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Human Reproduction > Week 3: Pregnancy 2 > Flashcards

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

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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)

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3
Q

When is a developing baby at the greatest risk for teratogens

A

the embryonic stage (weeks 3-8)

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4
Q

When is the embryonic stage?

A

Weeks 3-8

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5
Q

Teratogenicity in weeks 9+

A
  • Minor anomalies
  • growth disturbance
  • stillbirth
  • preterm delivery
  • neurodevelopmental effects
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6
Q

Critical periods of teratogenicity

A
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7
Q

Teratogenicity throughout gestation

A

development of parts to embryonic age

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8
Q

What is a teratogen?

A

Teratogens are agents that alter the structure and/or function of the fetus

from greek “teras” = monster

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9
Q

Teratogen criteria

A
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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)
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11
Q

Super infamous historic medical teratogen

A

Thalidomide

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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
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13
Q

Thalidomide mechanism of teratogenicity

A

The drug restricts blood vessel angiogenesis

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14
Q

Thalidomide Mnemonic

A

Limb defects with Thalimbdomide

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15
Q

FDA 5 letter drug classification system

A
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16
Q

Replacement of the FDA 5 letter classification system

A
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17
Q

DES AKA

A

Diethylstilbestrol

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18
Q

What is Diethylstilbestrol

A

Synthetic estrogen hormone analog

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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
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20
Q

What is the Cockscomb cervix?

A

Maternal DES exposure

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21
Q

DES cervix and vagina

A
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22
Q

Known teratogenic medications

A
  • Ace inhibitors
  • ARBs
  • Alkylating agents
  • Aminoglycosides
  • Anti-epileptics
  • AED
  • Folate antagonists
  • Isotrenitoin
  • Lithium
  • Methimazole
  • Methotrexate
  • Misoprostol
  • Tetracyclines
  • Warfarin
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23
Q

ARBs AKA

A

Angiotensin-II Receptor Blockers

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24
Q

ACE inhibitors AKA

A

Angiotensin-converting enzyme inhibitors

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25
Q

ACE inhibitors classification

A

Old pregnancy category: C or D

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26
Q

ACE inhibitors teratogenic effects

A

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
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27
Q

ACE inhibitors clinical considerations with pregnancy

A
  • Stop before pregnancy or ASAP with dx pregnancy
  • Captopril has been studied enough to be used in breastfeeding mothers
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28
Q

ARBs teratogen classification

A

Old category: D

Risk summary: All trimesters

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29
Q

ARBs Teratogenic effects

A
  • incomplete skull ossification
  • renal dysplasia
  • fetal effects hypotension
  • anuria
  • oliguria
  • IUGR
  • PAtent ductus arteriosus
  • Death
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30
Q

ARBs Teratogenic clinical considerations

A
  • Animal studies suggest toxic actions are most common after 3rd trimester exposure
  • Use should be avoided throughout pregnancy and breastfeeding
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31
Q

What are Alkylating agents?

A

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

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32
Q

Alkylating agents teratogenic classification

A

Old category: D and X

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33
Q

Alkylating agents teratogenic risk summary

A

All trimesters

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34
Q

Alkylating agents teratogenic effects

A
  • Cleft palate
  • renal agenesis
  • digital malformations
  • cardiac anomalies
  • cataracts
  • IUGR
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35
Q

Antimetabolites teratogenic classification

A

D and X

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36
Q

Examples of antimetabolites

A
  • Aminopterin
  • 5 FU
  • Methotrexate
  • Methylaminopterin
  • cytarabine
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37
Q

Antimetabolites teratogenic risk summary

A

All trimesters

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38
Q

Antimetabolites teratogenic effects

A
  • Cleft lip/palate
  • low set ears
  • cranial anomalies
  • anencephaly
  • IUGR
  • stillbirth
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39
Q

ACE inhibitors examples

A
  • Captopril
  • Enalopril
  • Lisinopril
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40
Q

ARBs examples

A
  • Cadesartan
  • Eprosartan
  • Losartan
  • Valsartan
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41
Q

Aminoglycosides teratogenic classification

A

old category: D

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42
Q

Aminoglycosides teratogenic risk summary

A

Trimester of risk is inconsistent

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43
Q

Aminoglycosides teratogenic effects

A

Gentamycin - ototoxicity and nephrotoxicity (selective uptake, cellular damage)

A mean guy hit the baby in the ear

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44
Q

Anti-epileptic Drugs AKA

A

AED

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45
Q

AED AKA

A

Anti-epileptic Drugs

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46
Q

First generation Anti-epileptic clinical considerations of teratogenicity

A
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47
Q

Examples of first generation Anti-epileptic Drugs

A
  • Phenytoin (Dilantin)
  • Carbamazepine (Tegretol)
  • Valproic acid
  • Phenobarbital
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48
Q

first generation Anti-epileptic Drugs teratogenic effects

A
  • 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
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49
Q

Valproic acid teratogenic classification

A

Old category: D

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50
Q

Valproic acid examples

A
  • Depakene
  • Depakote
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51
Q

