P

Pneumococcal Conjugate Immunization

http://www.cdc.gov/vaccines/hcp/vis/vis-statements/pcv13.html

Polio Immunization

http://www.cdc.gov/vaccines/hcp/vis/vis-statements/ipv.html

Premature Thelarche

What is premature thelarche?
What causes premature thelarche?
Who gets premature thelarche?
How does premature thelarche cause disease?
What are the common findings?
How is premature thelarche diagnosed?
How is premature thelarche treated?
What are the complications?
How is premature thelarche prevented?

Michael S. Kappy, M.D., Ph.D. Chief, Pediatric Endocrinology, The Children’s Hospital Denver, Colorado

What is premature thelarche?
Thelarche means “the beginning of breast development.” Therefore, if a girl begins to show breast enlargement at an early age (anywhere from birth to six years), it is called “premature thelarche.”
Technically, most cases of early breast enlargement are harmless, and do not progress significantly. They are not the beginning of (continued) breast development. They also are not usually associated with the development of the other physical signs of puberty, e.g., acne, pubic hair, periods, or rapid growth. Therefore, a better term for this condition is infantile, or early, “gynecomastia,” which only signifies that one or both breasts are enlarged.

What causes premature thelarche?
Studies of girls with early breast enlargement have not shown elevated blood levels of estrogen or any other abnormality. Occasionally, an ovarian cyst (or cysts) may be seen on a pelvic ultrasound, but this condition also may occur in girls without breast enlargement; therefore, it is not clear if the cyst(s) are secreting enough estrogen to cause the breast enlargement. Some physicians believe that the girls are just temporarily more sensitive to their normal blood levels of estrogen.

Who gets premature thelarche?
There is not one identifiable group of girls who develops early breast enlargement. However, it is a concern if a male infant or a young boy shows breast enlargement.

How does premature thelarche cause disease?
Premature thelarche is not a disease; instead, it is a normal finding in some young girls or female infants. If there are other signs of puberty, then a physician should evaluate the child for the causes of early puberty.

What are the common findings?
The common finding is the enlargement of one or both breasts. In simple premature thelarche, there are no other signs of pubertal development, and the child is growing at a normal-not an increased-rate.

How is premature thelarche diagnosed?
Most commonly, premature thelarche is diagnosed in a female infant or a girl up to three years of age. Occasionally, a girl from three to six years of age will show an enlargement of one or both breasts. However, after age six, the beginning of breast development is actually the beginning of puberty; however, it is a very slow form of development. In addition, girls with early breast development usually do not have early periods.
Typically, the girl has no other signs of puberty, and is growing at a normal, pre-pubertal growth rate, i.e., about two inches a year. Laboratory studies are not usually helpful, since they show low (pre-pubertal) concentrations of estrogen or other hormones that stimulate pubertal development. An x-ray of the hand shows a picture that is normal for the girl’s age, and not that of an older girl.

How is premature thelarche treated?
Treatment for early breast development is not necessary; however, the physician and the parents may want to monitor any changes in the girl’s breast size.

What are the complications?
Usually, there are no complications associated with early breast development. Since there is a very small chance that the girl is actually starting puberty, it is recommended that both the physician and the parents monitor her.

How is premature thelarche prevented?
Premature Thelarche cannot be prevented. Parents should be sensitive to their children’s concerns and encourage communication so as to alleviate anxiety or fears.

References
Kappy MS, Ganong CS. Advances in the treatment of precocious puberty. Adv Pediatr 1994;41:223-61.
About the Author
Dr. Kappy is a professor of pediatrics at the University of Colorado Health Sciences Center and the Chief of the Pediatric Endocrinology Department at The Children’s Hospital in Denver, Colorado.
He was a recipient of the Johns Hopkins University Distinguished Alumnus Award in 1996. His research interest include the treatment of precocious puberty and the effects of growth hormone in growth hormone-deficient individuals.
Copyright 2012 Michael S. Kappy, M.D., Ph.D., All Rights Reserved

Prematurity

What is prematurity?
What is important to know prior to the birth of a premature infant?
What is the chance of survival for a premature infant?
What is the delivery room management of the premature infant?
What problems can be expected in the nursery?
What needs to happen for my baby to go home?
What is the outcome for survivors of the intensive care nursery?

by Adam A. Rosenberg, M.D. Director of Newborn Services at University Hospital Professor of Pediatrics at the University of Colorado School of Medicine Denver, Colorado

What is prematurity?
Any infant born at less than 37 weeks gestation is by definition “premature.” Most infants born at 35 to 37 weeks gestation are relatively healthy, and they often have only brief hospital stays in normal newborn nurseries. The problems associated with premature infants occur with greater frequency in those of lower gestational age at birth, typically less than 35 weeks gestation.

