Tools of Prenatal Diagnosis

Tools of Prenatal Diagnosis
By:Julie Moldenhauer, MD
Reproductive Genetics
Maternal Fetal Medicine
Obstetrics and Gynecology

Objectives:
* Discuss various prenatal screening and testing tools
* Discuss the timing of the various tools in gestation
* Discuss benefits and risks of various options
* Review the difference between screening and testing
Baseline Risk for Birth Defects in the General Population is 3-5%
What Can We Diagnose in the Prenatal Setting?
* Structural Abnormalities
o Congenital heart disease
o Spina bifida
o Gastroschisis
* Chromosomal Abnormalities
o Trisomy 21
o Triploidy
* Infections
o Parvovirus
o Cytomegalovirus
o Toxoplasmosis
* Growth Abnormalities
* Hematologic Abnormalities
o Anemia
o Thrombocytopenia
* Functional Defects
o Arthrogryposis
o Renal dysfunction
* Syndromes
o Skeletal Dysplasia
o Diabetic embryopathy

Prenatal Diagnosis Tools

* History
o Personal History
o Family History
* Population Screening
* Serum Screening
* Ultrasound
* Fetal MRI
* Invasive Diagnosis
o Chorionic villus sampling
o Amniocentesis

History is a Screening Tool!
o Maternal Age
+ > 35 years at delivery
o Obstetric History
+ Prior baby born with Down syndrome
+ Prior stillbirth
o Medical History
+ Is mom diabetic? How well controlled is her sugar?
+ Does she have PKU?
+ Is she hypertensive?
o Medication Exposures
+ What medications?
+ When was the exposure?
o Environmental Exposures
+ Does she work in a preschool and was exposed to parvovirus?
+ Is she exposed to high doses of radiation?
o Family History
+ Brother with hemophilia
+ Uncle with cystic fibrosis
+ Ethnic background
+ Consanguinity

As maternal age increases, the risk for aneuploidy increases. This is due to maternal meiotic nondisjunction.
Maternal age > 35 at the time of delivery is considered “Advanced Maternal Age” or AMA
The risk for recurrence of chromosome abnormalities is dependent upon the genetic mechanism involved.
Trisomy: 1% or maternal age-related risk
Translocation:
Maternal carrier: 10-15%
Paternal carrier: 2%

Down syndrome phenotype caused by trisomy 21
Down syndrome phenotype caused by 14;21 translocation

Maternal Diabetes: Reproductive Risks
* Fetal and Neonatal
o Congenital anomalies: 6-12%
o Intrauterine fetal demise
o Macrosomia – Shoulder dystocia
o Growth restriction
o Hyperbilirubinemia
o Hypoglycemia
o RDS
o Polycythemia
o Organomegaly
o Long term – obesity and carbohydrate intolerance
* Obstetric
o Spontaneous preterm labor
o Polyhydramnios
o Preeclampsia (15-20%)
o Intrauterine growth restriction
o Shoulder dystocia
o Cesarean delivery

Caudal Regression Syndrome
Teratogen Exposure
Fetal growth
Organogenesis complete
Eyes, heart, lower limbs
Axial skeleton, limb buds, musculature
CNS
None, “ALL or NONE”
* Examples:
* Accutane
* ACE inhibitors
* Lithium
* Antiepileptic drugs (AEDs)
* Anticoagulants: warfarin
* Antidepressants
* Methotrexate
* Thalidomide

Teratogen Exposure
* Fetal effects are timing and dose dependent

* Each medication is assigned a pregnancy category based on available data; A-D, X
* www.Reprotox.org
* www.otispregnancy.org

Ultrasound images of fetal hydrops – abnormal collection of fluid in multiple body compartments.
Mom works at a daycare where there was a Parvovirus B19 or Fifth Disease outbreak 4 weeks ago. Parvovirus causes fetal aplastic anemia that can be life-threatening.

Suspicion of diagnosis by altered maternal serum titers of Parvo IgG and IgM and confirmed by amniotic fluid PCR for Parvo.
Confirmed Parvo infection in a fetus with hydrops can be treated with intrauterine blood transfusions.

