Patient Presentation
A 20-month-old male came to clinic for a febrile illness. He started to have a fever 36 hours ago up to 101.8° that responded to antipyretics. He was fussy and not drinking as well. There was some mild rhinorrhea but that had been present off and on as he had 2 older siblings and attended childcare. His mother denied any cough, obvious pain, rash, nausea, emesis, diarrhea or constipation. She said that his urine seemed more concentrated but was not frankly malodorous.

The past medical history revealed a history of grade I vesicoureteral reflux (VUR) that was being monitored by urology and which had improved from grade II that was diagnosed around birth. He was not on prophylactic antibiotics. He had not had any urinary tract infections diagnosed in the past when he had catheterized urine specimens for febrile illnesses. The family history was positive for his older brother with grade III VUR.

The pertinent physical exam showed a happy appearing toddler who was afebrile, had normal vital signs and growth parameters. His examination showed mild rhinorrhea.

The diagnosis of a toddler with likely viral illness was made, but because of the history, urology recommended to continue to perform urinalysis and culture with febrile illnesses. His mother agreed to the urine catheterization saying, “With his brother maybe needing surgery, I would rather do the cath and know if we need to give him antibiotics or do something else.” The laboratory evaluation of the urinalysis showed no signs of urinary tract infection and his culture eventually returned with no growth of pathogens.

Discussion
Vesicoureteral reflux (VUR) occurs when urine ascends from the bladder into the ureter. Primary VUR is the most common congenital anomaly of the urinary tract with an incidence of ~1%. Causes are abnormalities of the anatomic and/or physiological functions of the urinary collecting system. Abnormal reflux can cause serious problems including renal scaring or chronic kidney disease. Secondary VUR usually develops because of increased bladder pressure (e.g. posterior urethral valves, meatal stenosis, neurogenic bladder, etc.) or surgical procedures. VUR can also be transient such as bladder infections or bladder bowel dysfunction.

VUR is most commonly identified after a urinary tract infection (UTI), for follow-up of a previously diagnosed urogenital anomaly or screening of a sibling. UTIs are the most common presentation. Professional consensus recommends that males with first UTI should be evaluated for congenital anomalies of the urinary system and VUR. For females, some will also recommend this for first UTIs especially if there are risk factors for possible congenital anomalies or VUR, and it is recommended for recurrent UTIs. For most ages, males have a higher risk of VUR than females when presenting with a febrile UTI. Evaluation usually is renal ultrasound and may include voiding cystourethrogram (VCUG) or other studies.

Prenatal ultrasound often will identify hydronephrosis. This often resolves by birth or soon afterwards, but may identify continued VUR that needs monitoring or intervention. Resolution is more likely with younger ages (<1 year), lower grade of reflux, and asymptomatic presentation (i.e. prenatal hydronephrosis or sibling with VUR). Resolution for grades I-II are up to 80% but only 30-50% for grades III-IV during follow-up for 4-5 years. As noted, higher grades may not resolve and may require intervention to improve functional drainage and decrease the risk of renal scarring. Renal scarring is more likely in males, after repeated febrile UTIs and higher VUR grade.

VUR is graded based on the reflux into:

• I – non-dilated ureter
• II – non-dilated renal pelvis and calyces
• III – dilated renal pelvis and calyces
• IV – dilated renal pelvis and calyces with moderate ureteral tortuosity and fornices’ blunting
• V – gross dilation of renal pelvis and calyces with severe ureteral tortuosity and loss of papillary impressions

Examples of VUR on VCUG can be found here.

Learning Point
The risk for VUR in a sibling or child of a known VUR patient is high. The European Association of Urology noted that “[s]iblings of children with VUR had a 27.4% (3-51%) risk of also having VUR, whereas the offspring of parents with VUR had a higher incidence of 35.7% (21.2-61.4%).” Another study cites rates of 32% for siblings and 66% for parents. They also cite that “…VUR in siblings revealed that 52% had resolution of reflux after 18 months of followup, with yearly resolution rates of 28%.”

