YD, Delaney M. Transfusion in Pediatric Patients. Clinics in Laboratory Medicine. 2021;41(1):1-14. doi:10.1016/j.cll.2020.10.001

Chapman M, Keir A. Patient Blood Management in Neonates. Clinics in Perinatology. 2023;50(4):869-879. doi:10.1016/j.clp.2023.07.004

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Patient Presentation
A 6-year-old female was in clinic with her 2 and 4 year old siblings for her well child examination. She was healthy and gaining appropriate developmental milestones. As the pediatrician was leaving the mother asked about when and what types of pets were recommended for families. Her husband had grown up with dogs and she hadn’t had any animals as pets. “My husband wants to get a puppy for the kids now but I am not sure about it,” she said.

“We’ll,” the pediatrician started, “pets can be great for families but you need to have the right pet. Dogs can be wonderful but young ones are also more likely to be excited and could bite, and some breeds are gentler than others. Cats can also be good, but again bites and scratches can happen. There’s also the issue of taking care of the animals too like feeding and grooming. And your children aren’t old enough to take on much of that responsibility. Usually they should be around 5-6 years old. There’s also the issue of potential diseases that pets can spread. No one in your house has an immune problem right?” he asked. “No, but my mother-in-law is taking some medicine and comes to our house a lot,” she said. “That’s also a potential consideration. You might also consider a smaller animal like a gerbil or rabbit, or even fish which are pretty easy to take care of and generally don’t need as much attention. I’m not trying to stop you from any animal, but there are lots of considerations. I’ll print out some information from my professional society. I also bet there is information from the vet societies as well,” he continued.

Discussion
Pets can give social and emotional support for people and therefore many people have pets in their lives. Pet ownership comes with responsibilities for the health and well-being of the animals as well as safe-guarding the health of the people who own them.

Zoonoses are infections which spread from non-human vertebrates to humans. Some 70+ diseases are potential zoonoses. Rates are not uniform and depend on patient-specific factors, type of pet, how the pets are taken care of. Zoonoses can be spread by:

• Direct contact
  • By blood, saliva, urine, feces, mucous or other body fluids
  • Touching animals, bites, scratches, licking, cleaning up feces/urine, skinning/processing meat
  • Some examples include: Bartonella, Brucellosis, Hantavirus, Pasteurella, Rabies, Salmonella, Tularemia,
• Indirect
  • Animal fluids and skin/hair/feathers
  • Contact where animals live by touching, fomites and inhalation such as pet habitats, chicken coop, soil, aquarium water tank etc.
  • Some examples include: Clostridium, Campylobacter, Hantavirus, Leptospira, Salmonella, Toxoplasma, various worms
• Vectors
  • Bitten by fleas, mosquitos, ticks
  • Some examples include: Encephalitis viruses, Lyme Disease, Malaria, Plague, Rickettsia, Tularemia
• Foodborne and Waterborne
  • Ingesting animal feces in contaminated food or water, or undercooked or unpasteurized foods (meat, eggs, milk, etc.)
  • Some examples include: Brucellosis, Giardia, Leptospira, Salmonella,

A list of zoonoses with their common reservoir and vectors can be found here from the United Kingdom government.

Some of the more common pet-associated zoonoses include:

• Salmonella – amphibians, reptiles, poultry, hedgehogs, rodents
• Toxocara (round worm) – dog/cat feces ingested directly or through soil such as sandboxes, gardens
• Cat scratch (Bartonella henselae) – especially in young kittens
• Giardia – contaminated water
• Cryptosporidium – contaminated water

Learning Point
Considerations for choosing a pet include:

• Child age and developmental stage – generally at 5-6 years a child can understand instructions and follow them. Children can start to understand the responsibility of pet care.
• Animal characteristics – easy going animals that are people friendly such as beagles or retriever dogs are often better choices. Older animals that have been around people also can be good choices.
• Animal care – animals need to be taken care of in feeding, grooming, hygiene and general exercise and socialization. They also require appropriate veterinary care.
• Larger animals tend to need more care, whereas smaller ones need less but not always.
• Specific medical conditions – allergies to animal dander can be a real problem for some people. Also immunocompromised individuals can also be at higher risk for potential problems (see below)
• Specific animals – risk for zoonoses depends on the animal species and age.