Fetal Ultrasound Showing Cardiac Rhabdomyoma
Fetal MRI Showing Tubers
Prenatal Findings Consistent with Tuberous Sclerosis Confirmed as Neonate
Screening for Genetic Disease
Ethnic Group Disease
African American Sickle Cell Disease: 1/12
Mediterranean Beta-Thalassemia: 1/30
Southeast Asian Alpha-Thalassemia: 1/20
Caucasian Cystic Fibrosis: 1/25

ASHKENAZI JEWISH ANCESTRY
GENETIC CARRIER TESTING
Gaucher’s disease
Bloom syndrome
Mucolipidosis IV
Niemann-Pick disease type A
Fanconi Anemia Group C
Familial Dysautonomia
Cystic Fibrosis
Canavan disease
Tay-Sachs disease
Detection rate
Carrier Frequency
Disease Incidence
Testing and screening options should be made available to all pregnant women
Prenatal Screening & Testing
When Screening
(risk estimate)
Definitive
(Invasive)
First Trimester
FIRST screen*
Ultrasound
CVS

Second Trimester
Maternal Serum Screen*
Ultrasound
Amnio
Cordo
*First and Second Trimester Integrated and Sequential Screening

Test Performance
* Detection rate – the percentage of affected that are test “positive”
o (the higher, the better)
* False positive rate – the percentage of unaffected that are test “positive”
o (the lower, the better)

Goals in Prenatal Screening:
* High sensitivity - low false positive rate
* Wide availability
* Reproducibility and accuracy
o Human error, testing conditions

First Trimester Screening
o 11-13 6/7 weeks (CRL 39-79 mm)
o Maternal serum sample for PAPP-A and Free b-HCG
o Ultrasound for Nuchal translucency
o Detection Rates:
+ 80% for Trisomy 21
+ 90% for Trisomy 18
+ Does not screen for NTDs

PAPP-A
b-HCG
T21
T18

Increased NT vs Cystic Hygroma
* Increased NT > 95th%
o With or without septations
* Structural defects
o Heart defects most common
* Syndromic associations
* Chromosomal defects
o Exponential increase with increased NT
o 50% Down syndrome
o 25% Trisomy 13 or 18
o 10% Turner Syndrome
o 5% Triploidy
o 10% other

NT > 3 mm is ABNORMAL
Second Trimester Serum Screening: Chromosome Abnormalities

* Maternal Serum Screening
o 15-20 weeks
o Triple screen: 60% for T21
o Quad screen: 70% for T21
o Gestational Age Dependent**
* Targeted Ultrasound
o 50% aneuploid fetuses will have ultrasound markers
AGE +AFP +hCG +uE3 +InhA
DR at 5% FPR
2nd trimester
single double triple quadruple
Serum Screening Test Performance at a fixed 5% False Positive Rate (Dating by Ultrasound)

Prediction
SURUSS
FASTER
Second Trimester Serum Screening: Neural Tube Defects
* Neural Tube Defects
o Spina Bifida
o Anencephaly
* AFP increased in “open” defects
* Sensitivity
o 90% anencephaly
o 80-85% open spina bifida
* False positive – 3-4%
Interpreting a Quadruple Screen

Bottom Line: AFP is increased with NTDs and decreased with chromosome abnormalities

Elevated MSAFP
* Incorrect Dates – most common reason
* Multiples
* Congenital Nephrosis
* Ventral Wall Defects
* IUFD
* Adverse Pregnancy Outcomes
o Stillbirth
o Placental abruption
o Preterm labor
o Oligohydramnios
o IUGR

Ultrasound detection of aneuploidy
Nuchal Fold
CPC
Duodenal atresia
Pyelectasis
Clinodactyly
Second trimester sonographic markers of Down syndrome
AV Canal
Trisomy 18
Edward Syndrome
* Close to 90% detected by prenatal scan
* US:
o Growth restriction
o Clenched fists
o >90% with cardiac defects
o Multiple malformations
* Grim prognosis
o 50% Stillbirth
o 50% die within the first week
o 5-10% survive the first year

Trisomy 13
Patau Syndrome
Fetal Anatomy by Ultrasound
Ventral Wall Defect
Gastroschisis
NTDs
Lemon Sign
Banana Sign
Meningomyelocele Sac
Meningomyelocele Sac on Newborn
PGD: Preimplantation Genetic Diagosis
Pearls for Invasive Testing
* Risk for Sensitization
o Mom Rh negative – Rhogam
o Other antibodies may increase risk
* Risk for Infection transmission
o Hepatitis B
o Hepatitis C
o HIV
o Need to know familial mutations prior to performing invasive testing

