What Causes Anemia?

Patient Presentation
An 8-year-old female with an underlying genetic syndrome presented with some fatigue, cough and fever for 3 days. The patient had no bruising or bleeding symptoms. The past medical history showed her to eat a variety of pureed feeds and receive overnight continuous feeds through a gastrostomy tube. The liquid nutritional supplement did have iron in it. The family history was negative for any hematological problems including anemia. The review of systems was negative.

The pertinent physical exam showed a non-verbal female who looked mildly ill with a temperature of 38.0°C, heart rate of 96 beats/minute and respiratory rate of 24.
She was in her wheelchair. HEENT showed pale, non-icteric conjunctiva, mild rhinorrhea, with normal pharynx and ears. She did not have increased work of breathing and she had transmitted upper airway noises. Her abdomen was soft, non-tender without adenopathy and her G-tube area had normal skin. Rectal examination was negative for occult blood. She had no skin lesions. The laboratory evaluation included a complete blood count which showed a hemoglobin of 7.8 g/dL, MCV of 71 fl, and with normal platelets, white blood cells and cell subtypes. The peripheral smear showed small pale cells without abnormal shape. The reticulocyte count was low. Iron studies completed later were consistent with iron deficiency anemia. Lead and thyroid testing were negative.

The work-up included a chest radiograph that was negative. An ultrasound examination of her abdomen to evaluate for occult masses or other pathology was also negative. A review of her medications did not show any that caused bone marrow suppression or hemolysis.

The diagnosis of iron deficiency anemia and an upper respiratory tract infection were made. It was unclear why she had the iron deficiency anemia because it appeared that she should have had adequate nutrition from her oral and gastrostomy feedings. Iron supplementation was begun and a dietician reviewed her diet but did not recommend any additional changes. The patient’s clinical course over the next month showed that her upper respiratory tract infection had improved, but she was somewhat less energetic than she usually was. Her repeat laboratory testing showed a hemoglobin of 9.6 g/dL and a reticulocyte count of 18%. Her other hematologic indices also improved. She continued to have no obvious bleeding symptoms. At that time the physician elected to continue to monitor her and felt that her anemia and fatigue were still most likely due to nutritional deficiency and would monitor her closely.

Discussion
One of the most common problems in pediatrics is anemia. It is defined as “a lower than normal value for the related measurements of hemoglobin, hematocrit, and number of red blood cells”, usually 2 standard deviations below the normal for age. Normal hematological values change with age. For a discussion of which values are used click here.

The most common type of anemia in childhood is iron deficiency which is commonly caused by inadequate stores (e.g. premature infant), inadequate intake (e.g. poor nutrition) or blood loss (e.g. menses). Anemia screening is recommended at age 9-12 months, and for adolescent males and females during routine health examinations. As iron deficiency is the most common cause, often a trial of therapeutic iron (2-6 mg/kg/day of elemental iron) is started and then a complete blood count is rechecked ~ 1 month later. If iron deficiency is the cause then there should be an increase in the hemoglobin and hematocrit. If not, other causes must be sought. For a discussion of why anemias may not correct click here.

History is very important to help direct the evaluation and workup. A detailed dietary history including pica or lead ingestion can give clues to a possible dietary reason for the anemia, especially iron deficiency anemia. Blood loss history including trauma, bleeding or potential occult loss from the genitourinary tract are also very helpful. Bone marrow production problems (e.g. malignancy, infectious diseases) or hemolysis risks (e.g. sickle cell anemia) also must be looked for. Some causes have multiple etiologies such as a decreased red blood cell half life coupled with increased risk for hemolysis (e.g. sickle cell anemia).

Signs and symptoms of anemia include:

  • No symptoms
  • Developmental delay
  • Irritability
  • Heart failure
  • Lethargy and fatigue
  • Organomegaly – spleen, liver, lymph nodes
  • Pallor
  • Poor oral intake
  • Tachycardia
  • Signs of hemolysis – jaundice, paleness, dark urine
  • Stool color changes, blood in stool or urine
  • Weight loss

Review of the medical records for family history of anemia or hematopoietic diseases is very important along with reviewing any previous laboratory testing including neonatal screening. Sometimes much of the needed evaluation has already been previously completed for other reasons such as neonatal screening.

