Sensory Integration

All of us learn about and comprehend the world through our senses. All of the sensory input from the environment and from inside our bodies works together seamlessly so we know what’s going on and what to do.

Sensory integration is something most of us do automatically. Usually, sensory input registers well, gets processed in the central nervous system and then hooks up seamlessly with all of the other senses. This lets us think and behave appropriately in response to what’s going on.

Kids with sensory integration (SI) dysfunction experience the world differently. They don’t take in and use sensory information the same way. Their central nervous system responds to sensory input differently, so they’re not always getting an accurate, reliable picture of their bodies and the environment.

Think of sensory integration like an orchestra. You need the woodwinds section, the strings section, the percussion, the piano to all be in tune, playing in key at the right volume, all perfectly coordinated with each other. With SI dysfunction, the conductor isn’t controlling the music well. Different sections in the orchestra are out of tune and out of sync so it doesn’t sound right.

For a child with severe sensory issues, walking into the supermarket can feel like walking into a rock and roll concert. Such a child may be able to see and hear the fluorescent lighting flicker, a squeaky shopping cart may sound like thunder, the meat department may smell like a garbage dump, and navigating the aisles and other shoppers may feel like being on a bumper car ride. What seems normal to us can easily overwhelm a child with sensory problems.

Signs of Sensory Integration Dysfunction

• Out of proportion reactions: over or undersensitivity to touch, sounds, sights,
  movement, tastes, or smells
• Problems with vestibular (movement) and proprioceptive senses (body awareness)
• Bothered by particular clothing fabrics, labels, waistbands, etc.
• Avoids or excessively craves intense movement — slides, swings, bouncing, jumping
• Resists grooming activities such as brushing teeth and washing hair
• Avoids foods most children enjoy
• Gets dizzy easily-or never at all
• Seems clumsy or careless
• Often “tunes out” or “acts up”
• Poor attention and focus
• Uncomfortable in group settings
• Very high or very low pain threshold
• Squints, blinks, or rubs eyes frequently (may have an undiagnosed vision problem)

causes

Sensory problems result from neurological differences, and new research is being done to confirm this. It’s a difference in how the brain and nervous system are wired. Sensory problems are quite often seen in children born prematurely (especially the smallest and the youngest), those adopted from overseas, children who have experienced birth trauma or prolonged hospitalization, and those exposed to heavy metals. Sensory problems are a common symptom of other diagnoses including autism, attention deficit disorders, Down Syndrome, fragile X, anxiety and depression and others. A child may have such a disorder AND SI dysfunction. A child can just have sensory problems and nothing else. It’s estimated that there’s one child with sensory issues in every regular classroom, and somewhere between 50-80% of children have some degree of sensory problems in a classoom of children with autism spectrum disorders.

preemies and  high risk sensory integration problems

In the womb, a baby spends her time curled up, cozy and warm in the dark, listening to her mother’s heartbeat and muted sounds from the outside world. Meanwhile, her nervous system is developing at astonishing speed, forming thousands upon thousands of essential nerve cell connections. When a baby is born prematurely, her immature, disorganized nervous system isn’t ready to handle all of the sensory messages bombarding her.

Most NICUs do their best to minimize overstimulation, but the inevitable beeping and buzzing equipment, room lighting, and busy atmosphere can agitate sensitive preemies. The NICU primary care team—including neonatal nurses, occupational and physical therapists—work with parents to facilitate development. Usually, moms and dads are sent home with warnings to look out for signs of sensory issues and developmental delays in their babies.

Each baby is, of course, totally unique, but in general preemies tend to:

• be highly sensitive to noise, light, touch, and movement—even beyond the second birthday
• retain startle reflexes longer than usual
• have muscles that tend to be either stiff or floppy, or a mix of both. (Abnormal muscle tone in preemies often resolves itself by 12-18 months.)
• be very distractible and highly active—or extremely quiet and sleep more than expected
• have increased risk for vision problems
• often develop oral defensiveness because of negative oral experiences with feeding tubes, respirators and suctioning. This can interfere with feeding, as can abnormal muscle tone inside the mouth

  Most of sensory-based difficulties resolve as the baby’s nervous system matures, especially given informed parents like Mickey’s. They worked closely with an occupational therapist who helped them to understand and meet his sensory needs while avoiding sensory overload, e.g, the best ways to position him in his crib and for feedings, how to caress him with firm rather than light touch, how intensely to rock him, and so on).

Treatment

With appropriate interventions and time, most children develop needed central nervous system connections and sensory input starts getting more familiar and more comfortable. Not always, but most of the time, children can overcome their sensory problems, especially with parents who develop their own “sensory smarts.”

The first step is to get an evaluation from a qualified health care professional. This may be a developmental pediatrician or an occupational therapist who has special training and experience in this area. If your child is under age 3, you can get a multidisciplinary evaluation through your state’s Early Intervention program (see www.sensorysmarts.com for a link to your state’s EI program). If your child is over age 3, you can request an occupational therapy evaluation from your school district. You also have the option of hiring an OT privately, which may be covered by your health insurance.

Parenting a child with sensory issues takes a lot more creativity and willingness to do things differently. Traditional parenting methods often don’t work. Expecting a child to “get over it” and go ahead and tolerate something intolerable just isn’t going to work

source : comeunity.com

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phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

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Clinical and Editor in Chief :

WIDODO JUDARWANTO

email : judarwanto@gmail.com,

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

ABSTRACT

Background Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.

Methods We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1–receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.

Results All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.

Conclusions Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations. (ClinicalTrials.gov number, NCT00069329 [ClinicalTrials.gov] .)

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Supported  by
CLINIC FOR CHILDREN 

Yudhasmara Foundation 

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646

http://childrenclinic.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

email : judarwanto@gmail.com

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.

