What Other Abnormalities are Associated with Prune Belly Syndrome?

Patient Presentation
A general pediatrician on-call for a regional children’s hospital received a telephone call from a physician in a distant emergency room.
The physician said, “Do you know this 5 month old boy with Eagle-Barrett syndrome?
Well today he has a fever to 103° Celsius, and has been having some emesis.
I’ve already done his laboratory work and his urine has too numerous to count white blood cells, some red blood cells and bacteria on the gram stain.
He also has a total white blood cell count of 18,500 with a 72% left shift and his CRP is 4.5. Looks like he has pyelonephritis again.
I’ve already done his blood and urine cultures and given him some ceftriaxone.
I’d like to transfer him to your institution because you usually care for him there.”While the emergency room physician was talking, the pediatrician was trying to remember what Eagle-Barrett syndrome was.
When the pediatrician asked, the emergency room physician replied, “Oh, it’s Prune Belly syndrome that’s why you guys take care of him.”The general pediatrician suddenly realized the significance of all the other information that the emergency room physician had given him, and also that he was not the appropriate pediatrician to be contacted at the children’s hospital.
After asking a couple more questions about the patient’s status and treatment and arranging the transportation to the children’s hospital,
the pediatrician told the emergency room physician, “I’m not a nephrologist and these children are usually taken care of by them. I am going to contact the nephrologist and if he has any other questions or suggestions for treatment he will call you back directly.
The child most likely will be going to the nephrology service but we will work that problem out here.
If you have any other questions, you can call me back or can call the nephrologist.”After finishing, the general pediatrician contacted the nephrologist who agreed that the diagnosis of pyelonephritis was logical and that the patient was being appropriately treated.
He also agreed to admit the child onto the nephrology service.
The patient’s clinical course showed that he had Pseudomonas pyelonephritis that was treated successfully with ciprofloxacin.

Discussion
Prune Belly syndrome is characterized by various anatomical urinary tract anomalies, cryptorchism and deficiency of abdominal wall musculature. It has a characteristic distended abdomen with wrinkled skin which gives rise to the name.
This syndrome was first described in 1839 by Frohlich. In 1950 Eagle and Barrett described 9 cases and later other physicians suggested Eagle-Barrett syndrome as an alternative eponym.

The incidence is approximately 1:40,000 live births. Females can have an incomplete form of the syndrome but obviously cannot have cryptorchism. They may have other genital abnormalities such as vaginal agenesis, hydrocolpos, and bicornuate uterus.
The severity varies from lethality in utero, to children with abnormal musculature and undescended testes but with normal renal function.
Patients may be identified in utero because of screening ultrasounds or because of uterine measurements being small for dates secondary to decreased urine production.
In the neonatal period, the infants usually present with the characteristic shriveled abdominal skin.
Urological abnormalities include:

  • Cryptorchidism – testes usually at the level of the iliac vessels.
  • Urethra – anterior is usually normal, posterior is often dilated. Some have posterior urethral valves.
  • Prostate is absent or hypoplastic
  • Epididymis, vas deferens and seminal vesicles are often abnormal and contribute to infertility
  • Bladder is smooth walled, may be dilated, have diverticula or patent urachus,
  • Urachus is patent
  • Ureters are often are dilated, elongated and tortuous with little or no peristalsis. Vesicoureteral reflux is found in 70% of patients.
  • Kidneys may be dyplastic or have multicystic dysplastic kidney disease. Amount of renal parenchymal disease determines ultimate renal function

The treatment is a combination of medical and surgical interventions.
Surgery may include a variety of urinary diversion and reconstructive surgeries to improve urinary stasis and prevent infections. Early orchiopexy is indicated.
Abdominoplasty may also be indicated.
Medical treatment includes monitoring and treatment of renal insufficiency as well as prophylactic antibiotics to decrease infections.

