Maternal & Fetal Health - Sood

Question 1

Why and how do T₃ & T₄ levels increase during pregnancy?

Answer 1

• Increased thyroxin binding globulin (TBG) levels cause a decrease in free T₃/T₄
  
  • Decreased clearance of TBG (due to estrogen[?])
  • Increased liver production of TBG
• Pituitary senses low free T3/T4 and increases TSH production
• Placenta also stimulates T3/T4 release via hCG

Question 2

How would placental production of hCG affect TSH levels?

Answer 2

hCG stimulates T3/T4 release from the thyroid, which would decrease TSH release via negative feedback.

Question 3

Review:

Name three thyroid antigens which autoantibodies can be produced against in the context of autoimmune thyroid diease. Which antigen can have blocking and stimulating antibodies raised against it?

Answer 3

• Thyroglobulin (Tg, aka colloidal antigen)
• Thyroid peroxidase (TPO)
• TSH receptor
  
  • Abs can be blocking (e.g. autoimmune thyroiditis) or stimulating (Graves’)

Question 4

How common are Tg or TPO autoantibodies in women of child-bearing age?

Answer 4

10-20%

[Wiki states Hashimoto’s has a prevalance of ~1:1000. The lecture goes on to state that most women with autoabs do not suffer sufficient thyroid destruction to cause hypothyroidism. So it seems having the autoabs does not imply a clinically significant disease.]

Question 5

What are the side effects of iodine deficiency in a pregnant woman?

Answer 5

• Goiter in the mother
• If severe, neurocognitive impairment / mental retardation / deaf-mutism in the offspring
• (Keep in mind - higher dietary requirement in pregnancy)

Question 6

What complications of pregnancy are noted in women with Tg or TPO autoabs?

Answer 6

Associated with pregnancy loss, recurrent miscarraiges, and preterm delivery

Question 7

Your patient is a 27yo pregnant female in her 1st trimester of pregnancy, presenting with heat intolerance, palpitations, increased sweating, and anxiety. She denies nausea or vomiting. You suspect Graves’ disease, but anti-TSH receptor autoAbs are negative.

1. What other process might be responsible for her symptoms?
2. If the patient instead presented with a CC of nausea & vomiting, and you saw that she was no longer gaining weight at a normal rate despite her pregnancy, what would you suspect?

Answer 7

1. Gestational Hyperthyroidism
   
   • Transient & observed in first half of pregnancy
   • 1-3% of pregnancies
   • Due to excess production or activity of hCG
2. Hyperemesis Gravidarum
   
   • Nausea, vomiting & weight loss
   • 0.05% to 1% of pregnancies

Question 8

What are the symptoms of a thyrotoxic crisis?

What are potential consequences of this condition?

Answer 8

• aka Thyroid Storm
  
  • fever
  • tachycardia
  • seizures
  • restlessness / confusion
  • diarhhea
  • vomiting
  • cardiac arrythmia
• Can result in shock, coma, or death

Question 9

What are 5 potential complications of Grave’s disease in the context of pregnancy?

Answer 9

• Increased abortion risk
• Preterm labor
• Low birth weight
• Stillbirth
• Preeclampsia

Question 10

What advice would you give a young woman recently diagnosed Graves’ Disease if she told you she planned on becoming pregnant soon?

Answer 10

• The disease needs to be treated several months before pregnancy
  
  • Circulating autoAbs that cross the placenta pose serious risk to the fetus
  • These Abs persist for months following surgical or radioactive thyroid ablation

Question 11

What is the cause of Sheehan Syndrome?

Where is it most common?

Answer 11

• Ischemic injury to the hypothalamic-pituitary axis following severe hemorrhage and hypotension at delivery
• Susceptibility is due to increased size of the pituitary during pregnancy and the low-flow, low-pressure nature of the portal circulation
• Most common in parts of the world where deliveries are not performed in healthcare facilities

Question 12

If a woman developed Sheehan Syndrome shortly following delivery, what symptoms might she notice quickly and thus present with?

Answer 12

• Failure of lactation
• Failure of hair growth over areas shaved for delivery
• Poor wound healing following a cesarean delivery
• Weakness

Question 13

Why does some healthy pregnant women develop a temporary loss of vision in the outer halves of their left and right visual fields?

Answer 13

Bitemporal hemianopia

• Lactrotroph cells of pituitary increase 20-60% by the 3rd trimester
• Entire pituitary gland also increases in wieght by 30%
• Increased size places pressure on the optic chiasm, which causes the visual disturbance.

Question 14

In general terms, what are the major hemodynamic (vessel) changes of pregnancy?

Answer 14

• Increased capacity and reduced resistance
  
  • Decreased vascular resistance
  • Arterial compliance
  • Vascular capacitance

Question 15

What changes in renal function occur during pregnancy?