Questions for Further Discussion
1. What are potential complications of acute pyelonephritis? A review can be found here
2. What are causes of gross hematuria? A review can be found here
3. What are the most common organisms causing UTI in neonates, toddlers, school age children and teenagers?

Related Cases

Disease: Viral Infections | Vesicoureteral Reflux | Kidney Diseases

Symptom/Presentation: Fever and Fever of Unknown Origin | Urine

Specialty: Infectious Diseases | Nephrology / Urology

Age: Toddler

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: Ureteral Disorders and Urinary Tract Infections.

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.

Mattoo TK, Mohammad D. Primary Vesicoureteral Reflux and Renal Scarring. Pediatric Clinics of North America. 2022;69(6):1115-1129. doi:10.1016/j.pcl.2022.07.007

Hari P, Meena J, Kumar M, et al. Evidence-based clinical practice guideline for management of urinary tract infection and primary vesicoureteric reflux. Pediatric Nephrology. 2024;39(5):1639-1668. doi:10.1007/s00467-023-06173-9

Update and Summary of the European Association of Urology/European Society of Paediatric Urology Paediatric Guidelines on Vesicoureteral Reflux in Children – ScienceDirect. Accessed October 6, 2025. https://www-sciencedirect-com.proxy.lib.uiowa.edu/science/article/pii/S0302283823032980?ref=pdf_download&fr=RR-9&rr=98a632a73b77accf

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

Patient Presentation
A 13.5 year-old female came to clinic as she and her mother were very concerned about menarche initiation. The past medical history and record reviewed showed at 11 years 4 months she was Tanner II for breast and pubic hair development, and at 12 years 8 months she was Tanner III for both. She had no known chronic health problems and during a private interview she denied any sexual activity.

The family history revealed that her mother had menarche at age 13, and also had no abnormal gynecological or obstetric problems. The patient had a younger sister who was age 10 years. Her father’s pubertal history was unknown. There was a maternal aunt with “early onset” hypothyroidism. The review of systems was negative for pelvic or abnormal pain, large changes in weight, cold/heat intolerance, constipation, headache, visual changes, or galactorrhea. She also denied any abnormal eating patterns or excessive exercise.

The pertinent physical exam showed normal vital signs with her weight and height around the 50%. She had increased her height by approximately 9 cm in the past year. She was Tanner IV for breast and pubic hair. Her external genital examination showed normal structures including an open hymenal ring.

The diagnosis of a healthy female with likely normal progression of puberty was made. She and her mother were quite anxious and wanted testing. Her pregnancy test was negative, and hormonal levels were normal for age/pubertal stage. The patient’s clinical course 3 months later showed some spreading of pubic hair. One month later her mother sent a message to the office that menses had started. By age 15 years 0 months, she had normal menstrual cycling.

Discussion
There is a wide range of normal pubertal development and “normality” is a common question that both patients and families have. Breast budding and testicular enlargement onset can be less obvious but menarche is usually more obvious and therefore families become concerned when menarche doesn’t occur at the time they expect. Delayed puberty is onset of secondary sexual characteristics occurring > 2 standard deviations from the mean for gender, which in females is age 13 for breast development and 14 years for testicular development in males. Pubertal onset range is usually 8-13 years in females and 9-14 years in males.

Primary amenorrhea is “…no period by age 14 years in the absence of growth or development of secondary sexual characteristics, or no period by age 16 regardless of the presence of normal growth and development with the appearance of secondary sex characteristics.” Primary amenorrhea initial evaluation usually includes history, physical examination, along with pregnancy testing, thyroid stimulating hormone, follicle stimulating hormone, and luteinizing hormone testing. Bone age may also be considered especially if constitutional delay is being considered. Pelvic ultrasound to determine if there is a uterus and ovaries or other anatomic abnormalities can also assist in the early evaluation. Karyotyping, testosterone levels, and imaging of the brain/pituitary/hypothalamus may also be needed as part of the evaluation. Consultation with endocrinology and/or gynecology can also be helpful for both clinicians and families.