Chorionic Villus Sampling
* Performed 10-14 weeks
* Does not test for ONTD
* Technique – “Placental biopsy”
o Transabdominal
o Transcervical
* Risk for limb reduction defects if performed < 9 weeks
* Loss rate 1/100-1/200
* Risk for mosaicism (~1%)

Transcervical
CVS
Transabdominal
Performed at 10-14 weeks
Amniocentesis
* > 15 weeks
* Loss rate 1/200 (probably closer to 1/300-1/500)
* Tests for ONTD
* Technique
o Fine gauge needle
o Ultrasound guidance
o Aspiration of 20-30 cc of fluid

PERFORMED ROUTINELY 15-20 WEEKS
Ultrasound Guided Procedure
AMNIOCENTESIS
Cordocentesis
* Percutaneous Umbilical Blood Sampling
* Loss rate 1/100-1/200
* Typically done after 18 weeks
* Ability for:
o Rapid karyotype
o Blood/platelet counts
o Direct fetal injections/transfusions

Fetal Blood Sampling
“PUBS”
Conclusions

* Many options for screening and testing.
* Prenatal screening should provide the most effective test to the greatest number of women.
* The best method of screening is yet to be determined.
* Patient preference should be considered.
* Testing and screening should be available to all women.

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Menopause

Menopause
Division of Urogynecology and Reconstructive Pelvic Surgery
Department of OB/GYN

Epidemiology
* Average age is 51.4 years
* 95% confidence interval of Bell Curve gives a range of 45-55 years. Less than 2% occur before age 40.
* Factors associated with early menopause
o Cigarette smoking (1.5 yrs earlier)
o History of short intermenstrual interval
o Family history
o Chemo / Radiation / Genetic factors
* Unrelated to number of prior ovulations, pregnancies, use of OCPs, height, weight, age at menarche, race, class or education

Elderly Population
* In 2000, life expectancy:
o Women 79.7 years
o Men 72.9 years
* Once you reach 65:
o Women expect to live until 84.3 years old
o Men expect to live until 80.5 years old
* Therefore, more than 1/4 of a woman’s life is spent in menopause

Peri-menopause
* Peri-menopause
o Transitional period
+ Hallmark is menstrual irregularities
# Shortened cycle length
# Skipped cycles
# 10% of women will have abrupt cessation of menses
+ Median length of 4-5 years
o Median age of onset is 47.5 years

Physiology
General feature is depletion of follicles with loss of granulosa and thecal cell function
* 6-7 million oocytes at 20 weeks fetal age
* 1 million oocytes at birth drop to 400,000 at puberty
* 300-400 ovulatory events over lifetime
* Accelerated follicular loss 2-8 yrs before menopause

Physiology
* Granulosa cells produce less inhibin, which provides negative feedback for FSH secretion by the pituitary gland.
* Increase in FSH levels
* After menopause, LH levels are also elevated.
* Would you check a FSH or LH level to diagnose menopause?

Symptoms
* Menstrual irregularities is the primary reason women seek medical attention
* Cycles shorten as increased FSH triggers early ovulation
* Skipped cycles due to anovulation
* Long periods of anovulation can lead to excessive estrogen states and irregular, unexpected menses
* Do you think the perimenopausal women can get pregnant?
o YES
o Guinness World Record = 57 yrs & 120 days
o So, remember to recommend contraception. Low does oral contraceptives may be used in women without contraindications (i.e. smoking).
* Hot Flushes
o Subjective feeling of intense heat followed by skin flushing and diaphoresis.
o Sudden dilation of peripheral vasculature secondary to abrupt estrogen withdrawal. Skin temperature increases and core temperature drops.
o Usually, occurs for a few seconds to minutes.
o Duration is about 1-2 years. 25% for > 5 years.
* Genitourinary atrophy
o A variety of symptoms
o Atrophic vaginitis, urethritis, recurrent UTIs, dyspareunia
o Pelvic organ prolapse is NOT caused by estrogen deficiency
* Urinary Incontinence
o Atrophy of estrogen-dependant tissues such as the urethra may contribute to existing causes for urinary incontinence
o Typically addressed with local application of estrogen cream
* Sexual Disturbances
o Decreased interest in sexual activity
+ May be related to decreased testosterone levels
+ May be related to psychosocial stressors
o Anatomic changes secondary to estrogen deficiency
+ Atrophy of vaginal mucosa and lower urethra
+ Thinning of vaginal mucosa with decreased lubrication and elasticity, leading to dyspareunia
* Sleep Disturbances
o Estrogen appears related to producing restful, deep-stage sleep
o Hot flushes more common at night
+ Wakening or disruption of deep-stage sleep
+ Contributes to feeling of overall fatigue
* Mood Swings / Irritability / Depression
o NOT associated with menopausal hormone changes alone
o Stage of life associated with multiple changes (e.g., children leaving home, parents aging, retirement)
o Hot flushes and fatigue can lead to emotional lability
* Cognitive Function
o Some types of memory and brain function may be influenced by estrogen
o Some evidence suggests that Alzheimer’s disease is less frequent in estrogen users and the effect was greater with increasing dose and duration of use.