(Hint: Think of the hemodynamic changes)

Answer 15

• Increased renal blood flow
• Increased glomerular filtration
• Increased RAAS activation
  
  • ​Note: causes reduced response to infused pressor compounds

Question 16

Define gestational hypertension.

Answer 16

Typical criteria of HTN (>140mmHg systolic and/or >90mmHg diastolic) in a pregnant woman.

Question 17

What are ~7 symptoms of preeclampia?

What additional symptom makes for a diagnosis of eclampsia?

Answer 17

• Severe HTN (>160mmHg systolic / >110mmHg diastolic)
• Proteinuria (not always present but useful in making the Dx when present)
• “End organ dysfunction”
• Visual distubances & Headaches
• Epigastric pain
• Thrombocytopenia
• Abnormal liver function
• Seizures in the context of preeclampsia makes for a Dx of eclampsia

Question 18

What are the defining criteria of HELLP syndrome?

Answer 18

• Severe HTN plus:
• Hemolysis
• Elevated Liver enzymes (hepatic dysfunction)
• _L_ow _P_latelet count (thrombocytopenia <100,000/ul)

Question 19

What are **seven **potential maternal sequelae of severe HTN disorders during pregnancy?

Answer 19

1. Pulmonary edema
2. Stroke
3. Liver failure
4. Renal failure
5. Seizures
6. Death
7. Long-term risk to develop HTN and/or related disorders (outside of pregnancy)

Question 20

What are four potential fetal sequelae of severe HTN disorders during pregnancy?

Answer 20

1. Growth restriction in utero and small birth weight
2. Oligohydramnios (reduced amniotic fluid)
3. Indicated preterm delivery
4. Long term risk to develop metabolic and/or cardiovascular disorders

Question 21

What are five emerging hypotheses regarding

the pathophysiology of preeclampsia?

Answer 21

• Think decreased blood flow to the fetus/placenta
  
  • Placental hypoperfusion
  • Placental release of anti-angiogenic factors (sFlt1, sEng)
  • Defective trophoblast differentiation
    
    • Cells of the placenta that are important for implantation and interaction with the maternal uterus
  • Angiotensin autoantibodies
  • Incomplete spiral artery remodeling

Question 22

What are five risk factors for preeclampsia?

Answer 22

1. Primiparity (woman who is pregnant for the first time)
2. Past history / Family history
3. Preexisting medical conditions
   
   • Diabetes, BMI >26.1, Kidney Disease, aPLs (antiphospholipid Abs)
4. Multiple gestation
5. Maternal age <20 or >35

Question 23

What is the only known cure for preeclampsia?

Answer 23

Delivery.

Thus, timing of potentially required induced labor or cesarean section is decided baced on disease severity.

Question 24

What drug is given for seizure prophylaxis in pregnant women at risk for eclampsia?

Answer 24

Magnesium sulfate

Question 25

If a woman needs to undergo pre-term induced labor due to severe preeclampsia, what drug can be given to develop the infant's lungs? Is the drug given **antenatally **or **postnatally**?

Answer 25

**Betamethasone**, a glucocorticoid Given **antenatally**. Beneficial up to 34 weeks into pregnancy.

Question 26

What is mechanism of action of magnesium sulfate?

Answer 26

* **Unknown** * Alters **Ca²⁺ metabolism** so affects CV and neuro functions * May act as a **vasodilator**, reducing **cerebral edema**. * Likely acts at the level of the **NMJ** * Conveniently, also crosses the placenta and is neuroprotective for the fetus - useful for preterm births

Question 27

What are side effects of magnesium sulfate?

Answer 27

* Common & minor: * Warmth * Flushing * Nausea * Vomiting * **Rare but serious:** * **Loss of patellar reflex** * **Respiratory depression**

Question 28

How is magenium sulfate excreted?

Answer 28

Kidneys

Question 29

What is the mechanism of action of betamethasone?

Answer 29

Glucocorticoid that accelerates development of **type 1 and type 2 pneumocytes**. The resulting structural and biochemical changes (including **surfactant production**) improve lung mechanics.

Question 30

What are side effects of betamethasone?

Answer 30

* **Maternal fluid retention** * Transient increase in **fetal heart rate**

Question 31

What phenomenon may help explain why some adult diseases like metabolic syndrome are seen intergenerationally in families despite having no simple genetic inheritance pattern?

Answer 31

**"Prenatal programming" of adult disease** A pregnant woman with, for example, metabolic syndrome will have dysregulated nutrient transport to her fetus, stimulating fetal overgrowth. Fetal overgrowth is known to increase the risk of adult metabolic disease later in life. This may be a contributing factor for the development of several chronic syndromes.

Question 32

What does hemochorial mean? What does this mean for the human placenta?

Answer 32

Direct contact between the blood and the chorion It means that the mother's blood directly bathes the vili, and hormones/chemicals from the fetus/mom can affect each other

Question 33

What are some metabolic changes that occur during pregnancy? What is the basis of all these changes?