What is important to know prior to the birth of a premature infant?
Some treatments may be used in mothers who are at risk of having their baby early. Anyone who has had a previous preterm infant is at a “high risk” of having another preterm infant. Therefore, prenatal care should be sought with a caregiver who is up to date and comfortable with the management of a mother who is at risk for a preterm delivery.
When a mother is in preterm labor, she should be admitted to the hospital and placed on drugs to slow the progress of labor. Although these drugs will not delay delivery for very long in many cases, they often allow enough time to receive a full course of steroids (betamethasone or dexamethasone) to accelerate the maturation of the fetus. Steroids have been shown to decrease the rate of death of preterm infants, as well as decrease the rate of lung, intestinal, and brain complications.
When there is a risk of delivering a baby early, it is appropriate to ask if the nursery at the hospital is able to take care of a preterm baby. If not-if it is safe for the mother and fetus-they should be transferred to a facility that is capable of caring for the baby after birth. In addition, an expectant mother should talk with the hospital staff members who will care for the baby after birth. Issues to discuss include a review of the problems associated with prematurity, chances of survival, and the anticipated long-term outcome.

What is the chance of survival for a premature infant?
The survival of premature infants is determined by gestational age at delivery and birth weight. Infants born after 28 weeks gestation and 1,000 grams, or 3 pounds 3 ounces (454 grams equals 1 pound), have more than a 90% chance of survival. The rate of survival at 27 weeks and 900 grams is 80% to 85%, at 26 weeks and 800 grams is 75% to 80%, and at 25 weeks and 700 grams is 60%. Rates of survival drop off rapidly at less than 25 weeks, and they vary quite a bit among different nurseries.
The long-term outcome also is dependent on gestational age and birth weight. For babies of 26 to 32 weeks gestation, the rate of severe neurodevelopmental problems among survivors is about 10%; at 23 to 26 weeks, the rate increases gradually to 25% of survivors. Other long-term complications, including lung problems, vision disturbances, and hearing loss, are more common in babies of lower gestational age at birth.

What is the delivery room management of the premature infant?
Staff members who are experienced in the management of premature infants should be present in the delivery room. The infant must be kept warm; provided with adequate oxygen; and helped with breathing, if necessary. Most infants who weigh less than 1,000 grams at birth will require a breathing tube in their airway.

