Pregnancy Basic Concepts

Pregnancy: Basic Concepts Anna Mae Smith, MPAS, PA-C Associate Professor

Instructions for an Optimal Pregnancy
Begin planning well before pregnancy occurs.
don’t wait for pregnancy to occur
rubella testing at least 3 months prior to pregnancy
stop taking Ocs 3 months prior to pregnancy

Review the medical and family history risk factors.
arrange genetic counseling or testing before pregnancy if any of the following is possible or has occurred in either family:
Tay-Sachs
congenital abnormalities
Down’s syndrome
hereditary anemia
sicklecell anemia
testing for AIDS is recommended for all women before they become pregnant

Plan ahead if you have a serious medical condition
diabetes
epilepsy
take prescription medications for any reason
Talk to your clinician BEFORE stopping birth control.
medications may need to be changed
be sure overall medical condition is under good control
Take a vitamin that includes folic acid 0.4 mg daily; begin several months before you plan to be pregnant.

Avoid exposure to potentially toxic agents including:
alcohol, smoking, excessive caffeine
x-ray of the abdominal area
illegal drug use
megadose vitamins (or mega-anything-else!)
Do not take any medications until you have discussed with your clinician the possible effects on pregnancy.
prescription medications
over-the-counter medications

Make a healthy diet a top priority.
A restricted diet or weight loss can be dangerous for your fetus.
Do not eat raw meat or fish.
Avoid unpasteurized dairy products.
Aim for fitness, but with moderation.
Daily exercise is a good idea.
Some activities may not be wise during pregnancy:
prolonged aerobic activities
long-distance running
sports that may cause injuries
horseback riding
skiing

Minimize your risk of STD exposure.
avoid intercourse
use condoms
STDS can cause serious or lethal fetal complications:
herpes
gonorrhea
chlamydia
Avoid body temperature elevation.
Do not use a hot tub or sauna.
Try to avoid exposure to contagious viral illnesses such as influenza.

Avoid contact with cat fecal matter.
Toxoplasma infection - dangerous for fetus
wear gloves when gardening
have someone else empty the kitty litter
Have a pregnancy test and see your clinician as soon as possible if you think you are pregnant.
pregnancy dates most accurate if you have an exam within 2 weeks after missing your menstrual period
early pregnancy diagnosis is especially important if you plan to have prenatal genetic testing.

Watch for the danger signs of possible pregnancy complications.
most likely to cause symptoms within the first month or two of pregnancy:
spontaneous abortion (miscarriage)
ectopic (tubal) pregnancy
contact your clinician immediately if you have danger signs
danger signs
abnormal bleeding
cramping
abdominal pain

Goals of Pregnancy Diagnosis
Determine whether or not the woman is pregnant.
Identify possible problems that require further evaluation and/or emergency intervention
ectopic gestation
threatened abortion
Assess gestation length accurately (in weeks).
Help the patient make and implement her own plans for prenatal care or abortion.

Pregnancy Evaluation
review of pertinent history and symptoms
most common sign - an overdue menstrual period
determine LMP and PMP - provides accurate estimate of gestational age
determine date when pregnancy symptoms began:
1-2 weeks after fertilization
breast tenderness
nipple sensitivity
2 weeks after fertilization
fatigue
nausea
urinary frequency

laboratory test to detect human chorionic gonadotropin (HCG)
pelvic exam
confirms pregnancy test results
correlate uterine enlargement with menstrual dates
consider possible reasons for the discrepancy
ultrasound may be helpful
early signs of pregnancy (within 2-3 weeks after fertilization):
cervical softening
blurring of the cervico-uterine angle
uterine softening

Uterus Smaller Than Expected
fertilization later than dates suggest
ectopic pregnancy
incomplete or missed, spontaneous abortion
error in pregnancy test

Uterus Larger Than Expected
fertilization earlier than dates suggest
uterine leiomyomata (fibroids)
twin gestation
uterine anomaly
hydatidiform mole

HCG Levels During Pregnancy
Normal pregnancy
detected in serum at low levels as early as 7-9d after ovulation, very soon after implantation occurs
first 3-4 weeks after fertilization
HCG level in normal pregnancy doubles ~2d
serum HCG level reaches 50-250 mIU/ml by time of first missed menstrual period
peaks ~60-70d after fertilization, then decreases

Abnormal pregnancies - HCG levels often abnormal
elevated - multiple pregnancies
extremely high (million mIU/ml) - molar pregnancy (hydatidiform mole)
abnormally low -
spontaneous abortion
ectopic pregnancy
normal pregnancy that is earlier in gestation than menstrual dates suggest