It is also important to evaluate all components of the complete blood count to look for other abnormalities such as platelet or white blood cell count problems. Other related cases can be found here: Lymphocytosis, Eosinophilia, Thrombocytosis, and Thrombocytopenia.

Learning Point
The differential diagnosis of anemia includes:

  • Nutritional
    • Iron deficiency
      • Poor nutrition – inadequate iron intake, abnormal eating patterns
      • Other nutrient deficiencies – folate, B12, riboflavin, Vitamin C, copper
      • Excessive milk intake
    • Lead toxicity
    • Malabsorption
    • Prematurity because of inadequate stores
  • Anemia of chronic disease
    • Autoimmune diseases
    • Liver disease
    • Hypothyroidism
  • Hematological
    • Hematopoietic problem
      • Congenital aplastic anemia
      • Fanconi
      • Blackfan-Diamond
      • Schwachman
      • Malignancy
      • Transient erythroblastopenia of childhood
      • Medication or toxin exposure – anticonvulsants, Zidovudine
      • Storage diseases – lipids, Langerhans cell histocystosis
    • Hemolysis
      • Congenital hemolytic anemia
        • Membrane defects
          • Elliptocytosis
          • Hereditary spherocytosis
        • Enzyme defects
          • G-6-PD deficiency
          • Pyruvate kinase deficiency
        • Hemoglobin problems
          • Sickle cell disease
          • Hemoglobin S or C or other hemoglobinopathies
          • Sideroblastic anemia
          • Thalassemia
        • Immune hemolytic anemia – Rh or ABO incompatibility, cold agglutinin, warm agglutinin
        • Microangiopathic hemolytic anemia – hemolytic uremia syndrome, Kasabach-Merritt syndrome
        • Hypersplenism
        • Liver disease
        • Renal disease
        • Telangectasia
        • Wilson disease
        • Mechanical – artificial heart valve
        • Medication or toxin exposure – anticonvulsants, Zidovudine, aluminum, lead
      • Infectious disease
        • Congenital infection
        • Bacteremia/Septicemia/Disseminated intravascular coagulation
        • Malaria
        • Viral
          • Common viral infections
          • Congenital infections
          • Hepatitis
    • Blood loss
      • Epistaxis
      • Cephalohematoma
      • Gastrointestinal – inflammatory bowel disease, polyps, varices, Meckel’s diverticulum
      • Menses
      • Trauma
        • Other bleeding problems such as hemophilia or platelet disorders
        • Twin-twin transfusion
        • Placental/umbilical bleeding
        • Pulmonary hemosiderosis
        • Hemorrhagic disease of the newborn
        • Urinary – paroxysmal nocturnal hemoglobinuria
    • Other
      • Dilutional
      • Excessive phlebotomy
      • Munchausen syndrome or Munchausen by proxy

Questions for Further Discussion
1. On a peripheral blood smear, what types of findings are helpful in determining an anemia’s cause?
2. Anemia is often classified by red blood cell size. What are some of the common causes of microcytic, normocytic or macrocytic anemias?
3. What are indications for a bone marrow evaluation in a child with anemia?

Related Cases

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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

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

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.

Sheldon SH, Levy HB. Pediatric Differential Diagnosis. Second Edition. Raven Press: New York. 1985:12-15.

Cohen PS. Anemia, in Pediatrics A Primary Care Approach, Berkowitz CD ed. W.B. Saunders Co. Philadelphia PA. 1996;230-34.

Engorn B, Flerlage J. The Harriet Lane Handbook. 20th Edit. Elsevier Saunders. 2015: 308.

Sandoval C. Approach to the Child with Anemia. UpToDate. (online resource) (rev. 6/4/2015, cited 2/25/17).


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

What Causes School Absenteeism?

