Preconception Care: Intention to prevent congenital anomalies. Prevention of neural tube defects by folic acid supplementation. Glucose control in DM resulting in lower incidence of abnormalities. Proper nutrition, exercise, smoking cessation, abstinence from Alcohol Protection from radiation (x rays), and drugs to avoid teratogenicity Infection control: STD and rubella Tx, hepatitis immunity status
Prenatal Care GYN-Menstrual History / Parental medical history: DM, Htn, Cardiac, Thyroid, Anemia, Genetic disease, Habits: Tobacco, Alcohol, Drugs, Diet, Activities, Caffeine intake, Meds Obstetric History: -Dates of all pregnancies including termination, spontaneous abortion -Outcome and gestational length of pregnancy -Neonatal complications, Rh incompatibility, Malformations -Weight, Apgar score, and number of live born infants. -Types of delivery: vaginal delivery, forceps, C-section, Breech Complications: Shoulder dystocia, premature labor, placenta previa, post-partum hemorrhage
Laboratory Evaluation-Baseline -CBC (Ht/Hb), U/A (protein, glucose, C/S), ABO blood type, Rh type -VDRL/RPR test, Cervical culture for GC and Chlamydia -Rubella antibody titer, Hepatitis B surface antigen, CMV titers, Toxoplasmosis antibody test - Hemoglobin electrophoresis for risk groups: Sickle cell in African American, B-thalassemia in Mediterranean -Tay-Sachs, Gaucher, Kanavan, Newman-Pick testing in Jews -HIV antibody testing if suspected ( patient authorization)
During Pregnancy 1. 10 weeks. Chorionic Villus Sampling (TAY-SACHS) 2. 15-18 weeks. Serum triple-screen for NTD (AFP, beta-HCG, estriol) or Serum quadruple by adding Inhibin. AFP down, B-HCG up, Estriol Down = DOWN Syndrome or chromosomal defect AFP elevated levels = Fetal neural tube defects 3. 15 -19 weeks. Amniocentesis (karyotypic/cong ab,), TAY-SACH TEST U/S ↑ 35 Y (risk of genetic or chromosomal disorders) 4. 26 weeks. Blood glucose screen (one hour Glucola test). 5. 26-32 weeks. Ht / Hb (Iron def.) and L/S ratio 2:1 (fetal lung maturity) 6. 34-36 weeks. Consider GC, Chlamydia, Herpes, Syphilis screening in high-risk women. 7. 36-37 weeks. Screening for G-B Streptococcus
Fetal Assessment Alfa feto-protein: increase: NTD, anencephaly, renal agenesis decrease: IUGR, Chromosomal Trisomies 13-18-21 Amniotic Fluid Volume Estimation: Oligohydramnio: (Less than 500 ml of fluid) ↓ of the amniotic fluid. Rupture of the membranes is the most common cause. Other causes include: Placental Insufficiency, Associated with renal or urologic abnormalities, IUGR, lung hypoplasia, premature rupture of membranes. Polyhydramnio: (More than 2L of fluid). Excess of amniotic fluid. It is associated with diabetes, CNS defects such as: Anencephaly, Neural Tube Defects. Suggestive of GI anomalies such as Upper Intestinal obstruction like: Duodenal atresia, tracheo-esophageal fistula.
Chorionic Villus Sampling: Done in the first trimester for genetic studies. The cells obtained are identical to those of the fetus, grown and analyzed. Complications include pregnancy loss and limb abnormalities. Amniocentesis: Amniotic Fluid (20 ml) is withdrawn under US guidance, and is analyzed for prenatal diagnosis of karyotypic abnormalities such as: congenital defects, fetal lung maturity, and NTD. Complications include pregnancy loss, amniotic fluid leakage, fetal injury This process is indicated for: Women over 35 y. of age: ↑ risk of malformations- 21, 18, 13 trissomy Women who had a child with a chromossomal abnormality. To rule out Inborn Errors of Metabolism
Test of Fetal Lung Maturity Lecithin: Sphingomyelin (L:S) Ratio Lecithin: phosphatidylcholine measured in the amniotic fluid, being the active component of surfactant. Is manufactured by alveolar type II cells. Sphingomyelin is a phospholipid, found in body tissues other than lungs. The L:S ratio compares levels of lecithin which increases in late gestation, to levels of Sphingomyelin that remains constant. The L:S ratio is 1:1 by 31-32 weeks, and 2:1 by 35 weeks gestation. L:S-2:1 Lungs are mature (98% accuracy). L:S-1.5-1.9 50% will develop Respiratory Distress Syndrome L:S-1-1.5 73% will develop Respiratory Distress Syndrome
OBSTETRIC COMPLICATIONS ASSOCIATED WITH FETAL OR NEONATAL RISK Vaginal Bleeding: In the 1 st or early in 2 nd trimester. due to threatened or actual spontaneous abortion Vaginal bleeding with Continuous Pregnancy: Fetus at risk for congenital or chromosomal disorders . Premature Rupture of Membranes: Occurs in absence of labor. Associated with risk of maternal or fetal infection: G-B Strep, E.coli, lysteria Prolonged Rupture of the Membranes: Greater than 24 Hours. Associated with risk of maternal or fetal infection: G-B Strep, E.coli, lysteria Toxemia of Pregnancy or Pre-Eclampsia: Is probably of vascular etiology that may result in: Maternal HTN, IUGR IU asphyxia. Vaginal Bleeding that is painless: Is not associated with labor. Occur in late 2nd or in the 3rd trimester. Often is Placenta Previa -
Abnormalities of Placenta: Large infarcts: Associated with mal-nutrition. Placenta Previa: Premature separation of placenta and impairment of fetal O2 Large Placenta: Associated with erythroblastosis fetalis and maternal diabetes. Amniom Nodosum: Associated with hypoplastic lung and polycystic kidneys Small Placenta: Associated with SGA infant. Amniotic Fluid: Clear: Normal Dark Green: Meconium stained. Consider recent IU anoxia Yellow: Intrauterine anoxia episode of 10 days previously Clots: Placental hemorrhage Light Green: Bile stained. Consider intestinal obstruction. Brown-Hazel: Fetal death
PLACENTA PREVIA PLACENTA PREVIA OCCURS WHEN ANY PART OF THE PLACENTA IMPLANTS IN THE LOWER UTERINE SEGMENT
ABRUPTIO PLACENTA COMPLETE OR PARTIAL PLACENTAL SEPARATION FROM THE DECIDUA BASALIS AFTER 20 WEEKS GESTATION
Malformation abnormality of embryonic morphogenesis of tissue. It usually results from genetic, chromosomal, or teratogenic influences. Malformations often require surgical intervention. Deformation represents a change in shape, form, or position of a normal body part or organ due to exposure to mechanical or extrinsic forces. Majority of deformations respond to medical therapy alone Disruption represents a defect caused by a breakdown in a normal body part or organ. A classic example is the combination of clefting, constriction bands, and limb reduction defects associated with the presence of amniotic bands . Dysplasia is characterized by abnormal organization of cells within tissue, which usually has a genetic basis. An example is achondroplasia, the most frequent form of skeletal dysplasia. Each of these categories can have a sequence associated with it. Sequence refers to a recognizable pattern of multiple anomalies that occurs when a single problem in morphogenesis cascades, resulting in secondary and tertiary errors in morphogenesis and a corresponding series of structural alterations. Pierre-Robin Association An association is a pattern of malformations that occurs together too frequently to be due to random chance alone, but for which no specific etiology is yet recognized. Mosaicism Presence of two or more genetically different cell lines in the same individual, where one is normal. Karyotype test to detect abnormal numbers of chromosomes and deletions, translocations, large enough to be seen by light microscopy. FISH Fluorescence in situ hybridization: Hybridization of a fluorescently tagged DNA probe to chromosome, allow a detection of submicroscopy deletions and duplications classifications of structural anomalies
ABNORMALITIES OF AUTOSOMES 1- DOWN SYNDROME- TRISOMY 21 2-TRISOMY 13 3-TRISOMY 18
TRYSSOMY 21- DOWN SYNDROME Is a syndrome consisting of multiple abnormalities. It is the most common autosomal chromosomal abnormality. Incidence: 1:600 live births Male : Female ratio is 1.3:1 Maternal age: 15-29 years 1/1500 30-34 years 1/800 35-39 years 1/250 40-44 years 1/100 Over 45 years 1/50 Genetics: 90-92% of cases are due to chromossomal non-disjunction (failure to segregate during meiosis) in the maternal DNA and 3% in the paternal DNA 4% due to Translocation between chromossome 21 and 14 1% Mosaic
S/S: General: Short stature, Hypotonia , mongoloid facies, Head: Brachicephaly w/ a flattened occiput , Microcephaly, delay closure of fontanels Eyes: Upward palpebral fissures, inner epichantal folds, Brushfields spots (specking of the iris), lens opacities, cataracts, nystagmus Ears: Small, prominent, low-set Nose: Small, flat or depressed nasal bridge Mouth: Palate high and narrow Tongue: Macroglossia, open mouth, protrusion of the tongue (small mandible and maxilla) Teeth: Missing in 50%, small, hypoplastic, irregular placement Neck: Short appearance, sometimes webbed, atlanto-axial instability Heart: Assess for murmurs, arrhythmias (AV canal), cyanosis. CHD, VSD Abdomen: Diastesis recti, ↑ frequency of duodenal/esophageal atresia Genital: in Males: small penis, cryptorchidism Extremities: Hands with short metacarpals and broad phalanges. 5th finger with hypoplasia of the mid phalanx (clinodactily) , syndactily Simian crease (single transverse palmar crease). Wide gap between 1st and 2nd toe (sandal Gap) Skin: Infant: Cutis marmorata, velvety skin. Adolescent: Coarse, dry skin Neurology: Poor Moro reflex, mental retardation, Developmental delay.
Increased risk for: Leukemia, hypothyroidism, cataracts, Otitis media LAB: -Prenatal karyotyping via amniocentesis or chorionic villus sampling. -Chromossomal karyotype on cultured lymphocytes from peripheral blood. You do it postnatally, if you suspect Down -Auditory brain stem evoked response at 6 months of life. Vision at 4 Y. -TSH, T4 Imaging: Fetal U/S: Polyhydramnio ECHO/ CX-Ray: R/O cardiac disease TX: *Supportive *Genetic counseling *Referral to specialists
TRYSSOMY 13- PATAU’S SYNDROME 1/7000 live births Highly lethal within the first 3 months of life. Survival after 6 month is 5% S/S: General: prenatal/postnatal growth retardation, Developmental Delay Head/Face: Severe brain abnormalities ( holoprosencephaly ) ( failure of the forebrain to divide properly) Scalp defect (aplasia cutis congenita) Microphaltmia, corneal abnormalities Cleft lip/palate Microcephaly Deafness Low set of ears Chest: Congenital heart disease (ASD, VSD, PDA), missing ribs. Extremities: Overlapping of fingers / toes, polydactily, hypoplastic and hyperconvex nails Others anomalies: Cystic kidneys, hooked penis Dx: Karyotype study with FISH analysis Most children die in the first year. Survivors are retarded
Trisomy 13 at age 7 years (survival beyond the first year is uncommon). He is deaf and legally blind.