Copyright © 2009, Clinic For Children Information Education Network. All rights reserved.

Matthew J. O’Connor, MD

Department of Pediatrics, University of Virginia Health System, Charlottesville, Virginia

Frank T. Saulsbury, MD

Department of Pediatrics, University of Virginia Health System, Charlottesville, Virginia, fts@virginia.edu

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This report describes a 7-week-old infant with incomplete and atypical Kawasaki disease, an acute vasculitis that predominantly affects infants and children. The patient was refractory to 2 doses of intravenous immunoglobulin and to high-dose intravenous methylprednisolone. He became afebrile only after 2 doses of infliximab. His prolonged, recalcitrant course was complicated by the development of peripheral gangrene and giant coronary artery aneurysms. Infants with incomplete and atypical Kawasaki disease are prone to intravenous immunoglobulin treatment failure and are at risk for the development of coronary artery aneurysms. In such patients, we suggest that consideration be given to early aggressive therapy with corticosteroids or infliximab added to intravenous immunoglobulin.

Key Words: atypical Kawasaki disease • peripheral gangrene • infliximab

Clinical Pediatrics, Vol. 46, No. 4, 345-348 (2007)
DOI: 10.1177/0009922806294842

Supported  by
CLINIC FOR CHILDREN 

Yudhasmara Foundation 

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646 

http://childrenclinic.wordpress.com/ 

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

email : judarwanto@gmail.com

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.

Copyright © 2009, Clinic For Children Information Education Network. All rights reserved.

source : clinical cardiology, Images Paediatr Cardiol 2003;16:36-48

Supported  by
CLINIC FOR CHILDREN 

Yudhasmara Foundation 

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646 

http://childrenclinic.wordpress.com/ 

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO 

email : judarwanto@gmail.com

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.

Copyright © 2009, Clinic For Children Information Education Network. All rights reserved.

Rheumatic diseases are rarely encountered in newborns and fall broadly into three groups: (a) transplacentally acquired immunological diseases such as neonatal lupus and neonatal antiphospholipid syndrome; (b) genetic conditions such as the chronic infantile neurologic cutaneous and articular (CINCA) syndrome (also known as neonatal-onset multisystem inflammatory disease – NOMID); and, (c) other miscellaneous disorders that may rarely present in neonatal period such as Kawasaki disease, Behçet’s disease and systemic–onset type of juvenile idiopathic arthritis (JIA). 

A variegated group of rheumatic disorders may occur in neonates. These disorders fall broadly into three groups: (i) transplacentally acquired immunological diseases such as neonatal lupus and neonatal antiphospholipid syndrome, (ii) genetic conditions such as the chronic infantile neurologic cutaneous and articular (CINCA) syndrome, and (iii) other miscellaneous disorders such as Kawasaki disease, Behçet’s disease and systemic JIA that may rarely present in neonatal period. Those fetuses and infants at greatest risk for transplacentally acquired disease due to the maternal rheumatic disease should be under close observation in order to anticipate perinatal problems and to take prompt preventive and therapeutic measures. Early recognition and referral to the pediatric rheumatologist is important for effective management of neonates and could help avoid the possible serious complications of these diseases. In addition, appropriate counseling of the parents and family of the affected neonate is necessary in transplacentally acquired and genetic diseases.

            Neonatal lupus and neonatal antiphospholipid syndrome are considered in vivo models of passively acquired autoimmune diseases, which result from the transplacental passage of specific maternal autoantibodies . There are many maternally derived autoantibodies which are capable of binding to fetal antigens, but only a few bring about neonatal illness. The most prominent fetal or neonatal effects are observed in transplacental passage of autoantibodies that have a causative role in the pathogenesis of autoimmune disease. Transport of maternal autoantibodies across the placenta is a selective process that begins at about 12 weeks of gestation and accelerates after 22 weeks of gestation. The bulk of transferred autoantibodies belong to the subclasses IgG₁/IgG₃, and the time course of clinical symptomatology often parallels the presumed half life of IgG immunoglobulins. Conversely, if autoantibodies are demonstrable in the neonate in the absence of clinical effects, they may only be an epiphenomenon of the maternal disease.

Neonatallupus erythematosus is an immune-mediated disease that rarely is associated with congenital heart block. Transient hepatitis, thrombocytopenia and anemia can also occur.

We describe a case of neonatal lupus erythematosus and review the clinical and laboratory manifestations of this rare disease. Its only clinical sign might be an annular facial rash. The rash is usually diagnostic, but can be confused with other annular lesions. Because of the possible serious complications of undiagnosed lupus, a thorough evaluation of both child and mother is required when this diagnosis is entertained.

            CINCA syndrome is a member of the rapidly expanding family of autoinflammatory disorders characterized by self-resolving attacks of fever accompanied by somewhat specific clinical features . These disorders have been extensively characterized recently, with a growing identification of genes involved in the pathogenesis.

This review focuses on recent advances relevant to primary-care physicians in the understanding of neonatal rheumatic diseases. The clinical features and possible pathogenic mechanisms of these diseases are described, with particular emphasis on their early clinical recognition. The literature search engines included PubMed, MEDLINE and Science Citation Index. The relevant articles were also identified by searching the references of available meta-analyses and review articles, and bibliography of pertinent references. 