Patient Presentation
A 14-year-old male came to clinic because he was worried about school. He had been in a car accident and had been out of school for a few weeks. He described initially going back to school and found it very physically tiring and he was behind in his classes. “It’s just really hard for me to get around the school and then I don’t know what is going on in my classes. I like seeing people but it’s really hard,” he stated. He went on, “It’s just easier for me to stay home and try to catch up, but I’m falling farther and farther behind. I’m not really sure what to do.” He and his parents describe how he tried to return to school for half-days, but this was too tiring for him. “It’s just easier for us to have him at home, so we don’t have to leave work to pick him up early,” his mother said. “I missed a lot of work because of the accident,” she confided. “We’ve tried to help him with his homework but he is behind his friends,” they stated. “The school had offered some tutoring but he’d have to be at school to do that,” his father went on. “I really don’t want to be in a class where everyone is so much farther ahead than me,” the teenager stated. He says he was sleeping better recently than he had after the accident, denied flashbacks or anxiety about the accident, or worries about his family.

The past medical history revealed that he had always been a little more anxious. “He’s the worrier in the family. He’s always been more worried about how he’ll do in the baseball game or on the test, but when it comes time to do those things he’s just fine,” they noted. The pertinent physical exam showed a well-appearing male. His vital signs were normal. He still had a cast on his left leg. Healing scars on his face and arms from lacerations were noted.

The diagnosis of school refusal along with anxiety, being behind academically, being deconditioned, and healing fractures were made. The pediatrician recommended several steps to gradually get him back into school. He recommended a meeting with his guidance counselor, school administration, parents and the teenager to figure out how to address the mobility issues at school so he wouldn’t be so tired, and develop a plan to gradually catch him up academically to his classmates. “You might be surprised how many other kids have had the same problems and the school can help. Maybe the first couple of days you will only go to school for a couple of hours and you can work in the library with one of the teachers. Then maybe increase this to half a day for another week. Then you might start to feel less tired and can stay longer the next week. I bet you probably have a friend or two in class who could leave a couple minutes before the bell and be able to push your wheelchair to your next class so you won’t have to use all your energy just getting around too. There are lots of possibilities,” the pediatrician said. “Maybe a friend or two could come over after school and you could do some school work or just hang out for a bit,” he went on. “I miss playing in the band and its first period in the morning” the boy offered. “We’ll maybe for the first couple of days, you can go to band, and afterward one of your friends can help you to the library to meet with a teacher. Band is a great thing to help you regain your strength, plus its always fun to make music,” he encouraged the teen. “I also think that it would be helpful to talk with a counselor about some of the worries you have in general and about school. I think that person can help you to learn some ways to better help yourself when you start being worried,” the pediatrician suggested.

The patient’s clinical course at followup 1 month later showed that the teen was in school for 1/2 day consistently. He was still behind in some of his classes but was making progress. He had one meeting with counselor and his cast was to be removed in ~2 weeks. “I’m still worried about my classes and being so far behind, but once my cast is off I think I’ll do better,” he stated. It was a slow process but over the next 6 weeks he eventually returned to school full-time consistently.

Discussion
School within society is an institution designed to provide learning opportunities to students under the direction of teachers. The curriculum is usually designed to provide academic content in formal subjects necessary for the adult world (such as instruction in mathematics, language, science, social studies, arts, physical education) but also other knowledge and skills for the adult world (i.e. personal safety, communication skills, working in teams, etc.). Specific schools may or may not offer specific courses of instruction such as religious education, learning disability education, gifted/talented education, vocational education, etc.. In the developed and developing world, most individuals have attended some type of formal schooling at some time in their lives. Formal education is usually viewed as desirable even in locations where formal education may be less common as it is seen as an avenue for improved job opportunity, and economic and social improvement. All, or almost all students, at one point or another, wish they didn’t have to go to school. Absenteeism for some children becomes a problem. It affects ~ 1 of 7 children in the United States or ~6 million children.