TRYSSOMY 18 - EDWARDS TRYSSOMY Incidence: 1:5000 live births Highly lethal within the first 3 months of life. 10% survive the 1 st year Only 5% live up to 1 year of life S/S: Prenatal/postnatal growth deficiency, premature birth, Developmental Delay Head/face: Small and premature appearance, Microcephaly Narrow nose and hypoplastic nasal alae Narrow bifrontal diameter, Prominent occiput Micrognathia , Cleft lip/palate, low set of ears Chest: Congenital heart disease (ASD,VSD, PDA). Short sternum, Extremities: Clinodactily, clenched hands with overlapping 2 nd -5 th fingers , hypoplastic nails rocker-bottom feet Dx: Karyotype study with FISH analysis 50% die in first week, 99% die by 1 year
Trisomy 18 (Edwards syndrome), exhibiting characteristic facial features, short sternum, overlapping fingers with clenched fists, and a left-sided clubfoot
ABNORMALITIES OF SEX CHROMOSSOMES 1- TURNER SYNDROME 2- KLINEFELTER SYNDROME
TURNER SYNDROME 45X, XO (mosaic) Karyotype. Absence of one X chromosome 1/2000 births Clinical manifestations: Short Stature, Low hairline, webbed neck, underdeveloped breasts wide hypoplastic nipples, horseshoe kidney, Shield (broad) chest Heart: CoA, bicuspid aortic valve and high BP. Neonates: Carpal/pedal edema can reappear in adolescence (lymphedema) Primary amenorrhea: No estrogen production with ↑ gonadotropins ovarian failure. Delayed puberty gonadal failure, sterility, Infantile uterus, sparse pubic and axillary hair Mental development is normal, having problems in the spatial perceptual ability Dx: Chromossomic (Karyotype) study. Often, the missing sex chromosome is paternally derived EKG, Renal US, Hearing screening Tx: Girls with Turner syndrome should receive appropriate hormone therapy during adolescence such as Growth hormone, and estrogens replacement to ensure normal sexual characteristics
KLINEFELTER SYNDROME 47, XXY karyotype (80%) Incidence of 1/1000in males Postpubertal males signs appears: Male Infertility from hypogonadism with hypospermia or aspermia. (Seminiferous tubular function is lost, causing infertility) Small and soft testes, gynecomastia , small penis Tall stature with intelligence in the normal range, may have educational/psychological problems Long limbs, Scoliosis may develop during adolescence. Behavioral problems may be more common than in the population at large Dx: Gonadotropins levels are elevated unless normal levels of testosterone are produced. TX: Testosterone replacement injections : promotes secondary sexual characteristics.
A, Relatively narrow shoulders, increased carrying angle of arms, female distribution of pubic hair and normal penis but with small scrotum due to small testicular size. B, Small testes and penis. C, Gynecomastia
FRAGILE X SYNDROME Fragile X syndrome is a X-linked condition caused by allelic expansion (mutation) of a trinucleotide repeat disorder CGG in the FMR1 gene. Incidence: 1 / 4000 S/S: Developmental delay: speech delay, poor motor coordination, learning disabilities Behavioral disorder: Disciplinary problems, temper tantrums, hyperactivity, mood disorders, schizoid personality, and significant disturbances in affect, socialization, and communication Cognitive impairment: Decrease IQ 28-49 range Head/Face: Macrocephaly, Long Face, Large forehead, Prominent ears, Prominent mandible, Flattened nasal bridge Hyperextensible joints, Velvety skin Mitral Valve Prolapse Macroorchidism( adolescence) Dx : DNA molecular genetic test: Southern blot analysis of DNA extracted from cells, usually in blood Polymerase chain reaction (PCR) analysis of DNA, is done with less blood Tx: Early intervention, including speech and language therapy and occupational therapy. Stimulants, antidepressants, and antianxiety drugs may be beneficial for some children
Fragile X Syndrome. A and B, Note the long, wide, and protruding ears, elongated face, and flattened nasal bridge. C, Macro-orchidism in adult man with fragile X syndrome.
fragile X syndrome. Note the prominent and elongated ears and long face.
DISORDERS OF IMPRINTING 1- PRADER-WILLI SYNDROME 2- ANGELMAN SYNDROME
PRADER-WILLI SYNDROME A chromosome deletion of 15q11-q13 including the Prader-Willi critical region of the paternally derived chromosome 15 (majority of cases). Maternal uniparental disomy (UPD) child inherits both copies of chromosome 15 from mother S/S: Newborn: hypotonia, history of decreased fetal movement in utero poor sucking and swallowing FTT baby's cry may be weak Mental retardation motor development/speech is delayed Infancy Hypotonia Hyperphagia Morbid Obesity (trunk, buttocks, proximal limbs) Facies: bifrontal diameter is narrow, the eyes are often described as "almond shaped," strabismus is not unusual. Skin: Hypopigmentation, hair blonde to light brown, blue eyes Extremities: Hands and feet are small from birth Short stature Genitals: Penis and testes are hypoplastic in males. Menarche in females is delayed or absent, and menses, when present, are sparse and irregular. Gonadotropic hormone levels are reduced in both sexes. Infertility is the rule. Lab: High resolution karyotype, Methylation studies, Appropriate DNA FISH probes Tx: Supportive, multispecialty
Prader-Willi syndrome. A, This patient demonstrates the marked obesity characteristic of Prader-Willi syndrome. Excess fat is distributed over the trunk, buttocks, and proximal extremities. B and C, Small hands (and feet) and a hypoplastic penis and scrotum are other typical features.
Prader-Willi syndrome (note the inverted V-shaped upper lip, small hands, and truncal obesity).
ANGELMAN SYNDROME Angelman syndrome are disorders that derive from abnormalities of imprinted genes. The critical region of chromosome 15q11-q13 for Angelman syndrome is located adjacent to the Prader Willi critical region. Paternal UPD (uniparental disomy) child inherits both copies of chromosome 15 from father Incidence of 1 in 15,000 to 1 in 20,000 live births. S/S: Neuro: Developmental delay, Hypotonia Severe cognitive deficits; speech is impaired or absent Spontaneous laughter Major motor seizures are common. Gait is ataxic, with toe-walking (abnormal puppet-like gait) Jerky arm movements/hand flapping. Head/Face: Microbrachycephaly Maxillary hypoplasia Large mouth Prognathism Short stature (in adults)
Dx: Because of complexity of the diagnostic process, families of children suspected should be referred for genetic evaluation and diagnostic testing DNA methylation analysis identifies approximately 80% of AS and is the single most sensitive test for AS. If DNA methylation analysis is normal, UBE3A sequence analysis is the next appropriate diagnostic test. If the DNA methylation analysis is positive, the next step is FISH analysis. If the FISH analysis is normal, studies using DNA polymorphism analysis can be used to distinguish UPD (uniparental disomy).
Marfan Syndrome Is a genetic disorder of connective tissue that is inherited as an autosomal dominant trait. The site of the genetic abnormality or mutation is the Fibrillin gene on chromosome 15. S/S: Eyes: Subluxation of the lens usually displaced in an upward direction. Myopia and astigmatism are common risk for developing glaucoma, cataracts, and retinal detachment in adulthood. Iridodonesis (tremulosness of the Iris) Musculoskeletal: arachnodactyly, joint hyperextensibility due to ligamentous laxity tall stature with long, thin extremities an arm span that exceeds height pectus excavatum or carinatum Pes planus and thoracolumbar kyphoscoliosis The incidence of hernias, both inguinal and femoral Heart: Mitral valve prolapse (MVP) progressing to mitral insufficiency Aortic aneurysm (changes in the root and ascending aorta) Acute aortic dissection before 10y. Presence of a high arched palate is common. Marfan individuals are of normal intelligence, an occasional patient may have learning disabilities. Dx: Clinical, Echo/MRI, Multispeciaty, Slit-Lamp Tx: Beta-Blockers, Elective aortic repair, Bacterial Endocarditis prophylaxis, bracing/surgery for scoliosis Angiotensin II receptor blockers (restore the walls of aorta)
A and B- prominent arachnodactyly of both fingers and toes. clubbing due to associated cardiopulmonary problems and the flattening of the arch of his foot. C- severe pectus carinatum D- significant kyphosis and joint contractures, long arms.
A young man with Marfan syndrome, showing long limbs and narrow face.
NOONAN SYNDROME Noonan syndrome is an autosomal dominant, mutations in PTPN11 —a gene on chromosome 12q24.1. genetic disorder that shares a number of clinical features with Turner syndrome . present in 1 in 1000 to 1 in 2500. is seen in both males and females S/S: Head/face webbing of the neck, Hypertelorism, epicanthus, downward slanted palpebral fissures, ptosis, micrognathia, ears are low set and posteriorly rotated. Hair can be coarse and curly, and the posterior hairline is often low. High-frequency sensorineural hearing loss is common. Chest/Heart: pectus carinatum or pectus excavatum, congenital heart disease ( pulmonary stenosis, ASD), septal hypertrophy, Hypertrophic cardiomyopathy is found in 20% and can be severe as to necessitate cardiac transplant Musculoskeletal: short stature, clinodactyly , cubitus valgus, IQ is 86. Verbal IQ tends to be better than performance IQ. intelligence are usually normal. Coagulation abnormalities (factors XI/XII) are found in approximately one third of cases. Puberty can be delayed. Cryptorchidism, small testes when present in males, can result in sterility. Females are fertile. Dx: Clinical, Chromosomal studies Tx: Human growth hormone has resulted in improvement in growth velocity , specialties
Note the widely spaced eyes, low-set ears, webbing of the neck, shield chest, pectus, and increased carrying angle of the arms.
CORNELIA DELANGE SYNDROME Most cases are the result of autosomal dominant mutations in the NIPBL gene on chromosome 5p13 S/S: Intrauterine growth retardation, persistent postnatal failure to thrive, moderate to severe cognitive impearment Head/Facies: Microcephaly with a flat occiput and low hairline Long eyelashes, medial fusion of eyebrows (synophrys), facial hirsutism, Small nose with anteverted nostrils; long philtrum; micrognathia Downturned upper lip with cupid's-bow shape Heart: Congenital heart disease Extremities: small hands and feet, hypoplastic limbs, and even phocomelia. Skin: Hirsutism is generalized and distinctive Cutis marmorata is a frequent feature. Genitals Males: hypospadias with cryptorchidism is common Females: may have a bicornuate uterus. Most affected adults are short in stature. Dx: Chromosomal analysis Prognosis: survival and normal development is poor
A and B, Facial features seen in an infant and an older child include finely arched heavy eyebrows, long eyelashes, small upturned nose, long smooth philtrum, and Cupid's-bow mouth. C, Small hands, hypoplastic proximally placed thumb, and short fifth finger with mild clinodactyly Cornelia de Lange Syndrome
WILLIAMS SYNDROME Williams syndrome is a an autosomal dominant disorder caused by a deletion of about 26 genes from the long arm of Chromosome 7. affects an estimated 1 in 7,500 to 10,000 people. S/S: Developmental delay, highly verbal and sociable, Tend to love music, mild to moderate mental retardation Neonatal hypercalcemia Head/Face: Hoarse voice, Microcephaly Hyperacusis, Fullness around eyes and lips, medial eyebrow flare, Flattened nasal bridge, epicanthal fold, Stellate pattern of iris, long philtrium Short Stature Poor visual-motor integration skills Heart: Congenital heart defects (supravalvar aortic stenosis, pulmonary stenosis, VSD, ASD) Musculoskeletal: pectus excavatum , abnormal side-to-side or front-to-back curvature of the spine (scoliosis or kyphosis), an awkward gait. mild to moderate mental retardation Dx: FISH analysis Tx: Symptomatic care is mostly supportive, Multispecialties <ul><li>None </li></ul><ul><li>General Discussion </li></ul>Williams syndrome, also known as Williams-Beuren syndrome, is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, a varying degree of mental deficiency, and distinctive facial features that typically become more pronounced with age. Such characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also occur including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots. Williams syndrome may also be associated with heart (cardiac) defects, abnormally increased levels of calcium in the blood during infancy (infantile hypercalcemia), musculoskeletal defects, and/or other abnormalities. Cardiac defects may include obstruction of proper blood flow from the lower right chamber (ventricle) of the heart to the lungs (pulmonary stenosis) or abnormal narrowing above the valve in the heart between the left ventricle and the main artery of the body (supravalvular aortic stenosis). Musculoskeletal abnormalities associated with Williams syndrome may include depression of the breastbone (pectus excavatum), abnormal side-to-side or front-to-back curvature of the spine (scoliosis or kyphosis), or an awkward gait. In addition, most affected individuals have mild to moderate mental retardation; poor visual-motor integration skills; a friendly, outgoing, talkative manner of speech; a short attention span; and are easily distracted. In most individuals with Williams syndrome, the disorder appears to occur spontaneously for unknown reasons (sporadically). However, familial cases have also been reported. Sporadic and familial cases are thought to result from deletion of genetic material from adjacent genes (contiguous genes) within a specific region of chromosome 7 (7q11.23). Resources This is an abstract of a report from the National Organization for Rare Disorders, Inc. ® (NORD). A copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html The information provided in this report is not intended for diagnostic purposes. It is provided for informational purposes only. NORD recommends that affected individuals seek the advice or counsel of their own personal physicians. It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report. This disease entry is based upon medical information available through the date at the end of the topic. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. For additional information and assistance about rare disorders, please contact the National Organization for Rare Disorders at P.O. Box 1968, Danbury, CT 06813-1968; phone (203) 744-0100; web site www.rarediseases.org or email firstname.lastname@example.org Last Updated: 8/15/2006 Copyright 1986, 1987, 1988, 1989, 1992, 1993, 1995, 1996, 1998, 1999, 2000, 2002, 2003, 2006 National Organization for Rare Disorders, Inc. E-mail This | P rint This Copyright 1989, 1995, 1996, 1997, 2003 National Organization for Rare Disorders, Inc. This information is not intended to replace the advice of a doctor. By using AOL Body, you indicate that you have read, understood, and agreed to our Terms of Service, Use of Content Agreement and AOL Body Advertising Policy. Read more about our content partners . August 15, 2006 Last updated:
Williams Syndrome: wide-set eyes, upturned nose, large maxilla, prominent philtrum, and pointed chin.
