Congenital disorders Flashcards
Four questions to ask in guiding medication use in pregnancy:
- Question 1: Is the symptom to be treated self limited and/or amenable to nonpharmacologic management?
- Question 2: If the medication is not administered, what are the possible outcomes for mother and fetus?
- Question 3: What data is available on the safety of this medication in pregnancy and is there a similar drug with better safety data available that could be used instead?
- Question 4: How is the patient’s (and the provider’s) understanding and value system affecting decisions about the use of this medication in pregnancy?
types of maternal substance use
- Tobacco Use ( OTC)
- Rx - SSRIs, Anticonvulsants, Retinoids
- Marijuana, cocaine, heroin, hallucinogens, inhalants, methamphetamine, prescription psychotherapeutics used non-medically, and ETOH
- 86% of pregnant opioid-using women reported their pregnancy was unintended
NAS (neonatal abstinence syndrome) defined as:
- Neonate has intrauterine exposure to substance
- Depends on drug, length of use, amount used , use close to delivery , etc)
- S/Sx of withdrawal apparent
- Baby will stay in the hospital for treatment
screening for maternal substance use
- Initial presentation at first prenatal visit ideal with repeat screening at every trimester and periodically
- Begin with questions about lawful substances (cigarette smoking and alcohol), followed by misuse of OTC meds, next Rx drugs, and so on
- Determine route of administration (PO, intranasal, subQ, IV)
- Urine screening is MC to assess mother’s use
s/s of anticonvulsant substance use
- Small head circumference
- Anteverted nares
- Cleft lip / palate
- Distal digital hypoplasia - specifically with phenytoin (Dilantin)
- Spina bifida - specifically with valproic acid
s/s of isotretinoin
- 33% exposed in 1st trimester have developmental toxicity
- 40 % will miscarry
- CNS malformations, congenital heart defects, TEF, small or absent ears
s/s SSRI use
- May express symptoms of NAS
- CNS signs - irritability, seizure
- Motor signs - agitation, tremor, hypertonia
- Rsp - increased respirations, nasal congestion
- GI - diarrhea, vomiting, feeding difficulty
effects of tobacco maternal substance use
- Associated with low birth weight, infant’s ability to be comforted, with exaggerated startle reflex and tremor
- Transferred through the placenta and may reach up to 15% greater concentration than in the mother
s/s of FAS (Fetal Alcohol Syndrome)?
how to dx?
- Short stature
- Poor head growth - intrauterine and postnatal
- Developmental delay
- Midface hypoplasia
- Poorly developed philtrum, thin upper lip, narrow palpebral fissures, short nose with anteverted nostrils
- Cardiac anomalies, genital anomalies, neural tube defects
- Neurobehavioral - Poor judgement, inappropriate social interactions
- Dx: strictly based on maternal hx and clinical findings. No blood test.
effect of marijuana maternal use
- Increased risk of depression in childhood
- Hyperactivity, impulsivity, inattention, and delinquency
effects of opiates maternal use
- Most drastic effect on mother and fetus
- Withdrawal symptoms
- Low birth weight
- Prematurity
- IUGR: intrauterine growth restriction
- Heroin withdrawal may start at 24 hrs after birth and peak at 48-72 hrs, but may be delayed as long as 6 days
*
Benzos / Barbiturates - Due to longer half life, withdrawal may not start for ?