Adverse Health Effects
* Cardiovascular Disease
o Leading cause of death in US women (f/b malignancies, cerebrovascular disease and MVAs)
o Death rate for CV disease is 3X the rate for breast cancer and lung cancer.
o Changes in lipid profile in menopause
+ Increased LDL
+ Decreased HDL
+ ? Decrease in triglycerides
* Osteoporosis
o Spinal bone density peaks at 20 years, while cortical bone density peaks in late 20s
o Rate of loss of 0.5%/year prior to age 40, then anywhere from 2-9%/year for first 10-15 years after menopause
o Primary loss is trabecular bone, leading to compression fractures, loss of height, kyphosis
o Osteopenia = BMD between -1 and -2.5 SD of a young, white adult woman.
o Osteoporosis = BMD -2.5 or greater SD
o 25-50% of women will have spinal compression fractures by age 70
o 20% of Caucasian women age 80 will have hip fractures, with 15-20% mortality.
o Annual incidence is 1.3% after age 65
o High risk:
+ Caucasian, Asian
+ Thin, inactive, smokers
+ High caffeine/alcohol intake, low dietary calcium, high dietary protein and phosphates
+ H/o oligomenorrhea, excessive exercise, eating disorder
+ Medical conditions – hyperthyroid, cancer, myeloproliferative disorders
o Low Risk:
+ African American
+ Obese, active
o Protection:
+ Ca supplements (1200mg, 1500mg)
+ Weight-bearing exercise
+ HRT: estrogen increases
# Intestinal calcium absorption
# Renal conservation of calcium
# Increases 1,25-dihydroxyvitamin D (active form)
+ Vitamin D (400-800IU)

Hormone Replacement
* Types of hormone replacement
o Estrogen alone (for women without a uterus)
o Estrogen and progesterone
+ Sequential
+ Continuous
o Local estrogen
o SERM’s (Selective Estrogen Receptor Modulators)

HRT - Advantages
1. Relief of vasomotor symptoms
+ HRT is effective in reduces the number of hot flashes
+ 6-8 weeks to see maximal effect
+ Combination HRT (0.625mg estrogen/2.5mg MPA)
+ What about lower doses of HRT?
# For combination HRT, all doses resulted in similar relief of symptoms
# For estrogen alone, most relief with higher doses
2. Vaginal atrophy

# Menopause thins the vaginal epithelium and increases the vaginal pH (> 6.0).
# Estrogen decreases the vaginal pH, thickens the vaginal epithelium and reverses vaginal atrophy.
# Less atrophic changes with higher doses of HRT
3. Bone protection

+ Reduction of bone loss
+ Prevents OP-related hip fractures
+ Protects the spine and the small bones
+ WHI: 5 fewer hip fractures per 10,000 person-yrs
4. Colon cancer

o Some observational studies have suggested a reduced risk.
o WHI: 6 fewer cases / 10,000 person-yrs
1. Endometrial cancer
+ 8-10 fold increased risk with unopposed estrogen.
+ PEPI: unopposed estrogen x 3 yrs = 24% with atypical hyperplasia (vs 1% women on placebo)
+ Risk is increased with:
# Increased duration and dose
# Continuous versus cyclic therapy
# Absence of a progestin
2. Breast cancer

o Meta-analysis of 51 case-controlled & cohort studies showed no increased risk with short-term use.
o After 5 years of use, risk increased by 35%.
o WHI: 8 more invasive cases / 10,000 person-yrs
o Women diagnosed with breast cancer while using HRT have been shown to have better survival

HRT - Disadvantages

3. Thromboembolic disease

o Increases risk for DVT 2 – 3.5 fold
o Strokes: 8 more / 10,000 person-yrs
o PEs: 8 more / 10,000 person-yrs

HRT - Disadvantages

4. Cardiovascular disease:

o Traditionally, HRT was thought to provide protection against coronary heart disease (CHD)
o Observational studies found lower rates of CHD in postmenopausal women on HRT.
o The consensus was that CHD was about 35-50% lower in women using HRT.
o Many studies showed that HRT improved lipid profiles.