People who are higher risk for serious illnesses from zoonoses include children < 5 years, those older than 65 years, pregnant women and those who are immunocompromised.

Recommendations to protect people from zoonoses include:

• Washing hands after being around animals or cleaning up after them. Running water and soap are best. If not available then using hand sanitizer with 60% alcohol content is a second choice but hand sanitizers do not get rid of all types of organisms.
• Arthropod protection using insect sprays and protective clothing.
• Keep sandboxes covered when not in use, and fence gardens if appropriate.
• Food handling safety – thorough washing of fruits and vegetables, and appropriate handling of protein (meats, fish, dairy, etc) to prevent spread to surfaces and utensils. Proper kitchen sanitizing is important, along with food storage.
• Petting zoos or other animal exhibits are also a risk as the animals tend to be younger and more likely to have or spread a zoonoses. Be aware that animals may be in other environments such as daycare facilities or schools or when traveling. Neighbors and friends may also have animals.
• Avoiding bites, scratches and saliva from animals. Young animals tend to get more excited and will bite, scratch or lick more often. Likewise small children tend to do the same and therefore the combination of both increases the risk. Children should be supervised around any animal.
• Children should be taught never to approach or touch an unfamiliar animal or any wild animals in order to avoid scratches/bites; this includes deceased animals in the environment. They should also be taught not to tease or abuse an animal. Children may not understand that taking away a toy from an animal may make them more aggressive for example.
• If there is an immunocompromised individual in the environment, then additional precautions should be taken such as having that person not handle the animal including grooming and cleaning up feces/urine. Animals should have routine veterinary care and in addition may require additional care such as deworming more often. Also puppies and kitten less than 6 months old are discouraged if acquiring a new pet.

Questions for Further Discussion
1. What pets are common in your patient population?
2. What zoonoses are common in your patient population?
3. What other recommendations do you give to your families with pets?
4. What animals are considered emotional support animals? A review can be found here

Related Cases

Disease: Pets and Animals | Animal Diseases and Your Health | Pets and Pet Health

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: General Pediatrics | Infectious Diseases

Age: Infant

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews. Information prescriptions for patients can be found at MedlinePlus for these topics: Animal Diseases and Your Health and Pet Health.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

McBride DL. Reducing the Risk of Pet-Related Infections to Children. Journal of Pediatric Nursing. 2016;31(1):107-108. doi:10.1016/j.pedn.2015.09.010

Tips for Choosing the Right Pet for Your Family. HealthyChildren.org. December 12, 2019. Accessed December 1, 2025. https://www.healthychildren.org/English/safety-prevention/at-home/Pages/Before-Choosing-a-Pet.aspx

Campbell SB, Nelson CA, Hinckley AF, Kugeler KJ. Animal Exposure and Human Plague, United States, 1970-2017. Emerg Infect Dis. 2019;25(12):2270-2273. doi:10.3201/eid2512.191081

Halliday JEB, Carugati M, Snavely ME, et al. Zoonotic causes of febrile illness in malaria endemic countries: a systematic review. Lancet Infect Dis. 2020;20(2):e27-e37. doi:10.1016/S1473-3099(19)30629-2

Garcia-Sanchez P, Aguilar-Valero E, Sainz T, et al. Immunocompromised Children and Young Patients Living with Pets: Gaps in Knowledge to Avoid Zoonosis. Transbound Emerg Dis. 2023;2023:2151761. doi:10.1155/2023/2151761

Zhang YF, Li SZ, Wang SW, et al. Zoonotic diseases in China: epidemiological trends, incidence forecasting, and comparative analysis between real-world surveillance data and Global Burden of Disease 2021 estimates. Infect Dis Poverty. 2025;14:60. doi:10.1186/s40249-025-01335-3

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Patient Presentation
A 9-year-old male came to clinic with a 2-day history of left scrotal discomfort. He had played in a soccer tournament the day it began and denied any trauma to the genital area. He initially thought it was due to chaffing of his undergarment during the tournament, but the discomfort had increased and was now mildly painful. It had awoken him up in the night, but he did not tell his parents until the morning of evaluation. He said there was no swelling or redness to the testicle and that he hadn’t noticed any changes in the pain with movement of the testicle. He denied any problems with the right testicle and scrotum. He denied any masses or swellings in the genital area and also denied any dysuria or discharge from his penis. He had had an upper respiratory infection the week before. He denied anyone inappropriately touching him or sexual contact.