HCG Levels After Pregnancy
initial decrease is quite rapid
HCG levels after 2 weeks - < 1% of the level at the time the pregnancy was terminated
after full-term delivery
<50mIU within 2 wks
undetectable after 3-4 wks

after first trimester abortion
initial HCG levels much higher
may be as high as 150,000 mIU at 8-10 wks gestation
may still be as high as 1,500 mIU at 2 wks post-AB - all pregnancy tests still positive
HCG may be detectable by sensitive tests 40 d after 1st trimester AB
consider serial quantitative HCGs-
continuing IUP
retained placenta fragments
ectopic pregnancy
HCG level should decline with half-time of disappearance of no more than 24-48 hours

Positive Evidence of Pregnancy
demonstration of the fetal heart
transvaginal U/S - 4-6.5 wks after conception
transabdominal U/S - 8 wks (menstrual age)
doppler - 10-12 wks
fetoscope - 17-19 wks
appreciation of fetal movement - after 19 wks gestation

visualization of the fetus
normal IUP by U/S - 5-6 wks of amenorrhea - appears as ring or circular structure within the uterus - gestational sac
by 8 wks of amenorrhea - fetal echoes within sac - measurement of crown-rump length
blighted ovum = loss of definition of gestational sac or absence of fetus by 7-8 wks of amenorrhea
by 11 wks of amenorrhea - gestational sac not distinctly visible, cardiac activity identified
by 16 wks of gestation, fetus can usually be seen on x-ray films

Probable Evidence of Pregnancy
enlargement of the abdomen
12 wks uterus is palpated abdominally
uterine changes
changes from pear-shape to globular contour
Hegar sign = palpable softening of the lowest part of the corpus at ~6 wks
McDonald sign = when the uterine body and cervix can easily be flexed against one another

cervical changes
Goodell sign = softening of the cervix, by beginning of 2nd month
Chadwick sign = mucous membranes of the vulva, vagina, and cervix become congested and have blue-violet hue, between 6th & 8th wks
palpation of the fetus - ballottement
Braxton-Hicks contractions
near the end of the 1st trimester
painless and irregular contractions
positive pregnancy test

Presumptive Evidence of Pregnancy
cessation of menses
8% of pregnant women have a small amount of bleeding on or before 40th day - implantation
breast changes
heavy sensation
tingling and soreness
vaginal mucosa and skin changes
blue-violet hue of vulva and vagina
increased pigmentation - linea nigra, chloasma
appearance of abdominal striae

nausea
1/2 of pregnant women
between weeks 2 & 12 of pregnancy
subsides 6-8 wks later
occasionally persists throughout pregnancy
only rarely first occurs after 1st trimester
most severe upon awakening; tends to lessen as day progresses
simple treatments
crackers before arising
frequent snacks
avoidance of foods that prompt nausea
medication occasionally required

bladder irritability
early in pregnancy, enlarging uterus puts pressure on bladder
increased urinary frequency
usually resolves by 2nd trimester
returns late in pregnancy when fetal head descends into the pelvis

fatigue
common, sometimes severe
often out of proportion to what would be expected
usually resolves by week 20
perception of fetal movement
multipara - between weeks 16 & 18 - aware of “fluttering” => fetal movement => quickening
primipara - several weeks later than above

Differential Diagnosis of Pregnancy
leiomyomas
ovarian cysts
hematometra
pseudocyesis (imaginary pregnancy)
most often occurs in women nearing menopause
also occurs in young women who have a strong, unfulfilled desire for pregnancy

Fetoplacental Unit
largely controls the endocrine events of the pregnancy
input from
fetus => most active and controlling role in its growth and maturation and probably also parturition
fetal adrenal gland
placenta
mother

Fetal Adrenal Gland
major endocrine component of fetus
larger than fetal kidney in midpregnancy
consists of
outer, definitive or adult zone
secretes
glucocorticoids
mineralocorticoids

later develops into the 3 components of adult adrenal cortex
zona fasciculata
zona glomerulosa
zona reticularis
inner, fetal zone
constitutes 80% of fetal gland
primarily secretes androgens during fetal life
involutes following delivery
completely disappears by end of 1st year of life
fetal adrenal medulla
synthesizes and stores catecholamines
poorly developed
role during fetal growth and maturation is not known

Placenta
Produces both steroid and peptide hormones
amounts vary with gestational age
precursors for progesterone synthesis come from the maternal circulation
placenta lacks the enzyme 17alpha-hydroxylase
cannot directly convert progesterone to estrogen
must use androgens from fetal adrenal