Valproic acid teratogenic clinical considerations

A
  • Fetal levels are more than 2x maternal levels
  • Risk is dose-dependent and folate sensitive
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52
Q

Valproic acid teratogenic risk summary

A

Neural tube defect 1-2% risk

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53
Q

Valproic acid teratogenic effects

A
  • Craniofacial
  • Limb abnormalities
  • Heart
  • CNS dysfunction
  • Developmental delay
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54
Q

Carbamazepine examples

A
  • Tegretol
  • Atretol
  • Convuline
  • Epitol
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55
Q

Carbamazepine teratogenic effects

A
  • Facial dysmorphism
  • Spina bifida 0.5-1% risk
  • Distal phalange and fingernail hypoplasia
  • Developmental delay
  • Neonatal cholestatic jaundice
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56
Q

Oxycarbazepine teratogenic classification

A

old category: C (registry available)

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57
Q

Oxycarbazepine teratogenic risk summary

A

not felt as teratogenic as tegretol

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58
Q

Oxycarbazepine examples

A

Trileptal

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59
Q

Oxycarbazepine teratogenic effects

A
  • High risk of Steven Johnson Syndrome
  • Skin lesions
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60
Q

Second generation AEDs examples

A
  • Lamotrigine (lamictel)
  • Toriramate (Topamax, Trokendi XR, Qudexy)
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61
Q

Second generation AEDs Lamotrigine & Toriramate teratogenic classification

A

NAAED pregnancy registry

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62
Q

Second generation AEDs Lamotrigine & Topiramate teratogenic effects

A
  • 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
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63
Q

Examples of Folic Acid antagonists

A
  • Aminopterin
  • Carbamazepine
  • Cimetidine
  • Methotrexate
  • pemetrexed
  • Phenytoin
  • Phenobarbital
  • Proguanil
  • Primethamine
  • Triamterene
  • Trimethoprim
  • Valproic acid
64
Q

Folic Acid antagonists teratogenic classification

A

Some D and some X

65
Q

Folic Acid antagonists teratogenic risk summary

A

First trimester of risk during closure of the neural tube

66
Q

Folic Acid antagonists teratogenic defects

A
  • Variable
  • Neural tube defects
67
Q

Folic Acid antagonists teratogenic clinical considerations

A
  • 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
Q

Isotretinoin classifcation

A

Old category: X

69
Q

Isotretinoin teratogenic Risk summary

A

All trimesters

critical window of exposure is 3-5 weeks

70
Q

Isotretinoin teratogenic defects

A
  • deformities of the cranium, ears, micrognathia, limbs, liver, hydrocephalous, microcephaly, heart defects, craniofacial alterations, cleft palate, NTDs, thymic aplasia, renal alterations, cognitive defects
71
Q

Isotretinoin main teratogenic ingredient

A

Retinoic acid or retinol derivatives (Vitamin A derivatives)

72
Q

Retinoic Acid or Vitamin A derivatives teratogenicity

A
73
Q

Lithium is an?

A

Alkali metal

74
Q

Lithium teratogenic classification

A

Old category: D

Pregnancy registry available

75
Q

Lithium teratogenic risk summary

A

May cause fetal harm

76
Q

Lithium teratogenic defects

A

increased risk of cardiac defects (eg Ebstein’s Anomaly in some studies but not in others)

77
Q

Lithium teratogenic clinical considerations

A
  • 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
Q

What is Ebstein’s Anomaly?

A

The tricuspid valve is displaced inferiorly to the right ventricle and atrial septal defect

79
Q

Methimazole teratogenic classification

A

Old category: D

80
Q

Methimazole teratogenic risk summary

A

Largely the first trimester is risky

81
Q

Methimazole teratogenic defects

A
  • Scalp defects (aphasia cutis)
  • possible chanal and esophageal atresia
  • absent or hypoplastic nipples
82
Q

Methimazole teratogenic clinical considerations

A
  • Switch to PTU in the first trimester
  • Higher choanal and esophageal atresia with exposure in weeks 3-7
83
Q

What is Tetracyline?

A

Antibiotic used to treat acne and some respiratory conditions

84
Q

Tetracyline teratogenic risk summary

A
  • 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
Q

Tetracyline teratogenic effects

A

“Teethracylclines”

  • 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
Q

Warafarin AKA

A

Coumadin

87
Q

Warafarin teratogenic classificaiton

A

old category: X

88
Q

Warafarin teratogenic risk summary

A

ALL

89
Q

Warafarin teratogenic effects

A
  • Deformities of the skeleton
  • hypoplastic nose
  • eye abnormalities
  • brachycephaly
  • scoliosis
90
Q

Warafarin teratogenic clinical considerations

A
  • 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
Q

Fetal warfarin syndrome

A
92
Q

Other teratogens

A
  • Maternal diabetes
  • Mercury
  • X rays
  • Excessive vitamin A
  • Potassium iodide
93
Q