Learning Point
Other associated abnormalities for patients with Prune Belly syndrome include:

  • Anorectal abnormalities – atrial septal defect, Tetrology of Fallot, ventriculoseptal defect
  • Cardiac abnormalities
  • Gastrointestinal abnormalities
    • Constipation – because of poor abdominal musculature
    • Hirschsprung disease
    • Imperforate anus
    • Malrotation and volvulus
    • Omphalocoele and gastroschisis
    • Stenosis and atresia
  • Motor developmental delay – because of poor abdominal musculature poorly assisting movement and balance
  • Orthopaedic abnormalities
    • Developmental hip dislocation
    • Congenital verticle talus
    • Pectus excavatum
    • Sacral Agenesis
    • Scoliosis
  • Respiratory problems
    • Pulmonary hypoplasia and neonatal problems such as respiratory distress syndrome
    • Respiratory infections – because of poor abdominal musculature

Questions for Further Discussion
1. What are the indications and preferred type of dialysis in patients with Prune Belly syndrome?
2. In general, what are the indications for kidney transplant?
3. How are misdirected telephone communications handled at your own institution and how could they be improved?
4. What are good resources for looking up medical eponyms?

Related Cases

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

Information prescriptions for patients can be found at MedlinePlus for these topics: Birth Defects and Kidney Diseases.

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

To view images related to this topic check Google Images.

Jennings RW.
Prune belly syndrome.
Semin Pediatr Surg. 2000 Aug;9(3):115-20.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1737-38.

Mahajan JK, Ojha S, Rao KL.
Prune-belly syndrome with anorectal malformation.
Eur J Pediatr Surg. 2004 Oct;14(5):351-4.

Abdominal Muscles, Absence of, with Urinary Tract Abnormality and Cryptorchidism. Online Mendelian Inheritance in Man.
Available from the Internet at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=100100 Page(rev. 9/7/2007, cited 8/11/08)

Franco I. Prune Belly Syndrome. eMedicine.
Available from the Internet at http://www.emedicine.com/med/TOPIC3055.HTM (rev. 1/18/2008, cited 8/13/08).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Interpersonal and Communication Skills

    18. Using effective nonverbal, explanatory, questioning, and writing skills, the healthcare professional uses effective listening skills and elicits and provides information.
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Professionalism
    20. Respect, compassion, and integrity; a responsiveness to the needs of patients and society that supercedes self-interest; accountability to patients, society, and the profession; and a commitment to excellence and on-going professional development are demonstrated.
    22. Sensitivity and responsiveness to patients’ culture, age, gender, and disabilities are demonstrated.

  • Systems Based Practice
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

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

    Date
    September 8, 2008

  • What Types of Foods Should Vegetarians Eat to Maintain Proper Nutrition?

    Patient Presentation
    A 16-year-old female came to clinic for health supervision.
    During the interview she said that over the past few months she had decided to become vegetarian.
    When further questioned, she said she initially stopped eating meat, fish and poultry and was eating eggs and dairy products, but recently she has stopped eating those also.
    She said that she is drinking soymilk, using some tofu, and “throwing some nuts on my salad.”She was not eating any other soy products and used few nut products or oils. She had been eating a fairly restricted diet of lots of “stir fried vegetables,” salads and bread.
    She said she didn’t do any reading about vegetarian diets or really plans any of her meals; she just eats what is available.
    She denied trying to lose weight, purging, increasing her exercise or being unhappy with her body image.
    Her motivation for beginning her vegetarian diet was that she thought that it would be healthier.
    The past medical history and social history revealed a healthy female living in an omnivore family.
    The pertinent physical exam showed a healthy appearing female. Her growth percentiles were in the 25-90%. She had maintained her weight over the past year and was Tanner stage IV for pubertal development.
    The diagnosis of a teenager who had begun a vegetarian diet without adequate nutritional information was made.
    As she also needed screening blood tests, laboratory evaluation included a complete blood count, B12 level, and fasting cholesterol and triglycerides.
    These were eventually normal with the exception of a hemoglobin of 12.2 mg/dl and hematocrit of 35%.
    She was counseled about the risks of poor nutrition and was interested in learning about different options to increase the variety of foods she ate and how to prepare them. A dietician appointment was arranged.
    She also willingly agreed to take a daily multivitamin with extra iron and was to follow up in 2-3 months.

    Discussion
    Vegetarians have a diet pattern that emphasizes consuming plant foods (i.e. vegetables, grains and nuts) and avoiding flesh food (i.e. red meat, poultry, fish).
    Some vegetarians include milk and egg products in their diets and would be more accurately described as lacto-ova-vegetarians.
    Vegans are vegetarians who avoid all animal products including foods such as dairy products, eggs, butter, honey and gelatin.