HRT - Disadvantages

4. Cardiovascular disease:

o What about secondary prevention? i.e. women who have a h/o coronary heart disease, does HRT help?
o Heart and Estrogen/Progestin Replacement Study (HERS) was a RCT, double-blinded study of 2,763 PM women with intact uteri and a h/o CHD
o 52% higher rate of major coronary events in the 1st year
o Then there was a reduction in the risk with longer use – i.e. 33% lower risk in the 4th and 5th years
o What about primary prevention? i.e. in healthy women, does HRT prevent CHD?
o Women’s Health Initiative (WHI)
o RCT of 16,608 postmenopausal women aged 50-79 years old with an intact uterus
o 40 different US centers
o Combination HRT – 0.625mg CEE and MPA 2.5mg vs placebo

Cardiovascular disease (WHI):
o 7 more CHD events
o 8 more strokes
o 8 more PEs
o 8 more invasive cancers
o Study stopped after 5.2 yrs (planned 8.5yrs) because of cases of breast cancer

SERMs
* Selective estrogen receptor modulators
* Work as agonists and antagonists depending on the tissue
* Raloxifene and tamoxifen

Estrogen Raloxifene Tamoxifen

Prevent OP
Risk Breast
Cancer
Hot Flashes
Endometrial
Cancer
Venous
Thrombosis
SERMs
* Overall, SERMs can help to prevent OP and breast cancer
* However, they aggravate hot flashes, the most common indication for estrogen therapy.
* Also, tamoxifen stimulates the endometrium.

Alternative Medicine
* Limited studies with relatively short duration of therapy and follow-up.
* Soy and isoflavones may be helpful in the short-term (< 2 yrs) for vasomotor sx and may protect against osteoporosis.
* 35-75mg qd isoflavones / day
* Black cohosh may be helpful in the short-term (< 6 mos) for vasomotor symptoms.

Summary
* Health Risks
o Osteoporosis
o Lipid abnormalities
o Cardiovascular disease
o Cancer
* Menopause is the natural course aging of the female reproductive system, driven by loss of oocytes
* Symptoms of menopause include:
o Menstrual irregularities
o Hot flushes
o Sleep disturbances
o Mood changes
o Sexual disturbances
o Urinary incontinence
o Cognitive function
o Hair growth

Hormone Replacement
Benefits
Detriments

* Vasomotor sx
* Vaginal atrophy
* Osteoporosis
* Colon cancer
* Endometrial ca
* Breast ca
* VTE
* CHD

Abnormal Bleeding
* A 44-year old woman presents for evaluation of abnormal menstrual bleeding. Her periods have been regular in the past but for the last 6 months she has had a period every 35-56 days, lasting 7-9 days. The bleeding is heavier than usual and she feels tired all the time. She has gained 15 lbs over the last 2 years, which she believes is due to lack of exercise and increased eating/sleeping. She complains that her skin is dry. Exam is unremarkable. What would your recommend next?
o Check pregnancy test
o Discuss exercise / eating patterns
o Check TSH, PRL
o Consider endometrial biopsy
o Expectant management versus hormonal management

Health Maintenance
* 58 year old postmenopausal woman referred to you by a friend. She has no known medical problems and is on no medications. Her social history is remarkable for an 80-pack/year history of tobacco use. Her physical exam is unremarkable. What are the important health maintenance aspects of the exam to focus on?
o Blood pressure
o Pelvic exam
o Breast exam / mammography
o Fecal occult blood
o Smoking cessation
o Flu shot
o Osteoporosis