Williams syndrome: broad forehead, short palpebral fissures, low nasal bridge, anteverted nostrils, long philtrum, full cheeks, and large and often downturned mouth.
MALFORMATION DUE TO AN INBORN ERRORS OF METABOLISM LYSOSOMAL STORAGE DISEASES Classification of Lysosomal Storage Disorders DISORDER CLASS UNDERLYING DEFECT Mucopolysaccharidoses Defective metabolism of glycosaminoglycans Sphingolipidoses and sulfatidoses Defective degradation of sphingolipids and their components Glycogen storage diseases Defective degradation of glycogen Oligosaccharidoses Defective degradation of the glycan portion of glycoproteins Mucolipidoses Defective degradation of acid mucopolysaccharides, sphingolipids and/or glycolipids
MUCOPOLYSACCHARIDOSES TYPE DISORDER ENZYME DEFICIENCY MPS I Hurler syndrome α-l-iduronidase Hurler-Scheie syndrome Scheie syndrome MPS II Hunter syndrome Iduronate sulfatase MPS III Sanfilippo disease Type A Heparan N -sulfatase Type B α- N -acetylglucosaminidase Type C Heparan- N -acetyltransferase MPS IV Morquio disease Type A N -Acetylgalactosamine-6 sulfate sulfatase Type B β-Galactosidase MPS VI Maroteaux- Lamy disease Arylsulfatase B MPS VII Sly disease β-Glucuronidase
MPS-I HURLER MPS type I is due to a mutation in the gene that codes for α-L-iduronidase (located on chromosome 4p16.3), which results in impaired degradation of dermatan and heparan sulfate S/S: Between 6-24 months (12 months), growth rate decreases and signs of developmental delay appears. Growth and Development ceases around 3 or 4 years, resulting in short stature with a shortened trunk, and progressive regression in cognitive abilities / milestones. Head/face: prominence of the forehead, broad nose with a flattened nasal bridge, enlargement and protrusion of the tongue, chronic hearing loss, corneal clouding , retinal degeneration or glaucoma; tonsillar / adenoidal hypertrophy predispose the child to URI , sleep apnea. Heart: Cardiomyopathy with asymmetric hypertrophy of the ventricular septum, Thickening of the aortic and mitral valves, which progress to valvular insufficiency. Abd: Hepatosplenomegaly results in a protuberant abdomen Skeletal: Dysostosis multiplex, progressive joint stiffness resulting in contractures. Hands are broad, fingers are short and clawed, Widening of the ribs into an oar shape Skin: Thickening of the skin with hirsutism Dx: Assay of skin fibroblasts for specific lysosomal hydrolases Tx: Enzyme replacement therapy
Hurler syndrome. A, The coarsening of facial features includes prominence of the forehead, a flattened nasal bridge, short broad nose, and widening of the lips. Features appear puffy due to thickening of the skin. B, Progressive joint stiffness and contractures lead to clawing of the hand.
MPS II- HUNTER SYNDROME Hunter syndrome is inherited as an X-linked recessive trait. Mild and severe forms of the disorder result from changes (mutations) of a gene (IDS gene) that regulates production of the iduronate sulfatase enzyme, needed to brake complex sugars produced in the body. The IDS gene is located on the long arm (q) of chromosome X (Xq28). S/S: Initial symptoms starts at two to four years of age. progressive growth delays, resulting in short stature; Head/Face: Macrocephaly. delayed tooth eruption, progressive hearing loss, thickening of the lips, tongue, and nostrils Heart: thickening of the heart valves leading to a decline in cardiac function Lungs: Obstructive airway disease Abd: Hepatosplenomegaly, joint stiffness, with restriction of movements; Skeletal: short neck and broad chest Two clinical forms of Hunter syndrome have been recognized: Early-onset , more severe form (MPS IIA), profound mental retardation may be apparent by late childhood. Late-onset , mild form of the disease (MPS IIB), intelligence may be normal or only slightly impaired. Dx: Clinical Diagnosis by measuring the iduronate-2-sulfatase (I2S) enzyme Tx: No treatment, supportive
Morquio Syndrome Morquio's syndrome is an autosomal recessive inheritance mucopolysaccharide storage disease. Error in Carbohydrate metabolism . It is a relatively rare dwarfism with serious consequences. Two forms are recognized, type A and type B. Type A is a deficiency of the enzyme N-acetylgalactosamine-6-sulfate sulfatase . Type B is a deficiency of the enzyme beta- galactosidase . S/S: Widely spaced teeth Corneal clouding Hearing loss Enlarged heart Abnormal skeletal development: Scoliosis Hyper mobile joints Large fingers Knock-knees, Short trunk with pectus carinatum Bell shaped chest (ribs flared) Severe growth retardation 82-115 cms Odontoid hypoplasia Compression of spinal cord Dwarfism The intelligence is normal . Dx: Biochemical markers: Type A: Increase urinary excretion of keratan sulfate/chondroitin-6-sulfate Type B: Increase urinary excretion of keratan sulfate Tx: Enzyme replacement therapy is not effective. Supportive
NEUROFIBROMATOSIS Neurofibromatosis is an autosomal dominant disorder producing tumors along the course of nerves and occasionally resulting in soft tissue or bony deformity. Neurofibromatosis has 2 forms: Type 1 (von Recklinghausen's) is most prevalent, causing neurologic, cutaneous, orthopedic symptoms Type 2 accounts for 10% of cases, manifesting primarily as congenital bilateral acoustic neuroma. Genetics: NF1 gene has been localized to chromosome 17. NF2 gene has been localized to chromosome 22. affects about 1 in 3000 individuals. Neurofibromas are benign tumors consisting of Schwann cells and neural fibroblasts. There are 4 types: Cutaneous neurofibromas are soft and fleshy Subcutaneous neurofibromas are firm and nodular. Nodular plexiform neurofibromas may involve spinal nerve roots produce intraspinal / extraspinal masses Plexiform neurofibromas : diffuse thickening of nerve, present at birth in the orbital or temporal region of the face. Causes overgrowth of an extremity and a deformity of the bone. There are 2 types of central (cranial nerve) neurofibromas: Optic gliomas, which may cause progressive blindness. NF-1 Acoustic neuromas (vestibular schwannomas), causes dizziness, ataxia, deafness, and tinnitus. NF-2
S/S: NF-1 2 or more must be present to diagnose Café -au- Lait (need > 6) .5mm in diameter in prepubertal children, >15mm in postpubertal individuals Lesions are medium-brown, over the trunk, pelvis, and flexor creases of elbows Axillary or inguinal freckling Neurofibromas (2 or more) or 1 plexiform neurofibroma Lisch nodules (Iris hamartomas) Optic Glioma (visual loss with optic atrophy) Osseous lesion such as a sphenoid dysplasia, thinning of long bone cortex with / without pseudoarthrosis A first-degree relative (i.e., parent, sibling, or child) with NF-1, according to these criteria Learning disabilities Increased risk for malignancy Short stature and macrocephaly Patients with NF-1 can be affected with various tumors of the brain, spinal cord, and peripheral nerves Hypertension in 10% NF-2 Bilateral acoustic neuromas. They cause hearing loss and unsteadiness, headache Bilateral 8th cranial (vestibulocochlear) nerve masses may be present. Family members may have gliomas, meningiomas, or schwannomas. Cataracts Dx: Clinical , DNA testing, Genetic counseling, MRI of Brain, X-Ray of Lower Extremities Tx: No treatment. Surgery, Irradiation, braces for scoliosis, psychological help
MAL FORMATION ASSOCIATED WITH IN UTERO TERATOGEN EXPOSURE 1- FETAL ALCOHOL SYNDROME 2- TOBACCO 3- MEDICATIONS 4- RECREATIONAL DRUGS
<ul><li>Fetal Alcohol Syndrome </li></ul><ul><li>Alcohol is teratogenic --> Fetal Alcohol Syndrome (FAS) </li></ul><ul><li>Even 1-2 drinks daily (30 cc of absolute alcohol) in early pregnancy may lead to FAS </li></ul><ul><li>1- Prenatal and postnatal Growth deficiency - With small-for-age weight, length, and/or head </li></ul><ul><li>circumference. </li></ul><ul><li>2. CNS disorders with signs of abnormal brain functioning, delays in behavioral development, and/or intellectual impairment. </li></ul><ul><li>3. At least two of the following: </li></ul><ul><li>Microcephaly, microphtalmia, long and smooth philtrum (the grove above the upper lip), </li></ul><ul><li>thin upper lip, flat nasal bridge, hypoplasia of nails and distal phalanges (fifth toes). </li></ul><ul><li>Occasionally, affected infants have eyelid ptosis, epicanthal folds, strabismus, small raised </li></ul><ul><li>hemangiomas, cervical vertebral abnormalities, and congenital heart disease. </li></ul><ul><li>4- weaker sucking responses </li></ul>
Effects of smoking in pregnancy <ul><li>-Increase in low birth weight (proportional to number of cigarettes) </li></ul><ul><li>-40% higher perinatal death </li></ul><ul><li>-Spontaneous abortion </li></ul><ul><li>-Significant decrease in IQ </li></ul><ul><li>-Smoking linked to 2700 SIDS deaths/yr in the US alone. </li></ul>
Caffeine: Coffee, Tea, Cola <ul><li>-One of the most popular “drugs” in the world. </li></ul><ul><li>-One cup coffee =70-100 mg, tea 40-50 mg, cola 30-40 mg caffeine </li></ul><ul><li>-Fetal levels are similar to maternal levels, and may alter fetal sleep patterns </li></ul><ul><li>-Moderate consumption (1-2 cups coffee/day) are probably safe. High doses (>5-6 cups/day) may cause spontaneous abortion, and possibly lower birth weight. </li></ul>
<ul><li>Aspirin: </li></ul><ul><li>Can cause bleeding, prolonged labor </li></ul><ul><li>Low dose maternal aspirin may be safe to the baby. Higher doses may cause </li></ul><ul><li>bleeding in neonates and should be avoided in pregnancy. </li></ul><ul><li>Ibuprofen ( Advil/Motrin ): To be avoided in pregnancy, sp. 3rd trimester. </li></ul><ul><li>Safe during breast feeding. </li></ul><ul><li>Acetaminophen ( Tylenol ): Safe for short-term use in regular doses. Toxic at high doses </li></ul><ul><li>to mom and baby. Compatible with breast feeding. </li></ul><ul><li>Anti-histamines : Diphenhydramine ( Benadryl ): Possibly safe (some reports of </li></ul><ul><li>malformations). C/I during lactation (babies are sensitive to </li></ul><ul><li>antihistamines) </li></ul>
Prescription drugs <ul><li>- Antibiotics: Most penicillins/cephalosporins are usually safe. Quinolones (Cipro), </li></ul><ul><li>aminoglycosides (e.g. Streptomycin, Gentamycin) are to be avoided. </li></ul><ul><li>- Anti-hypertensives: ACE inhibitors (Captopril, Enalapril) are usually avoided. </li></ul><ul><li>-Anticonvulsants: Valproate, Phenytoin, etc can cause malformations. </li></ul><ul><li>-Retinoids (retinoic acid): Severe CNS abnormalities, Ear malformations (small or absent) </li></ul><ul><li>-Diphenylhydantoin : Hypoplasia of 5 th nail of toe or finger, small nails, flat nasal bridge, </li></ul><ul><li>cleft lip/palate, gum hyperplasia, hypertelorism, malformed ears </li></ul><ul><li>-Warfarin : abnormal cartilage development. Deafness, and blindness </li></ul><ul><li>-Thalidomide : Upper/lower limb phocomelia </li></ul>
