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NGD > Teratogens + Congenital anomalies +neonatal pharmacology > Flashcards

Teratogens + Congenital anomalies +neonatal pharmacology Flashcards

1
Q

Teratogen definition

A

agent that can produce a permanent alteration of structure/function in an organism after exposure during embryonic/fetal life
No absolute teratogens- display effects under certain circumstances
Almost any agent toxic to mom can damage embryo

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2
Q

Factors affecting teratogenicity

A 
Nature of the agent
Dose - for most agents, only in presence of maternal toxicity
Route
Gestational timing
Concurrent exposures
Genetic susceptibility
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3
Q

Methylene blue considerations

A

given orally/iv for methemoglobinemia
given by intra-amniotic injection to assess PROM and in twin amniocentesis
Near term: hemolytic anemia, jaundice in newborn after intramniotic injection
16 weeks: multiple intestinal atresia in fetus after intramniotic injection

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4
Q

Critical period

A

usually has occurred before mom knows they’re pregnant
Greatest susceptibility of 0-8 weeks embryonic age
0-2 wks: relative insusceptibility - all or none, can repair or won’t implant
CNS susceptibility continues throughout pregnancy

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5
Q

Chorionic villi sampling - limb reduction defects

A

Exposure after limb formation
Transverse terminal LRDs increased, esp distal digital defects
Risk greater and defects more severe with earlier CVS
Vascular disruption?
similar effect with misoprostil
similar effect with cocaine, other v/c agents

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6
Q

Maternal diabetes teratogenicity

A

Heart defects (2-3%)
neural tube defects (1-2%; spina bifida, anencephaly)
proximal femoral hypoplasia
holoprosenencephaly

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7
Q

Maternal obesity embryonic risk

A

neural tube defects

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8
Q

Maternal antibodies risk to fetus

A

Rh disease: hydrops, death, severe anemia
Antiplatelet antibodies: proencephaly
Autoimmune endocrinopathies
SLE –> heart block, chondrodysplasia punctata

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9
Q

Birth defects due to teratogens

A

1-2% maternal metabolic disease
~1% maternal antibodies
2-3% infections

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10
Q

Infectious agents that can be teratogenic

A 
Syphilis
Toxoplasmosis
Rubella
CMV
Varicella
HIV
Parvo
LCMV
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11
Q

Teratogenic physical agents

A

Radiation: large doses, not X-rays
radioactive iodine after 13 weeks gestation can destroy fetal thyroid gland
CVS
Early amniocentesis (

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12
Q

Environmental toxins (teratogenic)

A

limited by dose and maternal toxicity
Methyl mercury
- ingestion of toxic amounts in food
- Minamata disease: cerebral palsy, intellectual disability, blindness, microcephaly

PCBs:

  • rice oil disease: fetal growth retardation, “cola-coloured” parchment-like skin
  • features resolve with time
  • maternal ingestion of toxic amounts in food
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13
Q

Drugs of abuse -teratogenic

A

ALCOHOL: FASD, full form from severe chronic alcoholics
Cigarettes: v/c, small babies, miscarriage
Cocaine: vascular disruption
Toluene by inhalation

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14
Q

Medications that can be teratogenic

A 
Thalidomide
cytotoxic agents
androgenic hormones
DES
valproic acids
phenytoin
phenobarbital
trimethadione
carbamazepine
primidone
accutane
lithium
warfarin
misoprostol
fluconazole 
trimethoprim
ACEi
ATII inhibitors
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15
Q

Anomaly definition

A

any abnormal deviation from expected in structure, form, or function
does not imply a specific cause

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16
Q

Etiology of congenital abnoramlities

A

2-3% at time of birth
3-5% at one year of life (+ internal anomalies not obvious at birth, like congenital heart defects)
Etiologic heterogeneity
cause cannot be determined by appearance alone
Important to determine whether isolated/part of a more generalized pattern
- isolated: often multifactorial
- generalized: usually not multifactorial

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17
Q

Minor anomalies

A

14% newborns
includes ear tag/pit, single palmar crease, D5 clinodactyly
usually of no functional significance
may be characteristics of certain patterns of anomalies e.g. Down syndrome
more likely to have major congenital anomaly if there are multiple minor ones