School refusal (sometimes also referred to as school phobia or school avoidance) is most common in the 5-7 year olds and the 11-14 year olds, i.e. around the entry to school or middle school, but can occur at all school ages. School refusal often occurs after a time where the child has spent more time with the parent (school vacation or short illness) or after a stressful event such as a death in the family, or moving. Children entering school may be concerned about the new situation and appropriately are concerned about separating from their parents. This is a normal experience and usually improves within a short amount of time with reassurance and beneficial classroom experiences. Older children may have true fears about school based on their experiences such as bullying, violence or fearing a particular adult. Other children have continued separation issues from their parents and yet still want the school experience. This often occurs when parents are experiencing life stressors themselves such as an illness, death, divorce, loss of job etc.. Children may feel that they need to be with the parent more than being at school.

Children often have externalizing behaviors such as tantrums, sleep problems including nightmares and enuresis, obsessive-compulsive symptoms, and other fears. Physical complaints are common such as stomachache, headache, or sore throat, which often occurs on school mornings but improves as soon as the child is allowed not to attend school. Children may be more clingy, follow parents around the house and express excessive worry about the parent or other things such as monsters, weather events (i.e. tornados, lightening, etc..), fires, burglers, etc..

Once children start into a pattern of avoiding school and isolating themselves, it become more difficult to re-integrate. Understanding the underlying reason or reasons (often this is multifactorial), along with adult support (such as parents, general education and special education teachers, guidance counselors, school administrators, mental health providers, physicians, etc..) can assist the student to re-integrate and be successful at school. Communication and setting reasonable expectations are important. Reentry plans are important and can be simple or more elaborate. A slow-to-warm kindergartener may just need the kindergarten teacher to meet him at the school door for a few more days. A teenager returning after a traumatic event may need a gradual progressive plan that extends the amount of time and activities at school over 1 or more weeks. The student should know who they can talk with or where to go if they are feeling overwhelmed, but also should not excessively use those resources to get out of regular classroom activities. Other strategies include encouraging/enforcing regular routines at school and home, assigning a peer/buddy to assist the child, providing appropriate academic supports including flexible scheduling or alternative educational placements, addressing school/community safety issues, and encouraging extracurricular/community activities.

Truancy is different than school refusal as truant students do you not have emotional problems associated with going to school, often hide their absences from parents and authority figures, and are engaged in their preferred activities or may be involved in illegal activities. The juvenile justice system has as one of its goals to assist youth into developing other prosocial skills including returning to school. Homelessness also contributes to absenteeism but is not school refusal.

Learning Point
Reasons for school absenteeism include:

  • School refusal/phobia
    • Anxiety
      • Separation anxiety
      • School/performance anxiety
      • Generalized anxiety disorder
      • Obsessive compulsive disorder
      • Post traumatic stress disorder
      • Panic attacks
      • Other fears – agoraphobia
    • Depression
    • Inadequate schooling/education
    • Learning disabilities
    • Physical illness, especially chronic illness
    • Physical safety issues at school/community, including bullying and violence
    • Parent related problem
      • Abuse
      • Mental illness
      • Physical illness
      • Poor parenting skills
      • Lack of basic needs – food, clothing, shelter
      • Stressful life events
  • Truancy*
    • Mental health issues including anxiety, depression, personality disorders
    • Substance abuse
    • Poor social situation/environment
    • Poor social skills
    • Poor parenting skills/parental monitoring
    • Inadequate schooling/education
    • Learning disabilities
  • Physical illness or pregnancy
  • Other
    • Lack of basic needs especially homelessness

*reasons often overlap with school refusal

Questions for Further Discussion
1. What parent education do you offer for separation anxiety in young children?
2. What often do you offer for teens who are behaviorally defiant?

Related Cases

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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Phobias and Child Behavior 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.

Kidger J, Araya R, Donovan J, Gunnell D. The effect of the school environment on the emotional health of adolescents: a systematic review. Pediatrics. 2012 May; 129(5):925-49. Epub 2012 Apr 2.

American Academy of Child and Adolescent Psychiatry. School Refusal. Available from the Internet at https://www.aacap.org/AACAP/Families_and_Youth/Facts_for_Families/FFF-Guide/Children-Who-Wont-Go-To-School-(Separation-Anxiety)-007.aspx (rev. 10/2013, cited 2/21/2017).