The past medical history was negative for any genitourinary problems including no kidney problems or urinary tract infections. The family history was negative for genitourinary abnormalities. The review of systems was negative for fever, chills, nausea, emesis or diarrhea.

The pertinent physical exam showed a male with normal vital signs including a temperature of 98.8F and normal growth parameters at the 75-90%. He was Tanner I for pubic hair and testicular size. His testicles were symmetrically located in the scrotum when observed without obvious erythema or masses to the scrotum. The phallus was circumcised and normal. The left testicle showed mild pain with palpation of the epididymis and possibly the testicle itself, but it was more prominent over the epididymis. There were no obvious masses of the testicle or along the cord. There was no change in pain with testicular elevation. No inguinal hernias were palpated.

The diagnosis of acute epididymitis with possible orchitis was made. The laboratory evaluation included a urinalysis that was normal and the urine culture was pending. The pediatrician discussed the patient with the on-call urologist who was comfortable with treating him with supportive care and monitoring without further evaluation or empiric antibiotics. The patient’s clinical course showed that he had similar pain for another 48 hours and then this declined until he was pain free by 6 days after the onset. He never was febrile nor had any urinary symptoms, and it was felt this was possibly due to a post-viral infection.

Discussion
In acute epididymitis there is usually an insidious onset of a painful epididymis with swelling and inflammation. Often the testicle itself is also involved and this condition is called epididymo-orchitis. The term epididymitis will be used here. Epididymitis is a common cause of acute scrotal pain with about 1/3 of prepubescent boys presenting with this problem. Some studies show a bimodal distribution of infancy and prepuberty, while others show a peak in prepuberty or late adolescence. With epididymitis, there is normal placement of the testes and normal cremasteric reflex. Scrotal edema may occur and there may also be dysuria. The exact mechanism is not known but may be because of “…urinary outflow obstruction which leads to reflux of urine into the ejaculatory duct.” The actual cause if often not identified (< 10% is cited) but is likely viral infections, post-infection inflammation or trauma in younger boys, but in adolescents and adults sexually transmitted infections are more common. Common pathogens in younger males are adenovirus, enterovirus and Mycoplasma. In adolescents, Neisseria gonorrhea and Chlamydia trachomatis may occur. E. coli is also common if there are associated anatomic abnormalities. As some studies have found that epididymal aspirates correlate with urine culture, urine culture is used as a marker for bacterial analysis.

Learning Point
As some studies have found that epididymal aspirates correlate with urine culture, urine culture is used as a marker for bacterial analysis. Assessment includes evaluation of other causes of scrotal swelling or testicular pain (see Questions for Further Discussion below) and usually a urine culture, and testing for sexually transmitted infections (STIs) in the appropriate age range. Testing for both gonorrhea and chlamydia is recommended as concomitant STIs may occur together. Treatment for younger, prepubescent males is mainly supportive including ice, rest and anti-inflammatory medication. Antibiotics are often not recommended in this age group unless there is a higher risk of a serious bacterial infection such as an anatomic abnormality, neonatal age, or being immunocompromised. For adolescents and young adults, empiric treatment with antibiotics against common infections, and definitive treatment for positive urine culture or STI testing is recommended. Although in general there are good outcomes for epididymitis occurring in the pediatric age range, testicular abscess or infarction can occur.

Questions for Further Discussion
1. What causes scrotal swelling? A review can be found here
2. What causes testicular pain? A review can be found here
3. What is a spermatocele?

