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PCOM Board Review: Pediatrics Tod Winslow, DO March 5, 2016 S Overview S Newborn S Growth and Development S Infectious Disease S Musculoskeletal Newborn S Neonate/Newborn: First month of life S Infant: First year of life S Neonatal resuscitation: Review BLS, NRP, ACLS, etc S APGAR’s Appearance Pulse Grimace Activity Respirations Newborn Sign 0 1 2 HR Absent <100 ≥ 100 Respiratory effort Absent Slow/irregular Good/crying Muscle tone Limp Some extremity flexion Active motion Response to bulb in nostril No response Grimace Cough/Sneeze Color Blue/pale Pink body/Blue extremities Completely pink Newborn S Nutrition S Breast milk (and most formulas) 20 calories/ounce (1oz = S S S S 30mL) Energy requirement = Fluid requirement 0-10kg 100 kcal/kg 100 mL/kg 11-20 50 kcal/kg 50 mL/kg ≥20kg 20 kcal/kg 20 mL/kg Newborn S Can lose up to 10% of birth weight the first few days S Should be back to birth weight by two weeks of life S ≥ 6 wet diapers/day; 1-3 stools/day S Vitamin D: 400 IU/day – should be sent home from nursery on Vitamin D (MVI) Newborn Rashes Newborn Rashes Newborn Rashes S Erythema Toxicum Neonatorum: 50% full term infants, begin at 24-48 hours (can begin up to 10 days out). Fades within one week. S Salmon Patch “Stork Bite” “Angel’s Kiss” >50% newborns, due to capillary malformations. Fade within first year. S Capillary Hemangioma: Rapid growth first 6 months, plateau period, then slow involution: 25% disappear by age 3, 50% by age 4, 75% by age 6. Newborn Rashes Newborn Rashes S Milia: S Retained keratin in the dermis S 1 to 2 mm white/yellow papules S Resolve in 1 to 3 months S Miliaria Rubra: Heat Rash S Small erythematous papules and vesicles Newborn Rashes Newborn Rashes S Acne Neonatorum S Hormonal stimulation of sebaceous glands S Resolves within 4 months S 2.5% benzoyl peroxide lotion S Transient Neonatal Pustular Melanosis S Pigmented macules in Vesiculopustules - no erythema S Vesicle ruptures leaving scale/pigmented macule S Fades in 2 to 4 weeks Newborn Rashes Newborn Rashes S Seborrheic Dermatitis S Erythema and greasy scale S Scalp, face, ears, neck and diaper area S Resolves in weeks to months S White Petrolatum, Coal Tar shampoo, HCT 1% S VS. Atopic Dermatitis – no pruritis S Develops after 3 months of age. Newborn Cardiology S Cardiology S VSD 25%, PDA 10%, most others 1-5% S VSD: Loud holosystolic murmur, LLSB. May not hear in nursery due to higher right sided pressures first few days of life. S PDA: Continuous machine-like murmur. S Both represent left-to-right shunts and are often present with other cardiac anomalies. Newborn Cardiology S Tetralogy of Fallot S Pulmonic Stenosis S RVH S VSD S Overriding Aorta S Clinical manifestations: First few years of life S Play/DOE/Lay down/Play cycle S Tet spells: Exertional dyspnea, hypercyanosis, and possibly syncope Newborn Jaundice S Neonatal Jaundice in Term Infants S Physiologic Jaundice S <5mg/dL/24 hours S On 2nd or 3rd day of life S Peak 2nd to 4th day S Resolve 5th to 7th day S Never reaches 12mg/dL Newborn Jaundice S + Coombs: Rh, ABO, or minor antigen incompatibility S - Coombs: S Breast feeding jaundice: due to decreased enterohepatic circulation S Breast milk jaundice: Late onset jaundice due to antibodies S Hemorrhage (cephalohematoma) S G6PD deficiency, Hereditary spherocytosis, etc. Direct hyperbilirubinemia – rare – think biliary atresia or some other cause of obstruction. Newborn Jaundice S Prevention S Promote/support breast feeding – 10 to 12 feeds/24 hours S Measure bilirubin in all jaundice infants < 24 hours S Interpret levels based on age in hours S Identify/monitor higher risk infants S Preterm - < 37 weeks S Macrosomia/GDM S Siblings S Bruising/cephalohematoma S Jaundice < 24 hours S Provide written instructions for parents S Follow-up after DC Newborn Jaundice S Treatment: S Use Nomogram to plot bilirubin level based on age(hours) S Fix underlying cause S Phototherapy (converts indirect bilirubin