    What constitutes being a vegetarian to one person, may have a different meaning for another person. In a national study, 2.5% of the participants (aged > 6 years of age) considered themselves to be vegetarian.
    When 24-hour diet records were examined, only 0.9% of the participants did not eat red meat, poultry or fish.

    Infants, children and adolescents with well-planned vegetarian and vegan diets grow and develop normally.
    For adults, there is data to support a decreased risk of some types of cancer, diabetes, coronary artery disease, hypertension and obesity.
    Besides these advantages, some people choose vegetarian and vegan diets for economic, environmental and religious reasons.

    In general, infants should be breast feed for up to one year if possible.
    Soy formulas are available and are recommended for vegetarian and vegan infants who are not breastfeeding.
    Commercial soymilk should not be started until after one year of age because of the low bioavailability of iron and zinc in soy. Some commercial soymilk may not be fortified with Vitamin D and calcium and therefore labels need to be checked.
    Parents and other caretakers need to be careful with choking hazards such as nuts and raw vegetables.
    If growth is a concern, supplementing avocado, nut or seed butters, tofu, and vegetables oils can increase calories.
    Sometimes a restrictive vegetarian diet can be masking an underlying eating disorder.

    Learning Point
    Primary nutrients to be concerned about for vegetarians and vegans are noted below along with examples of foods that are high in these nutrients.
    Soy products includes items such as tofu and tempeh, soybean oil, soymilk, soy cheese, soy yogurt, etc.

    • B12 (cobalamin) – breads, cereals, dairy products, eggs, fortified soy products, nutritional yeast, and supplements.
      It is important to have adequate sources of B12 particularly if a vegan.

    • Calcium – brocoli, collard greens, dairy foods, figs, kale, black strap molasses, sesame seeds, and fortified soy products.
    • Iron – bulgur wheat, dried beans, dried fruits, fortified cereals and grains, and fortified soy products.
      Adding a Vitamin C source when eating a plant food for iron increases its absorption (i.e. orange, strawberries, tomatoes).

    • Omega-3 Fatty Acids – canola oil, ground flaxseed, flaxseed oil, soy products, walnuts, walnut oil, and sea vegetables.
    • Protein – dairy products, eggs, grains, legumes, seitan (a wheat product), and soy products.
      Because of the low absorbability of amino acids found in plant sources a higher intake of protein may be necessary

    • Vitamin D – dairy products, fortified soy products, sunlight.
    • Zinc – cereals, whole grain, legumes, miso (made from soybean, wheat or barley), soy products, wheat germ, and yeast.

    Questions for Further Discussion
    1. What vegetarian meals options are available for children in the local school district?
    2. Where in the local community can patients and families get nutritional information, particularly for vegetarians?

    Related Cases

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

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

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

    To view images related to this topic check Google Images.

    Mangels AR, Messina V.
    Considerations in planning vegan diets: infants.
    J Am Diet Assoc. 2001;101(6):670-7.

    Messina V, Mangels AR.
    Considerations in planning vegan diets: children.
    J Am Diet Assoc. 2001;101(6):661-9.

    Haddad EH, Tanzman JS.
    What do vegetarians in the United States eat?
    Am J Clin Nutr. 2003 Sep;78:626S-632S.

    Dunham L, Kollar LM.
    Vegetarian eating for children and adolescents.
    J Pediatr Health Care. 2006;20(1):27-34.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Professionalism

    22. Sensitivity and responsiveness to patients’ culture, age, gender, and disabilities are demonstrated.

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

    Date
    September 2, 2008

  • How Do You Treat Invasive Salmonella Infections?