Peptide Hormones
Human Chorionic Gonadotropin (hCG)
secreted by trophoblastic cells of the placenta
maintains pregnancy
consists of 2 subunits: alpha and beta
alpha subunit is shared with
luteinizing hormone (LH)
thyroid-stimulating hormone (TSH)
begins to rise 8 d after ovulation (9 d after midcycle LH peak)

hCG levels peak at 60-90 d and then decline to a moderate, more constant level
first 6-8 wks of pregnancy
maintains corpus luteum
ensures continued progesterone output until progesterone production shifts to the placenta
it may also
regulate steroid biosynthesis in the placenta and the fetal adrenal gland
simulate testosterone production in the fetal testicle
not verified: immune suppression

Human Placental Lactogen (hPL)
originates in the placenta
antagonizes the cellular action of insulin
decreases glucose utilization
may play a role in shifting glucose availability toward the fetus
maternal serum concentrations parallel placental weight - rises throughout gestation to maximum levels in last 4 weeks
accounts for 10% of all placental protein production
low values found with:
threatened abortion
IUGR

Prolactin
peptide from the anterior pituitary
normal nonpregnant levels are ~10 ng/ml
during pregnancy, levels rise in response to increasing maternal estrogen output that stimulates the anterior pituitary lactotrophs
decidua is a secondary source, but contributes little to the plasma pool
amniotic fluid levels exceed those in the circulation

main effects of prolactin
stimulation of milk production
in second half of pregnancy, prolactin from fetal pituitary may stimulate fetal adrenal growth
may also play a role in fluid and electrolyte shifts across the fetal membranes

Steroid Hormones
Progesterone
most important human progestogen
in luteal phase, induces secretory changes in the endometrium
in pregnancy, higher levels induce decidual changes
sources of progesterone
up to 6-7th week of pregnancy, major source is the ovary => essential for continuation of the pregnancy
thereafter, the placenta

other actions of progesterone
prevents uterine contractions
may also induce some immune tolerance for the products of conception
the fetus inactivates progesterone by
transformation to corticosteroids
by hydroxylation
conjugation to inert excretory products
placenta can convert the inert material back to progesterone
Estrogens
Both fetus and placenta are involved in the biosynthesis of estrone, estradiol, estriol

Estriol is most abundant estrogen in human pregnancy
Sudden decline of estriol in maternal circulation may indicate fetal compromise
Anencephalic fetuses
lack a hypothalamus and have hypoplastic anterior pituitary and adrenal glands
estriol production is only ~10% of normal
estriol determinations have been used as a means of monitoring fetal well-being, however present use is limited
estriol measurements have generally been replaced by biophysical assessments

Androgens
originate mainly in the fetal zone of the fetal adrenal cortex
secretion is stimulated by ACTH and hCG
fetal adrenal favors production of DHEA over testosterone and androstenedione, and it sulfurylates almost all steroids
fetal androgens enter the placental circulation and serve as precursors for estradiol and estriol
fetal testis also secretes androgens, particularly testosterone which is converted within target cells to dihydrotestosterone => required for the development of the male external genitalia. Main tropic stimulus = hCG

Glucocorticoids
cortisol derived from circulating cholesterol
maternal plasma cortisol concentrations rise throughtout pregnancy
the diurnal rhythm of cortisol secretion persists
metabolized by both fetal adrenal and the placenta
cortisol is important in the maturation of the lungs
promotes differentiation of type II alveolar cells
promotes the biosynthesis and release of surfactant into the alveoli (surfactant decreases the force required to inflate the lungs)

Summary of Pregnancy Hormones
HCG
First hormonal signal of pregnancy.
Functions to maintain the ovarian corpus luteum.
Progesterone
Supplied primarily by the corpus luteum.
Suppresses uterine contractility
Is important for breast development in preparation for lactation.
Required to maintain the pregnancy.

Estrogens
Supports growth and maintenance of the uterus
Cooperates with progesterone to promote breast development.
Relaxin
may have a role in cervical ripening
Oxytocin
causes uterine contractions
role in initiating labor is unclear
administered oxytocin can induce labor only at or near term

Placental lactogen (hPL)
Regulates maternal metabolism, favoring use of maternal resources to benefit the fetus.
Alpha-fetoprotein (AFP)
Produced by the fetal liver.
Tends to be elevated in pregnancies supporting fetuses with neural tube defects (spina bifida) and is lowered in cases of Down’s syndrome.
Prolactin
Stimulates milk production during lactation.
Prostaglandins
major role in the initiation and control of labor