into water soluble form). Decision to use based on plotting newborn on chart for age, TSB, and risk factors. Newborn - Eyes S Conjunctivitis: S If chlamydia, occurs between 8 and 14 days with a watery discharge. Need to treat with ORAL erythromycin. S Esotropia: If intermittent, likely to resolve by 6 months of age, so no need to refer to ophthalmology until then. S Lacrimal Duct Obstruction: Excessive tearing, usually unilateral. Likely to resolve by 12 months, so no need to refer to ophthalmology until then. Newborn - GI S Failure to pass Meconium – 1st 24 hours S Pyloric Stenosis: Non-bilious “projectile” vomiting at around 3 weeks of life. “Olive-like” mass palpated S Gastroesophageal Reflux S Gastroesophageal Reflux Disease SIDS S Sudden Infant Death Syndrome S Unexplained death of infant < 1year during sleep S RISK FACTORS S S S S S S S S S S <37 weeks EGA, weight < 2500 gms Bed sharing < 12 weeks or at ANY time Maternal ETOH Household smoke exposure Soft bedding Car seat/stroller use No prenatal care and Poverty Males sex Black, Native American, Native Alaskan Overheating/excess Bundling SIDS S BACK to SLEEP Campaign S PRONE and SIDE SLEEPING POSITIONS S Including use of a care seat or stroller S Risk Reduction S Exclusive BREASTFEEDING at 1 month of age S Pacifier use S Asian/Pacific Islander ethnicity S Home Apnea Monitors Growth and Development Age Expressive Response % intelligible speech to stranger 12 months 1 word 2 years 2 word phrases (“want cookie”) 50% 3 years 3-4 word sentences. Uses pronouns and plurals (“I want a cookie.”) 75% 4 years Tells a story 100% Red Flags Suggesting Need for Immediate Speech-Language Evaluation Age 12 months Receptive — Expressive Does not babble, point, or gesture 15 months Does not look at or point to 5 to 10 objects or persons when named by parents Does not use at least three words 18 months Does not follow one-step directions Does not say “mama,” “dada,” or other names 2 years Does not point to pictures or body parts Does not use at least 25 words when named 2.5 years Does not verbally respond or nod/shake head to questions Does not use unique two-word phrases, including noun-verb combinations 3 years Does not understand prepositions or action words Does not follow two-step directions Does not use at least 200 words Does not ask for things by name Repeats phrases in response to questions (echolalia) At any age — Has regressed or lost previously acquired speech/language milestones Adapted with permission from Schum RL. Language screening in the pediatric office setting. Pediatr Clin North Am. 2007;54(3):432. Growth and Development S Evaluation S Appropriate growth chart S Infants – weight, length, head circumference S 2 – 20 y/o – weight, height and BMI S Variation should stay within 2 bands S Birth weight S Doubles by 4 months S Triples by 12 months Growth and Development S Birth to 18 months S Catch-up or catch-down S Growth genetically determined by midparental height S 2 years to Adolescents S Growth hormone S Adolescents S Sex hormones are predominant factor Growth and Development S Evaluation S History & PE S Growth Velocity S Midparental Height S Bone Age S LAB Endocrine – normal/over weight S GI/Nutrition/Systemic Disease – under weight S Genetic S Growth and Development S Constitutional Growth Delay S Most common cause of short stature in children S Growth delay between 3 months and 3 years S Delay in puberty so remain behind on growth curves until later in adolescence S Growth and development are appropriate for skeletal age, but not biologic age S Familial Short Stature S Follows growth curves and bone age S Look at the parents! S Idiopathic Short Stature S no identifiable pathology S > 2 standard deviations below with normal bone age and growth velocity Infectious Disease S Fever: 100.4 Fahrenheit/38 Celsius. Appropriate biologic response to infection. Not caused by teething. S Febrile Seizures: S Seizure in absence of: intracranial infection, history of afebrile seizure, metabolic