Maternal diabetes teratogenic effects

A
  • 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
Q

IDM AKA

A

infants of diabetic mothers

95
Q

Congenital malformations in IDM

A

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
Q

Proposed etiology of diabetic embryopathy

A
  • Hyperglycemia
  • Hyperketonemia
  • Oxygen free-radicals
97
Q

Maternal hyperglycemia teratogenic clinical considerations

A
  • 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
Q

Hyperglycemia teratogenic effects

A
  • 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
Q

Oxygen free-radicals

A

Result of glucose metabolism

Increased lipid peroxidation

  • direct effect on DNA
  • Imbalance between prostaglandins and prostacyclins
100
Q

Classic diabetic embryopathy

A

Caudal Regression Syndrome

101
Q

Caudal Regression Syndrome

A
  • 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
Q

Sironmella

A
  • Diabetic embryopathy
  • Absence of hind limbs, external genitalia, anus and rectum
  • Potter sequence secondary to bilateral renal agenesis
103
Q

Organ systems invovled in diabetic embryopathy

A
104
Q

How to manage diabetic pregnancy

A

Management is prevention

Glycemic control prre-conceptual or early pregnancy goal < 6

105
Q

What is mercury

A

Mercury is an element that can collect in oceans, lakes and streams

106
Q

Mercury teratogenic considerations

A
  • 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
Q

Methymercury teratogenic considerations

A

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
Q

X ray risk of teratogenicity

A
109
Q

Mechanism of fetal harm from alcohol

A
110
Q

FAS AKA

A

Fetal alcohol syndrome

111
Q

Fetal alcohol syndrome teratogenic effects

A
  • Syndrome of birth defects caused by prenatal exposure to alcohol
  • growth deficiencies
  • head and facial malformations
  • microcephaly
  • neurocognitive effects
112
Q

FAE AKA

A

Fetal alcohol effects

113
Q

Fetal alcohol effects teratogenic effects

A

Less severe than FAS

  • Lowered IQ
  • Hyperactivity
  • growth deficiencies
  • Head and facial malformations (eg flat philtrum, mid facial hypoplasia)
114
Q

Leading cause of non-genetic and preventable cause of developmental delay

A
115
Q

Cigarette smoking teratogenicity

A
116
Q

Tobacco teratogenicity

A
117
Q

Cocaine teratogenicity

A
118
Q

Methamphetamines teratogenicity

A

gastroschisis

119
Q

TORCH Stands for?

A
120
Q

Index of suspicion for TORCH infections

A
121
Q

Diagnosing TORCH infections

A
122
Q

Toxoplasmosis teratogenicity

A
123
Q

Toxoplasmosis clinical presentation

A
124
Q

Clinical features of toxoplasmosis

A
  • Cerebral calcificiations
  • Chorioretinitis
  • HydroCephalous
  • Convulsions
125
Q

Toxoplasmosis 4 Cs

A
126
Q

Treatment of cerebral calcifications due to toxoplasmosis

A

Pyrimethamine

127
Q

Treatment of Chorioretinitis due to toxoplasmosis

A

Sulfadiazine and folinic acid

128
Q

Congenital syphilis

A
129
Q

Fetal risks of congenital syphilis

A
130
Q

Early congenital syphilis first 5 weeks

A
131
Q

Late congenital syphilis

A
132
Q

Clinical features diagnosis and Tx of congenital syphilis

A
133
Q

Parvovirus B19 overview

A
134
Q

Congenital parvovirus B19 teratogenic risk summary

A
135
Q

Parvovirus B19 in pregnancy

A
136
Q

Congenital parvovirus 1st trimester infection

A
  • 10% miscarriage
  • ventriculomegaly
  • calficiations
  • limb defects
  • echogenic bowel
  • liver calcifications
  • Parvovirus had an affinity for erythroid precursor cells, cardiac myocytes and platelets
137
Q

Congenital parvovirus 2nd-3rd trimester infection

A
  • Fetal anemia
  • Myocarditis
  • secondary hydrops
138
Q

Clinical features, diagnosis and treatment of congenital parvovirus B19

A
139
Q

Congenital varicella

A
140
Q

Clinical features, diagnosis and treatment of congenital varicella

A
141
Q

Congenital rubella

A
142
Q

Rubella effects

A
143
Q

Clinical features, diagnosis and treatment of rubella

A
144
Q

Congenital CMV

A
145
Q

Congenital CMV

A
146
Q

Congenital Herpes

A
147
Q

Clinical features, diagnosis and treatment of congenital CMV

A
148
Q

Clinical features, diagnosis and treatment of congenital HSV

A
149
Q

TORCH …. Z

A
150
Q

Congenital Zika virus

A
151
Q

Zika virus congenital infection

A
152
Q

Zika ventriculomegaly and macrocephaly

A
153
Q

Fetal brain disruption sequence

A
154
Q

Zika virus and other birth defects

A
155
Q

Clinical features, diagnosis and treatment of Congenital zika

A
156
Q

DES identify

A

vagina and cervix

Human Reproduction (40 decks)

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