NEONATAL LUPUS

Neonatal lupus erythematosus is an uncommon immune-mediated disease associated with the transplacental transfer of maternal immunoglobulin G autoantibodies. In 95% of cases the autoantibody is anti-Ro (SS-A), but it can be anti-La (SS-B) or anti-U₁RNP.Any of these autoantibodies can be found alone or in combination. There are even reports of histologically documented cases of neonatal lupus erythematosus where none of the above-listed antibodies were found. This finding suggests that some cases can be mediated by antibodies other than anti-Ro (SS-A), anti-La (SS-B) or anti-U₁RNP or perhaps by some factor or cofactor yet to be determined. In cases where only anti-U₁RNP antibodies are found, only cutaneous disease has been reported

A child will develop neonatal lupus erythematosus simply because its pregnant mother has anti-Ro (SS-A) antibodies. Neonatal lupus erythematosus occurs only in about 1% of these neonates. If a anti-Ro (SS-A)-positive mother has one child with neonatal lupus erythematosus, only 25% of subsequent children born to this mother will be so affected.These numbers are low, which is another reason to suspect a cofactor is involved in the pathogenesis of neonatal lupus erythematosus. Although congenital heart block can be found with this condition, it is rare. Its incidence ranges from 15% to 30% of affected infants.This form of congenital heart block is associated with high morbidity; 50% to 70% of patients require pacemakers. Transient forms of hepatitis, thrombocytopenia, and anemia can also occur.

Skin lesions and heart block are seen simultaneously in less than 10% of patients with neonatal lupus erythematosus.Cutaneous lesions consist of transient nonscarring erythematous annular plaques with a predilection for periorbital and photodistributed areas. Lesions generally appear within the first 2 months of life and resolve within 4 to 6 months when maternal antibodies disappear.Rarely, remnant telangiectasias can occur at previously affected sites.

A considerable proportion of mothers of affected infants are asymptomatic (40%). They might have Sjöogren’s syndrome, systemic lupus erythematosus, rheumatoid arthritis, overlap syndrome, or even leukocytoclastic vasculitis.Asymptomatic mothers do not invariably become ill, and if they do develop lupus erythematosus, it is not likely to be life threatening.Although neonatal lupus erythematosus has a very characteristic appearance, tinea faciei, a photodistributed drug eruption, urticaria, and annular erythemas are in the differential diagnosis. The diagnosis of neonatal lupus erythematosus is generally based on clinical findings when there are maternal and or neonatal autoantibodies. Determination of titers for antinuclear antibody, anti-Ro (SS-A), anti-La (SS-B) and anti-U₁RNP antibody is recommended for diagnosis. Liver function tests and a complete blood count should also be obtained. Skin biopsy is usually not required to establish the diagnosis. Histologic findings are similar to those of subacute cutaneous lupus erythematosus. All patients suspected of having neonatal lupus should have a thorough cardiac examination.

Management of the cutaneous lesions of neonatal lupus erythematosus requires sun avoidance, sunscreen, and low-potency topical corticosteroids to hasten resolution.

Neonatal lupus is a rare disease of the developing fetus and neonate acquired from the transplacental passage of specific maternal autoantibodies, in particular those directed against the extractable nuclear antigens Ro (also called SSA) and La (also called SSB) . Anti-Ro/La antibodies are present in a high percentage of patients with systemic lupus erythematosus (SLE) and Sjögren’s syndrome, but mothers with a known connective tissue disease and positive anti-Ro/La antibodies have only about 1-5% risk of delivering a child with neonatal lupus . On the other hand, neonatal lupus can be seen in the offspring of mothers who do not have any signs or symptoms of a connective tissue disorder, and the first demonstration of anti-Ro/La antibodies in these mothers occurs during the pregnancy or after delivery of an affected child.  

Clinical features

            The clinical features most clearly associated with neonatal lupus include cardiac disease, skin disease, hepatobiliary disease and cytopenia. The noncardiac manifestations of neonatal lupus are generally transient, resolving by 6 months of life coincident with the disappearance of maternal autoantibodies from the infant’s circulation. The most frequent lesion of cardiac neonatal lupus is complete (i.e., third degree) heart block, which is almost always permanent.

The classic presentation of neonatal lupus is one of a fetus or newborn discovered to have a slow heart rate due to congenital heart block in the absence of a structural heart disease. Many cases are discovered in utero, most commonly between 18 and 24 weeks of gestation. The identification of fetal bradycardia (i.e., heart rate less than 120 per minute) by either auscultation or routine obstetric ultrasound requires that the mother be referred for immediate fetal echocardiography to confirm the presence of heart block and to document the degree of the block. Autoimmune-associated congenital heart block can be first, second, or third degree, and may or may not be progressive after detection in utero or postnatally . Only second or third degree heart block is clinically manifested as bradycardia. It is estimated that up to one third of pregnancies complicated by fetal complete heart block result in intrauterine death, which is usually related to intractable heart failure and development of hydrops fetalis. Besides congenital heart block, other cardiac manifestations have been reported, such as myocarditis, dilated cardiomyopathy, sinus bradycardia, QT interval prolongation and, rarely, structural heart defects .

The skin rash of neonatal lupus characteristically appears a few days or weeks after birth, particularly after sun exposure. It consists of annular  or elliptical erythematosus plaques   most often located on the scalp, face and extremities. Skin lesions are transient, lasting weeks to months; these usually resolve without scarring. Hypopigmentation is frequent and may be a prominent feature. Rarely, remnant telangiectasias can occur at previously affected sites . The differential diagnosis of isolated cutaneous neonatal lupus includes tinea faciei, a photosensitive drug eruption, urticaria, seborrheic dermatitis and annular erythemas.

Hepatic dysfunction occurs in approximately 15% of cases with neonatal lupus and can present as severe liver failure in utero or after birth, transient cholestatic hepatitis and transient elevations of aminotransferases. Hepatobiliary disease may occur as the sole clinical manifestation, but is commonly associated with other manifestations of neonatal lupus .

Occasionally, newborns of mothers with anti-Ro/La antibodies may present with hematological manifestations including thrombocytopenia, anemia and neutropenia . There have also been several case reports of various neurological manifestations associated with neonatal lupus .