18
Q

Types of congenital anomalies

A

malformation
disruption
deformation

19
Q

Malformation anomalies

A

primary error of normal development/morphogenesis of an organ or tissue
may have a variety of causes
abnormal development from early in embryogenesis

20
Q

Malformation examples

A

syndactyly
most spina bifida
most cleft palate
most congenital heart lesions

21
Q

Disruption anomalies

A

morphologic defects resulting from a breakdown, or interference with, an originally normal developmental process
sometimes called secondary malformation
may result from extrinsic factor, like infection or trauma
not usually caused by single gene or chromosomal abnormality
may occur at any time during gestation

22
Q

Examples of disruptions

A

amniotic band disruption

Porencephaly

23
Q

Amniotic band disruption

A

amnion ruptured –> filmy strands may constrict arm –> amputation
usually sporadic

24
Q

Porencephaly

A

due to infection/bleed?
disruption of previously normal brain tissue
large cyst in brain

25
Q

Deformation anomalies

A

abnormalities of form or position caused by nondisruptive mechanical forces
mechanical interference with normal growth, functioning or positioning of fetus in utero
Constraint may predispose to deformation
- first pregnancy: smaller, tighter uterus –> club feet, abnormal skull shape
- uterine malformation
- unusual fetal positioning: bum first –> flat head due to uterine pressure
Oligohydramnios
Multifetal pregnancy: no room

Usually happens in 2nd trimester
can often be treated by mechanical means

26
Q

Patterns of multiple anomalies

A

Sequences
Developmental field defects
Syndromes

27
Q

Sequence anomalies

A

derived from a single structural defect/deformation

cascade of anomalies

28
Q

Oligohydramnios sequence

A

No kidneys in fetus;leak;blockage of urine
If early: babies don’t breathe well –> poor lung fxn and development
club foot
Potter’s faces (squished): flat nose, deep crease on cheeks, large ears –> flattened by endometrial muscles since no cushioning
Prune belly: bladder so large –> poor lung development

29
Q

Pierre Robin Sequence

A

tiny jaw
tongue gets misplaced, high in mouth, get in way of palatal shell formation –> U-shaped cleft palate (as opposed to usual V)
genetic/sporadic

30
Q

Myelomeningocoele sequence

A

spina bifida/NTD
involev nerves to bowel, bladder, lower limbs
club feed and other positional abnormalities

31
Q

Developmental field defect

A

patterns of anomalies resulting from disturbed development of a morphologic field
Field: region of embryo that develops in a related fashion

32
Q

Holoprosencephaly

A

abnormality of midline brain development
face would be affected similarly to brain
commonest cause = trisomy 13

33
Q

Syndrome anomaly

A

patterns in which all of component anomalies are thought to be pathogenically related
implies a similar etiology in all affected individuals
Down syndrome
Marfan syndrome

34
Q

Transplacenta therapeutic drugs

A

Folic acid, vitaming B12 for NT

betamethasone for lung maturation

35
Q

Intraamniotic therapeutic drugs

A

thyroxine for lung maturation

36
Q

Therapeutic drugs given directly to fetus

A

umbilical vein/im injection

digoxin and amiodarone for fetal cardiac arrhythmias

37
Q

Drug exposure through breastfeeding

A

breast milk pH

38
Q

Absorption of drugs in infants

A

Oral: increased gastric pH
Topical: thinner stratum and greater skin hydration - increased absorption

39
Q

Distribution of drugs in infants

A

TBW highest at birth
BBB: immature in neonates - increased conc of lipid-soluble and some small, polar drugs in CNS
Plasma proteins: concentration/binding affinity both reduced
- 2x lower serum albumin
- lower doses of highly protein-bound drugs
- increased risk of drug interactions due to drug displacement from protein binding sites

40
Q

Metabolism of drugs in infants

A

neonates not born with a full compliment of P450 enzymes

41
Q

Renal excretion in infants

A

elimination of renally excreted drugs decreased due to reduced GFR and renal tubular secretion (20% of adult function for the 1st year of life)
need longer dosing intervals
use pediatric-specific equations to estimate creatinine and GFR

NGD (16 decks)

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