Abnormal Bleeding
* A 47 year old woman, G2P2, presents with menstrual cycles varying in length from 20 to 40 days. Until 9 months ago she had regular 28 day cycles. She reports frequent hot flushes. She recently resumed sexual activity and uses no contraception, but she does not desire pregnancy. She does not smoke and has no other medical problems. Her physical exam is unremarkable. What are her options for cycle control?
o Low dose combination oral contraceptive
o Continuous low dose estrogen and progestin menopause regimen
o Cyclic progestin therapy for 12 days a month
o Continuous low dose estrogen (0.625mg conj EE)
o Estradiol vaginal ring

Osteoporosis

* A menopausal patient with osteoporosis has been reading information on the Internet about different treatment modalities for osteoporosis. She wishes to know more about what therapies are actually available and how they work?
o Estrogen: Reduces osteoclast activity
o SERMs: Reduces osteoclast activity
o Bisphosphonates: Reduces osteoclast activity
+ Take on empty stomach, first thing in AM with 8oz water and no food for 30 minutes
+ Take sitting up due to esophagitis risk
+ Calcium supplementation within 4 hours
o Calcium / Vitamin D supplements

Menopause.ppt

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Physiologic Changes in Pregnancy

Physiologic Changes in Pregnancy
By:Thomas S. Ivester, MD, MPH
Maternal-Fetal Medicine

Relevance of OB physiology
* 5-10 % of women in ER are pregnant
o Many don’t know or show
* Any female of reproductive age could be pregnant
o Should be assumed so!
* Virtually every organ system affected
* Can touch almost any specialty

Case history
Case 1

* 36 y.o. female presents to ER
* CC: Fatigue, dyspnea, chest pain
* HPI:
o Progressive SOB and dyspnea over several weeks.
o Poor exercise tolerance and easy fatigability
+ ‘get winded after 1 flight of stairs’
o Substernal chest pain, peaks in morning and night
o Nocturnal cough, semi-productive – clear
o Leg swelling
o polyuria
* PMH
o Mild obesity
* Ob/gyn – menses at age 12; irregular menses; no pregnancies
* Meds
o Oral contraceptives
o multivitamins
* Social
o Married for 2 years. No exposures

Case 1: PE
* Skin
o warm, clammy. Mild facial acne and increased hair – medium coarseness
* HEENT
o NC/AT. Nasal mucosa slightly hyperemic.
o Mild non-nodular thyromegaly
* CV
o Tachycardia (HR 107)
o + JVD
o 2/6 systolic murmurs over pulmonic and aortic v.
* Chest
o Clear bilaterally. Diaphragm elevated with decreased excursion
* Ext
o 1+ pretibial pitting edema
* Abd
o Skin – spider angiomata and striae. Medium course hair, infraumbilical.
o Distended, firm, non-tender.

Studies / labs
* EKG:
o Sinus rhythm; tachy; Left axis deviation
* CXR:
o Lungs clear. Cardiomegaly. Increased vascular markings
* Labs:
o Hct 32% (low); WBC 12 (high)
o Cholesterol 300 mg/dl
o D-dimer elevated
o Potassium and creatinine low

What does she have???
General Principles
* Most changes begin early
o Even before pregnancy recognized
* Most are hormonally driven
o Progesterone, estrogen, renin / aldosterone, cortisol, insulin
o Some ‘mechanically’ driven
* Designed to optimize conditions for fetus & prepare for delivery
o Delivery of oxygen & nutrients
Cardiovascular & Hematologic
* Vascular
o Decreased tone / vaso-relaxation
+ SVR decreased 20%
o Positional effects
o Placenta – low resistance shunt
* Hematologic
o Blood volume increases 50-100%
o RBC increases 25-40%
+ Relative anemia (“physiologic”)

Hematologic
* Hypercoagulable
o Estrogen & Vascular stasis
o Increased risk for thromboembolic disease
+ Increase in fibrinogen, all coag factors except II, V, XII
+ Fall in protein S and sensitivity to APC
* Fall in platelets and factor XI and XIII
* Increase in WBC

Changes in the Pump
* Cardiac axis displaced cephalad and left
o PMI lateral & elevated (not just due to baby!)
+ Altered thoracic dimensions
o Left axis deviation
* Murmurs > 96%
o Virtually all valves
+ Esp. Aortic and Pulmonary
+ Mammary Souffle
* Rate – increased (80’s typical)
* Ventricular distention – 25% increase
* Rhythm
o Non-specific ST & T changes
o Increase in dysrhythmias
+ Physiologic hypokalemia
* Anatomy
o LVH & Pericardial effusion
* Function
o Increased & markedly fluctuating output