disturbance. S 2-5% children ages 6 months to 5 years (peak 18 months) S Risk of recurrence 14-70% depending on risk factors (<18 months, fever less than 1 hour prior to seizure, temp < 104, first degree relative with febrile seizure) S 2% lifetime risk of epilepsy Infectious Disease S Sepsis S <28 days with fever: S Admit to hospital, LP, Blood cultures, Urine culture, IV antibiotics S 28-90 days with fever: S If non-toxic appearing with normal WBC’s and normal UA, blood and urine cultures, close follow-up, +/- LP & Ceftriaxone S Otherwise, admit to hospital, LP, Blood cultures, Urine culture, IV antibiotics Infectious Disease Infection Bugs Antibiotics Meningitis <1 month LEG Listeria, Enterics (especially E.coli), GBS Ampicillin + Cefotaxime OR Ampicillin + Gentamicin Meningitis 1-3 months NEHSG Neisseria meningitides, Enterics, H. flu, Strep pneumo, GBS Ampicillin + Cefotaxime OR Ceftriaxone Meningitis >3 months minus Enterics and GBS Cefotaxime or Ceftriaxone + Vancomycin Infectious Disease S UTI S VCUG’s no longer recommended for febrile UTI’s in children S S S S 2-24 months unless abnormal renal ultrasound Still get renal sonogram for girls with febrile UTI’s 2-24 months and boys of any age PEES: Proteus, E. coli, Enterococcus, S. saprophyticus PO: Cephalosporins, TMP/SMX IV: Cephalosporins, Ampicillin + Gentamicin Infectious Disease S Acute Otitis Media: S Acute onset, Middle Ear Effusion (MEE), Signs/Symptoms of Middle Ear Inflammation S MEE: Bulging, decreased mobility, or AFL behind TM. S Inflammation: Erythema of TM on exam, or distinct otalgia S Bacterial 75% of time: S. pneumo (40%), H. flu (30%), Morexella catarrhalis (15%) Infectious Disease Age Toxic appearing, persistent otalgia for > 48 hours, temp ≥ 102.2, or uncertain access to follow-up Non-toxic, otalgia not persistent, temp < 102.2, and certain access to followup < 6 months Antibiotics Antibiotics ≥ 6 months Antibiotics Observe for 48-72 hours Infectious Disease S Acute Otitis Media: S Amoxicillin 80-90mg/kg per day (high dose to overcome resistant S. pneumo) divided twice daily S Amoxicillin-clavulanate if accompanying conjunctivitis (think H. flu) or if failure with Amoxicillin S Non-type 1 PCN Allergy – cephalosporins, if Type-1 PCN allergy, macrolides or Clindamycin S Analgesics (oral and/or ear drops) Infectious Disease S Otitis Media with Effusion (OME) S MEE without inflammation or severe illness S Treatment is observation for up to three months, then tympanostomy tubes if not resolved Infectious Disease S Bronchiolitis: S Most common cause of infant hospitalization in 1st year S Lower respiratory tract infection/bronchiolar inflammation S Most commonly caused by RSV S Bronchodilators are now contraindicated in infants < 24 months – increased tachycardia/decreased O2 saturation S Corticosteroids/Aerosolized Epi/Hypertonic Saline Saline/ Antibiotics – CONTRAINDICATED S High Risk - <12 weeks, Prematurity, Cardiopulmonary Disease, Immunodeficiency S Prophylaxis – Palivizumab(Synagis) – high risk infants only Infectious Disease S Pneumonia S S. pneumo and Viral - high dose amoxicillin sufficient until preschool age S Add macrolides for atypical coverage at age 4 Infectious Disease S Pertussis: “Whooping Cough” S Catarrhal stage (common cold symptoms) S Paroxysmal stage (paroxysmal cough) S Convalescent stage (waning of cough over weeks to months) S Treat with macrolides, most effective if given during catarrhal stage but should be given at any phase to prevent spread. S Immunize, immunize, immunize! Infectious Disease S Antibiotic contraindications S Ceftriaxone in neonates (up to 28 days) S Displaces bound bilirubin and thus can cause hyperbilirubinemia S Tetracyclines under age 8 S Tooth discoloration S Fluoroquinolones in children and adolescents S Cartilage/Joint damage S Erythromycin under 1 month S Pyloric stenosis Infectious Disease/Rashes Infectious Disease/Rashes S Roseola Infantum(exanthema subitum) S Human herpesvirus 6 S Infants/children <3 