CUTANEUS NEONATAL LUPUS

Pathogenesis

            Presumably, the fetus develops normally until maternal IgG antibodies against the Ro and La proteins are actively transported across the placenta beginning at 12 weeks of gestation. Although the Ro and La proteins are normally intracellular and thus inaccessible to circulating antibodies, they are expressed on the developing fetal heart at different stages of gestation. It has been demonstrated that anti-Ro/La antibodies bind to fetal but not adult heart, and direct binding to fetal cardiac proteins may trigger an inflammatory response and cause tissue damage . Despite exposure to the identical circulating autoantibodies, the maternal heart is never affected.   

            The exact pathogenetic mechanism of non-cardiac manifestations is still unknown, but it has been hypothesized that the timing of transplacental passage of maternal autoantibodies coincides with the period of maximal vulnerability of selected fetal organs .

Finally, it should be emphasized that specific maternal autoantibodies are probably necessary, but are not sufficient, for development of neonatal lupus. Several concomitant maternal, fetal or environmental risk factors may contribute to the pathogenesis of this disease.

Management

            Prior to the development of fetal echocardiography, auscultatory evidence of regular bradycardia alerted the clinician to the congenital heart block, which could only be confirmed after birth. Fetal echocardiography is now used to establish the diagnosis of congenital heart block and it is recommended that the fetuses of all women with anti-Ro/La antibodies be evaluated by serial echocardiography. Echocardiograms are done weekly from 16 to 26 weeks and every other week until 32 weeks. A recent major advance in echocardiography was the development of a new non-invasive Doppler technique to measure the mechanical PR interval, which has made possible the in utero detection of first-degree heart block in the absence of an electrocardiogram. This technique allows earlier diagnosis and has paved the way for effective prenatal treatment in fetuses with incomplete heart block .

            The most common prenatal interventions attempted are systemic glucocorticosteroids and medications to treat heart failure. The rationale for treatment of identified heart block with glucocorticosteroids is to diminish the cardiac inflammatory injury and to lower the maternal autoimmune response. Dexamethasone, which is not metabolized by the placenta and is available to the fetus in an active form, is given at a dose of 4 mg/day. Fetal risks secondary to dexamethasone include oligohydramnios, intrauterine growth retardation and adrenal suppression. Sympathomimetics, diuretics and fetal pacing are reserved for those cases where the fetus is in a life-threatening situation with hydrops and deteriorating cardiac function .

Postnatal treatment of the symptomatic infant with complete heart block is based on pacemaker implantation, and supportive treatment for low output or congestive heart failure. 

Cutaneous manifestations of neonatal lupus generally do not require any treatment; however; topical application of a mild glucocorticosteroid cream may hasten the resolution of the lesions and be used for cosmetic reasons. All infants whose mothers have anti Ro/La antibodies should be protected from excessive exposure to the sun, which may induce or exacerbate skin lesions. In most cases, hepatobiliary and hematological manifestations are self-limited and the usual approach to management is reassurance to the parents and continued observation of the infant (including determination of titers for antinuclear antibodies and antibodies against extractable nuclear antigens, liver function tests, complete blood count and electrocardiogram) at least until transplacentally acquired autoantibodies become undetectable.           

Prognosis     

Nearly all children with complete heart block require implantation of a pacemaker at some point in their lives, frequently in the neonatal period . Despite early pacing, complete heart block carries high neonatal morbidity and high mortality during the first 12 months of life .

If a mother has already had one child with congenital heart block, there is approximately a 15 to 20% risk of having another child with the same problem, supporting close fetal echocardiographic monitoring and considering therapeutic interventions .

Apart from cardiac disease, children with neonatal lupus grow and develop normally. They have only a slightly higher risk for developing autoimmune disease later in life attributable to the genetic predisposition . Parents of these infants should be counseled that the risk of their offspring developing autoimmune diseases is similar to the risk in children of women with SLE or another connective tissue disease.  

NEONATAL ANTIPHOSPHOLIPID SYNDROME

            Neonatal antiphospholipid syndrome (APS) is a rare clinical entity characterized by neonatal thrombotic disease [3]. Autoantibodies that have been causally associated with neonatal APS include antiphospholipid antibodies (aPL), namely the β₂ glycoprotein I – dependent anticardiolipin antibodies and lupus anticoagulants. These autoantibodies have a well-recognized pathogenic role in thrombotic diathesis and have been associated with a number of obstetric complications such as recurrent pregnancy loss, pre-eclampsia, fetal growth retardation and pre-term delivery [26]. While women with aPL  show an unusually high incidence of pregnancy complications, the aPL-related thrombosis in their offspring seems to be exceedingly rare. The low frequency of neonatal thrombosis has been attributed to the lack of the most known “second hit” risk factors in infants (such as atherosclerosis, cigarette smoking, oral contraceptives etc.), and to a low transplacental passage of IgG2 subclass of aPL, which are responsible for most clinical pathogenicity .

            Neonatal thromboses associated with transplacentally acquired aPL were most commonly described in cerebral vessels and abdominal organs; however, vascular occlusion in APS may involve the arteries and veins at any level of the vascular tree and in all organ systems . Special concern is needed particularly when dealing with aPL-positive infants who are exposed to other acquired thrombotic risk factors (i.e., central vascular catheters, sepsis, prematurity, congenital heart disease), and possibly inherited prothrombotic disorders (i.e., deficiencies of antithrombin III, protein C, protein S, factor V Leiden mutation). There have also been scattered reports of thrombotic events in the fetuses of aPL-positive women, resulting from intra-uterine exposure to aPL .