Learning Point
The differential diagnosis of primary amenorrhea includes:
(Note: percentages do not include delayed puberty and pregnancy)

• Constitutional delay of puberty
• Pregnancy
• Anatomic outflow tract (~20% of causes)
  • Imperforate hymen
  • Mullerian agenesis
  • Transverse vaginal septum
  • Cervical agenesis
  • Androgen insensitivity syndrome
• Ovarian dysfunction (~50% of causes)
  • Chromosomal abnormalities
    • Turner syndrome – very common cause, most common individual cause
      • Fragile X variation
      • Swyer’s syndrome
    • Inflammatory disorders
    • Chemotherapy/radiotherapy
    • Polycystic ovarian syndrome
• Pituitary dysfunction (pituitary and hypothalamic dysfunction ~ 25% of causes)
  • Pituitary tumors
    • Hyperprolactinoma
    • Adenomas
    • Glioma
    • Meningiomas
  • Diabetes insipidus
  • Empty sella syndrome
  • Pituitary infarction
• Hypothalamic dysfunction
  • Functional amenorrhea – very common cause
    • Severe or chronic illness
    • Stress
    • Disordered eating
    • Weight loss such as exercise
  • Kallman syndrome
  • Miscellaneous infiltrative or inflammatory disorders
    • Brain tumor
    • Cranial radiation
    • Syndromes
• Other (~ 5% of causes)
  • Hyperthyroidism
  • Hypothyroidism
  • Diabetes, uncontrolled
  • Androgen use, exogenous
  • Congenital adrenal hyperplasia

Questions for Further Discussion
1. What are causes of secondary amenorrhea? A review can be found here
2. Patients with Turner’s syndrome can have what types of problems? A review can be found here
3. What are potential causes of linear growth delay? A review can be found here

Related Cases

Disease: Primary Amenorrhea | Menstruation

Symptom/Presentation: Amenorrhea

Specialty: General Pediatrics | Endocrinology | Obstetrics / Gynecology

Age: Teenager

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: Menstruation

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.

Heiman DL. Amenorrhea. Primary Care: Clinics in Office Practice. 2009;36(1):1-17. doi:10.1016/j.pop.2008.10.005

Kanabolo D, Rodriguez J, Waggoner D, et al. A Phenotypic Female Adolescent with Primary Amenorrhea and Dysmorphic Features. Pediatr Ann. 2019;48(12):e495-e500. doi:10.3928/19382359-20191118-02

Garg A, Vash-Margita A, Simoni MK. Abnormal Puberty and Amenorrhea: A Review. Pediatr Ann. 2025;54(9):e294-e301. doi:10.3928/19382359-20250707-03

Marsh CA, Grimstad FW. Primary amenorrhea: diagnosis and management. Obstet Gynecol Surv. 2014;69(10):603-612. doi:10.1097/OGX.0000000000000111

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

Patient Presentation
A 17-year-old female came to clinic for her health maintenance visit. She was a senior in high school and was planning on living in the dormitories when she starts college the following year. There were no health concerns. The pertinent physical exam revealed a healthy female with normal vital signs and normal physical examination.

The diagnosis of a healthy female was made. “I recommend that you get the Meningitis B vaccine today. It helps to protect against a meningitis which is a bad brain infection. It can occur in group settings like dorms so we recommend it for college-bound students. You’ll need one now and one again after at least 6 months,” the pediatrician recommended. “Didn’t I already get the meningitis vaccine last year?” she asked. “Right. You did but that is a different vaccine. That one is for meningitis groups A,C, W and Y. Meningitis B is different, and was developed differently, so we do it separately. There is a combination vaccine with all 5 types in it, but I don’t have that one. There’s been some problems with insurances paying for the combination. Your insurance will pay for the separate Meningitis B vaccine. What questions do you have about it or meningitis?” he went on. After discussion with her and her parent, she agreed to all recommended routine health surveillance including HIV screening and all vaccines.