Related Cases

Disease: Epididymitis | Testicular Disorders

Symptom/Presentation: Scrotal Pain

Specialty: Nephrology / Urology

Age: School Ager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Testicular Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Cristoforo TA. Evaluating the Necessity of Antibiotics in the Treatment of Acute Epididymitis in Pediatric Patients: A Literature Review of Retrospective Studies and Data Analysis. Pediatr Emerg Care. 2021;37(12):e1675-e1680. doi:10.1097/PEC.0000000000001018

Norton SM, Saies A, Browne E, et al. Outcome of acute epididymo-orchitis: risk factors for testicular loss. World J Urol. 2023;41(9):2421-2428. doi:10.1007/s00345-023-04500-1

Hoffmann K, Gopal M. Paediatric acute epididymo-orchitis temporally related to SARS-CoV-2 infection: A case series and review of the literature. Journal of Pediatric Urology. 2024;20(1):91-94. doi:10.1016/j.jpurol.2023.09.017

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Patient Presentation

Some general pediatricians were discussing the new recommendations from the Federal Drug Administration (FDA) for the use of leucovorin to treat cerebral folate deficiency. “I’ve had a couple of families who just wanted more information and wanted to know if their child might benefit. I had another family who just wanted me to give them leucovorin,” said one. “I had one family who wanted me to order antibody testing. The testing from what I have read isn’t FDA approved,” another replied. “I think what we all want is the best for the kids and families. Maybe this is going to be the beginning of some additional treatment options for some families, but from what I’ve read probably not for most families. The answer is always “more research is needed,””the third commented.

Discussion

Leucovorin is also known as folinic acid, calcium folinate, or 5-formyl tetrahydrofolic acid. Folinic acid exists in nature whereas folic acid is a synthetic, water-soluble form of Vitamin B9 or folate. Folic acid needs to be converted to folinic acid to be biologically active. Folate is often added to foods to fortify them. A review of what foods have folic acid in them can be found here.

There is growing recognition of the possibilities that targeted metabolic therapies could play in the management of patients with specific subsets of Autism Spectrum Disorder (ASD). The FDA approved leucovorin for cerebral folate deficiency in September 2025. The FDA news release and Federal Register state approval is for “cerebral folate deficiency” but it appears that approval may be for patients with FOLR1 gene variants. [Additional information was not available from the FDA at the time of this writing]. FOLR1-related cerebral folate transport deficiency is among “…several causes of folate deficiency restricted to the central nervous system characterized by very low levels of cerebrospinal (CSF) folate in the absence of clinically significant systemic folate deficiency.” GeneReviews® notes that as of 1/11/24, 35 individuals from 21 families have been reported with FOLR1-related cerebral folate transport deficiency. Other causes of CNS folate deficiency include disorders of transport in the choroid plexus due to mitochondrial dysfunction, several hereditary disorders of folate metabolism and FOLR1 autoantibodies.

There have been some studies of patients with ASD who tested positive for anti-folate receptor antibodies who were treated with leucovorin and who showed some improvements. One example is a randomized-controlled, double-blinded, placebo-controlled trial published in 2024 which included 80 participants who were followed for 24 weeks. Other examples include an open-label trial of 44 children with ASD with followup for 4 months, and another double-blind placebo controlled trial with 48 children followed for 3 months. Note that these are studies with small numbers of patients, followed for only a relatively short period of time. Also prevalence in the general population of these antibodies is estimated at 7-15%, so the antibodies are not a specific indication of ASD. Current testing for antibodies is not FDA approved or cleared. This means that testing including “…clinical interpretation standards, validation, and analytic performance are established by the performing laboratory rather than by an FDA-reviewed labeling process.” For proprietary reasons, some or all of the testing procedures and result interpretation criteria are not available for review.

Learning Point

Leucovorin’s FDA-approved indications for use are for treating:

• Chemotherapy side-effect modulator such as methotrexate
• Megaloblastic anemia
• Cerebral folate deficiency

Leucovorin is not FDA approved for all patients with ASD.

The American Academy of Pediatrics (AAP) notes that there are limits to the current research on leucovorin use in patients with ASD including that there are few patients in the studies, there are concerns about some of the study methods, most of the studies are from the same group of researchers and the studies need reproducibility from other research groups to verify the results, large safety and efficacy trials have not been completed, and “[a] conclusion of all of the published studies is that more research is needed, and the AAP concurs.”