THALIDOMIDE Thalidomide is a sedative-hypnotic medication. The drug is a potent Teratogen. Severe birth defects may result if the drug is taken during pregnancy. Children were born with: Missing or malformed limbs( phocomelia) (bilateral) No ears or deafness Missing or extra fingers or toes Partial or total loss of sight Improper formation of the heart, kidney and other internal organs Improper formation of the anus and/or genitalia Cleft Palate Flattening of the bridge of the nose
Suggested guidelines for drug screening of the neonate <ul><li>Urine, meconium, or hair analysis should be performed if: </li></ul><ul><li>A) Mothers have a history of any one of: </li></ul><ul><ul><li>1) Hx of drug abuse in present or past pregnancy </li></ul></ul><ul><ul><li>2) Limited prenatal care (<5 visits ) </li></ul></ul><ul><ul><li>3) Hx of Hepatitis B, HIV, Syphilis, Gonorrhea </li></ul></ul><ul><ul><li>4) Unexplained placental abruption / premature labor </li></ul></ul><ul><li>B) Infants who exhibit any one of the following: </li></ul><ul><ul><li>1) Unexplained neurological complications (e.g. intracranial hemorrhage/infarction, seizures) </li></ul></ul><ul><ul><li>2) Evidence of possible drug withdrawal ( e.g. hypertonia, irritability, trembling, muscle rigidity, constipation or diarrhea) </li></ul></ul><ul><ul><li>3) Unexplained IUGR </li></ul></ul>
How effective is screening? <ul><li>Urine Drug Screening (UDS): </li></ul><ul><li>Most often can detect cocaine (up to 8 hrs in mom, 72 hrs in baby), </li></ul><ul><li>opiates (morphine and heroin up to 48 hrs), </li></ul><ul><li>amphetamines (48 hrs), </li></ul><ul><li>Barbiturates, benzodiazepines (short acting 48 hrs, long acting 7 days), </li></ul><ul><li>Hair analysis: Useful till 3 months age. </li></ul>
Marijuana (pot/joint): Effect on the Baby <ul><li>- Cannabis sativa . </li></ul><ul><li>Second commonest substance abused (after tobacco). </li></ul><ul><li>May be associated with growth retardation </li></ul><ul><li>May be associated with abnormal neurological development </li></ul><ul><li>May be associated with prematurity (very doubtful) </li></ul><ul><li>Effects more likely to occur with heavier use </li></ul>
Cocaine (crack/coke ) <ul><li>- Inhibits re-uptake of sympathomimetics (Epinephrine, NE), causing Tachycardia, </li></ul><ul><li>hypertension, vasoconstriction </li></ul><ul><li>-Cocaine easily passes into fetus through placenta </li></ul><ul><li>-Decreases blood flow to uterus, decreases fetal oxygenation and intestinal blood flow. </li></ul><ul><li>- Lower birth weight, smaller head size (smaller brain), shorter length, greater risk of IUGR, and </li></ul><ul><li>genito-urinary and cardiac defects </li></ul><ul><li>-Lower scores on neonatal and childhood developmental exams </li></ul><ul><li>-Increased risk for necrotizing enterocolitis, even in term babies </li></ul><ul><li>-Increased risk for SIDS </li></ul><ul><li>-Increased risk for cerebral stroke/hemorrhage </li></ul>
Amphetamines <ul><li>- Stimulant drugs which work in a manner similar to cocaine </li></ul><ul><li>-Problems similar to cocaine/polydrug use: LBW </li></ul><ul><li>Prematurity </li></ul><ul><li>Neonatal withdrawal </li></ul><ul><li>Case series of congenital brain hemorrhage/infarction. </li></ul><ul><li>-Lower scores in neurodevelopment (infancy) and aggressive behavior (at 8 yrs of age) </li></ul><ul><li>-LSD often diluted with amphetamines. Direct effect of LSD alone difficult to determine. </li></ul>
Morphine/Heroin/Methadone/Demerol <ul><li>Withdrawal symptoms are the main risk (40-80%). </li></ul><ul><li>Symptoms: </li></ul><ul><li>Abnormal sleep pattern </li></ul><ul><li>Irritability </li></ul><ul><li>Seizures </li></ul><ul><li>Fever </li></ul><ul><li>Sweating </li></ul><ul><li>Tachypnea </li></ul><ul><li>Poor feeding </li></ul><ul><li>Loose stools </li></ul><ul><li>Vomiting. </li></ul><ul><li>Symptoms may occur much later and last longer (2-30 days) with methadone </li></ul>
Narcotics: effects on the baby <ul><li>- Increased incidence of low birth weight, IUGR, prematurity. </li></ul><ul><li>-2/4 fold higher risk for SIDS., Resp. Depression. </li></ul><ul><li>-Long-term developmental abnormalities (lower scores on IQ & language tests even when placed in foster homes) </li></ul><ul><li>-Associations include an increased risk for: </li></ul><ul><li>sexually transmitted diseases </li></ul><ul><li>hyperbilirubinemia </li></ul><ul><li>poor social situation (true for all drugs of abuse) </li></ul>
CONGENITAL ANOMALIES Innumerable congenital anomalies, many of a minor nature, can be noted at birth. Although any single minor malformation may be of little medical consequence, the identification of three or more in a single infant may be a clue to more serious errors of morphogenesis The majority of minor external anomalies involve the hands, feet, and head
DELIVERY ROOM RESUSCITATION PROCEDURES *Resuscitation begins before delivery. *Obstetric chart to be discussed with obstetrical team *Know what type of anesthesia is going to be used *Check if neonatal resuscitation equipment is working and ready *Check if resuscitation drugs are available and in place
DELIVERY PROCEDURES FOR ALL NEWBORNS 1 -Suction Nose/Oropharinx- Suction the mouth first , then the nose before the infant take his first breath because suction of the nose first, induce gasping 2- Clamp AND CUT the umbilical cord, within 30-60 seconds of age. Milk the cord if it is necessary, before clamping it. 3- Place the newborn in a 15-degree Trendelemburg’s position in a warmed resuscitator with overhead radiant heater. Dry to avoid excessive heat loss, since chilling acidosis. 4- EXAMINE THE CHILD-APGAR. Aspirate the mouth, pharynx, nose. The suction should not take more than 10 sec. Beware of direct vagal nerve stimulation by the catheter tip vaso-vagal reflex with bradycardia and/or laryngeal spasm resulting into apnea, asphyxia and depression. 5- Once the Newborn is stabilize, and breathing vigorously: *Administer Vit-K 1 mg IM preventing hemorrhage in Newborn *Silver Nitrate 1% sol. or Erythromycin 0.5% ophtalmic oint. *ID- foot printing
Milking the umbilical cord is not indicated in those cases: Materno-fetal blood incompatibility Prematurity Intracranial hemorrhage It is indicated in the following cases: C-section, placing the newborn in a lower level than the mother Premature placental separation Anemic newborns
THE APGAR SCORING SCALE *Simple assessment of intrapartum stress, cardio-pulmonary, and neurologic adaptation to a new independent life and an objective idea of how much resuscitation an infant will required at birth. *Evaluate the newborn at 1, 5 and 10 minutes after birth. *Causes of low Apgar: -Asphyxia -Prematurity -Maternal Drugs -Fetal Sepsis -Fetal CNS and Resp. Depression
Apgar Scores The Apgar score should be assigned at 1, 5, 10 minutes Sign Score 0 Score 1 Score 2 Heart Rate Absent Below 100 Above 100 Respiratory Effort Absent Weak, irregular, or gasping Good, crying Muscle Tone Flaccid Some flexion of extremities Well flexed, or active movements of extremities Reflex Irritability No response Grimace or weak cry Good cry Color Blue all over, or pale Blue Extremities Body Pink Pink all over
APGAR CLINICAL MANAGEMENT OF THE NEWBORN Apgar Score at 1 minute: 7-10 Normal Newborn 4- 6 Moderately depressed newborn 0- 3 Severely depressed newborn Normal Newborn: Brief suctioning and a slap/massage on the soles/back Moderately Depressed Newborn Infants: Oxygen, Positive pressure by bag and Mask, Efficient suctioning, Warm environment . Severely Depressed Newborn Infants: Keep in warm environment, efficient suctioning, oxygen. Maintain open airway, umbilical catheterization, IV line (fluid, drugs) Endotracheal intubation with artificial respiration or by Bag and mask. Cardiac massage, Usage of medications.
<ul><li>Place Under radiant hood </li></ul><ul><li>Dry thoroughly </li></ul><ul><li>Remove wet linen </li></ul><ul><li>Position </li></ul><ul><li>Suction mouth then nose </li></ul><ul><li>Tactile stimulation </li></ul>Evaluate Respirations Spontaneous HR <100 Evaluate HR Inj. Narcan Drug Depressed Yes No HR <60 Ct Ventilation + Chest compression Drugs if: HR <80, after 30 secs PPV +100% O2 + chest compression HR 60-100 -HR increasing Ct ventilation -HR not increasing (<80) Ct chest compression HR >100 look for spont. Resp DC ventilation Evaluate color >100 Observe and Monitor Oxygen Pink or Peripheralcyanosis Blue 15-30 sec Overview of Resuscitation American Heart Association PPV 100% O2 None or Gasping
Failure to breath after birth PO2 falls immediately to near zero Acidosis Asphyxia Brain damage or Aggravation of an existing CNS injury
Triangle of Resuscitation Most common treatment Least common treatment Keep dry & warm Suction & stimulation Oxygen Establish effective ventilation Bag &mask Tracheal Intubation Chest compressions Drugs
PHYSIOLOGY OF ASPHYXIA- APNEA PRIMARY APNEA: With decrease of oxygen, rapid breathing starts. If asphyxia continues, the respiratory movements cease, the HR falls, and the infant enters a period of apnea known as primary apnea. If given O2 and stimulations during this period, it will induce breathing SECONDARY APNEA: With continuation of asphyxia, the infant develops deep gasping breathing, the HR fall, and BP begins to fall. Respiration becomes weaker until the infant take a last gasp and enters a period called secondary apnea. In this period, the HR, BP, oxygen in blood (PaO2) fall further. The infant is unresponsive to stimulation, and artificial ventilation with oxygen (PPV) is started.
FETAL AND NEWBORN PHYSIOLOGY ADAPTATION When born, his Liquid habitat became airborne and his nutrition will come from different ways and sources. The oxygen given by his mother through the placenta, now comes through a mixture in the air, by a new process; the pulmonary respiration. The organic elements and minerals will not come anymore via maternal circulation, it will come through the complex process of digestion, absorption and assimilation. Also excretion, becomes a vital part of these complex processes.
The 1 st breath begin after the NB leaves the vaginal canal, requiring a: 1-Lung expansion is due: to a large negative intra-thoracic pressure followed, by a strong cry sufficient to open the adhesion between the alveolar walls humidified by the amniotic liquid. 2-Pressure of 15-25 cm/H2O is necessary for this expansion. For the subsequent respiration, it is needed a pressure of 1/3 to ¼ of the first. 3-The umbilicus clamping ↑ BP, and massive stimulation of the sympathetic nervous system With the onset of Respiration and lung expansion, pulmonary vascular resistance ↓ with the gradual transition from fetal to adult circulation, with the closure of foramen ovale and ductus arteriosus Also: the first respiration is done through the: - The sensorial stimuli represented by being exposed to a colder air than the one inside the uterus. -Difference between intrauterine pressure and atmospheric pressure -Complete reabsorption of the lung fluid -Adequate quantity of surfactant in the alveoli , preventing atelectasia In the premature, areas of atelectasia are common and persist for a longer period .
