Week 3: Pregnancy 2 Flashcards
1
Q
Teratogenicity in weeks 1-3
A
Teratogen exposure in the preimplantation to implantation phase usually leads to an “all or none” period with either miscarriage or no effect
2
Q
Teratogenicity in weeks 3-8
A
The developing baby is at greatest risk for major abnormalities during the embryonic stage (weeks 3-8)
3
Q
When is a developing baby at the greatest risk for teratogens
A
the embryonic stage (weeks 3-8)
4
Q
When is the embryonic stage?
A
Weeks 3-8
5
Q
Teratogenicity in weeks 9+
A
- Minor anomalies
- growth disturbance
- stillbirth
- preterm delivery
- neurodevelopmental effects
6
Q
Critical periods of teratogenicity
A
7
Q
Teratogenicity throughout gestation
A
development of parts to embryonic age
8
Q
What is a teratogen?
A
Teratogens are agents that alter the structure and/or function of the fetus
from greek “teras” = monster
9
Q
Teratogen criteria
A
10
Q
Classes of teratogens
A
- Known teratogenic medications
- Substances of abuse
- Infections (TORCH) et al (and others)
- Maternal diabetes
- environmental/chemical (eg mercury, X ray)
11
Q
Super infamous historic medical teratogen
A
Thalidomide
12
Q
Thalidomide teratogenic effects
A
- born without ears was first
- phocomelia (flipper-like arms and legs)
- deformed eyes, heart, GI, GU anomalies and deafness
13
Q
Thalidomide mechanism of teratogenicity
A
The drug restricts blood vessel angiogenesis
14
Q
Thalidomide Mnemonic
A
Limb defects with Thalimbdomide
15
Q
FDA 5 letter drug classification system
A
16
Q
Replacement of the FDA 5 letter classification system
A
17
Q
DES AKA
A
Diethylstilbestrol
18
Q
What is Diethylstilbestrol
A
Synthetic estrogen hormone analog
19
Q
Diethylstilbestrol teratogenic effects
A
- Clear cell adenocarcinoma in exposed female offspring “DES Daughters”with the risk being highest in their teens and early 20s but also reported in their 30s and 40s
- T-shaped uterus
- Hooded cervix
- Hypoplastic cervix
- Cockscomb cervix
- Pseudopolyp
- Infertility
- tubal pregnancy
- preterm delivery
- risk of male reproductive issues in male offspring
20
Q
What is the Cockscomb cervix?
A
Maternal DES exposure
21
Q
DES cervix and vagina
A
22
Q
Known teratogenic medications
A
- Ace inhibitors
- ARBs
- Alkylating agents
- Aminoglycosides
- Anti-epileptics
- AED
- Folate antagonists
- Isotrenitoin
- Lithium
- Methimazole
- Methotrexate
- Misoprostol
- Tetracyclines
- Warfarin
23
Q
ARBs AKA
A
Angiotensin-II Receptor Blockers
24
Q
ACE inhibitors AKA
A
Angiotensin-converting enzyme inhibitors
25
ACE inhibitors classification
Old pregnancy category: C or D
26
ACE inhibitors teratogenic effects
First trimester:
* Bony malformations
* calvarial hypoplasia
* limb contractures
* patent ductus arteriosus
second or third trimester:
* Fetal and neonatal renal failure with oligohydramnios
* IUGR
* leading to pulmonary hypoplasia, hypotension, death
27
ACE inhibitors clinical considerations with pregnancy
* Stop before pregnancy or ASAP with dx pregnancy
* Captopril has been studied enough to be used in breastfeeding mothers
28
ARBs teratogen classification
Old category: D
Risk summary: All trimesters
29
ARBs Teratogenic effects
* incomplete skull ossification
* renal dysplasia
* fetal effects hypotension
* anuria
* oliguria
* IUGR
* PAtent ductus arteriosus
* Death
30
ARBs Teratogenic clinical considerations
* Animal studies suggest toxic actions are most common after 3rd trimester exposure
* Use should be avoided throughout pregnancy and breastfeeding
31
What are Alkylating agents?