Answer 33

Hyperinsulinemia Insulin Resistance Hyperlipidemia Hypertriglyceridemia Hyperketonemia These changes give the fetus the most access to glucose and amino acids.

Question 34

What three changes are seen regarding insulin in pregnancy?

Answer 34

Higher circulating glucose in fed state Hyperinsulinemia Insulin Resistance

Question 35

What changes are seen in the following organs during pregnancy? Pancreas Adipose Tissue Brain Liver

Answer 35

## Footnote Pancreas- hyperplasia of beta cells, hyperinsulinemia Adipose Tissue- accelerated lipid catabolism Brain- leptin resistance Liver- insulin resistance, minimal protein catabolism, and hyperketonemia

Question 36

What nutrients are transported to the fetus? How are they transported?

Answer 36

Amino acids- active transport Glucose- facilitated diffusion Fatty acids- diffusion/placental metabolism

Question 37

Why does the simulated diabetic state of pregnancy benefit the fetus?

Answer 37

The fetal glucose transporter has a very high affinity for glucose and saturates at 360 mg/dL. With a higher need for nutrients and a higher affinity transporter, the fetus benefits greatly from the diabetic state.

Question 38

What causes gestational diabetes?

Answer 38

Pregnancy is a stress test. If the mother already has glucose abnormalities, pregnancy might push her over the edge. Pre-existing Insulin resistance worsened Hyperinsulinemia from lowered capacity for production Circulating antibody changes

Question 39

What effect does diabetes have on the fetus? What problems could this cause as a neonate?

Answer 39

Hyperglycemia causes the fetus to become hyperinsulinemic. The extra glucose is stored as fat and causes macrosomia. Early in the pregnancy, it can lead to congenital abnormalities. As a neonate outside of a hyperglycemic environment, the blood sugar can crash causing hypoglycemia in an hyperinsulinemic baby.

Question 40

What are some risk factors for congenital diabetes? Who should be tested and when?

Answer 40

* Obesity * Hx of diabetes * Family Hx * Non-white All pregnanct women should be tested; at the first prenatal visit for high risk women and between weeks 24-28 for everyone.

Question 41

Gestational Diabetes What are some implications for the fetus? What are some implications for the mother?

Answer 41

Fetus * Macrosomia * Polyhydramnios * neonatal hypoglycemia * risk of birth trauma * metabolic disorders Mother * Future risk of diabetes

Question 42

Why are statistics on pregnancy and maternal health important?

Answer 42

* Sentinel indicators of a communities quality of healthcare * Poor fetal care may lead to disease as an adult * Maternal organ malfunctions in pregnancy indicate latent pathology that could cause disease later

Question 43

What constitutes direct maternal death? What consitutes indirect maternal death?

Answer 43

A death resulting directly from pregnancy, labor, delivery, post-partum conditions, or pregnancy (75-80%) A death caused by an aggrevation of an underlying condition because physiological stress of pregnancy

Question 44

What is the maternal mortality rate? What is the maternal mortality ratio?

Answer 44

Rate MM Rate= (# of deaths)/(# of women of reproductive age)\* 10000 MM Ratio= (# of deaths)/ (# of live births) \* 10000

Question 45

What is the leading cause of maternal mortality world wide? What is the leading cause in the United States?

Answer 45

Hemorrhage, hypertensive disorders, infections/sepsis Cardiovascular disease, infection/sepsis, and "non-cardiovascular disease" Incidence of coronary syndromes are increasing due to increased obesity, diabets, hypertension, and older age at pregnancy

Question 46

What is the definition of a post-partum hemorrhage? What can cause it?

Answer 46

Blood loss \>500mL in a vaginal birth or \>1000mL in a C section Uterine Atony -80% Congenital or Acquired Coagulation Defects Trauma Placenta Accreta

Question 47

What can cause antepartum hemorrhage?

Answer 47

Placental Abruption- 30% Vasa previa- rare Uterine Rupture- rare Placenta previa- 20%

Question 48

How do you calculate the following: Infant Mortality Rate Fetal Mortality Rate Neonate Mortality Rate Perinatal Mortality Rate

Answer 48

## Footnote IMR=(# of infant deaths)/(# of live births) \*1000 FMR= (# of fetal deaths)/(# of total births) \*1000 NMR= (# of neonatal deaths)/(# of live births) \*1000 PMR=(# of neonatal deaths)+(# of stillbirths)/ (# of total births) \*1000 Notice that for statistics involving death around birth, TOTAL births are used in the denominator.

Question 49

Which vaccines should be updated for women hoping to get pregnant? What other things should be included in preconception care?

Answer 49

Varicella, Rubella, Hepatitis B Get chronic diseases undercontrol, start folic acid, assess for tetratogen exposure, genetic counseling