United States Department of Education. Chronic Absenteeism in The Nation’s Schools. Available from the Internet at https://www2.ed.gov/datastory/chronicabsenteeism.html (rev. 10/27/2016, cited 2/21/17).

Fernandez-Suarez A, Herrero J, Perez B, Juarros-Basterretxea J, Rodriguez-Diaz FJ. Risk Factors for School Dropout in a Sample of Juvenile Offenders. Front Psychol. 2016 Dec 26;7:1993.

National Association of School Psychologists. School Refusal: Information for Educators. Available from the Internet at http://www.nasponline.org/Documents/Resources%20and%20Publications/Handouts/Families%20and%20Educators/School_Refusal_Information_for_Educators.pdf. (cited 2/21/17).

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

How Good Are Ankle Rules for Determining If a Patient Needs An X-Ray?

Patient Presentation
A 16-year-old male came to clinic with a 24 hour history of right ankle injury. He had been playing basketball and had an inversion injury. He denied any pops or other sounds at the time. He had not been able to walk right after the injury. He had elevated the leg, used intermittent ice and had some ibuprofen, yet he was still having a reasonable amount of pain and was still limping. The past medical history was negative for other extremity injuries.

The pertinent physical exam showed a well-appearing male with normal vital signs and growth parameters. His left ankle was moderately bruised and swollen over the lateral malleolar area. He had tenderness over the posterior talofibular and fibulocalcaneal ligaments. There was no tenderness along the fibula itself but the swelling made the examination difficult to tell. He also wasn’t sure if there was pain near the 5th metacarpal. The medial malleolus, tibia and navicular had no pain with palpation. There was no other foot pain and he was neurovascularly intact.

The diagnosis of a possible ankle sprain versus fracture was made. The pediatric resident said that he knew that there were criteria for when you should get an ankle x-ray but wasn’t sure what they were nor how good they were for diagnosing fractures. The attending physician reviewed the Ottawa Ankle Rules with him, demonstrating that the patient was not able to walk and had swelling that compromised the examination making it difficult to tell if there was point tenderness in some key areas or not. The radiologic evaluation showed no fracture. The patient was placed into a removeble aircast and crutches. He was referred to physical therapy for rehabilitation as the patient was finishing his basketball season but was starting another sport in 3 weeks.

Discussion
Ankle sprains result from force around the ankle that exceeds the tensile strength of the supporting ligaments of the ankle but less than that which breaks the ankle bones. The ankle capsule – ligament complex has 5 primary ligaments:

Medial ankle – the deltoid is the strongest ligament in the ankle and has two parts:

  • Superficial deltoid ligament – runs from the medial malleolus to the calcaneus posteriorly
  • Deep deltoid ligament – runs from medial malleolus to the talus

Lateral ankle – these ligaments act like 3 guidewires to the lateral ankle and are generally injuried in the following order:

  • Anterior talofibular ligament – runs anteriorly to the lateral malleolus
  • Fibulocalcaneal ligament – runs laterally to the lateral malleolus
  • Posterior talofibular ligament – runs posterior to the lateral malleolus

Most ankle injuries involve an inversion of the ankle. The ability to walk generally excludes a fracture. People with third-degree ankle sprains often give a history of an audible snap. The physical examination revels intact skin with swelling. Pain upon motion is common as is point tenderness over the ligaments. An anterior drawer sign indicates anterior talofibular ligament rupture.

Clinical decision rules are tools to help clinicians make diagnostic decisions. There are two validated ankle decision rules that can help clinicians determine if an ankle injury requires a radiograph.

The Ottawa Ankle Rules
An ankle radiograph is only recommended if there is any pain in the malleolar areas plus one of the following

    1. Bone tenderness posterior aspect of the distal 6 cm of the tibia
    2. Bone tenderness posterior aspect of the distal 6 cm of the fibula
    3. Inability to bear weight (taking 4 complete steps)

A foot series radiograph is only recommended if there is any pain in the midfoot areas plus one of the following

    1. Bone tenderness of the navicular bone
    2. Bone tenderness at the 5th metatarsal
    3. Inability to bear weight (taking 4 complete steps)

The Ottawa Ankle Rules are used in the adult and pediatric populations.