What problems can be expected in the nursery?
Thermoregulation
Preterm infants are not able to maintain their body temperature without an external heat source. Initially, heat will be provided with an overhead warmer that responds to the baby’s temperature and provides adequate warmth to maintain a normal body temperature. The warmer provides easy access to the baby for necessary cares during the early, “unstable” period. When more stable, the baby will be moved into an incubator to maintain a warm environment. Most infants are able to move into an open crib at a weight of approximately 1,800 grams.
Nutrition
Initially, premature infants are given all the necessary fluid, calories, protein, sugar, and fat in their veins. When their condition stabilizes, a feeding tube into their stomachs can start. The amount of feeds starts at a very low level, and it is advanced slowly over 3 to 7 days to “full” feeds. At this point, the infant no longer needs fluids or nutrition into their veins. Once full feeds are achieved, anticipated rates of weight gain are 10 to 25 grams per day. Breast milk is the food of choice, but formulas developed for preterm infants are an acceptable substitute. A baby will be able to begin “nipple” feeding from a bottle at about 33 to 34 weeks post conception.
Monitoring
All babies in intensive care nurseries have their heart rates, breathing, and, in some cases, blood pressure monitored continuously. Blood oxygen also can be monitored with a pulse oximeter in infants with lung and heart problems. A pulse oximeter uses a light source, wrapped around the infant’s foot or hand, to measure the amount of oxygen carried by the hemoglobin in the red blood cells. At the start, a sick baby will usually have an indwelling tube in an artery (usually the umbilical artery in the cord that was connected to the placenta in the uterus) to sample blood for tests without having to draw blood from the infant. A tube also may be placed in the umbilical vein to give fluids and nutrition. These tubes are usually kept in the infant for 3 to 10 days depending on how sick they are.
Lung problems
Hyaline membrane disease (HMD) or respiratory distress syndrome (RDS). By 24 weeks gestation, there is adequate surface for gas exchange (bringing oxygen to the blood and removing carbon dioxide) in the lung; however, a necessary element for survival is missing. The natural tendency of a lung is to collapse when a person breathes out. Once collapsed, it is very difficult to reopen the lung. A chemical called surfactant is produced in the lungs to lower surface tension as the lungs get smaller during exhalation. This chemical prevents a total collapse of the lungs and allows easy re-expansion with inhalation.
Preterm babies have little or no surfactant in their lungs, and they would die from respiratory failure without intervention. The frequency of surfactant deficiency ranges from nearly 100% at 24 weeks gestation, to 60% at 28 weeks and 25% at 32 weeks. To treat this condition, babies are given surfactant substitutes through their breathing tubes into the lungs and to help them breathe with breathing machines called ventilators. Depending on their gestation at birth, premature infants will remain on the ventilator from a few days to up to about 6 weeks.
When babies are ready to come off the ventilator, they are “extubated” (removal of the breathing tube) to either nasal CPAP (provides low pressure through a device placed in the nose to help keep the lungs expanded) or to a bubble with extra oxygen placed over the head. Ultimately, supplemental oxygen can be delivered with a small hose under the nose called a nasal cannula.
Apnea and bradycardia (A&B spells). At the time of birth, preterm infants have an immature respiratory drive. This results in spells when they “forget” to breathe (apnea). If these spells are long enough, they result in a decrease in blood oxygen and then a slowing of the heart rate (bradycardia). Sometimes, these episodes resolve themselves, while, in other cases, the infants need to be stimulated to restart breathing. If the spells are bad enough or occur with a frequency of more than 6 to 10 times per day, they can be treated medically with caffeine (like in coffee) citrate.
In most infants, this is successful; however, if this treatment fails, it is sometimes necessary to place the infant back on nasal CPAP or the ventilator. Infants born beyond 28 weeks gestation generally outgrow these spells by 37 weeks post conception. In infants born at lower gestational ages, the spells may last longer.
Chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD). The combination of prematurity, oxygen exposure, and mechanical ventilation can result in lung injury to preterm babies. The consequence of this lung injury is chronic lung disease. CLD can prolong ventilator courses in small preterm infants (less than 1,200 grams) and result in a long-term oxygen need that can sometimes extend to home care. The frequency of this complication is greatest in the least mature infants, and, in those infants less than 26 weeks gestation at birth, it can occur in over 75% of cases. However, the lungs still generate new gas exchange surface until adolescence so the vast majority of infants outgrow this problem.
Patent ductus arteriosus (PDA)
The major heart-related problem in premature infants is PDA. The ductus is a structure that is present in a fetus connecting the main blood vessel that goes to the lungs from the heart to the main blood vessel that goes to the rest of the body. In the fetus, very little blood goes to the lungs because the fetus does not breathe air. The ductus allows the majority of the blood that is headed from the heart to the lungs to cross to the circulation to the body, bypassing the lungs. At birth, it is supposed to close.
In preterm babies, this closure may not occur. After birth, if this vessel is open, too much blood ends up going to the lungs, making it harder for an infant to breathe or to be ventilated. To close this blood vessel, the medication indomethacin is used. This works over 75% of the time; however, if it fails, a surgical closure is needed. Fortunately, it is a brief procedure that can be done at the bedside with almost uniformly good results.
Necrotizing enterocolitis (NEC)
The most important intestinal complication in preterm babies is NEC. This disease is the result of periods of low blood flow to the intestine, intestinal immaturity, and infection. When a baby develops this problem, they cannot be fed into the intestine and require 10 to 21 days of nutrition in their veins. In addition, a large tube is placed in the stomach to keep air out, and antibiotics are given. Many of the cases respond to this treatment, but, in some cases, surgery is needed to remove parts of the intestine that have died.
Intraventricular hemorrhage (IVH)
The internal structures of the brain in a preterm infant are at risk for hemorrhage. The bleeding is usually the result of a previous period of low blood flow, and occurs in the first four days of life. Diagnosis of the bleeding is performed with bedside ultrasound exams. The degree of bleeding is graded from 1 to 4. Grade 1 and 2 bleeds are small, and they do not increase the infant’s risk of neurodevelopmental abnormalities, while 33% of the babies with grade 3 and 4 bleeds will suffer severe neurologic injury, and another 33% will suffer lesser deficits. The final neurologic complication in preterm babies is injury to the motor tracts in the brain called periventricular leukomalacia (PVL), which causes cerebral palsy-a movement disorder with spasms that can impair the ability to walk.
Retinopathy of prematurity
The retina of the preterm infant is not fully “vascularized”(i.e., the blood vessels are not fully developed) at birth. The infant is at risk for a process called ROP, which, in its worst form, can lead to detachment of the retina and blindness. In babies born at less than 28 weeks or 1,500 grams, an ophthalmologist will perform a screening exam at 6 weeks of age.
Follow-up exams will then be performed until any ROP resolves, and the retina is fully vascularized. ROP is graded from 1 to 5 for severity. The process resolves spontaneously in most infants, but those infants who reach an advanced stage 3 of disease are at a high risk for detachment of the retina. These infants require treatment with laser therapy, which often can save the vision in the affected eye(s).
Anemia of prematurity
Because of blood sampling for tests and conditions that cause blood loss, such as inventricular hemorrhage, many preterm babies will require red blood cell transfusions. To decrease the number of transfusions given and to minimize donor exposure, preterm babies can be treated with the hormone erythropoietin, which stimulates red blood cell production in the body.
Hyperbilirubinemia (jaundice)
Virtually all preterm babies will develop jaundice. Jaundice is caused by an accumulation of the yellow pigment “bilirubin,” which is the breakdown product of hemoglobin from the red blood cells. A preterm infant cannot effectively clear the bilirubin in the liver. If too much bilirubin accumulates in the blood, it can cause brain damage. To help these infants in clearing the bilirubin to prevent brain damage, they are placed under phototherapy (“bilirubin lights”).
Infection
Some preterm deliveries are the result of an infection in the uterus, which also can lead to an infection in the baby. In addition, infants in the intensive care nursery are at an increased risk for infection due to indwelling lines and tubes, as well as a compromised immune (“infection fighting”) system. Thus, the risk of infection is high. If there is concern that an infant might be infected or there is a proven infection, the infant is treated with antibiotics-an event that is likely to occur more than once during the nursery stay.

What needs to happen for my baby to go home?
Most preterm infants are ready for discharge at or a few weeks before their due date. The criteria for discharge include the ability to maintain body temperature in a crib, adequate oral intake to sustain consistent growth, and resolution of apneic and bradycardic spells. Occasionally, infants who are otherwise doing well may be sent home on partial tube feedings.
In addition, if A&B spells are not completely resolved, but are not felt to be life threatening, some physicians will send a baby home on a heart monitor. If an infant needs supplemental oxygen at discharge, a test needs to be performed prior to going home to be sure if the oxygen were to fall off that the blood oxygen does not drop to dangerously low levels.