Substances that cause replacement of hydrogen by an alkyl group in a biologically important molecule, specifically: with mutagenic activity that inhibits cell division and growth and used to treat some cancers and autoimmune disorders
32
Alkylating agents teratogenic classification
Old category: D and X
33
Alkylating agents teratogenic risk summary
All trimesters
34
Alkylating agents teratogenic effects
* Cleft palate
* renal agenesis
* digital malformations
* cardiac anomalies
* cataracts
* IUGR
35
Antimetabolites teratogenic classification
D and X
36
Examples of antimetabolites
* Aminopterin
* 5 FU
* Methotrexate
* Methylaminopterin
* cytarabine
37
Antimetabolites teratogenic risk summary
All trimesters
38
Antimetabolites teratogenic effects
* Cleft lip/palate
* low set ears
* cranial anomalies
* anencephaly
* IUGR
* stillbirth
39
ACE inhibitors examples
* Captopril
* Enalopril
* Lisinopril
40
ARBs examples
* Cadesartan
* Eprosartan
* Losartan
* Valsartan
41
Aminoglycosides teratogenic classification
old category: D
42
Aminoglycosides teratogenic risk summary
Trimester of risk is inconsistent
43
Aminoglycosides teratogenic effects
Gentamycin - ototoxicity and nephrotoxicity (selective uptake, cellular damage)
**A mean guy** hit the baby in the **ear**
44
Anti-epileptic Drugs AKA
AED
45
AED AKA
Anti-epileptic Drugs
46
First generation Anti-epileptic clinical considerations of teratogenicity
47
Examples of first generation Anti-epileptic Drugs
* Phenytoin (Dilantin)
* Carbamazepine (Tegretol)
* Valproic acid
* Phenobarbital
48
first generation Anti-epileptic Drugs teratogenic effects
* Orofacial clefts
* dysmorphic facial features
* Nail and digit hypoplasia
* Cardiac defects
* IUGR
* Microcephaly
* Developmental delay
* Neuroblastomas
* Cleft palate
* Can be affected by congenital enzyme deficiency
49
Valproic acid teratogenic classification
Old category: D
50
Valproic acid examples
* Depakene
* Depakote
51
Valproic acid teratogenic clinical considerations
* Fetal levels are more than 2x maternal levels
* Risk is dose-dependent and folate sensitive
52
Valproic acid teratogenic risk summary
Neural tube defect 1-2% risk
53
Valproic acid teratogenic effects
* Craniofacial
* Limb abnormalities
* Heart
* CNS dysfunction
* Developmental delay
54
Carbamazepine examples
* Tegretol
* Atretol
* Convuline
* Epitol
55
Carbamazepine teratogenic effects
* Facial dysmorphism
* Spina bifida 0.5-1% risk
* Distal phalange and fingernail hypoplasia
* Developmental delay
* Neonatal cholestatic jaundice
56
Oxycarbazepine teratogenic classification
old category: C (registry available)
57
Oxycarbazepine teratogenic risk summary
not felt as teratogenic as tegretol
58
Oxycarbazepine examples
Trileptal
59
Oxycarbazepine teratogenic effects
* High risk of Steven Johnson Syndrome
* Skin lesions
60
Second generation AEDs examples
* Lamotrigine (lamictel)
* Toriramate (Topamax, Trokendi XR, Qudexy)
61
Second generation AEDs Lamotrigine & Toriramate teratogenic classification
NAAED pregnancy registry
62
Second generation AEDs Lamotrigine & Topiramate teratogenic effects
* Small risk of isolated, non-syndromic cleft lip +/- cleft palate
* NAAED pregnancy registry reported in 2011 that an increased risk of oral clefts in infants exposed to topiramate monotherapy during the first trimester of pregnancy
63
Examples of Folic Acid antagonists
* Aminopterin
* Carbamazepine
* Cimetidine
* Methotrexate
* pemetrexed
* Phenytoin
* Phenobarbital
* Proguanil
* Primethamine
* Triamterene
* Trimethoprim
* Valproic acid
64
Folic Acid antagonists teratogenic classification
Some D and some X
65
Folic Acid antagonists teratogenic risk summary
First trimester of risk during closure of the neural tube
66
Folic Acid antagonists teratogenic defects
* Variable
* Neural tube defects
67
Folic Acid antagonists teratogenic clinical considerations
* approximately 50% of NTD can be prevented
* USPHS recommends all women of childbearing age take 0.4 mg of folic acid daily and patients taking folic acid antagonists to take 4.0 mg per day
68
Isotretinoin classifcation
Old category: X
69
Isotretinoin teratogenic Risk summary
All trimesters
critical window of exposure is 3-5 weeks
70
Isotretinoin teratogenic defects
* deformities of the cranium, ears, micrognathia, limbs, liver, hydrocephalous, microcephaly, heart defects, craniofacial alterations, cleft palate, NTDs, thymic aplasia, renal alterations, cognitive defects
71
Isotretinoin main teratogenic ingredient
Retinoic acid or retinol derivatives (Vitamin A derivatives)
72
Retinoic Acid or Vitamin A derivatives teratogenicity
73
Lithium is an?