2 wks
Illicit drugs cause ____ and ____ in the baby due to passing across the placental barrier
- dependence, tolerance
- After crossing, they accumulate in the fetus because of immaturity of renal function and the enzymes used for metabolism
s/s Neonatal Abstinence Syndrome
- High-pitched cry
- Jitteriness
- Tremors
- Convulsions
- Sweating, fever
- Mottling
- Excessive sucking and rooting
- Poor feeding
- Vomiting and diarrhea
dx NAS
Blood tests, urine toxicology, meconium analysis, cord blood, hair
scoring using Finnegan CNS
- high pitched cry
- high pitched at peak - 2
- high pitched throughout - 3
- scored if crying is prolonged - sleep
- score longest uninterrupted interval of sleep
- scoring for premature infant on 3 hr feeds
- 1 if < 2hrs, 2 if < 1 hr, 3 if does not sleep - moro reflex
- hyperactive - pronounced jitteriness of hands
- markedly hyperactive - jitteriness/clonus of hands/feet
NAS scoring
- first abstinence score should be recorded approx 2 hrs after birth or admission
- dynamic, all s/s observed during scoring interval are included in point-total for that period
- if infant’s score at any scoring >8, scoring is increased to 2-hrly and continued for 24 hrs from last total score of 8 or higher
- if pharm is not needed, infant is scored for first 4 days of life at 4-hrly interveals
tx for NAS
- Opioids - 1st line (morphine or methadone)
- Phenobarbital - 2nd line for opioid withdrawal seizure activity and polydrug exposure
-
Fentanyl - analgesic in the NICU
- Administered with morphine
prevention of sx in mother with maternal substance use
- If opiate dependent - switch to methadone is preferable to detoxification
- Buprenorphine (Subutex / Suboxone): Prenatal exposure required less morphine, with shorter recovery time and less hospitalization for infants than Methadone - High dose of BZD - medical detoxification to minimize or prevent withdrawal symptoms
- Test for STDs at initial screen and repeat third trimester
what med has a higher rate of retaining Mother in tx program
Methadone
what med is better for the baby
lower rates of withdrawal
higher birth wts
Buprenorphine - suboxone
what immunization is CI in pregnant women
live vax
Cautioned to be given to children of women who may be or may become pregnant within a 4 week period of receiving the vaccine
types of Aneuploidy- abnormal number of chromosomes
- Trisomies 13, 18, 21
- extra chromosome in some or all of the body’s cells - Klinefelter Syndrome (47, XXY)
- Monosomies: Turner Syndrome (45, X)
types of autosomal dominant disorders
- Marfan’s Syndrome
- Achondroplasia- dwarfism
types of autosomal recessive disorders
- CF
- PKU
a X-linked recessive diseases
Fragile X Syndrome
Gives you information about how genetic conditions might affect your family
Genetic Counseling
Genetic counseling referrals may be given for:
- Planning to become pregnant
- During pregnancy
- Caring for children
Candidates for prenatal screening or diagnostic testing
- ACOG - all women should be offered aneuploidy screening in early pregnancy.
- Quadruple Screening Blood test (B-hCG, AFP, Inhibin A, Estriol)
- ACOG also states all women should have option of invasive dx testing instead of screening, regardless of maternal age.
Reasonable for women of any age at a high risk of having an offspring with Down Syndrome or other aneuploidies. state the indications:
- A positive screening test for common Trisomies
- A previous pregnancy complicated by fetal Trisomy
- Current pregnancy with At least one major or two minor fetal structural abnormalities
- A chromosomal disorder or a partner with one
MC invasive dx testing for down syndrome or other aneuploidies
Choroid villus sampling or Amniocentesis
Protocols for prenatal screening for Down Syndrome and other congenital disorders have been implemented because:
The burden of disease for the affected individual and his/her family can be significant.
- Accurate prenatal tests are readily available
- Prenatal diagnosis gives parents options-
- An opportunity to plan for the birth of an affected child
- Pregnancy termination
Most common abnormality of chromosome number
Trisomy 21
40% of trisomy 21 have what common abnormality/condition
cardiac abnormalities
T/F: Adult women with Trisomy 21 are fertile with ⅓ offspring born with DS. Males infertile
T
at what age is trisomy 21 at greatest risk
35
trisomy 21 s/s
- Normal birth weight
- Hypotonia
- Flattened occiput, nasal bridge
- Upslanting of the palpebral fissures, epicanthal folds
- Large, protruding tongue
- Single Palmar creases and wide gap between first and second toes
- Cognitive delay
common other conditions in trisomy 21
- ⅓ - ½ have congenital heart disease
- GI anomalies - feeding issues and constipation
- Up to 30% with esophageal and duodenal atresia
- Celiac disease - Hypothyroidism
- Polycythemia at birth with prolonged jaundice
- 12-20 fold increase of leukemia in children with Down Syndrome
dx trisomy 21
Measure Quad Screen on all pregnancies (Week 14-18 gestation)
- Maternal alpha-fetoprotein (AFP) - low in 50% of trisomies
- Unconjugated estriol
- Inhibin A
- Human chorionic gonadotropin (HCG)
HCG & Inhibin = HIGH; everything else is LOW
Quad screen recommended for:
- Have a family history of birth defects
- Are 35 years or older
- Used possible harmful medications or drugs during pregnancy
- Have diabetes and use insulin
- Had a viral infection during pregnancy
- Have been exposed to high levels of radiation
tx for trisomy 21
- Screening for autoimmune disorders - celiac, thyroid
- Surgical intervention for cardiac and GI abnormalities
- Developmental support
- Special education- IEPs
- Therapies - PT, speech, occupational
trisomy 18 - what % lead to spontaneous abortion
85%
trisomy 18 is MC what sex?