What is the outcome for survivors of the intensive care nursery?
Neurodevelopmental handicaps may occur in survivors of the intensive care nursery. These handicaps include cerebral palsy, which can be severe enough to prevent a child from walking, and cognitive deficits, which can be severe enough to prevent a child from learning to talk or read. Fortunately, deficits this severe occur in the minority of survivors, but others may have lesser deficits that cause delayed motor development, learning disabilities, and behavioral disorders, such as attention deficit disorder (hyperactivity).
The rates of abnormalities are higher in babies of lower gestational age at birth, particularly those born at 25 weeks or less. Although ROP rarely causes blindness, vision problems may still occur. The frequency of hearing loss is increased compared to term infants. The consequences of chronic lung disease are an increased rate of hospital readmission during the first two years of life, a continued oxygen need, and an increased incidence of asthma-like symptoms.
Finally, preterm infants are at an increased risk for poor weight gain, and they may require nutritional supplements or special formulas. Most premature infants who “graduate” from an intensive care nursery do quite well; however, coordinated follow-up to address all of their needs is of paramount importance.

References
Fanaroff A.A., Martin R.J. (editors): Neonatal-Perinatal Medicine. Diseases of the Fetus and Infant, 6th ed., Mosby, 1997.
Zaichkin J.: Newborn Intensive Care. What Every Parent Needs to Know. NICU Ink, 1996.
About the Author
Dr. Rosenberg graduated from Vanderbilt Medical School in 1976. His Pediatric Residency was at the University of Colorado and his Neonatal Fellowship was fulfilled at Johns Hopkins University. He is the Director of Newborn Services at University Hospital in Denver and Professor of Pediatrics at the University of Colorado School of Medicine.
His professional interests include newborn brain injury and long-term follow up of high-risk newborns. Some of his personal interests include tennis, skiing and youth sports programs.
Copyright 2012 Adam A. Rosenberg, M.D., All Rights Reserved

Prematurity, Retinopathy of

What is retinopathy of prematurity?
What causes retinopathy of prematurity?
Who gets retinopathy of prematurity?
How does it cause disease?
Common findings
Treatment
What are the complications?
How do you prevent it?
What research is being done?
Links to other information

David W. Johnson, M.D. Assistant Clinical Professor Department of Ophthalmology University of Colorado Health Sciences Center Denver, Colorado
What is retinopathy of prematurity?
Retinopathy of prematurity is a disease of the retinal blood vessels that can occur in extremely premature infants. The retina is the inner lining of the eye that consists of specialized nerve cells necessary for sight. Blood vessels in the retina develop first from the optic nerve area at the very back of the eye, with growth of blood vessels within the retina toward the front of the eye. The normal process of retinal blood vessel growth is sped in premature infants, leading to the formation of abnormal blood vessels and scar tissue.

What causes retinopathy of prematurity?
Researchers have discovered several risk factors for retinopathy of prematurity. One of the most significant risk factors is prematurity (born before 34 weeks of pregnancy). Another risk factor is low birth weight (less than 1500 grams or approximately 3 pounds). In the past, extremely high levels of oxygen therapy necessary for the survival of premature infants were thought to contribute to retinopathy of prematurity. However, with the precision of modern oxygen monitoring techniques now available, it is unlikely that excess oxygen causes this disease. Retinopathy of prematurity also has been reported in infants who receive no supplemental oxygen. In experiments, retinopathy of prematurity has been produced in animals by conditions simulating low-oxygen levels.

Who gets retinopathy of prematurity?
Infants weighing less than 1250 grams have an approximately 50% chance of developing some retinopathy of prematurity. As birth weight decreases, the likelihood of retinopathy of prematurity increases. More than 90% of infants weighing less than 750 grams develop retinopathy of prematurity. The same trend holds true in relation to when an infant is born. Approximately 30% of infants after 32 weeks of pregnancy develop retinopathy of prematurity, and greater than 80% of infants less than 28 weeks of pregnancy develop retinopathy of prematurity.

How does it cause disease?
The growth of normal retinal blood vessels may be sped, with normal vessels only growing to the middle of the retina. Beyond this, the retina has no blood vessels. Most likely, a chemical signal is then sent out that stimulates the remaining retina to grow new blood vessels. The new blood vessels are abnormal and frail, and they can bleed and scar easily. If enough of this scar tissue is present, it can pull on the retinal tissue, causing a traction retinal detachment. If the situation progresses further, a total retinal detachment can occur, leading to vision loss and, possibly, loss of the eye.