Alkali metal
74
Lithium teratogenic classification
Old category: D
Pregnancy registry available
75
Lithium teratogenic risk summary
May cause fetal harm
76
Lithium teratogenic defects
increased risk of cardiac defects (eg Ebstein's Anomaly in some studies but not in others)
77
Lithium teratogenic clinical considerations
* This drug is only recommended for use during pregnancy when there are no alternatives and the benefit outweighs the risk
* Monitor serum lithium
* Monitor newborns for: lithium toxicity (hypertonia, hypothermia, cyanosis, ECG changes) and hypothyroidism
78
What is Ebstein's Anomaly?
The tricuspid valve is displaced inferiorly to the right ventricle and atrial septal defect
79
Methimazole teratogenic classification
Old category: D
80
Methimazole teratogenic risk summary
Largely the first trimester is risky
81
Methimazole teratogenic defects
* Scalp defects (aphasia cutis)
* possible chanal and esophageal atresia
* absent or hypoplastic nipples
82
Methimazole teratogenic clinical considerations
* Switch to PTU in the first trimester
* Higher choanal and esophageal atresia with exposure in weeks 3-7
83
What is Tetracyline?
Antibiotic used to treat acne and some respiratory conditions
84
Tetracyline teratogenic risk summary
* No birth defects shown in children who were exposed during the first trimester
* If taken after the 4th month there is a risk of causing discoloration of the baby's teeth
85
Tetracyline teratogenic effects
"**Teeth**racylclines"
* No birth defects shown in children who were exposed during the first trimester
* If taken after the 4th month there is a risk of causing discoloration of the baby's teeth
* It may also effect calcification of the bones and teeth and up to 40% depression of bone growth
86
Warafarin AKA
Coumadin
87
Warafarin teratogenic classificaiton
old category: X
88
Warafarin teratogenic risk summary
**ALL**
89
Warafarin teratogenic effects
* Deformities of the skeleton
* hypoplastic nose
* eye abnormalities
* brachycephaly
* scoliosis
90
Warafarin teratogenic clinical considerations
* Embryopathy is due to early use, bleeding in the CNS can cause later defects
* Stillbirth risk = 8%
* contraindicated in pregnancy with exception of maternal mechanical valves
* Verify pregnancy status prior to initiation, advise to use effective contraception during treatment and one month after the final dose
* switch to heparinoid w/ dx of pregnancy
91
Fetal warfarin syndrome
92
Other teratogens
* Maternal diabetes
* Mercury
* X rays
* Excessive vitamin A
* Potassium iodide
93
Maternal diabetes teratogenic effects
* Harmful effects on the fetus recognized over 100 years ago
* felt that lack of glycemic control during embryogenesis is the main factor in the origin of malformations
* risk 2-4 fold over non-diabetics
* 7-10 fold risk increase for major anomalies that are lethal or require major surgery
94
IDM AKA
infants of diabetic mothers
95
Congenital malformations in IDM
IDM = infants of diabetic mothers
Fuel-mediated teratogenesis-exposure of the embryo to an abnormal metabolic environment during the initial stages of embryogenesis results in abnormal development of the embryo
96
Proposed etiology of diabetic embryopathy
* Hyperglycemia
* Hyperketonemia
* Oxygen free-radicals
97
Maternal hyperglycemia teratogenic clinical considerations
* Dose and time dependent
* Rat studies post implantation rat embryo 100% teratogenic dose 950 mg/dL D-glucose
* Day 10 primary NTD
* Day 11 cardiac defects
* Day 12 no defects
98
Hyperglycemia teratogenic effects
* Dose and time dependent
* Specific ultrastructural changes
* decreased embryo size
* yolk sac malformations
* abnormal transport of nutrients
* arachadonic acid deficiency
* accumulation of sorbitol
* deficiency of myo-inositol
99
Oxygen free-radicals
Result of glucose metabolism
Increased lipid peroxidation
* direct effect on DNA