-At birth, alveoli are filled with “fetal lung fluid”. -It takes a certain amount of pressure in the lungs to overcome the fluid forces and open the alveoli for the first time. -Around 1/3 of fetal lung fluid is removed during vaginal delivery as the chest is squeezed lung fluid exits trough the nose and mouth. -Remaining fluid passes through the alveoli into lymphatics surrounding the lungs. How quickly fluid leaves the lungs, depends on the force of the first few breaths. The first few breaths of most newborn infants are extremely powerful, expanding the alveoli and replacing the lung fluid with air.
TORCH INFECTIONS Is an acronym for: Toxoplasmosis, Others-Syphilis, Varicella, EBV, Coxsackie Rubella CMV Herpes simplex, Hepatitis B
Toxoplasmosis: Transplacental infection by Toxoplasma gondii during pregnancy. parasite found in cats feces contaminate water and food. S/S: Fetus may grow slowly and born prematurely. Newborns may have: chorioretinitis, microcephaly, intracranial calcifications, jaundice, hepatosplenomegaly. Later sequela: blindness, deafness, mental retardation, seizures. Dx: IgM Elisa titers suggest infection in 75% of cases. TX: Pregnants should avoid raw meat and cat litter Transmission may be prevented if mother takes Spiramycin. Pyrimethamine and Sulfonamides can be taken later if fetus is infected Infected newborns are treated with: Pyrimethamine, sulfadiazine and Leucovorin. Inflamation of the heart, lungs or eyes is treated with corticoids.
Rubella: Transplacental infection with the Rubella virus during pregnancy. High risk during first trimester. S/S: Microcephaly, cataracts, Cardio Ds. (PDA, Pulmonary artery stenosis), deafness, mental retardation, IUGR, cloudy cornea (cataract, glaucoma), hepatosplenomegaly, Bluish red spots, bruising Dx: Elevation of antibody titers, viral cultures. Tx: Immunization before pregnancy Immunoglobulin injection, if pregnant women had contact with infected person
CMV: Transplacental infection or infected maternal secretions at delivery Patients are asymptomatic at birth. Newborn may become infected if breastmilk contains the virus, or in a blood transfusion S/S: 10% congenital infected have symptoms: Prematurity, IUGR, jaundice, microcephaly, chorioretinitis , periventricular calcifications, petecchia with thrombocytopenia Symptomatic CMV has 20% mortality rate. 90% survivors will have: mental retardation, hearing loss, visual defects, seizures. Dx: Elisa test: CMV IgM or IgG antibodies Isolate virus Cx: urine, CSF, saliva, amniotic fluid or placenta. Histological Exam: “owl’s eye” enlarged intranuclear inclusion cells PCR to detec viral DNA in CSF. X-Ray: Skull- calcifications Lab: thrombocytopenia, elevation of transaminases, conjugated hyperbilirubinemia. Tx: Gancyclovir- suppress replication, not erradicate virus. Repeated hearing test (sensorineural hearing loss in more than 65% survivors
Neonatal Herpes Simplex Virus Caused by HSV type-2, transmitted via infected vaginal tract. S/S: 1-4 weeks of birth: rash of fluid filled blisters appear. Later: Kerato-conjunctivitis, seizures-(temporal lobe predilection), lethargy, weakness, decrease muscle tone, Resp. distress, pneumonitis Dx: Culture or PCR of scrapings from lesions (vesicles). Positive culture or PCR of CNS fluid, Pleocytosis, or elevated protein: possible HSV Ds. Tx: Acyclovir IV. Eye infections is treated with Acyclovir IV and Trifluridine drops Perform cesarean in women with active lesions Varicella: Seen in 2% of pregnancies when mother contracts varicella in the 1 st trimester of pregnancy Clinical features: Limb hypoplasia, Cutaneous scars CNS abnormalities: Cortical Atrophy, Mental Retardation, Encephalitis Ocular Abnormalities: Microphthalmia, Cataract, Chorioretinitis DX: positive maternal Hx of varicella, physical findings Tx: Acyclovir IV, Multispecialists
Neonatal Hepatitis B infection Acquired during delivery from mothers that are asymptomatic HBV carriers Main risk is infant becoming carrier, resulting in chronic hepatitis and increasing the risk of hepatocellular carcinoma. DX: HBsAg serology Tx: Infants of infected mothers should receive Hep-B immuno-globulin and Hep-B vaccine within 12 hours after delivery. Screen all pregnant women for HBsAg
Congenital Syphilis Transplacental infection with Treponema pallidum during pregnancy, if mother acquires syphilis during pregnancy,or if she has been wrongly treated for syphilis in the past. Newborns often asymptomatics 3-12 weeks: jaundice, hemolytic anemia, coriza “snuffles, macular-papular rash palms/soles (flat copper colored rash) Permanent stigma: saddle nose deformity, saber shins ( periostitis, osteochondritis), Hutchinson’s teeth, intermittent fever, frontal bossing, painless joints effusions, may run from nose mucus, pus or blood. Hepatosplenomegaly DX: Rapid plasma reagin (RPR) titers Fluorescent treponemal antibody-absorption test (FTA-ABS) Treponemas can be seen on Darkfield microscopy from scrappings of lesions or body fluids TX: penicillin G
HIV Materno-fetal transmission during pregnancy or to the newborn during delivery, or after birth through breastfeeding SS: persistent trush, lymphadenopathy, hepatosplenomegaly, severe diarrhea, FTT, poor weight gain, recurrent viral and bacterial infections DX: PCR to detect viral nucleic acid in peripheral blood (HIV DNA by PCR) Elisa test for detection of antibodies, confirmation with Western-Blot TX: Nutritional support, Antiretroviral therapy ZDV-Zidovudine, and antibiotics for specific infections. Pneumocystis (carini) Jiroveci tx: TMX-SMX, IV Pentamidine
SEPSIS Definitions: Presence of pathogenic organisms or toxins in the blood or tissues, and the systemic response to them. Bacteremia: Is the presence of bacteria in the bloodstream detected by blood cultures. Etiology: G-: E. coli, K. pneumoniae, P. aeroginosa, Proteus, Neisseria meningitidis. G+: S. aureus, S.pneumoniae, S. pyogenes, Enterococci. Others: Fungi (2-3%), viral, rickettsia, protozoa. Most commons in the first 4 weeks of life are: G-B Streptococcus Gram negative (E.coli) Lysteria monocytogenes Hx. of hospitalization: S. aureus, P. aeruginosa, klebsiela, S. epidermidis Older infants and children: S. pneumonia, N. meningitides, H. influenza-B Risk Factors: G-/Septicemia: Increases with diabetes, burns, urinary or GI infection, immunosuppressive diseases G+: Usage of IV catheters, mechanical devices, IV drug use, burns. Fungal Septicemia: Immunosuppressed, prolong use of antibiotics. Splenectomized patients: S. pneumoniae, H. influenza, N. meningitidis
Sepsis/ Meningitis: Etiologic agents: Neonates: Streptococcus agalacteae (#1) ,Escherichia coli (#2) Listeria monocytogenes (#3), Staph aureus, Candida albicans Children : Streptococcus pneumoniae (#1 in greater than 5 years) Hemophilus influenzae type B (#1 in less than 5 years) Neisseria meningitidis, salmonella typhimurium Treatment: Neonates: Ampicillin + Aminoglycosides Ampicillin+ Cefotaxime (Claforan) Children: Cefotaxime (Claforan) +/- Vancomycin Ceftriaxone (Rocephin) +/- Vancomycin
STAGES OF SEPSIS Systemic Inflammatory Response Syndrome (SIRS) Is a response to an inflammation or injury that can be infectious or noninfectious defined by having several sign and symptoms.: Two or more of the following: -Temperature of > 38oC or < 360C -Heart rate of > 100 BPM -Respiratory rate of > 20 or Paco2 < 32 torricelli. -WBC count >12.000/mm3 or < 4.000, or 10% immature forms (bands) Sepsis SIRS plus a culture-documented infection Severe Septic Shock Sepsis plus organ dysfunction, hypotension (despite fluid resuscitation-decrease of systolic BP< 90mm), hypoperfusion, plus organ dysfunction (including acidosis, oliguria, acute mental status changes)
S/S: Fever or hypothermia , Chills, Altered Mental status, cold/clammy extremities, and oliguria Assess chest: tachypnea , rales, dyspnea, increase RR. Assess circulation: HR, BP, Skin color, capillary refill, tachycardia Assess mental status: level of alertness, confusion, agitation Presence of petecchia/purpura: Meningococcemia or DIC If SIRS is identified and reversed early, the subsequent inflammatory cascade can often be avoided. This damage result in increased cardiac output, peripheral vasodilation, increased tissue oxygen consumption, and a hypermetabolic state (shock). If SIRS is not identified and reversed early, cardiac output may fall, peripheral vascular resistance may increase, and shunting of blood may ensue (shock). This results in resultant tissue hypoxia, end-organ dysfunction, metabolic acidosis, end-organ injury and/or failure, and death.
LAB WORK-UP: CBC with platelets: Elevated WBC count w/ increased band left shift or leukopenia. Thrombocytopenia: DIC Lytes: metabolic acidosis Glucose: Hypoglycemia Blood Culture/Sensitivity Urinalysis / Urine culture Culture from sputum, Lumbar (CSF) and skin ABG: Monitor acid-base status BUN/ Creatinine Lumbar Puncture: R/O meningitis PT, PTT, Fibrinogen: Monitor DIC Chest X-Ray/ MRI/ Cat-Scan/ Ultrasound
<ul><li>The Listernick Approach </li></ul><ul><li>Above all, use wisdom guided by experience </li></ul><ul><li>Consider blood culture if: Fever above 39 C </li></ul><ul><li>No localizing signs </li></ul><ul><li>Pneumococcal vaccine less than 3 doses </li></ul><ul><li>Something not quite right </li></ul><ul><li>Limit use of empiric IM Ceftriaxone </li></ul><ul><li>Consider UA + Urine Culture if: Fever more than 2 days </li></ul><ul><li>No localizing signs </li></ul><ul><li>Any girl or boy with less than 12 months </li></ul>
Therapy of Septic Shock <ul><li>Ensure a patent airway (consider endotracheal entubation) </li></ul><ul><li>Keep Respiratory and Hemodynamic support: </li></ul><ul><li>SO2>92%, consider ventilator for hypoxia or resp. muscle failure, Supplemental Oxygen </li></ul><ul><li>Assist ventilation as needed (bag-valve, respirator) </li></ul><ul><li>Optimize intravascular volume: IV/PO NS to keep BP>60mmHg. </li></ul><ul><li>To avoid pulmonary edema, keep CVP between 10-12 cm H2O </li></ul><ul><li>Administer antimicrobial therapy Neonates: Ampicillin/gentamicin, cefotaxime, ceftriaxone </li></ul><ul><li>Older children according to culture and sensitivity </li></ul><ul><li>Administer vasoactive drugs: Dopamine, Dobutamine </li></ul><ul><li>Inotropic agents: Dopamine 5-20mg/kg/min </li></ul><ul><li>Dobutamine 5mg/kg/min </li></ul><ul><li>Correct hypoglycemia (dextrose), acidosis (sodium bicarbonate) </li></ul><ul><li>Drain or erradicate focus of infection. </li></ul><ul><li>Prevention: Vaccine for: H. influenza-b, S. pneumonia </li></ul>
PHENYLKETONURIA (PKU)-PHENYALANINE Autosomal recessive disease, there is an enzyme deficiency of phenylalanine hydroxylase with failure in converting phenylalanine in tyrosine Incidence: 1:12000 live births. Accumulation of Phenylalanine: -Classic PKU: > 20 mg/dl -Atypical PKU: 12-20 mg/dl -Can result from deficiency of cofactor tetrahydrobiopterin (BH4) Symptoms: Development delay, Mental retardation, Seizures, Eczema, blue eyes, Hyperactivity, Aggressive behavior, Blond hair, Musty/Mousy Odor Treatment: -Phenylalanine restricted diet instituted by 3 weeks of age. -Frequent monitoring of blood levels and diet adjustments -Cofactor defects require BH4 replacement Early Tx prevents mental retardation and neurological abnormalities
CONGENITAL HYPOTHYROIDISM Usually cause by a genetic malformation/functioning of the thyroid gland. 90% due to dysgenesis. Also, error in hormone synthesis, secretion, metabolism. Other causes: maternal iodine deficiency, maternal antithyroid medication or fetal exposure to iodine, radiation therapy. Incidence: 1:3500-5000 live births. S/S: head circumference ↑ , large fontanel, abdominal distention, lethargic and poor feeding, jaundice, umbilical hernia, constipation, macroglossia, pale cold and mottled skin, poor cry, poor motor development, edema of extremities.