Common findings
An ophthalmologist experienced in the examination for this condition can diagnose retinopathy of prematurity. A set of dilating drops is placed in each eye to dilate the pupil. The infant is examined with an instrument to keep the eyelids open (called a lid speculum), and the retina is inspected with an ophthalmoscope. The eyeball may be manipulated to complete the examination.
The area (zone) of retinal involvement and the severity (stage) of the disease define retinopathy of prematurity.
Zone I is a circular area, roughly equivalent to the optic nerve and macular area in the center of the retina. Zone II is a larger circle surrounding this area, roughly equivalent to the middle of the retina. Zone III is the remaining anterior (or front) retina and represents an area of near maturity of the retinal vessels. Severe retinopathy of premature occurs most often in Zones I and II.
Stage I is defined as a line found at the border of the normal retina and the retina without blood vessels. Stage II is defined as a thickening of the line to form what is called a ridge. These stages probably represent growth of immature retinal cells. Stage III involves growth of new abnormal blood vessels, both on the ridge and elevated above the ridge into the vitreous (clear, gelatinous material between the retina and the lens) area. When Stage III blood vessel growth reaches a certain level, it is best treated by laser. Stage IV involves traction and detachment of the retina. This stage is divided into Stage IV-A, or detachment not involving the macula (area near the center of the retina where vision is most clear), and Stage IV-B, or detachment involving the macular or central retina. Stage V is defined as a total tractional retinal detachment for which there is often no effective treatment.
Plus disease is defined by abnormal vessels that are very tortuous, along with the findings listed above, usually indicating a situation that may require immediate treatment. Rush disease indicates unusually fast progression (1- to 2-week period) from no retinopathy of prematurity to disease that requires treatment.
Most retinopathy of prematurity does not require treatment and resolves on its own. The risk of developing disease that requires treatment is highly related to low birth weight and prematurity. In infants weighing less than 750 grams (approximately 1 1/2 pounds), 15% to 20% of infants developing any retinopathy of prematurity do go on to disease that requires treatment. For infants weighing greater than 1250 grams (approximately 2 3/4 pounds), only 2% of infants developing retinopathy of prematurity go on to disease needing treatment. Some retinopathy of prematurity that develops in the remainder of the infants ultimately resolves on its own.

Treatment
Earlier studies found a beneficial effect of cryotherapy (freezing treatment) to the peripheral areas of the retina (areas without blood vessels) in healing retinopathy of prematurity. Now, cryotherapy has been replaced largely by laser treatment. In both treatments, the peripheral areas of the retina are destroyed, leading to a decreased demand for the growth of new blood vessels. The abnormal new blood vessels then are seen to shrink away, leaving no further effect on the retina.
The ophthalmologist delivers the laser treatment through the dilated pupil with an indirect ophthalmoscope system (similar to the setup used for examination). The treatment generally takes 30-45 minutes per eye, and it often is performed in the neonatal intensive care setting. Intravenous (IV) sedation and pain relief commonly are used, and a breathing tube sometimes is necessary.
The infant usually is reexamined at 2-4 weeks. Re-treatments of problem areas occasionally are necessary. Progression of severe retinopathy of prematurity can occur despite successful cryotherapy or laser treatment. A small percentage of eyes continue on to traction retinal detachment despite adequate treatment.

What are the complications?
Continued retinopathy of prematurity with traction retinal detachment and loss of vision is the final outcome in some cases, although this risk is reduced greatly with well-timed treatment. Even if retinopathy of prematurity resolves on its own or if treatment is required, certain outcomes are common, including nearsightedness (difficulty seeing things far away). Other possible complications include amblyopia (weakened vision in one eye) or strabismus (misalignment of the eyes) with an eye deviating in (esotropia) or out (exotropia) when compared to the other eye. A pediatric ophthalmologist can address all these conditions in the follow-up stage.
Complications of laser treatment or cryotherapy include corneal burns or swelling (edema), lens burns or cataract formation, and vitreous hemorrhage or bleeding into the center cavity of the eye. As mentioned above, retinal traction and detachment can occur despite treatment.

How do you prevent it?
No proven treatment exists to prevent the occurrence of retinopathy of prematurity in infants who are at an increased risk. Careful monitoring of oxygenation status and examination of high-risk infants at 6 weeks after birth effectively identifies cases of retinopathy of prematurity that may need additional treatment. No correlation exists between lighting conditions in the nursery and the development of retinopathy of prematurity.

What research is being done?
The effect of supplemental oxygen on infants with Stage III is being studied in the S-ROP (Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity) trial. The initial results from this study indicate no firm beneficial effect of increasing oxygenation in Stage III of this condition. The multicenter CRYO-ROP (Cryotherapy for Retinopathy of Prematurity) study continues to observe infants in a phase III long-term follow-up study.

Links to other information
The American Academy of Pediatric Ophthalmology and Strabismus Web site has additional information on retinopathy of prematurity at http://med-aapos.bu.edu.
Informational brochures are available from The American Academy of Ophthalmology Web site at http://www.eyenet.org.

References
The Committee Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol. 1984 Aug;102(8):1130-1134.
The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. II. The classification of retinal detachment. Arch Ophthalmol. 1987 Jul;105(7):906-912.
Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Arch Ophthalmol. 1988 Apr;106(4):471-479.
Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. 3 ï¿½-year outcome-structure and function. Arch Ophthalmol. 1993 Mar;111(3):339-344.
About the Author
David W. Johnson, MD, is an ophthalmologist in private practice specializing in vitreoretinal surgery. He currently holds a teaching appointment as Assistant Clinical Professor in the Department of Ophthalmology at the University of Colorado Health Sciences Center in Denver. Dr. Johnson actively participates in the diagnosis and treatment of retinopathy of prematurity at several Denver area hospitals.
Copyright 2012 David W. Johnson, M.D., All Rights Reserved