    Patient Presentation
    A 16-year-old female came to the emergency room with a 36 hour history of diarrhea and emesis.
    She had been on a school trip in Europe and during the day she was leaving to return to the United States had 2 bouts of diarrhea, one of which was accompanied by emesis.
    During the flight back, she had more diarrhea and emesis. She then had to drive home 4 hours.
    At home she was taken to the emergency room where she was given intravenous fluids for dehydration.
    As she was being discharged she began to have a fever so she was admitted for further evaluation.
    Additional history revealed that the diarrhea did not contain blood or mucous and was described as watery. The emesis occurred usually around the time of the diarrhea.
    She could not remember how many episodes she had had, but did state that she had not eaten or drunk anything since being in Europe.
    She complained of crampy abdominal pain around the episodes, and nausea inbetween them.
    The past medical history and family history were non-contributory.
    The review of systems was negative for fever, chills, cough, upper respiratory symptoms, dysuria, or rashes.
    The social history revealed that she had traveled to several countries, had swum in a lake, and had eaten mainly eggs, rice and vegetables as she was a vegetarian.
    Several other students on the trip had been ill with diarrhea of short duration 3 days before her symptoms began.
    The pertinent physical exam at admission showed a tired, ill-appearing female with a temperature of 38.5 degrees Celsius.
    She had mild left lower quadrant tenderness with deep palpation without guarding. The rest of the examination was negative.
    The work-up was begun and included an abdominal radiograph and laboratory testing.
    Over the next 2-3 hours as the testing was being completed, her temperature increased to 40.3 degrees Celsius and she complained of neck and back pain.
    On repeat physical examination, she had a non-specific confluent red flat rash over her neck and upper shoulders. She complained of pain with flexion of her neck and legs at the hips.
    She had no abdominal tenderness at that time.
    The patient was begun on ceftriaxone intravenously and a lumbar puncture was performed which had a normal glucose, protein and cell count.
    As this was occurring her previous testing became available and showed hemoglobin of 13.2 g/dl, hematocrit of 37%, white blood cell count of 9.0 x 1000/mm2 with 900 neutrophils, 4140 bands, 1700 lymphocytes and 180 reactive lymphocytes.
    The C-reactive protein was 28.2 mg/dl and the erythrocyte sedimentation rate was 27 mm/hour.
    She continued to be febrile from 38-39.5 degrees Celsius over the next 10-12 hours, but her rash disappeared as did her neck and back pain.
    At this time, she became afebrile but began to complain of left lower quadrant pain again that now radiated to her umbilicus.
    The radiologic evaluation of an abdominal CT showed a non-inflamed appendix but with an appendicolith, a small amount of fluid in the pelvis and thickened bowel walls.
    Surgical consultation was obtained who took the adolescent to the operating room for an elective appendectomy due to the presence of the appendicolith and exploration.
    The appendix was normal with no abscess or perforation but the surgeons noted that the patient had an extremely inflamed colon.
    The patient continued to clinically improve on the ceftriaxone without fever, with 3-4 episodes of non-bloody, non-mucous diarrhea per day. On day 3, as she was being readied for discharge on home ceftriaxone, she began to have bloody diarrhea.
    Her initial stool culture was also now growing Salmonella, which was subsequently identified as Salmonella enteritidis confirming the diagnosis of enteric fever.
    She received a total of 10 days of ceftriaxone and at followup her diarrhea had resolved. Repeat stool cultures were negative.
    The airline, state public health department and the U.S. Centers for Disease Control were also contacted at various points during her illness to provide appropriate information to protect the public’s health.


    Figure 66 – Axial computed tomography image of the lower
    abdomen obtained with intravenous, oral, and rectal contrast reveals
    the cecum to be filled with liquid stool, a small appendicolith in
    the appendix medial to the cecum without evidence of appendicitis and
    mild thickening of the wall of the descending colon consistent with
    colitis.

    Discussion
    Salmonella is a highly contagious organism causing an estimated 17 million cases of typhoid fever and 600,000 deaths yearly worldwide.
    It causes a spectrum of illness. Most commonly it causes gastroenteritis with diarrhea, abdominal cramps and fever.
    Bacteremia may be intermittent or continuous
    Focal infections such as meningitis or osteomyelitis occur in up to 10% of patients with bacteremia.

    Enteric fever is caused by Salmonella typhi and other Salmonella serotypes when there is a protracted bacterial illness.
    It may begin gradually with constitutional symptoms (i.e. anorexia, headache, lethargy and malaise), fever, abdominal tenderness and pain, hepatosplenomegaly, and mental status changes. Diarrhea is common and may or may not be bloody.

    The transmission is mainly through food such as poultry, beef eggs and dairy products. Other food contaminated from humans may also transmit Salmonella such as vegetables, fruits and bakery products.
    Other transmission routes include contaminated water and contact with amphibians and reptiles.
    The incubation period for gastroenteritis is shorter usually 12-36 hours with a range of 6 -72 hours. The incubation period for enteric fever is longer; usual period is 7-14 days with a range of 3-60 days.