Lab: TSH elevated- assess functional capacity of thyroid gland, TSH decreased- Pituitary involvement. Decreased T4, T3 and Free T4 Antithyroid antibody Treatment: L-Thyroxine is used to maintain T4 levels in the upper half of the normal range. L-Thyroxine: Neonates: 10-15ug/kg/day Children: 4ug/kg/day Check T4 and Free T4 to monitor therapy every 6 months. Treatment within first 2 months of life is to prevent mental retardation and complications of the disease. If Tx delayed, IQ= 55
MAPLE SYRUP URINE DISEASE Autosomal recessive disease caused by deficiency of decarboxylase that initiates the degradation of three branched-chain amino acids: leucine, isoleucine and valine. Incidence: 1:200,000 live births S/S: Infants appear normal at birth. If untreated, by the end of 1-2 week will develop: Feeding intolerance (poor feeding), vomiting, typical urine odor “ burnt sugar” or ”maple syrup” Hallmark of Ds: Depression of CNS, alternating hypotonia/ hypertonia/seizure
It progresses to severe ketoacidosis and death. If survive the Neonatal period will have: Mental retardation Neurological Impairment Development Profound depression of CNS Lab: Large increases of those amino-acids in plasma, hypoglycemia, presence of ketonuria Tx : Diet avoiding those amino-acids, increase fluids, CH, glucose. Correct acidosis disturbance Hemo/Peritoneal dialysis is life saving during acidotic crises
GALACTOSEMIA Autosomal recessive disease due to deficiency of the enzyme Galactose 1-Phosphate uridyl-transferase. Is due to ingestion of Galactose (Lactose) Incidence: 1: 40,000 live births Symptoms: It happens always when the infant is fed with milk: no symptoms at birth, but jaundice, diarrhea, and vomiting makes the baby fails to gain weight FTT. If not detected immediately, it results in: *Liver failure (Hypoglycemia, Bilirubinemia ), Hepatosplenomegaly *Renal Tubular disorder (Acidosis, Glicosuria, albuminuria) *Lethargy, Feeding Intolerance, Failure to Thrive, Cataracts *Learning disorders in older children-mental retardation *25% will develop sepsis in first 1-2 weeks if untreated (E.coli) death
Screening: Neonatal heel screening Positive Clinitest in urine for reducing substances. If positive, remove galactose from diet. Diagnosis: Demonstrating reduction in Erythrocytes of: galactose-1-phosphate uridyl-transferase Treatment: *Is to avoid ingestion of galactose *Evaluate for sepsis and treat immediately, to prevent complications of mental retardation, cataracts and cirrhosis
SICKLE CELL DISEASE Autosomal recessive disease where Valine is subtituted for Glutamic acid at codon 6 on the B-globin chain of the Hb Normal red blood cells contain hemoglobin A. Patients with sickle cell ds. have RBC containing mostly hemoglobin S, an abnormal type of hemoglobin. These RBC become sickle-shaped (crescent-shaped), having difficulty passing through small blood vessels. The most common types of sickle cell disease are 3 forms of genotypes: HbSS Ds (sickle cell anemia), HbSC Ds (sickle-Hb C Ds), HbS-B Sickle Beta Thalassemia. Incidence: 1:500 ( in the Black population) live births.
Why is it important to know if I have sickle cell trait? Sickle cell trait is inherited from one’s parents, like hair or eye color. If one parent has sickle cell trait there is a 50% (one in two) chance with each pregnancy of having a child with sickle cell trait. If both parents have sickle cell trait there is a 25% (one in four) chance with each pregnancy of having a child with sickle cell disease. When affects one chromossome, the heterozygous condition S.C. Trait When affects both chromossomes, the homozygous condition S.C. Ds When one chromossome makes HbS and the other makes no hemoglobin (B-thalassemia trait) HbS-B. Sickle cell Ds is a lifelong illness that result in serious health problems. For this reason, trait awareness is very important.
Hemoglobin A: Is a normal Hb that exist after birth. It is a tetramer with 2 alpha and 2 Beta chain (A2B2) Hemoglobin A2: Is a minor component of the Hb found in RBC after birth, and consist of 2 alpha and 2 Delta chains (A2d2). Less than 3% of total Hb Hemoglobin F: Is the predominant Hb during fetal development. The molecule is a tretamer of 2 alpha and 2 Gamma chains (a2g2). Hemoglobin S: Is the predominant Hb in people with sickle cell disease. The alpha chain is normal. The disease-producing mutation exists in the beta chain, giving the molecule the structure, (a2bS2). People who have one sickle mutant gene and one normal beta gene have sickle cell trait which is benign. Hemoglobin C: Results from a mutation in the beta globin gene and is the predominant Hb found in people with Hb C disease (a2bC2).
S/S: -Appears at about 6 months of age when HbF is substituted by HbS -Early signs are delayed: growth and development, fever, infections Hallmark is Fever Characterized by: hemolisis, vascular occlusion, infection. Hand/foot Syndrome- Dactylitis: -Most common age: 6 months to 3 years ( range 3 months – 5 years) -Often the first clinical manifestation -Symmetrical painful swelling of hands/feet. Refuses to bear weight. Fever Sudden and massive splenic sequestration: (acute blood trapping in spleen resulting in fall in Hb due to sickling). Leading cause of death in children under 5 years. S/S: spleen enlarged and tender, Hct ↓ by 25%, platelets under 100.000, ↑ in Reticulocytes, pallor, anemia (hemolysis), fatigue Due to Splenic dysfunction by intravascular sickling of red cells, this is accentuated by: Hypoxia, Dehydration and Acidosis
Bacterial Infection: Acute Chest Syndrome (Pneumonia): - Seen in more than 50% of Sickle cell patients. -Leading cause of mortality in sickle Cell disease Sepsis: Younger children: S. pneumoniae Older children: G-/Salmonella Symptoms : Varying degrees of Fever, Cough, Chest/Back pain Tachypnea, ↑ RR, Flaring, Grunting, Hypoxemia Painful Vaso-Occlusive crises: Pain in large joints, muscle, abd. pain, back pain, knee, shoulder, elbow. Priapism Seen in children after the age of 3-4 years Swelling, tenderness, decrease of ROM at site of pain. Pain triggers: stress, infection, menses, trauma, change of weather. Aplastic Crisis: Decrease of RBC production due to decrease of HB/Retic Count. Parvovirus B-19 (mc) Anemia (hemolysis), Fatigue . Other Ds: Meningitis, Osteomyelitis (Salmonella), Sepsis (mcc-death)
LAB: Hemoglobin Electrophoresis is definitive diagnosis: Absence of hemoglobin A Presence of hemoglobin S with mild elevation of hemoglobin F Sickle cell anemia: Hgb-S 85-98% Hgb-F 2-20% Hgb A2 2-4% Sickle Cell trait has the abnormal Hgb-S of 40% and Hgb-A of 60% in RBC. It rarely causes any medical problems, and do not develop sickle cell DS CBC: low Hb (6-10gm/dL)/Ht presence of sickle cells/ Howell-Jolly Bodies on peripheral smear Reticulocytes: elevated X-Ray: evidence of osteolysis, periostitis, bone reabsoption. Bone Scan: differentiate bone infarction from osteomyelitis Chemistry: LDH- ↑ , AST- ↑ Unconjugated bilirubin- ↑
Tx: * Hydroxyurea- decrease number and severity of crises. *Pain: NSAID’S or narcotics (Demerol or Morphine Sulfate) *VOC- fluids (Hydration), Oxygen, warmth. *Blood transfusion during aplastic or sequestration crises (fall in Hb) *Ceftriaxone, Cefuroxime: S. Pneumonia, H. influenza *Erythromycin: Mycoplasma Pneumonia *PCN prophylaxis *Pneumoccocal vaccine, influenza virus vaccine, Hib/ Hep-B vaccine specially in patients with splenectomy *Bone marrow transplantation. *Genetic counseling
CONGENITAL ADRENAL HYPERPLASIA (CAH) Congenital adrenal hyperplasia is a group of genetic disorders, characterized by inadequate synthesis of cortisol (glucocorticoid), aldosterone (mineralocorticoid), or both because of an autosomal recessive genetic defect in one of the adrenal enzymes. In the most common form , 21- hydroxylase deficiency accumulate and are shunted into adrenal androgens. The consequent excess androgen secretion causes varying degrees of virilization in external genitals of affected female fetuses; no defects are discernible in external genitals of male fetuses. Complete 21- hydroxylase deficiency, the salt-wasting form, accounts for 75% of deficiency cases. The salt-wasting form is the most severe form of 21-hydroxylase deficiency; aldosterone is not secreted and salt is lost, leading to hyponatremia, hyperkalemia, and increased plasma renin activity. Partial 21- hydroxylase deficiency causes a less severe, non–salt-losing form, in which aldosterone levels are normal or only slightly decreased. *Incidence: 1:10,000/15,000 Live Births
S/S: Non-Salt losing: Males: External genitalia ambiguous: incompletely virilized Testes are rudimentar. Absence of Wolffian duct structures: (seminal vesicle, epididymus, vasa deferens) Premature sexual development: Penis and scrotal enlargement, acne, hyperpigmentation of genitals, appearance of pubic hair, voice deepening Females: External genitalia virilized (clitoris enlargement, labial fusion, acne, pubic and axillary hair development, deep voice) Ovaries present, testes are absent, present Mullerian structures (uterus, fallopian tube, upper vagina)
Salt Losing: FTT, dehydration, anorexia, vomiting. Cardiovascular collapse. Female infants with salt-wasting form will have : ambiguous external genitals, clitoral enlargement, fusion of the labia majora, urogenital sinus rather than urethral / vaginal openings reproductive function may be impaired as they reach adulthood, they may have labial fusion anovulatory cycles or amenorrhea. Some males infants have normal sexual development, are fertile as adults, but others have Leydig cell dysfunction, and decreased testosterone, and impaired spermatogenesis. Manifest as adrenal crisis: lethargy, hypotension, hypoglycemia, hyponatremia, hyperkalemia, shock as well as virilization.
Screening: Levels of 17-hydroxyprogesterone elevated Levels of 17-ketosteroids elevated Serum testosterone ( elevated) Aldosterone (decreased) Serum cortisol (low) hyponatremia, hyperkalemia, hypoglycemia Treatment: -Glucocorticoid therapy: cortisone acetate IM 2-3 days -Mineralocorticoid therapy: fludrocortisone acetate (Florinef) -Surgical correction of female virilization -Prevent salt-losing crisis - Na supplementation -Refer to an Endocrinologist and a Geneticist.