Pulmonary Hypertension

What is pulmonary hypertension?
What causes pulmonary hypertension?
Who gets pulmonary hypertension?
How does it cause disease?
What are the common findings?
How is pulmonary hypertension diagnosed?
How is pulmonary hypertension treated?
What are the complications?
How can pulmonary hypertension be prevented?
What research is being done?
Links to other information

Dunbar Ivy, MD Assistant Professor of Pediatrics Director of Pediatric Pulmonary Hypertension Program and the Pediatric Heart Lung Center University of Colorado Health Sciences Center and the The Children’s Hospital Denver, CO Trish Eells, RN, MS, CPNP Pediatric Heart Lung Center The Children’s Hospital Denver, CO
What is pulmonary hypertension?
Pulmonary hypertension (PH) occurs when there is high blood pressure in the lungs. Pulmonary hypertension is a disease that involves both the heart and the lungs. Without treatment, the blood pressure in the lungs continues to rise over time, and it eventually may result in heart failure.

What causes pulmonary hypertension?
There are two types of pulmonary hypertension: primary and secondary. Primary pulmonary hypertension (PPH) means that there is no known cause for the pulmonary hypertension. It is a disease that is still not well understood. It may be associated with certain conditions, such as HIV, diet pill use, drug abuse, or exposure to various toxins. Secondary pulmonary hypertension (SPH) means that there is a disease or a condition that caused the pulmonary hypertension to develop. The pulmonary hypertension developed after, or secondary to, the other disease. Conditions or diseases that may lead to pulmonary hypertension include congenital heart defects, persistent pulmonary hypertension of the newborn, chronic lung diseases, autoimmune diseases, and liver disease.

Who gets pulmonary hypertension?
Pulmonary hypertension may be diagnosed in infancy or later in life. Pulmonary hypertension affects people of all races and backgrounds.

How does it cause disease?
In pulmonary hypertension, the blood vessels in the lungs constrict, i.e., they become smaller than normal. This constriction causes the pressure to build up in the vessels. The heart must work harder to try and push through the blood.

What are the common findings?
Because the heart must work harder to push through the blood, people with pulmonary hypertension often feel tired and may be short of breath, especially after activity. Other complaints may include dizziness, chest pain, fainting spells, and palpitations. People with pulmonary hypertension have a wide variety of symptoms; no two patients are the same. Sometimes, the complaints seem to come and go, with certain days being better than other days.
Pulmonary hypertension is a disease that worsens over time. As the pressure in the lungs gets higher, the heart must continue to work harder. Over time, the heart may not be able to pump as well. Some patients may notice swelling of their legs and their feet. They may develop tenderness over their liver. Some people may have trouble sleeping at night, requiring two or more pillows to get comfortable. The extra fluid in their lungs may cause this discomfort. Oxygen levels in the blood may become lower than normal, causing the lips and the nails to have a bluish tint to them. The fingertips may begin to bulge in appearance. Often, there are changes in appetite, and weight loss.

How is pulmonary hypertension diagnosed?
Most patients with pulmonary hypertension have had symptoms for about two years before they are diagnosed with the condition. This is because many of the symptoms are so subtle in the beginning, and they are similar to other conditions. It is important that a patient with pulmonary hypertension selects a physician and a center with experience in treating it. To diagnose pulmonary hypertension, a doctor conducts a variety of tests. The doctor performs a complete physical exam, with careful attention to a cardiac exam. A physician checks for unusual heart sounds that may indicate higher pressure in the lungs. The doctor also looks for certain physical findings, such as enlarged neck veins or swelling, which are associated with pulmonary hypertension.
A variety of blood tests are used to check blood counts and to assess liver and kidney function. It is important to look for the presence of other diseases, such as congenital heart disease. An electrocardiogram, or an EKG, is performed to look for evidence of a thickened heart, or abnormal heartbeats. Pulmonary function tests are done to look for any underlying lung disease that may be causing the symptoms. A ventilation perfusion scan looks for clots or blockages in the blood vessels of the lungs. A six-minute walk may be performed to determine the amount of distance that can be walked in this time period. This measurement is useful to follow once treatment begins for pulmonary hypertension.
An echocardiogram, which is an ultrasound of the heart, is very important. The echocardiogram allows a doctor to look at the heart and to find any structural problems that may exist. It also allows a doctor to look at the overall heart function and size, and to estimate pulmonary artery pressures.
A right-heart catheterization is the most important test used to diagnose pulmonary hypertension and to decide treatment options. This procedure involves placing a catheter in the groin and threading it up to the right side of the heart and into the pulmonary artery. In this position, it is possible to measure directly the pulmonary artery pressures, the filling pressures of the heart, and the cardiac output. The heart catheterization also allows a doctor to exclude any type of structural abnormality. During the procedure, a variety of medications are administered. These medications may include oxygen, nitric oxide, and prostacyclin. After each medication is given, the above measures are repeated. Future treatment options are determined based on the pulmonary artery pressures that are obtained after these medications.