Blood Pressure
Pregnancy Adaptations
Anatomical considerations
Uterine Position over Time
Cardiac Output – Positional Effects
* Aorto-caval Compression
Labor Changes
* SVR – Increased 10-25% with CTX
* Volume – autotransfusion 300-500cc
* Cardiac output -
o <3cm Increased 17%
o 4-7cm Increased 23%
o >8cm Increased 34%
The Fetus and Placenta
* Fetus (aka – “the parasite”)
o A sensitive survivor
o A window
* Placenta
o A veritable hormone factory
o Receives 20-25% of cardiac output*
+ 750-1000 ml/min
+ Refractory to vasoactive meds
o Uses as much O2 as fetus

Normal physiology or disease?
Signs & Symptoms of Normal Pregnancy that may Mimic Heart Disease
* Signs
o Peripheral edema
o JVD
* Symptoms
o Reduced exercise tolerance
o Dyspnea
* Auscultation
o S3 gallop
o Systolic ejection murmur
* Chest x-ray
o Change in heart position & size
o Increased vascular markings
* EKG
o Nonspecific ST-T wave changes
o Axis deviation
o LVH
Other systems
Changes in the Filter
* Renin – stimulated by progesterone
o Also made by placenta
o Angiotensinogen Angiotensin I Angiotensin II Aldosterone Distal tubule
+ Net absorption of Na+
+ Excretion of K+
+ Water retention: 6-8 liters
* Increased renal blood flow
o 50-75% increase
o GFR – 50% increase
o Decreased Albumin = lower colloid oncotic pressure

Other urinary tract changes
* Ureteral dilation / hydroureter
o Smooth muscle relaxation
o Later exacerbation by uterine obstruction
o Urinary stasis*
* Dilation of pelves and calyces
* Increased kidney size
Lungs and respiration
Respiratory Adaptations
o No change in rate or IRV
o Thorax
+ Tr. Diameter 2cm; circumference 5-7cm
o Increased minute ventilation
o Reduced FRC – 20%
o Increased Tidal Volume – 30-40%
o Compensated respiratory alkalosis
+ pH 7.4+
+ PaO2; PaCO2 (40 – 30)
+ Drives gradient b/w mom and fetus

Respiratory Changes
Gastrointestinal
* Slowed GI motility
o Constipation, early satiety
* Relaxation of LES
o GERD
* Nausea / vomiting
o Often proportional to HCG level
* Liver / gallbladder
o Biliary stasis, cholesterol saturation
+ More stones
o Coagulation factors
o Increased binding proteins (thyroid, steroid, vitamin D)
Other “Adaptations”

* “I can’t see my feet!!!”
o Altered center of gravity
o Altered gait
o Greater joint laxity
+ Widening of symphysis pubis
+ Affects other joints
+ Thorax; widened costovertebral angle
o Fatigue / somnolence

Integumentary Changes
* Spider angiomata and palmar erythema
* Hair growth (abdomen and face)
* Mucosal hyperemia
* Striae gravidarum
* Hyperpigmentation (esp. linea nigra)
o Rashes and acne relatively common
Other Endocrine
* Pancreas
o Carbohydrate metabolism -Insulin resistance
+ Human placental lactogen, cortisol
* Thyroid Function
o Increased TIBG (via liver)
o Increased total T4 and T3
+ free levels unchanged
+ HCG suppresses TSH
* Adrenal function
o Free plasma cortisol is elevated
+ CRH from placenta stimulates ACTH
Immunology

* Must adapt to accept ‘allograft’
* Immune response altered, but not deficient
* Modulates away from cell-mediated cytotoxic effects
o Progesterone effect
o NK cells decrease by 30%
o Enhanced humoral / innate immunity
+ Immunoglobulins still active
+ IgG crosses placenta
o More susceptible to CMV, HSV, Varicella, Malaria
o Decrease in symptoms of some autoimmune disorders

Pregnancy – not a disease

* Profound changes in physiology and anatomy
* Affects most organ systems
* Can dramatically impact disease states, susceptibility, and treatment
* Almost all will encounter and treat pregnant women
o Even if you don’t know it
* Under-appreciation of changes will lead to suboptimal treatment or outright mistakes

Physiologic Changes in Pregnancy.ppt

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