3x female to male ratio
95% of trisomy 18 have what defect
heart
s/s trisomy 18
- SGA, Dysmorphic features
- Overlapping fingers and rocker-bottom feet
- clenched fists
- dysplastic/malformed ear
- small mouth, jaw, and short neck
dx trisomy 18
genetic testing
tx trisomy 18
- Supportive
- Support groups
- Termination of pregnancy
trisomy 13 -Abnormalities in what organ systems
every organ system
Most are incompatible with life
trisomy 13 MC in what sex
female - 60%
s/s trisomy 13
- FTT, apneic spells, seizures, cognitive disabilities, deaf
- cleft palate
- Aplasia cutis congenita (Cutis aplasia)
dx and tx for trisomy 13
genetic testing
supportive - therapy, support groups, termination
T/F Klinefelter syndrome is MC in advanced maternal age
T
Most common genetic cause of hypogonadism and infertility in men
Klinefelter Syndrome
Extra X Chromosome arises from nondisjunction in either the sperm or egg
s/s Klinefelter syndrome
- Usually recognizable at age 15-16
- Gynecomastia
- Tall, long limbs
- Normal pubic hair but gonadal dysgenesis
- Small testis
- Lack of libido
- Minimal facial hair - Normal to low IQ
- Most men are infertile due to few viable sperm
may have XXY, XXXY, or XXXXY. - if so, the more X they have the more intellectually impaired
what signs should alert clinicians to klinefelters
Progressive development of pubic and axillary hair in the presence of infantile testicular volume
dx and tx for klinefelter syndrome
- genetic testing
- testosterone replacement
Sex chromosome disorder caused by loss of part or all of an X chromosome
turners
s/s turner syndrome
- Low-set malformed ears, flattened nasal bridge
- Triangular facies - Web neck
- Shield chest with widened nipple distance
- Aortic valve defects, coarctation
- Genitourinary malformations
- Horseshoe kidney - Short stature
- Absent puberty (primary amenorrhea)
- Infertility
tuners - Infertility is not correctable with ___. Pregnancy dangerous due to ?
- estrogen
- high potential for heart disease and aortic dissection while pregnant .
tx for turners
- Tx should begin in early childhood
- androgens, human growth hormones, small doses of estrogen and later progesterone.
dx and tx Turners
- Diagnosis - Genetic Testing
- Tx
- Estrogen therapy to permit development of secondary sex characteristics and normal menstruation
- Growth hormone to help their heights - Counseling for child
- Low fertility rate with high chance of spontaneous miscarriage, stillbirth, chromosomal abnormalities - Prenatal U/S and chromosome analysis
Autosomal dominant connective tissue disorder
Children may present with a positive family hx
Marfan’s syndrome
Marfan’s is a Mutation in what gene
fibrillin 1 gene on chromosome 15q21.1
s/s Marfan’s
- Cardiac
- Progressive dilation of the aortic root
- Dysrhythmias - Orthopedic
- Tall, thin body,& long,thin face
- Pectus excavatum or carinatum
- Scoliosis
- Pes Planus (flat footed)
- Joint Laxity - Ophthalmologic/oral
- Dislocation of lens
- Cataracts
- Down-slanting palpebral fissures
- High-arched palate/crowded dentition
dx Marfan’s
- Ghent criteria - Calculate Marfan Score
- Genetic testing
complications of Marfan’s
- Progressive scoliosis
- Astigmatism, myopia, lens dislocation
- MVP, progressive aortic root dilation - causing aortic insufficiency, aneurysmal rupture, progressive valvular incompetence
tx Marfan’s
- Serial ECHOs
- BB for cardiac abnormalities (decrease wear and tear on aorta and lower preload.
- Surgery when aorta reaches 5.5 cm
- Losartan - slows rate of aortic root dilation
- Frequent eye exams
- Restriction of strenuous exercise
- Genetic evaluation in adolescents / genetic counseling
Most common inherited cause of mental retardation / cognitive disability in males
Fragile X Syndrome
gene that causes of Fragile X Syndrome
FMR1
fragile X s/s
- Intellectual disabilities, such as Autism spectrum disorder or pervasive developmental disorder
- Oblong face with large ears
- Large Testis
- Hyperextensible joints
- MVP
dx and tx fragile X
- DNA testing, after genetic testing to look specifically for the FMR1 mutation
- Genetic counseling, Behavioral therapy, Other specialties- psych, developmental specialists
- MC life-shortening autosomal recessive genetic disease among Caucasians
- Pulmonary infection, pancreatic insufficiency and elevated sweat chloride test
CF
median survival age for CF
39
what gene determiens CF
Chromosome 7 - CFTR
complications of CF
- Nose - Rhinitis, nasal polyps, sinusitis
- Rsp tract- epithelium of patients with CF exhibits marked impermeability to chloride and excessive reabsorption of sodium - results in decreased mucociliary transport (pseudomonas and staph aureus infections)
- Bronchitis, pneumonia, atelectasis, pneumothorax, resp failure / mucoid impaction - GI - Meconium ileus or peritonitis, volvulus, rectal prolapse, intussusception, growth failure (due to malabsorption)
- GU -
- Infertility - abnormal mucus in sperm and fallopian tubes, delayed puberty (due to nutritional def and underweight), digital clubbing
- > 95% are infertile
pathophys CF
- Lack of normal CFTR function alters Cl- conductance in the sweat gland = excessively high sweat Na and Cl levels
- When the protein is not working correctly, Cl (component of salt) becomes trapped in cells