<ul><li>CYSTIC FIBROSIS </li></ul><ul><li>Autosomal Recessive Ds. and most lethal inherited metabolic disorder in the white population affecting the exocrine glands </li></ul><ul><li>Incidence: </li></ul><ul><li>1: 2000 live births in the Caucasian population </li></ul><ul><li>Genetics: </li></ul><ul><li>defect on long arm of chromossome 7 with a F-508 codon mutation </li></ul><ul><li>S/S: </li></ul><ul><li>Characterized: thick, sticky mucus secretions that clogs lungs/pancreas </li></ul><ul><li>Lungs: </li></ul><ul><li>Thick secretions obstruct airways leading to severe and recurrent infections ( S.aureus and </li></ul><ul><li>P. aeroginosa)- Pneumonia- Bronchiectasy- Fibrosis and poor lung function </li></ul><ul><li>Pancreas </li></ul><ul><li>Obstructed glands ducts prevent enzymes from being released, leadingto a fat/protein malabsorption malnutrition and FTT (steathorrhea) </li></ul><ul><li>Intestinal obstruction at birth, known as meconium ileus in 5-10% of CF patients </li></ul><ul><li>Other S/S: </li></ul><ul><li>Rectal prolapse, digital clubbing (hypoxemia), salty sweat, recurrent sinus infections, </li></ul><ul><li>persistent cough, bulky foul- smelling stools, hypoxia, cyanosis, male infertility. </li></ul>
LAB: Sweat chloride above 60mEq/L is positive Pulmonary Function test Sputum culture, Lytes, CBC CXR: Hyperinflation, peribronchial thickening, atelectasis, bronchiectasis Stool trypsin levels ( trypsin deficiency) Detection of Delta F-508 genotype by DNA analysis Treatment: Genetic Counseling Treat specific pathology with ATB of broad spectrum Diet: high caloric intake diet with nutritional supplement Vitamins, Inhalations, Physical Therapy, Oxygen Pancreatic enzymes (enteric coated) Mucolitic: N-acetyl cysteine DNAse inhaled-thin the mucus plug Lung transplantation/ Gene therapy
CLASSIFICATION: Infants are classified as: Preterm (< 37- 6/7 weeks gestation) Term (37- 6/7- 41- 6/7weeks gestation) Postterm (42 weeks gestation) WEIGHT- GESTATIONAL AGE ASSESSTMENT *Preterm Infants: Less than 37 weeks *Term Infant: 37-42 weeks *Post Term Infant: Greater than 42 weeks *Extremely Low Birth Weight: Less than 1000g *Very Low Birth Weight: Less than 1500g *Low Birth Weight: Less than 2500g *Average Term Weight: 2800-3500g *Large Birth Weight for Term: Over 4000g
Small for Gestational Age (SGA): Is a 2 standard deviations below mean weight for gestational age or below the 10th percentile. Concern: ↑caloric need, ↑mortality, ↑ri sk for malformation/infection Symmetric: Growth retardation of all parameters HC=Wt=Length (33% of SGA) Genetic: Small maternal size, Congenital Abnormalities Chromosomal Abnormalities (trisomies 21,18,13,Turner) Intrauterine infections: Torch (CMV), Tbc, Malaria Environmental: Drugs (heroin, Ethanol, Diphenylhydantoin) Smoking, X-Rays Asymmetric: HC=Length > weight (55% of SGA) Uteroplacental insufficiency due to HTN, Pre-eclampsia, Renal Ds ↑ age above 35 years, multiple gestation Combined: 12% of SGA. Drugs, Smoking, Placental insufficiency.
Small for Gestational Age: *IUGR Type I: From conception to 24 weeks maternal HTN/DM/drugs, fetal infections *IUGR Type II: From 24 to 32 weeks placental insufficiency *IUGR Type III: After 32 weeks maternal malnutrition / hypoxemia, placental infarct
Intrauterine growth retardation. This term baby weighed only 1.7 kg. The head appears disproportionately large for the thin, wasted body. This resulted from placental insufficiency late in pregnancy. Hypoglycemia may be a complication
Appropriate for Gestational Age (AGA) Large for Gestational Age (LGA): Define as 2 standard deviations above mean weight for gestational age or above the 90th percentile. Can be seen in infants of diabetic mothers, in constitutionally large infants with large parents, Hydrops fetalis, Beckwith’s syndrome, Weight over 4000g Complications: Hypoglycemia, Increased rate of injury at birth
Large-for-gestational-age infant. This infant of a diabetic mother weighed 5 kg at birth and exhibits the typical rounded facies.
DUBOWITZ-GESTATIONAL AGE CHART BALLARD GESTATIONAL AGE CHART
DUBOWITZ-GESTATIONAL AGE CHART BALLARD GESTATIONAL AGE CHART
Scarf sign. The elbow cannot be drawn, with gentle traction on the upper extremity, across this term infant's chest (A). This is in contrast to the marked flexibility of a preterm infant of 29 weeks' gestation (B).
SQUARE WINDOW TEST 45 DEGREE ANGLE BETWEEN PALM AND FOREARM
PREMATURITY Child born before the 38 th week of gestation from the 1 ST day of the LMP It is responsible for most of the newborn diseases and mortality. Anatomical characteristics: Weight: Less than 2500g Height: Less than 45cm HC: Less than 32cm PREMATURITY CAUSES: Maternal: Age: Under 18 and above 35 years Smoking Anomalies: Miomas, Adnexal tumors, Placental Insufficiency Placenta abruptio, Placenta previa Infections: Toxoplasmosis, Syphilis, Rubella, CMV,UTI Chronic Disease: Anemia, Heart disease, Hypertension Drug abuse Precarious prenatal care Lower Socioeconomic status Deficient nutrition: protein ingestion lower than 50g/day Fetal: twins, genetic, polyhydramnio
Physiological Characteristics: Increase risk of infection: Due to immunologic immaturity Increase handling time Decrease transmission of maternal antibodies Increase risk of neonatal jaundice: Due to hepatic immaturity: Low amount of Vit-K Decrease elements of the prothrombinic complex Prolong jaundice Capilar fragility Increase risk of hemorrhagic disturbances Frequent hemorrhage, mainly in brain (germinal matrix and extend to ventricles) High risk of having developmental delay, cerebral palsy, or learning disorders. Increase frequency of respiratory disturbances: Apnea, asphyxia, RDS due to pulmonary immaturity (lower # of alveoli) Immaturity of respiratory centers Weakness of respiratory muscles The area of brain that controls the breathing is so immature, that the newborns breathe inconsistently with short pauses in breathing, or present periods where breathing stops for 20 seconds or longer (apnea)
Increase risk in the Fluid/electrolytic disturbances: Renal immaturity, with difficult to regulate amount of water and salt in body Decrease capacity of metabolites excretion Increased risk of metabolic disturbances: Hypoglycemia, acidosis, hypocalcemia, hypomagnesemia Increase risk for desnutrition: Suction and swallowing impaired Digestion and absorption of fat and Vit (ADEK) Protein and glucose levels are low (without regular feedings) Precarious body temperature control: Due to immaturity of thermoregulatory centers. Larger corporeal area in relation to weight lose heat faster Absence of sweat Decrease of subcutaneous tissue Exposed to cold temperature, they generate extra body heat, increasing rate of metabolism, Decreasing their gain weight.
S/S: -Small size -Large head in relation to size of body -Anterior and posterior fontanels wide open -Bone separation in skull -Small facies and old age look (senile) -Trunk large and elongated -Skin: Shiny, soft ,red and pink/red at beginning -Visible veins under skin -Short legs and thin, with few creases on soles of feet -Lanugo covering his body that give him a simian aspect -Subcutaneous fat tissue is scarce -Absence of testicle in scrotum in boys, absence of labia majora not yet covering the labia minora in girls -Reduced muscles tone -General aspect of fragility, weak cry and scream, sleeps most of the time -Weak suction, poor coordinated sucking and swallowing reflexes.
PREMATURITY: Delivery Room Management: Airway Breathing Circulation Oxygen (hood, cannula, CPAP, vent) Surfactant to avoid RDS Temp regulation (warmer, saran wrap, blankets, hat) Chest Compressions/ epi as needed NICU: Respiratory support as needed, using minimal O2 (prevent ROP) Sepsis (ampicillin, gentamicin initially) Temperature (incubator with 40-60% humidity) Feeding (fortified breast milk) Anemia
TX: 1- Maintain infant temperature in Neutral Thermal range Avoid Hyperthermia: tachypnea, tachycardia, apnea Avoid Hypothermia: ↑ O2 need apnea, acidosis/hypoglycemia 2- Maintain a clear airway Prevent Asphyxia 3- Control of vital signs Fall of temp- sepsis, raise of RR- RDS 4- Administer Vit K Prevent hemorrhagic disease 5- Weight daily Up gain-edema, lost weight-dehydration
6- Bathe daily and restrict handling Minimize skin colonization 7- Obtain baseline of Dextrotix Monitor hypoglycemia 8- Obtain a baseline Hb/Ht Monitor Anemia 9- Guthrie test at 1 st day and at time of discharge Prevent Inborn Errors of Metabolism 10- Administer Vit. ADC / iron Prevent Vit. Deficiency/anemia 11- Administer food trough NG Prevent malnutrition, increase calories. 12- Immunization: Influenza vaccine starting at 6 months of age. 2 doses. Heptavalent Pneumococcal conjugate vaccine: At 2 months (PREVNAR Synagis vaccine: RSV- once a month for 6 months
Premature Skin: Translucent paper-thin skin with a prominent venous pattern
Normal Full Term Infants All full term infants should be examined 6 hours later and daily. Evaluate for: malformations, establish normalcy of growth/function, document physical findings. Prenatal and delivery history should be reviewed. Measure TC, HC, Length (crown to heel), Weight Weight/Gestational Age: LGA, AGA, SGA Newborn Screening for metabolic diseases: PKU-Phenylketonuria Sickle Cell Disease Congenital Hypothyroidism Maple Syrup Urine Galactosemia Cystic Fibrosis Plus other 35 test
Newborn Physical Examination-Vital Signs Height: Range of 48-52 cms (18- 20 inches) Weight: Range of 2800- 3500 kgs ( 5 ½ -9 pounds) HC: 34-35 cm TC: 32 cm Normal temp: 98.6F Rectal 1 degree higher than axillar/oral Pulse: 120-160 bpm. Declines as the child grows BP: After 3 years of age Respiration: 40/60 newborn (abdominal breathing), 20/40 toddlers HR: 100-160 bpm in the newborn. 120 when awake and 70/80 when asleep. Heart murmur can be heard, but only 10% associated with heart ds. Check Femoral pulses
- Record passage of first urine or stool. Failure to pass after 24-48 hrs, suspect UTI anomalies or intestinal obstruction (MECONIUM ILEUS) - Observe: Jaundice, vomiting, dyspnea, cyanosis, tremors, convulsion, lethargy, hypothermia, pallor, monitor temperature - Hepatitis B prophylaxis: If mother is Hepatitis-B antigen positive or active Hepatitis-B: IM injection of hepatitis-B immune globulin plus hepatitis –B vaccine. First 12 hours -Hypoglycemia: Defined as blood glucose of < 40-45mg/dL. Requires oral or IV glucose. Common in premature infants, infants who are small for gestational age, infants of diabetic mother Cord Blood: all infants at birth. Used for blood typing, Coombs testing if mother is Type O or Rh negative Newborn genetic screen for Inborn Errors of Metabolism: PKU, Galactosemia, Congenital Hypothyroidism, Sickle Cell Disease, Cystic Fibrosis, CAH, performed at 48 hours of age.