S Macular/maculopapular S High Fever >102, well appearing child S Mild cough, rhinorrhea, mild diarrhea S Fever resolves then onset of rash S Starts on trunk/spreads peripherally S Lasting 1 to 2 days S DDx: measles Infectious Disease/Rashes Infectious Disease/Rashes S Fifth Disease “Erythema Infectiosum” S Human Parvovirus B19 S Slapped-cheek appearance S Lace-like rash on trunk, moving to arms, thighs, and buttocks S Rash preceded by brief and mild illness (fever, sore throat, malaise, myalgias, headache) by 7 days S Facial rash 2 – 4 days, Reticular rash 1 to 6 weeks S Can cause fetal hydrops, IUGR, and fetal death Infectious Disease/Rashes Infectious Disease/Rashes S Henoch-Schonlein Purpura S Most Cases < 10 y/o, Peak age 6 S TRIAD: Palpable Purpura(normal PLT), Abdominal Pain(60%) and Arthritis(75%) S Petechial rash that develops into purpura on buttocks, lower extremities, and hands – trunk and face are spared S Abdominal pain ranges from mild colic to severe pain (hemorrhage or intussusception in 5%) S Knees and ankles most common sites of arthritis S 40 - 50% have renal involvement (ranges from hematuria or proteinuria to ESRD in 1 to 5%) S Early treatment with Prednisone Infectious Disease/Rashes Infectious Disease/Rashes Infectious Disease/Rashes S Hand, foot, and mouth disease S Coxsackie Virus - enteroviruses S Late summer/fall S Prodrome of low grade temp, anorexia, malaise, URI symptoms S 90% have oral lesions (palatal erythema and ulcers) S 2/3 have shallow yellow ulcers surrounded by halos on hands and feet Kawasaki Disease/Rashes Kawasaki Disease/Rashes Infectious Disease/Rashes S Kawasaki’s Disease S “FEEL My Conjunctivitis” S Fever – x 5 days S Erythematous Rash – maculopapular/polymorphous S Extremity involvement – erythema/desquamation S Lymphadenopathy - cervical S Mucus membrane involvement –cracked/red lips, strawberry tongue S Bilateral conjunctivitis S Coronary artery aneurysms – Transthoracic Echo S Treat with high dose aspirin and IVIG Infectious Disease/Rashes Infectious Disease/Rashes S Scarlet Fever S 10% of Streptococcal tonsillopharyngitis S Group A beta-hemolytic streptococci – pyrogenic exotoxin S Fever, Sore Throat first S Sandpaper rash S Pastia lines S White strawberry tongue, palate petechiae S Rapid Strep Antigen test in office/Throat Culture S PCN/Cephalosporin/macrolides/Clinda Infectious Disease/Rashes Infectious Disease/Rashes S Pityriasis Rosea S Herald Patch – 80% S Peripheral scale overlying pink thin papules S Bilateral, symmetrical, Christmas tree pattern S Mild URI may precede rash S 2 to 12 weeks S ? Human herpes virus 6 and 7 Infectious Disease/Rashes Infectious Diseases/Rashes Infectious Disease/Rashes S Tinea Corporis/Capitis/Cruris/Pedis/Manus/unguium S KOH microscopy, fungal culture S Scaling/circumscribed alopecia with broken hair follicles S Erythematous annular patch with raised border and central clearing S Capitis – oral griseofulvin or terbinafine(Lamisil) Infectious Disease/Rash Infectious Disease/Rash S Impetigo S Vesicles or Pustules with thick yellow “honey” crust S Face and extremities most common S Streptococcus pyogenes S Topical Mupirocin ointment or oral PCN S Bullous form in neonates – Staph aureus Infectious Disease/Rash Infectious Disease/Rash S Molluscum Contagiosum S Poxvirus S Children 2 to 11, Adolescents – sexually active S Flesh colored, pearly papules with central umbilication S Watchful waiting – months to years S Cryotherapy, imiquimod(Aldara) or intralesional immunotherapy S Treat underlying atopic dermatitis to prevent spread Infectious Disease/Rash Infectious Disease/Rashes S Herpes Gladiatorum S Wrestlers - 75%+ exposure by college S Vesicular rash on red base S Localized patches – associated with areas of abrasions/friction S Highly contagious S Treat with antiviral – valacyclovir, acyclovir S Suppression therapy for season Infectious Diseases S Mononucleosis/EBV S Sore throat, fever S tonsilar enlargement S Fatigue S Lymphadenopathy S pharyngeal