    Salmonella has more than 2,640 serotypes. Human disease causing organisms are classified according to their O-antigen group (A-E).
    In the US about 50% of all Salmonella is caused by Salmonella typhimurium (B), Salmonella enteritidis (D) and Salmonella Newport (E).
    Salmonella typhi is a D serotype.

    A carrier state is not uncommon with 45% of children < 5 years old and 5% of older children and adults being still excreting organisms in their stool 12 weeks later.
    At one year, 1% of patients still excrete organisms.
    Unfortunately instead of eliminating carriage, antibiotics tend to increase the carrier state. Enteric fever patients (~15%) may relapse requiring re-treatment.

    Learning Point
    Patients with localized invasive disease are initially treated with an expanded-spectrum cephalosporin such as cefotaxime or ceftriaxone. Once susceptibility results become available, ampicillin, ceftriaxone or cefotaxime for susceptible strains lasting at least 4 weeks in duration is recommended.
    This should be increased to 6 weeks for meningitis. Localized disease means patients with abscess, meningitis, osteomyelitis, or patients with HIV and bacteremia.

    For patients with invasive, nonfocal infections (e.g. bacteremia or enteric fever) the administration route, drug choice, and duration are based on the strain susceptibility, clinical response, host and site of infection.
    A minimum 10-14 days of antibiotics is recommended. Salmonella typhi can be multidrug-resistant, and empiric treatment with an expanded-spectrum cephalosporin, azithromycin or fluoroquinolone may be necessary.

    Chronic carriage of Salmonella typhi in children may be treated with high-dose parenteral ampicillin or high-dose oral amoxicillin with probenecid. Ciprofloxacin is recommended for adults.
    Cholecystectomy is sometimes indicated for adult patients where gallstones contribute to the carrier state.

    Questions for Further Discussion
    1. What are the indications for corticosteroid use in patients with Salmonella?
    2. What are the indications for typhoid vaccine use?
    3. What commonly prescribed travel medication needs to be administered after oral typhoid vaccine because of potential interactions?
    4. What percentage of patients with Salmonella get enteric fever?

    Related Cases

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

    Information prescriptions for patients can be found at MedlinePlus for these topics: Salmonella Infections and Food Contamination and Poisoning.

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

    To view images related to ther topic check Google Images.

    Graham SM.
    Salmonellosis in children in developing and developed countries and populations.
    Curr Opin Infect Dis. 2002 Oct;15(5):507-12.

    American Academy of Pediatrics. Salmonella, In Pickering LD, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2006;579-584.

    Linam WM, Gerber MA.
    Changing epidemiology and prevention of Salmonella infections.
    Pediatr Infect Dis J. 2007 Aug;26(8):7.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Interpersonal and Communication Skills

    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

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

    Date
    August 25, 2008

  • How Common is RhD Isoimmunization?

    Patient Presentation
    A 1-month-old female came to clinic for her follow-up evaluation.
    She was known to have RhD isoimmunization that had required one blood transfusion and phototherapy for 5 days after birth at 38 weeks gestation.
    She was seen at 10 days of age, was breastfeeding well, and was past her birth weight.
    Her mother reported that she was sleepier than her other two children. The infant cried and easily awoke to feed, fed well for 20-30 minutes and then generally fell back to sleep.
    She had no problems sucking, stopping to feed, sweating or color changes during feeding. Her mother also denied any bruising, bleeding or edema.
    She also had been urinating and stooling well and her mother reported that the jaundice seems to slowly be fading away.
    The family history was positive for the patient’s mother becoming Rh sensitized with her first pregnancy. Her second child did not require intrauterine or post-natal transfusions, but did require prolong phototherapy.
    The review of systems was otherwise normal.
    The pertinent physical exam showed a sleeping infant who appeared somewhat pale and slightly yellow on her skin and sclera. Her vital signs were normal with a heart rate of 145 beats/minute. Her weight was 3.92 kg (25-50%) and she had been gaining 32 grams/day.
    The cardiac examination showed a regular rate and rhythm with no murmur. The abdominal examination showed no hepatomegaly or masses.
    The laboratory evaluation showed a total and direct bilirubin of 8.9/0.3 mg/dl. Her complete blood count showed a hemoglobin of 7.4 mg/dl, hematocrit of 23%, platelets of 434 x 1000/mm2 and a reticulocyte count of 28%.
    The diagnosis of anemia and jaundice secondary to RhD isoimmunization was made.
    The physician contacted the hematologist who had seen the infant just after birth.
    The hematologist was comfortable continuing to monitor the patient as an outpatient as the infant did not have any signs or symptoms of end organ failure and had an expected reticulocyte response.
    The hematologist did note the sleepiness but felt that this could still be followed as an outpatient.
    The infant was to return to the clinic in one week for re-evaluation and sooner if her mother noted any difficulty eating, skin color changes, or any other concerns.