            Both aPL and anti-Ro/La antibodies may be simultaneously present in a woman with connective tissue disease making the distinction between neonatal lupus and neonatal APS sometimes difficult . In fact, some of the hematological and neurological manifestations reported in neonatal lupus could be related to the presence of aPL . At the present time, however, the exact clinical criteria for these clinical entities are not available.     

CHRONIC INFANTILE NEUROLOGIC CUTANEOUS AND ARTICULAR (CINCA) SYNDROME     

CINCA syndrome is a rare congenital inflammatory disease characterized by a triad of cutaneous rash, chronic meningitis and arthropathy . The gene defective in CINCA syndrome (CIAS1 gene; so named for cold-induced autoinflammatory syndrome) was identified by positional cloning and encodes a 920-amino acid protein cryopyrin, which is involved in the regulation of apoptosis . The CIAS1 gene is also the site of mutations causing two other autoinflammatory disorders, Muckle-Wells syndrome and familial cold autoinflammatory syndrome . Several distinct mutations have been identified in CIAS1 gene, but there is no apparent clustering of mutations associated with particular illness. Because of clinical similarities between these syndromes and the same apparent genetic basis, it has been proposed that they represent a spectrum of disease, with familial cold autoinflammatory syndrome the mildest and CINCA syndrome the most severe. Mutations in CIAS1 gene were only identified in approximately half of the patients with CINCA syndrome, which raises the possibility of genetic heterogeneity . 

The most striking feature of CINCA syndrome is the onset in the neonatal period. Persistent and migratory urticarial rash is often present at birth or develops within the first weeks of life. It can be confused with a systemic JIA rash, but is more pronounced and present for the life of the patient [42]. The joint manifestations usually begin in the first year of life and most commonly involve knees, ankles, elbows, wrists, hands and feet. They could be limited to mild arthritis during flare-ups or present with severe deforming arthropathy with typical radiographic changes . Joint enlargement in CINCA syndrome is described as hard and bony with deformities from epiphyseal and growth cartilage overgrowth, rather than the soft tissue and synovial proliferation seen in JIA. The most distinctive changes occur in the metaphyses and epiphyses of the femur, radius and tibia, resulting in premature growth plate closure and shortened long bones. A premature patellar ossification is frequent with a subsequent overgrowth of the patella. Neurological impairment results from chronic meningeal inflammation and is characterized by symptoms indicating meningeal irritation (i.e., headaches, vomiting, seizures, spastic diplegia) and progressive cognitive impairment. Significant sensory abnormalities including ocular manifestations, perceptive deafness and hoarseness commonly occur in older patients. In the worst cases, eye involvement can lead to a progressive visual defect and sometimes to blindness [45]. Distinctive morphological features with frontal bossing, hypoplastic midface, shortening of distal limbs with clubbing of the fingers and growth retardation have been described.

Laboratory investigations reveal iron-resistant hypochromic anemia, leukocytosis with neutrophilia and eosinophilia, high platelet counts, elevated erythrocyte sedimentation rate and polyclonal hypergammaglobulinemia. There are usually no autoantibodies or antigen-specific T-cells.

The course is one of a chronic, persistent inflammatory disease with numerous flare-ups associating fever, hepatosplenomegaly and lymphadenopathy. Significant musculoskeletal functional disabilities occur in more than 50% of those affected, and severe failure to thrive and short stature are present in virtually all patients. Progressive neurological involvement with consequent developmental delay can occur with time. The mainstay of current therapy for CINCA syndrome consists of symptomatic relief with the use of nonsteroidal anti-inflammatory drugs and glucocorticosteroids. Patients may also benefit from physiotherapy, splinting and occupational therapy. No therapeutic approach has been effective in altering the course of the disease.

OTHER DISORDERS

Systemic juvenile idiopathic arthritis (JIA)

            Neonatal onset of systemic JIA (Still’s disease) is exceedingly rare, but needs to be considered in the differential diagnosis of a neonatal rash associated with systemic inflammatory signs . A neonate with evanescent rash that appeared on the second day of life in association with fever has been reported . Over the first weeks of life, the infant developed lymphadenopathy and hepatosplenomegaly. At 15 months he presented with arthritis of the right knee joint, confirming the diagnosis of systemic JIA.      ’

Behçet’s disease

A transient form of Behçet’s disease may develop in a neonate of a mother with this disease. In all reported neonatal cases, mothers had oral and genital ulceration during the pregnancy . The condition is thought to be transmitted by an immune mechanism similar to the mechanism of neonatal lupus; however, the causative autoantibodies for neonatal Behçet’s disease have not been identified. The most common features of neonatal Behçet’s disease include fever, orogenital ulcerations, pustulonecrotic skin lesions, bloody diarrhea, stridor and intrauterine growth retardation. A case of transient neonatal Behçet’s disease with life-threatening complications has also been reported. This baby developed pyrexia, blood-streaked diarrhea, vasculitic skin lesions and recurrent oral and pharyngeal ulcers, resulting in progressive inspiratory stridor and respiratory arrest . Clinical manifestations of neonatal Behçet’s disease usually develop within 1 week of birth and resolve by the age of 8 weeks, supporting the hypothesis that the disease is caused by the transplacental passage of maternal antibodies. Healing of the severe ulceration may result in extensive scarring and therapeutic intervention with glucocorticosteroids is recommended after diagnosis. Before applying this treatment, a disseminated infection (e.g. herpesvirus, Staphylococcus) must be excluded.     

Polyarteritis nodosa and other rare vasculitides

Vasculitis in a neonate born to a mother with vasculitis is a rare event and only few isolated cases have been described. At least three cases of neonatal vasculitis have been reported in infants born to mothers with cutaneous polyarteritis nodosa [54-56]. During the neonatal period these infants developed cutaneous vasculitis manifested by livedo reticularis, cutaneous nodules and acral necrosis. In all the cases, the vasculitis was confined to early infancy, suggesting that the disease was caused by a maternal factor that crossed the placenta.     