How is pulmonary hypertension treated?
There are a variety of treatments available for pulmonary hypertension. Treatment is specific to each patient, and is based on the information obtained during the heart catheterization. When secondary pulmonary hypertension is present, it is important to identify and treat the underlying cause, whenever possible. Sometimes, despite treatment of the cause, the pulmonary hypertension may continue. At times, treatment of the condition may cause an improvement in the pulmonary hypertension.
Medical treatment options include a variety of medications taken by mouth. Drugs may be used to remove the extra fluid that sometimes is retained with pulmonary hypertension. Such medications are called diuretics, and include lasix or aldacatone. To help the right heart squeeze better, a medicine called digoxin may be used. Patients with pulmonary hypertension are at risk for clot formation in the small vessels of their lungs. Warfarin is used in patients with pulmonary hypertension to help keep their blood thin and to reduce the risk of clot formation. Oxygen may be prescribed for patients who have low levels of oxygen in their blood. Other patients may use it while sleeping, and often feel less tired upon awakening.
Calcium channel blockers, such as Nifedipine, work to lower the pulmonary pressures in approximately 40% of children with primary pulmonary hypertension. These medications work by dilating the arteries in the lungs, causing the pulmonary pressure to fall. Sometimes, if the arteries have become rigid over time, they will not relax with the calcium channel blockers.
Epoprostenol sodium-also called prostacyclin, Flolan, or PGI2-is an intravenous medication that was approved for the treatment of primary pulmonary hypertension in 1995. This medication is similar in structure and in function to a substance made in the body called prostaglandin. It works by dilating blood vessels, by reducing clot formation, by improving cardiac output, and by slowing the growth of smooth muscle cells.
The dose of prostacyclin is increased over time to achieve maximal benefit and minimal side effects. Side effects to the medication include jaw pain, rash, flushing, stomachache, diarrhea, headache, musculoskeletal pain, and depression.
Prostacyclin is not a very stable drug; therefore, it cannot be given by mouth. Currently, prostacyclin is given intravenously through a permanent catheter placed in the large veins of the body. The catheter, called a Broviac or a Hickman, must be placed in the operating room. The medication is given 24 hours a day on a portable infusion pump. The caregivers must learn to mix the medication daily and to administer it using the pump. Interruptions in the drug delivery, even if brief, may cause a sudden rise in the pulmonary pressures, resulting in a reappearance of the symptoms, or even death.
Prostacyclin therapy is considered life long. However, the long-term result with it is good, with the survival rate predicted to be over 80% in a 5-year time period.
The surgical treatment for pulmonary hypertension is a lung transplant, which permanently will rid a patient of the disease.

What are the complications?
Complications to therapy with prostacyclin include infection in the blood or at the site of the catheter, catheter fracture or displacement, and/or pump malfunction. Despite the current delivery method and the possible complications, children who are receiving intravenous prostacyclin tolerate it well. The vast majority of children attend school and participates in age-appropriate activities. Once treatment begins, their level of energy greatly increases.
Some patients with pulmonary hypertension undergo lung transplantation. There are complications related to a lung transplant that include rejection of the transplanted organ, and side effects to the transplant medications. Often, timing of the transplant is difficult to predict.
The major complication of pulmonary hypertension is right-heart failure. As the pressure in the lungs continues to build over time, the heart becomes a less effective pump. The right heart increases in size, and it eventually compromises the left heart function. Additional complications may include low platelet counts and severe bleeding in the lungs (called pulmonary hemorrhage). Without treatment, primary pulmonary hypertension is a fatal disease.

How can pulmonary hypertension be prevented?
Currently, primary pulmonary hypertension cannot be prevented. Research is being conducted to identify genetic markers of this disease, which would allow early screening of those individuals at risk for it based on their family history. Presently, it is recommended that immediate family members be followed by an echocardiogram every five years, or as needed, to assist with early diagnosis and treatment.
In secondary pulmonary hypertension, treatment of the underlying condition is vital. For a child with a congenital heart defect, it is necessary to stay in close contact with a cardiologist. The surgical repair of the heart defect must be considered based on the child’s condition.
Routine recommendations for children with pulmonary hypertension include annual flu vaccines, the use of antibiotics for significant upper respiratory tract infections, the treatment of a fever of 101 degrees or greater, a high fiber diet to prevent constipation and straining with bowel movements, and oxygen for airline travel.

What research is being done?
In recent years, a great deal of research has been devoted to pulmonary hypertension. Newer therapies include treatment with a more stable form of prostacyclin, called UT-15. This medication is injected beneath the skin in the abdomen, and it does not require a central line. The half-life of the medication is longer; therefore, the risk of complications with an abrupt halt in delivery is lower. Clinical trials of this medication are currently underway in the United States and in Europe.
An investigational gas, called nitric oxide, is being examined for its role in the treatment of pulmonary hypertension. This gas is a powerful dilator of the blood vessels in the lungs. It also works to prevent the platelets from clumping together. Many patients with pulmonary hypertension have received this gas in the hospital, and some patients have shown a lowering of their pressures and an improvement in their symptoms. A small number of patients have gone home with nitric oxide. Though the gas remains investigational, in the future, it may be more common to treat patients at home with it.
Endothelin blockers and thromboxane inhibitors are investigational medicines that would block the narrowing of the blood vessels (vasoconstriction) that occurs in pulmonary hypertension. If the vasoconstriction is blocked, it is thought that the resultant opening (vasodilation) of the blood vessels would lower the pulmonary artery pressure.
An oral form of prostacyclin is being tested for its use in treating pulmonary hypertension. This drug is similar to intravenous prostacyclin. It is a more stable form of prostacyclin, and can therefore be given as a pill taken several times a day.