HEAD: Caput Succedaneum- Diffuse edema of scalp soft tissue. Not limited to area of bones. Cephalohematoma- Accumulation of blood between periosteum and bone. Usually appears in one or both parietals bones, occasionally over occipital bone. Don’t cross suture line. Subdural Hemmorrhage- Mechanical Trauma, forceps Common in large infants Molding of the Head: Temporary misshaping of cranium (sutures) Fontanels (ant (1-4 cm)-enlarged: hypothyroidism, osteogenesis Imp. Small: craniostenosis (sutures), microcephaly Bulging: ICP, meningitis, hydrocephalus Sunken: Dehydration Posterior fontanel ( less than 1 cm ) Craniotabes: Small-softening of skull on sutures lines. disappears in days
Face– dysmorphic features (Down, Treacher-Collins, Pierre-Robin, Trissomy 13-18, newborn of diabetic mother, chromossomal Ds) Forceps mark. Facial nerve palsy observed when smiles/cries Facial Assymetry: soft tissue swelling in nose, mouth, chin , due to uterus positioning Eyes– Check pupillary size, reactivity to light, open symmetrically. Red reflex (leukocoria)- Cong. Glaucoma, cataract, Tumor Conjunctiva: erythema, exudate, edema, jaundice. Hypertelorism ( ↑ distance between orbits) Bluish sclera: Thin sclera Deep blue: osteogenesis Imperfecta Subconjunctival hemmorrage- birth pressure Check Iris- Brushfield spots, colobomas, heterochromia. Retina: developed at birth, with immobile lens. Poor visual acuity 20/400. Acuity improves fast over 6 months. Fixation/follow objects at 6-8 weeks. Nose– nose breathers (choanal atresia)- pass a catheter purulent nose discharge at birth suggest congenital syphilis Flaring of alae nasi: sign of respiratory distress
Ears– malformations, low set (treachers-collins), auricular pits (skin tags) Ear canal should be patent, and TM should be visible Asymmetry of ears, lipomas HEARING: well developed at birth. Neonates prefer speech sounds, human voices (hi-pitched). Will learn mothers voice and will prefer it to all others. Hearing test: Otoacoustic emission test : Several clicks is sent to baby’s ears. The hair cells inside the middle ear will capture the sound and send back an echo response that is measured by the equipment. First test to be performed Automated auditory brainstem response (AABR): This test measures brainwave response. It is a confirmatory test, but expensive test. SMELL: well developed. can recognized nursing mother breast pads TASTE: Prefer SWEET taste. Cry: Awake: Vigorous and loud when crying Resting: Rarely cries
Mouth Observe size, shape of mouth, tongue, palate integrity, uvula, gum cysts. Epstein pearls- epithelial cyst on the hard/soft palate margin Clefts lip/palate (check shape, integrity) Neonatal teeth (lower incisors), X-ray is needed to differentiate between: Predeciduous teeth- loose, roots are absent or poorly formed. Remove to avoid aspiration True Deciduous teeth: they should not be removed. Micrognathia (Pierre-Robin, treacher’s Collins) Esophageal atresia: ↑ drooling frothy saliva Macroglossia (Big tongue)–Congenital or acquired: hemangioma, ↓thyroid Beckwith’s Syndrome (macroglossia, gigantism, omphalocele, ↓ glycemia) Pompe’s disease (type II glycogen store disease) Microstomia: Trisomy 18-21 Macrostomia: Mucopolysaccharidosis Fetal Alcohol Syndrome: Fish mouth, enlarge philtrium Ranulas: small bluish white swellings on the floor of the mouth, are benign mucous gland retention cysts
Neck: Webbing- Turner Syndrome, Noonan’s Syndrome Clefts and masses: Midline: thyroid glossal duct cysts, Ant to SCM: Branchial cleft cyst. Whitin SCM: hematoma, torticollis Post. to SCM: Cystic hygroma Sinus tracts- remnants of branchial clefts Thyroid- Enlargement Short neck- Noonan’s, Turner, Palpate all muscles
Chest: Observation: chest symmetry, Tachypnea, grunting, sternal/intercostal retractions, pectus carinatum pectus excavatum, Breast Clavicles – fractures (bruising, crepitus, tenderness) MC Chest: ↑ AP diameter (barrel chest)-aspiration syndromes Lungs: Breath sounds- ↓ breath sounds or absence with Resp. distress and shift of mediastinum- pneumothorax, atelectasis Expiratory grunting, flaring-hyaline membrane Ds.
Heart Check for HR, PMI, murmurs, cyanosis, Pallor, BP , pulses pulses: Hypoplastic left heart pulses are ↓at all sites. Aortic coarctation, pulses are ↓ in lower extremities Check for signs of CHF: Hepatomegaly, gallop. Tachypnea, Rales/wheezing, tachycardia Murmurs: infant pink, well perfused, no resp. distress with symmetric and palpable pulses (R. brachial pulse same as femoral)- transitional murmur. Soft, 1/6, LU midsternal border. If after 24 hours, murmur persist, with a difference of pulse of 15mmhg (arm>leg) cardiologyst.
Abdomen: Check for softness, distention, bowel sounds, masses, diastesis recti, hernia, and abnormal shape, size or position of kidneys or other organs. Umbilicus – 2 arteries, 1 vein, Omphalocele, gastrochisis. Umbilical hernia: Due to weakness of the umbilical ring musculature Scaphoid abdomen- Diaphragmatic hernia Excessive drooling- GI catheter : esophageal atresia. Abdominal masses: Wilm’s Tumor, neuroblastoma Liver- palpated 1-2 cms below costal margin. Spleen- Tip palpated at the costal margin Kidneys- (left more than the right) can be palpated. If not palpated, think about Agenesis or hipoplasia. Large kidney may be due to Tumor, obstruction, cystic disease. Meconium should pass up to 48 hours of life Patency of anus and presence of fistulas
<ul><li>Genitalia: </li></ul><ul><li>Genitalia Ambigua- endocrinologyst </li></ul><ul><li>Male- Inspect the glans, urethral opening, prepuce, shaft, foreskin, testes </li></ul><ul><li>chryptorchidism, hypospadia, epispadia, hernias, hydrocele. </li></ul><ul><li>Testes should be onside scrotum </li></ul><ul><li>Failure to void: obstruction (tight foreskin), posterior urethral valves </li></ul><ul><li>First voiding is concentrated, and contain urates, staining the diaper pink to light red </li></ul><ul><li>Penis-2-3 cms lenght, phimosis. Brown color, rugated scrotum </li></ul><ul><li>Hydrocele will transiluminate </li></ul><ul><li>Testicular torsion !!! firm, bluish color, breech presentation, surgery </li></ul><ul><li>Inspect circumcised penis for edema, bleeding, incision. </li></ul><ul><li>Female– Inspect the labia, clitoris, urethral opening, external vaginal area, whitish, with or without blood </li></ul><ul><li>discharge, labial fusion and clitoral enlargement, Hymenal tag </li></ul>
Extremities/Skeletal: Check: fractures, absent fingers, congenital bands, clubfoot- (Talipes equinovarus) common in males, foot is turn downward and inward, sole is directed medially. Metatarsus Varus- Adduction of forefoot. Corrects spontaneously Palsies (brachial plexus injury) Palmar/Simian creases: Down Syndrome. Sometimes is a normal variant Polydactyly (x-ray- bony structures) Syndactyly (3 rd /4 th fingers and 2 nd /3 rd toes- surgery older age) Spine – Sacral dimples, hair tufts (spina bifida), scoliosis, meningocele, Kyphosis, Lordosis Hip dislocation: Barlow test (adduct the hip) Ortolani maneuver (abduct the hip) Affects more white females, affects more the left hip. 2 signs: shortening of leg, asymmetry of skin folds.
Neurologic: Symmetry of movements, irritability, alertness, posture Muscle tone: Hypotonia- Floppiness, head lag Hypertonia- ↑ resistance when arms/legs are extended. Tight clenched fists. Reflexes: Moro, rooting, sucking, grasping, fencing, stepping, placing Glabellar reflex (blink reflex) Reflexes must be symmetrical. Biceps jerk test C 5-6. Knee jerk test L 2-4 Ankle jerk test S 1-2 Truncal innervation reflex test T2 trough S1 Anal wink test S4-5 Sensory abilities- Hearing, smell Movement - Check for spontaneous movements of limbs, trunk, face, neck Fine tremor is normal, Clonic movements are not normal, related to seizures.
Posture: Term infants- Hips abducted and partially flexed and knees flexed Arms are abducted and flexed at the elbow. Fists are clenched with fingers covering the thumb Retina: developed at birth, with immobile lens. Poor visual acuity 20/400 Acuity improves fast over 6 months, with fixation/tracking well developed by 2 months. Cry: high pitch- CNS Ds (hemorrhage) Weak cry- Systemic Ds., Congenital Neuromuscular disorder S/S of neurologic disorders; Sx of ICP: Bulging Ant. Fontanelle, dilated scalp veins, setting-sun eyes, separated sutures Hypotonia/ Hypertonia/ Irritability/ Apathy Poor sucking and swallowing reflexes Shallow irregular respirations, Apnea Asymmetric or absent, depressed or exaggerated reflexes
Neurologic: Symmetry of movements: Injury to nerves of Brachial plexus: excessive traction on neck Erb’s-Duchenne palsy : -Injury of Superior brachial plexus (C5-C6) -Cannot abduct the arm at the shoulder, externally rotate the arm, supinate the forearm - “Waiter tip” position - wrist flexed . -Absent Moro reflex on affected side Klumpke: Injury of inferior brachial plexus (C7/8-T1) Paralyzed hand: Wrist drop Phrenic Nerve palsy: Injury to C3, 4, 5 Diaphragmatic paralysis Respiratory distress
<ul><li>SKIN: </li></ul><ul><li>Pallor respond well to warming. Associated with low Hb </li></ul><ul><li>Jaundice never appears before 24 hours of life, except can signal </li></ul><ul><li>serious hemorrhage/hemolytic disease. Hyperbilirubinemia </li></ul><ul><li>Cyanosis is common in newborns, mainly in prematures in hemolytic Ds. </li></ul><ul><li>Urgent treatment. Think Hypoxemia </li></ul><ul><li>Lanugo Fine hair on Shoulders, Ear, Back. Occur in prematures </li></ul><ul><li>Disappear within 2-3 weeks. </li></ul><ul><li>Normal/benign- Mongolian spots, nevi, erythema toxicum, pustular melanosis, milia, miliaria </li></ul><ul><li>The head hair are soft being abundant in some cases </li></ul><ul><li>The nails cross the length of the tip of fingers. </li></ul>
Skin: White Infants: Pink Color Black Infants: Reddish Color with scrotum, labia minora pigmented Newborn Infant: Vernix Caseosa: white-normal disappear in 12 hours Meconium-Fetal distress Green or yellow- Hemolitic disease Absence/Reduction- Post Maturity Term Infant Texture: Skin very smooth (like velvet) Premature Infant texture: Softer and Thinner, with wrinkles and scarcity of subcutaneous tissue. Post term Texture: Dry and Scaly
Vernix Caseosa: Soft white greasy cream made of sebum and desquamated epithelial cells covering the skin, mainly the preterm. Protects the infant I.U during delivery, against bruising. Lanugo: Fine hair on shoulders, Ear, Back. Occur in prematures Disappear within 2-3 weeks. The head hair are soft being abundant in some cases Pallor: Generalized Pallor may indicate Anoxia (slow pulse) or severe anemia (rapid pulse). Can be secondary to anemia, birth asphyxia, shock, PDA, low Hb.
Cyanosis: Central- bluish skin, including tongue and lips: Caused by low oxygen saturation in blood. Associated with congenital heart or lung Ds. Peripheral- bluish skin with pink lips and tongue: associated with methemoglobinemia. Is when Hb oxidizes from ferrous to ferric form. TX: use methylene blue Is also common in newborns, mainly in prematures in hemolytic Ds. Urgent treatment. Think Hypoxemia Plethora: Associated with Polycythemia (rosy red color. Order Hb) Jaundice (yellowish color): Associated with elevated bilirubin > 5mg/dl
TRANSIENT BENIGN VASCULAR PHENOMENA: Cutis Marmorata: Reticulated cyanosis or marbling of the skin involving the trunk and extremities. Response to temperature of the place (vasomotor instability) Acrocyanosis: Cyanosis in the extremity. If does not disappear within 12 hours or with warming, think cyanotic congenital heart disease. associated with hypoxia Harlequin color: Is a vasomotor instability, where lower half becomes bright red, and the upper half becomes pale. Can be benign, transient and last < 20 minutes or be a shunting of blood (pulmonary HTN or CoA).
BENIGN PUSTULAR DERMATOSES: Erythema toxicum: Appears 2/3 day of age. Erythematous macular-papular and vesicular rash. Disappear in a week or two. Wright’s stain shows sheets of Eos Transient Neonatal Pustular melanosis: Vesico-pustules or ruptured vesico-pustules with a collarette of scales in trunk or extremities. Last 48-72 hours Milia: Pin-head size, yellow-white epidermal cysts found in chin, nose, forehead. Retention of sebum in the sebaceous glands. Stays 2 months. Miliaria: Obstructed Eccrine sweat glands . Pinpoint vesicles on forehead scalp and skinfolds. Clear within a week.