Kawasaki disease

Kawasaki disease is rarely encountered in the neonatal period. Of the 105,755 patients with Kawasaki disease included in the Japanese database over 25 years, only six were neonates . The rarity of disease in neonates has been explained by the protective effects of the transplacentally transferred maternal IgG immunoglobulins. Alternatively, the rare incidence rate at this age may be explained by infection theory, since neonates usually stay at home and seldom have chance to be exposed to the infectious agents. The reported neonatal cases had a rapid and severe course, and usually presented with atypical clinical features. In particular, they had a higher incidence of cardiac complications and usually did not fulfill the established diagnostic criteria of Kawasaki disease .

Other miscellaneous disorders

A number of other unrelated disorders may present in the neonatal period and should be considered in the differential diagnosis. They include hyper-IgD syndrome, acute febrile neutrophilic dermatosis (Sweet’s syndrome), histiocytosis, mastocytosis, neonatal infections, as well as selected metabolic diseases and primary immunodeficiencies in which autoimmune disorders may occur . 

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60. Quartier P, Prieur AM. Immunodeficiency and genetic conditions that cause arthritis in childhood. Curr Rheumatol Rep 2002; 4: 483-93.
61. Abu-Ras R, Felser K, Rottem M. Maternal antiphospholipid syndrome presenting as neonatal lupus with congenital complete heart block in the fetus. IMAJ 2001; 3: 966-8.
62. Hariharan D, Manno CS, Seri I. Neonatal lupus erythematosus with microvascular hemolysis. J Pediatr Hematol Oncol 2000; 22: 351-4.
63. Besson-Leaud L, Fontan D, Billeaud C, Sandler B. Neonatal lupus erythematosus and neurologic involvement: an incidental association? Arch Pediatr 2002; 9: 503-5.
64. Prieur AM, Griscelli C. Arthropathy with rash, chronic meningitis, eye lesions, and mental retardation. J Pediatr 1981; 99: 79-83.
65. Hassink SG, Goldsmith DP. Neonatal onset multisystem inflammatory disease. Arthritis Rheum 1983; 26: 668-73.
66. Prieur AM. A recently recognized chronic inflammatory disease of early onset characterized by the triad of rash, central nervous system involvement and arthropathy. Clin Exp Rheumatol 2001; 19: 103-6.
67. Feldmann J, Prieur AM, Quartier P, et al. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet 2002; 71: 198-203.
68. Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 2002; 46: 3340-8.
69. Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of a new gene encoding a putative pyrin-like protein causes familial autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 2001; 29: 301-5.
70. Hashkes PJ, Lovell DJ. Recognition of infantile-onset multisystem inflammatory disease as a unique entity. J Pediatr 1997; 130: 513-5.
71. Kaufman RA, Lovell DJ. Infantile-onset multisystem inflammatory disease: radiologic findings. Radiology 1986; 160: 741-6.

Supported  by
CLINIC FOR CHILDREN 

Yudhasmara Foundation 

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646 

http://childrenclinic.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

email : judarwanto@gmail.com

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.

Copyright © 2009, Clinic For Children Information Education Network. All rights reserved.

Milia

MILIA AND BABY ACNE

These commonly occur on the face and scalp, and consist of tiny white papules which are usually discrete.  They can however occur anywhere, and may be present at birth or appear subsequently.  They usually resolve within a few months without treatment.

Milia are inclusion cysts which contain trapped keratinised stratum corneum.  They may rarely be associated with other abnormalities in syndromes including epidermolysis bullosa and the oro-facial-digital syndrome (type 1).

Similar lesions may be seen in the mouth in some infants.  When on the hard palate, they are referred to as Epstein’s pearls; when on the alveolar ridges, they are called alveolar cysts or Bohn’s nodules.

Mongolian spot

Blue-gray spots, commonly referred to as Mongolian spots, are large flat lesions that are usually found on the lower back or buttocks of infants at birth. They can occasionally be found on the legs or shoulders of infants, but this is less common. The color of blue-gray spots ranges from deep brown to slate gray or blue-black. They are caused by collections of pigment-producing cells (melanocytes) located in a deeper layer in the skin and are the most common type of birthmark.

The photos show a typical Mongolian spot with bluish discoloration.

This is a very common benign skin pigmentation occurring frequently in Polynesian, Asian and Mediterranean babies but also, though to a much lesser extent, in Europeans.

Although the intergluteal area is the most common site, similar lesions may occur over the trunk or extremeties and at times multiple lesions may be noted. Such lesions have been confused for bruises of child abuse. They gradually fade during the first few years of life

Sucking Blisters

These lesions are present at birth, most often over the dorsal and lateral aspect of the wrist. They may appear like well demarcated bruises or they may be vesicular. They can be either bilateral or unilateral. Less often, they may be noted more proximally in the forearm. The infant is noted to exhibit excessive sucking activity. The absence of lesions in other parts of the body and the otherwise well appearance of the infant would rule out pathological disorders presenting with similar lesions.

In the lower image, the blister present on the dorsal surface of the second finger burst open discharging yellow serous fluid. Such a lesion may be confused with bullous impetigo but the time of onset, the location and the examination should differentiate the two.

Benign Pustular Melanosis of the Newborn

Lesions are present at birth and are characterised by superficial pustules which rupture easily without any actual pus content, leaving a spot of hyperpigmentation. Some hyperpigmented lesions may be present at birth. Any area of the body may be involved. The pustules last for a day or two but the pigmented spots may persist for a long time. Aetiology is unknown. Smears from the pustules reveal polymorphonuclear leukocytes with absence of organisms.