    Discussion
    RhD isoimmunization luckily has decreased in incidence since the introduction of RhD immunoglobulin (RhIg) in 1968.
    There are 3 major rhesus antigens on red blood cells. The D antigen determines if a person has a positive or negative blood grouping.
    An RhD-negative woman is at risk of developing RhD isoimmunization when exposed to RhD-positive antigens from her RhD-positive fetus through fetal-maternal hemorrhage.
    Usually her initial antibody response is mainly composed of IgM which is a large molecule and cannot cross the placenta.
    But after this IgG is produced which can cross the placenta. A subsequent exposure to RhD-positive blood cells such as with a second pregnancy, produces a rapid and proliferative IgG response.
    The infant’s RhD-positive blood cells can then be attacked by the IgG causing fetal anemia, erythroblastosis fetalis and possibly intrauterine fetal death.

    Prophylactic RhIg can be given to women which binds to the infant’s red blood cells in the maternal circulation. This blocks the RhD-positive antigen on the infants red blood cells and the mother does not make an antibody reponse to the foreign RhD-positive antigen.
    If the mother does become sensitized at some point, she needs to be followed closely during any subsequent pregnancy. The fetus may need intrauterine transfusions.

    Neonates affected by RhD isoimmunization may need immediate blood transfusions after birth because of anemia. They are also at risk for severe jaundice.
    Both the anemia and jaundice may require exchange transfusion. Some neonates require later blood transfusions in the first few months of life and therefore need to be followed closely.

    Learning Point
    Without prophylatic RhIg, there is a 16% chance that an RhD-negative woman giving birth to an RhD-postive+ infant will become RhD isoimmunized.

    In 1991, the Centers for Disease Control estimated that the incidence of RhD hemolytic disease was 10.6 per 10,000 total births.
    This corresponds to ~4000 affected infants. In contrast, in 1970 two years after RhIg was licensed, the incidece was 45.1 per 10,000 total births.

    Although there has been a substantial decrease in RhD hemolytic disease over the past 40 years, other red cell antigens continue to cause isoimmunization for some women for which there is no current prophylactic treament available.
    For example, frequencies for all women with a positive antibody screen in a New York tertiary care health center were 18.4% for anti-D and 22% for anti-Kell.

    Questions for Further Discussion
    1. What are the indications for red cell blood transfusions?
    2. At what age is the physiological red blood cell nadir? How would this change if the infant was premature, or had intrauterine or neonatal blood transfusions?
    3. What are the current guidelines for adminstration with RhIg of a reproductive age female who has experienced a spontaneous abortion, threatened abortion, elective termination, or ectopic pregnancy?

    Related Cases

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

    Information prescriptions for patients can be found at MedlinePlus for these topics: High Risk Pregnancy and Blood and Blood Disorders.

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

    To view images related to this topic check Google Images.

    Geifman-Holtzman O, Wojtowycz M, Kosmas E, Artal R. Female alloimmunization with anti-
    bodies known to cause hemolytic disease. Obstet Gynecol 1997;89:272-5.

    Harkness UF, Spinnato JA.
    Prevention and management of RhD isoimmunization.
    Clin Perinatol. 2004 Dec;31(4):721-42, vi.

    De Boer IP, Zeestraten EC, Lopriore E, van Kamp IL, Kanhai HH, Walther FJ.
    Pediatric outcome in Rhesus hemolytic disease treated with and without intrauterine transfusion.
    Am J Obstet Gynecol. 2008 Jan;198(1):54.e1-4.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement

    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills

    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice

    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.

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

    Date
    August 11, 2008