inflammation S palatal petechiae S 15 to 24 years of age Infectious Disease S Mononucleosis/EBV Diagnosis S Heterophile Antibody – up to 90% accuracy S CBC – absolute lymph > 4,000 mm3 S EBV specific IgM and IgG S Treatment S Glucocorticoids S Antiviral Therapy S Complications S Splenic rupture/sports – 0.5% risk S Airway compromise S X-linked lymphoproliferative disorders/immunocompromised Musculoskeletal S Nursemaid elbow S Traction injury of 2-3 year olds S Can treat with hyperpronation or supination/flexion S Hyperpronation is the preferred method Musculoskeletal S Female Athlete’s Triad S Anorexia, osteoporosis, and amenorrhea S Transient Synovitis, Septic Hip, and Osteomyelitis S Assuming normal radiographs, if afebrile and normal CBC/ESR/CRP then likely Transient Synovitis (observe/NSAID’s) S If any of the above are present, obtain hip ultrasound and aspirate if effusion or, if no effusion, check MRI to rule out osteomyelitis Musculoskeletal S Slipped Capital Femoral Epiphysis (SCFE) S Overweight, Adolescent, Male > Female S Ice cream falling off of cone on hip x-ray S Treat with surgery S Apophysitis S Osgood Schlatter – Tibial tuberosity S Sever’s Disease – Insertion of Achilles tendon into calcaneous S Treat with rest, ice, and NSAID’s Questions S During rounds, you notice a new rash on a full-term 2-day old white female. It consists of 1-mm pustules surrounded by a flat area of erythema, and is located on the face, trunk, and upper arms. An examinatiion is otherwise normal, and she does not appear ill. Which one is the most likely diagnosis? A. Erythema toxicum neonatorum B. Transient neonatal pustular melanosis C. Acne neonatorum D. Systemic herpes simplex E. S. aureus species Questions S During rounds, you notice a new rash on a full-term 2-day old white female. It consists of 1-mm pustules surrounded by a flat area of erythema, and is located on the face, trunk, and upper arms. An examinatiion is otherwise normal, and she does not appear ill. Which one is the most likely diagnosis? A. Erythema toxicum neonatorum B. Transient neonatal pustular melanosis C. Acne neonatorum D. Systemic herpes simplex E. S. aureus species Questions S A 12 year old male is brought to your office by his parents because he has been limping for the past month. He says he has pain in the groin and knee, but the pain is poorly localized. On examination he is noted to be obese, with normal findings on examination of the knee. There is some decrease in internal rotation of the hip on the involved side. His gait is antalgic. The most likely cause of this problem is A. Unreported trauma B. Aspectic necrosis of the femoral head C. Reactive arthritis D. Juvenile rheumatoid arthritis E. Slipped capital femoral epiphysis Questions S A 12 year old male is brought to your office by his parents because he has been limping for the past month. He says he has pain in the groin and knee, but the pain is poorly localized. On examination he is noted to be obese, with normal findings on examination of the knee. There is some decrease in internal rotation of the hip on the involved side. His gait is antalgic. The most likely cause of this problem is A. Unreported trauma B. Aspectic necrosis of the femoral head C. Reactive arthritis D. Juvenile rheumatoid arthritis E. Slipped capital femoral epiphysis Questions S Which one of the following is an appropriate rationale for antibiotic treatment of Bordatella pertussis infections? A. It delays progression from the catarrhal stage to the paroxysmal stage B. It reduces the severity of the symptoms C. It reduces the duration of the illness D. It reduces the risk of transmission to others E. It reduces the need for hospitalization Questions S Which one of the following is an appropriate rationale for antibiotic treatment of Bordatella pertussis infections? A. It delays progression from the catarrhal stage to the paroxysmal stage B. It reduces the severity of the symptoms C. It reduces the duration of the illness D. It reduces