Links to other information
For more information on pulmonary hypertension, log on to: http://www.phassociation.com/.

References
Barst RJ. Recent advances in the treatment of pediatric pulmonary artery hypertension. Pediatric Clinics of North America 1999;46(2):331-45.
Ivy DD, Wolfe RR, Abman SH. Congenital heart disease. In Peacock AJ, ed. Pulmonary circulation: a handbook for clinicians. New York: Chapman and Hall Medical, 1996:449-66.
Ivy DD, Neish SR, Abman SH. Regulation of the pulmonary circulation. In Garson A, Bricker JT, Fisher DJ, Neish SR, eds. The science and practice of pediatric cardiology. Baltimore: Williams and Wilkins, 1998:329-47.
About the Author
Dr. Ivy is an assistant professor of pediatrics at the University of Colorado Health Sciences Center in Denver, Colorado, where he also serves as co-director of the pediatric cardiology fellowship program. Additionally, Dr. Ivy is director of the pediatric pulmonary hypertension program at the Pediatric Heart Lung Center. Board certified in both pediatrics and pediatric cardiology, his major scientific interests include pulmonary hypertension, pulmonary vascular biology, fetal circulation, cardiac intensive care, cardiac transplantation, and cardiac catheterization. Dr. Ivy has been instrumental in procuring grant monies for pulmonary and cardiac research. He is an accomplished clinician and investigator, authoring numerous papers, book chapters, presentations, scholarly reviews, and abstracts, for which he has been recognized with awards. Dr. Ivy is active in professional societies and institutional committees, in addition to participating on various journal review boards and partaking in visiting professorships.
Trish Eells, RN, MS, CPNP, is the coordinator for the Pediatric Heart Lung Center at The Children’s Hospital, and a nurse practitioner in the Pulmonary Hypertension Program. The Pulmonary Hypertension Program treats children with both primary and secondary pulmonary hypertension, and offers a variety of approved and experimental therapies.
Pulmonary Hypertension (PPH & SPH)
Overview
Programs & Treatments
Signs & Symptoms
Diagnosis & Tests

Overview
What is pulmonary hypertension?
Pulmonary hypertension (PH) is high blood pressure in the blood vessels that line the lungs. Because the vessels of the lung and the heart are physically connected, this makes blood pressure in the heart rise and forces the heart to work harder than normal. Pulmonary blood pressure rises when the blood vessels in the lungs get narrow and stiff.
If the condition goes untreated, the heart cannot push hard enough against the lung pressures and not enough blood reaches the lungs, which may eventually lead to heart failure.
What causes pulmonary hypertension in children?
There are several reasons a child could have pulmonary hypertension. Congenital Heart Defects are a common cause of hypertension in children.
Other causes include:
Lung disease
Sleep apnea
Altitude effects
Blood clotting disorders
Autoimmune diseases
Liver disease
Familial disease
In the above cases, the pulmonary hypertension is secondary because the rise in blood pressure was the result of another condition. This is known as secondary pulmonary hypertension (SPH).
Other times, there is no underlying reason causing the blood pressure increase. This is called primary pulmonary hypertension (PPH), also known as idiopathic pulmonary hypertension. Idiopathic pulmonary hypertension tends to affect girls more than boys. Children of any age can develop the condition.

Programs & Treatments
How is pulmonary hypertension treated?
There are many treatment options for kids and young adults with pulmonary hypertension (PH).
If the hypertension is secondary (meaning it is the result of another condition), the best treatment plan is to repair the underlying heart condition when possible. Treatments for congenital heart defects range from careful monitoring by a doctor to surgery.
Pediatric cardiologists use a variety of medications to treat pulmonary hypertension. Select childrenâ€™s hospitals participate in clinical trials to develop new medical treatments for kids with pulmonary hypertension.
Living with pulmonary hypertension
There is currently no cure for many forms of pulmonary hypertension, although close follow-up by a cardiologist with experience in treating PH can help your child live as normal a life as possible. The cardiologist will monitor your child’s pulmonary pressures and response to medications.

Signs & Symptoms
What are the signs and symptoms of pulmonary hypertension?
Children with pulmonary hypertension (PH) feel short of breath and tired, especially after activity. Symptoms of pulmonary hypertension can be confused with other conditions like asthma, sometimes leading to a delay in diagnosis and treatment.
Other symptoms include:
Blue tint to the skin, also called cyanosis
Swelling of the feet and ankles
Dizziness
Fainting
Recurrent nausea
Exercise intolerance
Chest pain

Diagnosis & Tests
How is pulmonary hypertension diagnosed?
If us suspects that your child has pulmonary hypertension, he or she will likely order more tests to confirm the diagnosis. Common tests include:
Blood tests
Chest x-ray
EKG
ECHO
Exercise or stress test
Diagnostic cardiac catheterization
Lung CT Scan
Abdominal ultrasound
Polysomnogram (a sleep study)
Ventilation/perfusion scan

Helpful Resources:
To learn more about pulmonary hypertension, visit the following websites:
Pulmonary Hypertension Association
The American Heart Association
The U.S. Library of Medicine
Pulmonary Hypertension Program at Childrenâ€™s Hospital Colorado

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