In the image to the left, this baby’s rash appeared on the second day of life which is atypical for this condition. The pustules were profuse, covering almost the entire body. Note very early pigmentation at around 1 o’clock. Wright stain from one lesion revealed neutrophils and no organisms.

Nappy Rash (Diaper Dermatitis)

Nappy rash is a common problem for neonates within the first few months of life. Whilst the exact aetiology of nappy rash is not clear, it is felt to be due to moisture in the nappy environment and from irritation from urine and stool. Many infants will be affected by superinfection with Candida albicans.

Typically in Candidal nappy rash, there is erythema in the perineal region, with satellite lesions which may coalesce. There is often an appearance of scale. In the images to the left from the same baby, satellite lesions are seen. Note that there are some lesions close to the umbilicus and extending around the flank. Swabs were positive for Candida.

Treatment primarily involves the use of a topical agent such as nystatin or miconazole. There should be liberal use of barrier creams, and soiled and wet nappies should be changed promptly. Oral nystatin may be used in conjunction with topical treatment, although this may not improve resolution. Occasionally, in severe cases, a mild topical steroid may be needed.

Conditions that need to be considered in the differential diagnosis include psoriasis, contact or irritant dermatitis, and zinc deficiency.

Neonatal acne

Neonatal acne may be present at birth, or develop over the first 2-4 weeks of life.  There is controversy over whether it is truly acne or whether it represents a form of pustular disorder in the newborn period.  As a result, the term neonatal cephalic pustulosis has been mooted.

The condition consists of pustules over the cheeks primarily, but also involves other areas of the face and the scalp.  As opposed to infantile acne (which develops after 2 months) and acne of adolescence, there are no comedomes in the neonatal form.  It may be difficult to differentiate between acne and miliaria rubra.

Neonatal acne resolves spontaneously and without scarring.

Seborrhoeic dermatitis

Seborrhoeic dermatitis primarily affects the scalp and intertriginous areas. It is most common in the first 6 weeks of life, but can occur in children up to 12 months of age.  Involvement of the scalp is frequently termed “cradle cap”, and manifests as greasy, yellow plaques on the scalp.  Other commonly affected areas include the forehead and eyebrows (as in the photo to the left), nasolabial folds, and external ears.  Involvement of skin creases, such as the nappy area, can lead to secondary Candidal infection and maceration.

The aetiology is unknown.  Treatment includes the use of a mild tar shampoo, oatmeal baths, and avoidance of soaps.  Occasionally, a mild topical steroid may be indicated.

Miliaria

Miliaria is due to obstruction of sweat and rupture of the exxrine sweat duct.  It is commonly seen secondary to thermal stress, particularly with crops of lesions over the face, scalp, and trunk. In neonates, there are two forms:

1. Miliaria crystallina (see image to the left), in which there are superficial vesicles which are 1-2mm in diameter.  The skin does not appear inflamed.

1. Miliaria rubra (also called “prickly heat”) results in papules and pustules from obstruction in the mid-epidermis.

It is important to ensure that the baby is not over-wrapped, and once the heat stress is removed the lesions usually resolve quickly.

Erythema Toxicum Neonatorum

 Onset in the second to third day of life, mostly in term babies of lesions characterised by a central whitish to yellowish papule surrounded by a halo of erythema, mainly over the trunk but also in the limbs and face. Lesions may intensify or coalesce particularly in response to local heat. They wax and wane over the ensuing 3 to 6 days. They are benign. Aetiology is unknown.

Supported  by
CLINIC FOR CHILDREN 

Yudhasmara Foundation 

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646 

http://childrenclinic.wordpress.com/

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO

email : judarwanto@gmail.com

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.

Copyright © 2009, Clinic For Children Information Education Network. All rights reserved.

Ritter’s disease

STAPHILOCOCCUS SCALDED SKIN SYNDROME

Myelomeningocele

TETANUS NEONATORUM

Supported  by
CLINIC FOR CHILDREN 

Yudhasmara Foundation 

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646 

http://childrenclinic.wordpress.com/ 

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO 

email : judarwanto@gmail.com

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.

Copyright © 2009, Clinic For Children Information Education Network. All rights reserved.