The AAP at the time of this writing states that “…the current evidence base remains too limited to support specific clinical recommendations” for use of leucovorin in patients with ASD.

The search for ASD causes and definitive treatment needs to continue with peer-reviewed research to answer these questions, and concurrently ensuring that patients and families are receiving the services and supports they need to live healthy lives as valued community members.

The President of the Society of Inherited Metabolic Disorders stated in a letter to the Department of Health and Human Services, “…[W]e want to reiterate a foundational principle: the presence of autism in any child is not the parents’ fault. As we continue to expand our understanding of the biological underpinnings of autism, compassion must guide our messaging, to avoid pointing blame and creating guilt.”

Questions for Further Discussion

1. What are some indications for genetic testing for individuals with neurodevelopmental delays? A review can be found here
2. What are some causes of intellectual disability? A review can be found here
3. What are indications for referral to speech therapy? A review can be found here
   
   

Related Cases

Disease: Leucovorin | Folic Acid | Autism | Genetic Disorders | Child Behavior Disorders

Symptom/Presentation: Behavior Problems | Developmental Delay

Specialty: Developmental Disabilities | Genetics | Neurology / Neurosurgery | Nutrition / Dietetics

Age: None

To Learn More

To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Autism and Leucovorin.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Frye RE, Rossignol DA, Scahill L, McDougle CJ, Huberman H, Quadros EV. Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder. Semin Pediatr Neurol. 2020;35:100835. doi:10.1016/j.spen.2020.100835

Panda PK, Sharawat IK, Saha S, Gupta D, Palayullakandi A, Meena K. Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial. Eur J Pediatr. 2024;183(11):4827-4835. doi:10.1007/s00431-024-05762-6

Goldman ID. FOLR1-Related Cerebral Folate Transport Deficiency. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews®. University of Washington, Seattle; 1993. Posted 1/11/24. Accessed October 28, 2025. http://www.ncbi.nlm.nih.gov/books/NBK599286/

Gristan YD, Patel P, Moosavi L. Folinic Acid. In: StatPearls. StatPearls Publishing; 2025. Accessed October 27, 2025. http://www.ncbi.nlm.nih.gov/books/NBK545232/

FDA News Release. FDA Takes Action to Make a Treatment Available for Autism Symptoms. FDA. September 22, 2025. Accessed October 27, 2025. https://www.fda.gov/news-events/press-announcements/fda-takes-action-make-treatment-available-autism-symptoms

Approval of Previously Withdrawn New Drug Application for WELLCOVORIN (Leucovorin Calcium) Tablets. Federal Register. September 24, 2025. Accessed October 28, 2025. https://www.federalregister.gov/documents/2025/09/24/2025-18510/approval-of-previously-withdrawn-new-drug-application-for-wellcovorin-leucovorin-calcium-tablets

OMIM®Folate Receptor, Alpha;FOLR1, Entry 136430.https://www.omim.org/entry/136430?search=136430&highlight=136430, Accessed 10/28/25

OMIM® Neurodegeneration due to Cerebral Folate Transport Deficiency; NCFTD. Entry 613068. https://www.omim.org/entry/613068?search=613068&highlight=613068. Accessed 10/28/25

Reigier DS. President of the Society for Inherited Metabolic Disorders. Letter to Robert F. Kennedy, Jr., dated October 1, 2025.

Frequently Asked Questions (FAQs) for Pediatricians and other Prescribing Pediatric Clinicians: Leucovorin Use in Autism and Cerebral Folate Deficiency. Accessed November 3, 2025. https://www.aap.org/en/patient-care/autism/use-of-leucovorin-in-autistic-pediatric-patients/frequently-asked-questions-faqs-for-pediatricians-and-other-prescribing-pediatric-clinicians/

Interim Guidance from the American Academy of Pediatrics: Use of Leucovorin in Autistic Pediatric Patients. Accessed November 3, 2025. https://www.aap.org/en/patient-care/autism/use-of-leucovorin-in-autistic-pediatric-patients/

Author

Donna M. D’Alessandro, MD

Professor of Pediatrics, University of Iowa