The Low Risk Ankle Rules
“The Low Risk Ankle Rules states that if a child with an ankle injury has a low-risk examination (i.e., tenderness and swelling isolated to the distal fibula and/or adjacent lateral ligaments distal to the tibial anterior joint line), ankle radiography may not be necessary to further exclude a high-risk ankle injury…”
A high-risk injury includes any fracture of the foot, distal tibia and fibula proximal to the distal physis, tibiofibuar syndemosis injury and ankle dislocations.”
Low risk injuries are managed by supportive splinting and returning to activities as tolerated. Low risk injuries would include avulsion fractures of the distal fibula or lateral talus, and non-displaced Salter-Harris type I and II of the distal fibula and lateral ankle sprains.

Obviously overall clinical judgment must be kept in mind. If there is significant swelling such that the entire area cannot be palpated properly, there is potential neurovascular compromise, the patient’s mental status is compromised, or for some other reason the area cannot be properly evaluated then radiographs should be considered.

Learning Point
A systematic review and meta-analysis of using the Ottawa Ankle rules found the sensitivity to be ~99% and specificity of ~35%. The pediatric age group has a slightly lower sensitivity (97.9%) and lower specificity (21%).
This study supports that if the clinical examination indicates a low risk injury, then radiographs are not indicated. If the examination indicates a potential high risk injury, then the radiographs would be indicated because the clinical examination cannot discern well enough if a fracture is present or not.

Use of the Low Risk Ankle Rule was evaluated in a Canadian study of 3-16 year old children. The study found a decrease in radiographs by 22% using the Low Risk Ankle Rules. Overall the sensitivity was 100% and the specificity was 53.1%.
This study supports that if the examination indicates a low risk injury, then radiographs are not indicated. Fractures that were missed in the low risk group (i.e. false negatives) were low risk fractures that were treated like ankle sprains. If the examination indicated a potential high risk injury, then the radiographs would be indicated because the clinical examination cannot discern well enough if a fracture is present or not.
This group also found cost savings of $37 Canadian dollars per patient.

While most of the studies using these ankle rules are in emergency departments or physician offices some time period after the injury, similar data has been shown for athletic trainers treating acute (<1 hour after injury) ankle injuries.
In this study, which utilized the Ottawa Ankle Rules, it is understandable that the need for radiographs was overestimated (i.e. false positive clinical examination) because of increased pain, guarding and/or unwillingness to bear weight right after the injury. In this study, the sensitivity was 88% but had 0 specificity. The authors point out that negative clinical findings ruled out the need for radiographs and decision making "…based on the totality of the examination findings is the best filter in determining referral for radiographs."

Questions for Further Discussion
1. What are the Ottawa Rules for knees?
2. What other validated clinical decision rules do you use?

Related Cases

    Symptom/Presentation: Pain

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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Ankle Injuries and Disorders and Sprains and Strains.

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.

Boutis K, Grootendorst P, Willan A, et. al.. Effect of the Low Risk Ankle Rule on the frequency of radiography in children with ankle injuries. CMAJ. 2013 Oct 15;185(15):E731-8.

Boutis K, von Keyserlingk C, Willan A, et.al.. Cost Consequence Analysis of Implementing the Low Risk Ankle Rule in Emergency Departments. Ann Emerg Med. 2015 Nov;66(5):455-463.e4.

Browne GJ, Barnett PL. Common sports-related musculoskeletal injuries presenting to the emergency department. J Paediatr Child Health. 2016 Feb;52(2):231-6.

David S, Gray K, Russell JA, Starkey C. Validation of the Ottawa Ankle Rules for Acute Foot and Ankle Injuries. J Sport Rehabil. 2016 Feb;25(1):48-51.

Beckenkamp PR, Lin CC, Macaskill P, Michaleff ZA, Maher CG, Moseley AM. Diagnostic accuracy of the Ottawa Ankle and Midfoot Rules: a systematic review with meta-analysis. Br J Sports Med. 2016 Nov 24. pii: bjsports-2016-096858. doi: 10.1136/bjsports-2016-096858. [Epub ahead of print]

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