• Fernandes A, Falcao AS, Silva RF, Gordo AC, Gama MJ, Brito MA, et al. Inflammatory signalling pathways involved in astroglial activation by unconjugated bilirubin. J Neurochem. Mar 2006;96(6):1667-79. [Medline].
• Pashapour N, Nikibahksh AA, Golmohammadlou S. Urinary tract infection in term neonates with prolonged jaundice. Urol J. 2007;4(2):91-4; discussion 94. [Medline].
  • Toietta G, Mane VP, Norona WS, Finegold MJ, Ng P, McDonagh AF, et al. Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci U S A. Mar 15 2005;102(11):3930-5. [Medline].
  • Urawa N, Kobayashi Y, Araki J, Sugimoto R, Iwasa M, Kaito M. Linkage disequilibrium of UGT1A1 *6 and UGT1A1 *28 in relation to UGT1A6 and UGT1A7 polymorphisms. Oncol Rep. Oct 2006;16(4):801-6. [Medline].
  • Vítek L. Etiology of fasting hyperbilirubinemia: genetic factors versus enhanced enterohepatic cycling of bilirubin. Gastroenterology. Nov 1999;117(5):1255-6. [Medline].
  • Risk factors for severe hyperbilirubinemia in neonates. Huang MJ, Kua KE, Teng HC, Tang KS, Weng HW, Huang CS.Pediatr Res. 2004 Nov;56(5):682-9. Epub 2004 Aug 19.
  • UGT1A1 gene polymorphisms in North Indian neonates presenting with unconjugated hyperbilirubinemia. Agrawal SK, Kumar P, Rathi R, Sharma N, DAS R, Prasad R, Narang A. Pediatr Res. 2009 Jun;65(6):675-80.
  • Unconjugated bilirubin exposure impairs hippocampal long-term synaptic plasticity. Chang FY, Lee CC, Huang CC, Hsu KS. PLoS One. 2009 Jun 11;4(6):e5876.
  • Hyperbilirubinemia diminishes respiratory drive in a rat pup model. Mesner O, Miller MJ, Iben SC, Prabha KC, Mayer CA, Haxhiu MA, Martin RJ. Pediatr Res. 2008 Sep;64(3):270-4.
  • [Prolonged icterus as a difficult diagnostic problem in small children--own observations] Kramer B, Dółka E, Michalecka J, Zentera K. Med Wieku Rozwoj. 2007 Jan-Mar;11(1):51-6. Polish.
  • [Arias icterus--prolonged unconjugated hyperbilirubinemia caused by breast milk] Mladenović M, Radlović N, Ristić D, Leković Z, Radlović P, Pavlović M, Gajić M, Puskarević M, Davidović I, Djurdjević J. Srp Arh Celok Lek. 2007 Nov-Dec;135 11-12:655-8. Serbian.
  • Urinary tract infections in infants: comparison between those with conjugated vs unconjugated hyperbilirubinaemia. Lee HC, Fang SB, Yeung CY, Tsai JD. Ann Trop Paediatr. 2005 Dec;25(4):277-82.
  • Neonatal hypopituitarism presenting with poor feeding, hypoglycemia and prolonged unconjugated hyperbilirubinemia. Scott R, Aladangady N, Maalouf E. J Matern Fetal Neonatal Med. 2004 Aug;16(2):131-3.
  • Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene. Maruo Y, Nishizawa K, Sato H, Sawa H, Shimada M.Pediatrics. 2000 Nov;106(5):E59.
  • Gilbert’s syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn. Monaghan G, McLellan A, McGeehan A, Li Volti S, Mollica F, Salemi I, Din Z, Cassidy A, Hume R, Burchell B.J Pediatr. 1999 Apr;134(4):441-6.
  • Breast milk beta-glucuronidase in breast milk jaundice. Yau KI, Chien CH, Fong LL, Chen CL.J Formos Med Assoc. 1992 Mar;91(3):287-93.
  • Fetal exposure to maternal hyperbilirubinemia. Neonatal course and outcome. Waffarn F, Carlisle S, Pena I, Hodgman JE, Bonham D. Am J Dis Child. 1982 May;136(5):416-7.
  • Prolonged neonatal jaundice: a manifestation of heterozygote state for Crigler–Najjar syndrome? Odièvre M, Luzeau R, Alagille D. J Pediatr Gastroenterol Nutr. 1982;1(2):239-41.
  • High milk lipase activity associated with breast milk jaundice. Poland RL, Schultz GE, Garg G.Pediatr Res. 1980 Dec;14(12):1328-31.
  • Proceedings: Relationship between milk feeding and prolonged unconjugated hyperbilirubinemia. Eylath U, Isacsson M. Isr J Med Sci. 1975 Nov;11(11):1219. No abstract available.
  • PROLONGED NEONATAL UNCONJUGATED HYPERBILIRUBINEMIA ASSOCIATED WITH BREAST FEEDING AND A STEROID, PREGNANE-3(ALPHA), 20(BETA)-DIOL, IN MATERNAL MILK THAT INHIBITS GLUCURONIDE FORMATION IN VITRO.ARIAS IM, GARTNER LM, SEIFTER S, FURMAN M.J Clin Invest. 1964 Nov;43:2037-47. No abstract available.

Supported  by
CLINICAL PEDIATRIC ONLINE 

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

WIDODO JUDARWANTO

email : judarwanto@gmail.com,

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

J Pediatr. 2009 Aug 13. [Epub ahead of print] PMID: 19683255 [PubMed - as supplied by publisher]

Chang PF, Lin YC, Liu K, Yeh SJ, Ni YH.

From the Department of Pediatrics (P.-F.C., Y.-C.L., K.L., S.-J.Y.), Far Eastern Memorial Hospital, Pan-Chiao, Taipei, Taiwan; and National Taiwan University Children’s Hospital (Y.-H.N.), Taipei, Taiwan.

OBJECTIVE: To test the hypothesis that a mutation in uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) gene of breast-fed infants is a contributory factor to prolonged unconjugated hyperbilirubinemia. STUDY DESIGN: Of 125 breast-fed term infants, 35 infants had prolonged unconjugated hyperbilirubinemia; another 90 breast-fed neonates without prolonged jaundice were control infants. The polymerase chain reaction-restriction fragment length polymorphism method was used to detect the known variant sites (promoter area, nucleotides 211, 686, 1091, and 1456) of the UGT1A1 gene. RESULTS: Of 35 breast-fed infants with prolonged unconjugated hyperbilirubinemia, 29 had at least 1 mutation of the UGT1A1 gene. Variation at nucleotide 211 was most common. The percentages of the neonates carrying the variant nucleotide 211 were significantly different between the prolonged hyperbilirubinemia group and control neonates. Male breast-fed infants had a higher risk than female infants for prolonged hyperbilirubinemia. CONCLUSIONS: Male breast-fed neonates with a variant nucleotide 211 in UGT1A1 have a high risk for developing prolonged hyperbilirubinemia.

Supported  by
CLINICAL PEDIATRIC ONLINE 

Yudhasmara Foundation

JL Taman Bendungan Asahan 5 Jakarta Indonesia

phone : 62(021) 70081995 – 5703646

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

Clinical and Editor in Chief :

WIDODO JUDARWANTO

email : judarwanto@gmail.com,

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.