* Imbalance between prostaglandins and prostacyclins
100
Classic diabetic embryopathy
Caudal Regression Syndrome
101
Caudal Regression Syndrome
* occurs 600x more frequently among IDM
* Spectrum of malformation
* cessation of growth of rostral portion of spinal cord
* abnormal neural, muscular, skeletal and vascular components
* can mimic VACTERL
102
Sironmella
* Diabetic embryopathy
* Absence of hind limbs, external genitalia, anus and rectum
* Potter sequence secondary to bilateral renal agenesis
103
Organ systems invovled in diabetic embryopathy
104
How to manage diabetic pregnancy
Management is prevention
Glycemic control prre-conceptual or early pregnancy goal \< 6
105
What is mercury
Mercury is an element that can collect in oceans, lakes and streams
106
Mercury teratogenic considerations
* Turns into methylmercury which is a neurotoxin found in most fish in at least small amounts
* Minamata disease is methylmercury poisoning with neurologic symptoms
* Fist epidemic southern coast of Yatsushiro sea and also Agano river
107
Methymercury teratogenic considerations
In high quantities, methylmercury can be toxic to the nervous FDA guidelines regarding types of fish to avoid and reduce
* Tilefish
* swordfish
* shark
* king mackerel
108
X ray risk of teratogenicity
109
Mechanism of fetal harm from alcohol
110
FAS AKA
Fetal alcohol syndrome
111
Fetal alcohol syndrome teratogenic effects
* Syndrome of birth defects caused by prenatal exposure to alcohol
* growth deficiencies
* head and facial malformations
* microcephaly
* neurocognitive effects
112
FAE AKA
Fetal alcohol effects
113
Fetal alcohol effects teratogenic effects
Less severe than FAS
* Lowered IQ
* Hyperactivity
* growth deficiencies
* Head and facial malformations (eg flat philtrum, mid facial hypoplasia)
114
Leading cause of non-genetic and preventable cause of developmental delay
115
Cigarette smoking teratogenicity
116
Tobacco teratogenicity
117
Cocaine teratogenicity
118
Methamphetamines teratogenicity
gastroschisis
119
TORCH Stands for?
120
Index of suspicion for TORCH infections
121
Diagnosing TORCH infections
122
Toxoplasmosis teratogenicity
123
Toxoplasmosis clinical presentation
124
Clinical features of toxoplasmosis
* Cerebral calcificiations
* Chorioretinitis
* HydroCephalous
* Convulsions
125
Toxoplasmosis 4 Cs
126
Treatment of cerebral calcifications due to toxoplasmosis
Pyrimethamine
127
Treatment of Chorioretinitis due to toxoplasmosis
Sulfadiazine and folinic acid
128
Congenital syphilis
129
Fetal risks of congenital syphilis
130
Early congenital syphilis first 5 weeks
131
Late congenital syphilis
132
Clinical features diagnosis and Tx of congenital syphilis
133
Parvovirus B19 overview
134
Congenital parvovirus B19 teratogenic risk summary
135
Parvovirus B19 in pregnancy
136
Congenital parvovirus 1st trimester infection
* 10% miscarriage
* ventriculomegaly
* calficiations
* limb defects
* echogenic bowel
* liver calcifications
* Parvovirus had an affinity for erythroid precursor cells, cardiac myocytes and platelets
137
Congenital parvovirus 2nd-3rd trimester infection
* Fetal anemia
* Myocarditis
* secondary hydrops
138
Clinical features, diagnosis and treatment of congenital parvovirus B19
139
Congenital varicella
140
Clinical features, diagnosis and treatment of congenital varicella
141
Congenital rubella
142
Rubella effects
143
Clinical features, diagnosis and treatment of rubella
144
Congenital CMV
145
Congenital CMV
146
Congenital Herpes
147
Clinical features, diagnosis and treatment of congenital CMV
148
Clinical features, diagnosis and treatment of congenital HSV
149
TORCH .... Z
150
Congenital Zika virus
151
Zika virus congenital infection
152
Zika ventriculomegaly and macrocephaly
153
Fetal brain disruption sequence
154
Zika virus and other birth defects
155
Clinical features, diagnosis and treatment of Congenital zika
156
DES identify
vagina and cervix