Discussion
Neisseria meningitidis is a major cause of morbidity and mortality including pneumonia, septicemia and meningitis. There are high case fatality and serious life-long complications for those that survive. There are 12 serotypes but A, B, C, W, X and Y cause almost all of the invasive meningococcal disease (IMD). The others are C, H, I, K, L, and Z. The epidemiology of which serotypes cause IMD is different geographically and changes over time. Most IMD cases are in children < 2 years of age, but in some countries there is also a small peak in late adolescence/early adulthood.

Crowded conditions especially when first exposed have a high risk of IMD including first year students in dormitories, military recruits and those exposed for events such as Hajj and Umrah pilgrimages. The Kingdom of Saudi Arabia requires vaccination against A,C,W,Y for these pilgrimages. Some health care providers will also recommend it for other global events such as the Olympics or World Cup Soccer because of crowded conditions. The 73rd World Health Assembly has approved a public health path to defeat meningitis by 2030.

Vaccines against A, C, W, and Y that are mainly used today are polysaccharide-conjugate vaccines.

Learning Point
Meningitis B vaccines “have been difficult to develop due to structural similarities of its capsular polysaccharide with human foetal neural cell adhesions modules, rendering it poorly immunogenic.” There was also the concern for inducing antoimmunity. It has taken more than 40 years to develop these effective vaccines.

In 2013, 4CMenB (Bexsero® from GSK) was approved again serotype B and started being used as part of the routine immunization schedule in the United Kingdom in 2015. It is a 4 component, recombinant, protein-based vaccine. In 2015, it was approved for use in the United states for 10-25 year olds. Since that time more countries are using it and another approved vaccine against serotype B, MenB-FHbp (Trumenba®, from Pfizer). PENMENVY® (from GSK) has serotypes A,B,C,W,Y antigens and was approved in February 2025 in the US.

The vaccines have been very effective including >80% effectiveness in infancy and protection lasting up to 3 years. They have been shown to be potentially effective against other serotypes, and in some studies to also be effective against nasal carriage. Protection is thought to be longer lasting in people > 5 years who receive the vaccine than those < 5 year olds. There is some data supporting additional protection against Neisseria gonorrhea as both organisms share some antigens.

Questions for Further Discussion
1. What meningococcal meningitis vaccines to you recommend and have available in your practice?
2. Where can you find vaccine schedules for other countries?
3. What are the different cerebrospinal fluid findings in different causes of meningitis? A review can be found here.
4. What causes encephalitis? A review can be found here.

Related Cases

Disease: Meningitis | Childhood Immunization

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: Infectious Diseases | Preventive Medicine and Health Maintenance

Age: Teenager

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: Meningitis and Vaccine.

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.

Rappuoli R, Pizza M, Masignani V, Vadivelu K. Meningococcal B vaccine (4CMenB): the journey from research to real world experience. Expert Review of Vaccines. 2018;17(12):1111-1121. doi:10.1080/14760584.2018.1547637

Garland JM. An Update on Meningococcal Vaccination. Rhode Island Medical Journal. Published online 2020.

Isitt C, Cosgrove CA, Ramsey ME, Ladhani SN, Success of 4CMenB in preventing meningococcal disease: evidence from real-world experience. Arch Dis Child 2020:105; 784-790.

Parikh SR, Campbell H, Bettinger JA, et al. The everchanging epidemiology of meningococcal disease worldwide and the potential for prevention through vaccination. Journal of Infection. 2020;81(4):483-498. doi:10.1016/j.jinf.2020.05.079

Meningitis. Accessed September 23, 2025. https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/meningitis

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

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