- Without proper movement of chloride, water cannot hydrate the cellular surface
- This leads the mucus covering the cells to become thick and sticky
s/s CF
- Respiratory Complications
- GI Complications
___ of the airway with pathogenic bacteria often occurs early in life.
What pathogens are ultimately isolated from the respiratory secretions of most patients.
Colonization
Staph aureus, Haemophilus influenzae. Pseudomonas aeruginosa
Persistent, productive cough, hyperinflation of the lung fields on CXR, and pulmonary function tests that are consistent with ___ ___ disease
obstructive airway
dx CF
- Newborn screening in most states
- Confirmed by positive sweat Cl test (>60 mmol/L)
- Pilocarpine used for sweat test: parasympathetic alkaloid that stimulates the secretion of large amounts of saliva and sweat - Lab testing for fecal elastase to measure pancreatic insufficiency
- DNA testing for CF
tx CF
- F/U with Pulmonology on a regular basis
- F/U with Infectious Disease
- Genetics
- Pancreatic enzyme replacement therapy (PERT)
- Antibiotic therapy, neb treatments, vest treatments
- Lung transplant
Autosomal recessive metabolic disease .
Lack the enzyme to break down phenylalanine .
PKU
PKU must be on what type of diet
protein restricted; restrict aspartame also (phenylalanine)
If diet not followed, run risk of developmental delay , seizures , intellectual issues, mental health issues .
Untreated PKU kids have what type of odor
musty or “mousy “
Caused by relative excesses or deficits of tissue along the linear anatomic planes
Can occur together or separately
Cleft Lip / Palate
Cleft Lip & Palate MC in which sex
Male predominance with both together; cleft lip more common in male, palate in female
cause of cleft lip/palate
third and eighth weeks gestation.
Occurs when the fusion of the face, around the sixth week, is disrupted
RF of cleft lip/palate
Multiple genetic (risk in 1st degree relatives) and environmental factors may be involved:
- Exposure to radiation
- Viral infections
- Metabolic abnormalities
- Teratogenic compounds (Phenytoin, Valproic acid, thalidomide, ETOH, tobacco, dioxins and herbicides)
dx and prevention of cleft palate
- Dx - 2nd trimester of pregnancy on U/S
- Prevention - ? high dose of folic acid and Multivitamins
tx cleft lip/palate
- Surgical closure (lip - usually by 12 months of age, followed by palate by 18 months of age)
- Speech therapy
- Pediatrician for OM/ ENT
- Dental help for chronic issues
- Speech therapy
- Genetic counseling
- cleft lip feeder/special bottles
Synthesis failure of the muscle cytoskeletal protein dystrophin on DMD gene on X chromosome
Duchenne Muscular Dystrophy
s/s Duchenne Muscular Dystrophy
- Proximal muscle weakness and hypertrophy of calf muscles
- Usually noticeable around 5-6 y/o
- Serum creatine kinase levels markedly elevated
dx Duchenne Muscular Dystrophy
- Previously muscle bx, now replaced by detecting duplications or deletions of the dystrophin gene
- ⅓ cases with (-) FHx are likely new mutations
prognosis duchenne musclar dystrophy
Death usually in 20’s due to cardiac or respiratory failure
tx Duchenne musclar dystrophy
Corticosteroids - maintaining strength
Genetic counseling
- Inherited genetic disorder involving a defect in the collagen and connective tissue synthesis and structure
- Joint hypermobility, cutaneous fragility (skin extensibility with scarring tendency), and hyperextensibility
Ehlers-Danlos Syndrome
beighton scoring system
- 5th finger
- thumbs
- elbows
- knees
- spine
scoring/criteria for brighton criteria
- 2 major criteria
- 1 major, 2 minor
- 4 minor
- 2 minor and unequivocally affected 1st-degree relative in FHx
major criterias for Brighton criteria
- beighton score >=4
- arthralgia for longer than 3 months in 4 or more joints