the risk of transmission to others E. It reduces the need for hospitalization Questions S Four weeks after successful initial treatment of unilateral otitis media in a 2-year-old male enrolled in day care, you reevaluate the child. He is asymptomatic, but you detect a middle ear effusion in the affected ear. They tympanic membrane is otherwise normal. The best management at this time would be A. Inflation of the eustachian tube by the Valsalva maneuver B. An antihistamine for 30 days C. Low-dose corticosteroids for 30 days D. Referral to an ENT specialist E. No further treatment, with reevaluation in 2 months Questions S Four weeks after successful initial treatment of unilateral otitis media in a 2-year-old male enrolled in day care, you reevaluate the child. He is asymptomatic, but you detect a middle ear effusion in the affected ear. They tympanic membrane is otherwise normal. The best management at this time would be A. Inflation of the eustachian tube by the Valsalva maneuver B. An antihistamine for 30 days C. Low-dose corticosteroids for 30 days D. Referral to an ENT specialist E. No further treatment, with reevaluation in 2 months Questions S A full term infant weighing 6lb 8oz at birth will typically weight 20lb at what age? A. 6 months B. 9 months C. 12 months D. 15 months E. 18 months Questions S A full term infant weighing 6lb 8oz at birth will typically weight 20lb at what age? A. 6 months B. 9 months C. 12 months D. 15 months E. 18 months Questions S Which one of the following jaundiced infants can be treated expectantly without a full workup for pathologic causes? A. A 12-hour-old term infant with a total bilirubin of 10 mg/dL B. A 1-day-old term infant with a total bilirubin of 20 mg/dL C. A 2-day-old term infant with a total bilirubin of 10 mg/dL D. A 1-week-old term infant with a total bilirubin of 25 mg/dL Questions S Which one of the following jaundiced infants can be treated expectantly without a full workup for pathologic causes? A. A 12-hour-old term infant with a total bilirubin of 10 mg/dL B. A 1-day-old term infant with a total bilirubin of 20 mg/dL C. A 2-day-old term infant with a total bilirubin of 10 mg/dL D. A 1-week-old term infant with a total bilirubin of 25 mg/dL Questions S Which one of the following is recommended to prevent SIDS? S A. Infants should sleep on a soft mattress. S B. The crib should be kept in the parents’ room, preferable next to the parents’ bed S C. A car seat may be used in place of a crib for naps S D. Infants with gastroesophageal reflux should be placed in the prone position for sleep References S Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders Elsevier; 2007 S Zitelli BJ, Davis HW. Atlas of Pediatric Physical Diagnosis. 4th ed. Philadelphia, PA: Mosby; 2002 S American Academy of Pediatrics. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006 S Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management. Urinary Tract Infection: Clinical Practice Guidelines for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months. Pediatrics 2011; 128;595 References S McLaughlin, MR. Speech and Language Delay in Children. Am Fam Physician. 2011 May 15;83(10):1183-1188 S Raghuveer TS, Cox AJ. Neonatal Resuscitation: An Update. Am Fam Physician. 2011 Apr 15;83(8):911-918. S Graves RC, Oehler K, Tingle LE. Febrile Seizures: Risks, Evaluation, and Prognosis. Am Fam Physician 2012 Jan 15;85(20:149-153. S Kalyanakrishnan R, Sparks RA, Berryhill, WE. Diagnosis and Treatment of Otitis Media. Am Fam Physician. 2007 Dec 1;76(11):1650-1658. S American Academy of Pediatrics. The Diagnosis and Management of Acute Otitis Media Pediatrics. 2013 Mar 1 vol 131 e964-e999. References S O’Connor, McLaughlin, Newborn Skin: Part 1 Common Rashes, American Fam Physician, 2008 Jan 1; 77(1):47-52 S McLaughlin, O’Connor, Newborn Skin: Part 2 Birth Marks American Fam Physician, 2008 Jan 1, 77(1):56 -60 S Adams, Ward, Garcia, Sudden Infant Death Syndrome, American Fam Physician, 2015 June 1, 91(1):778-783