Physical Changes in Pregnancy
skin
increased vascularity
increased pigmentation of face (chloasma), areola, abdomen (linea nigra), and genitalia
striae of breasts and abdomen
head
mild changes in scalp
excessive oiliness or dryness

eyes
vessel dilation in sclera
mouth
edematous, friable gums
chest/cardiovascular
increased respiratory effort and rate
progressive elevation of the diaphragm
hand/pedal edema by 3rd trimester
breasts
increased fullness, tenderness, and enlargement
excretion of colostrum - common by 3rd trimester

heart
exaggerated heart sounds
particularly functional murmurs in systole
abdomen
distention secondary to flatus and increased uterine size
diminished bowel sounds as peristaltic movements are slowed
enlarging uterus, which displaces abdominal organs

genitalia/reproductive
external
increased pigmentation
pubic hair may lengthen
near term, pelvic congestion and overall swelling of labia majora are common
vulvar varicosities
vagina
increased pelvic congestion and hypertrophy
rugation of vaginal mucosa is prominent
cervix
positive Chadwick’s sign (bluish/purple color)
may soften, dilate, and efface close to term
positive Goodell’s sign may be noted

uterus
positive Hegar’s sign (softening of the lower uterine segment) by 6 wks gestation
uterine enlargement occurs in linear fashion = 1 cm per week
12 wks - fundus at symphysis pubis
16 wks - fundus midway between the symphysis and the umbilicus
36th wk - fundus is just below the ensiform cartilage
lightening - fundal height drops slightly near term
maintains a globular/ovoid shape throughout pregnancy

adnexa
discomfort may be noted with exam due to stretching of the round ligaments throughout pregnancy
ovaries are not palpable once the uterus fills the pelvic cavity at 12-14 wks gestation
urinary
bladder may be palpable
incontinence is common, particularly with multiparity
rectal
increased vascular congestion with resulting hemorrhoids often noted

musculoskeletal
increased relaxation of pelvic structures
lordosis
sciatica (common)
endocrine
mildly enlarged thyroid
diffusely enlarged thyroid nodularity or increased firmness is abnormal

Physiological Changes of Pregnancy
50% increase in plasma volume
decreased Hct
physiological anemia
increased oxygen carrying capacity of RBCs compensates for volume expansion
40% increase in cardiac output
increase in stroke volume
increase in heart rate

fall in peripheral resistance
intravascular pressure
systolic pressure falls only slightly
diastolic pressure decreases markedly
BPs highest sitting, somewhat lower lying down, and lower still on one side
mechanical circulatory effects of the gravid uterus
displaces and compresses various abdominal structures
iliac veins
inferior vena cava

supine position accentuates venous compression => fall in venous return and decrease in CO
“ supine hypotensive syndrome”
significant fall in BP
sxs of nausea, dizziness, even syncope
bradycardia instead of tachycardia
venous compression elevates pressure in veins draining legs and pelvic organs
varicose veins in legs and vulva
hemorrhoids

late pregnancy can also partially compress aorta and its branches
Poseiro effect => aortic compression accentuated during uterine contractions => fetal distress when patient is in supine position
clinically suspected when femoral pulse not palpable
regional blood flow
blood flow to most regions of body increases and plateaus early
exceptions (blood flow increases with gestational age)
uterus
skin => elimination of heat
kidneys => elimination of waste material

total body oxygen consumption increases about 15-20%
1/2 of this increase is accounted for by the uterus and its contents
the remainder is mainly accounted for by increased maternal renal and cardiac work
renal plasma flow and the glomerular filtration rate (GFR) increase early in pregnancy and plateau at ~40% above nonpregnant levels

BUN values are lower due to increased glomerular filtration rate
in PIH, values increase to non-pregnant levels due to pathological arterial spasm and vasoconstriction
creatinine values are lower due to increased glomerular filtration rte
in PIH, values increase to nonpregnant levels due to pathological arterial spasm and vasoconstriction
renin-angiotensinsystem plasma concentrations are elevated of:
renin
renin substrate
angiotensin I
angiotensin II

platelets may decrease with severe preeclampsia
alkaline phosphatase may double - increases due to placental involvement
cholesterol levels not accurately reflected in pregnancy
serum iron levels decrease due to increased iron demands during pregnancy
total iron binding capacity (TIBC) increases
estrogen increases ability for iron to bind to transferrin, which regulates transport in the body

insulin effects and glucose metabolism
insulin response to glucose stimulation is augmented
by 10th wk of normal pregnancy and to term
fasting concentrations of insulin are elevated
glucose is reduced
until midgestation => improved IV GTT (OGTT unchanged)
anabolic actions of insulin potentiated during first half of pregnancy
after early pregnancy
insulin resistance emerges => glucose tolerance impaired
prolonged elevation of glucose after meals
FBS still reduced

thyroid panel
triiodothyronine (T 3 ) decreases due to increase of thyroid binding blobulins by estrogen
thyroxine (T 4 ) increases:
basal metabolic rate increases by 25%
increased thyroid binding globulins
TSH - most sensitive indicator for hypothyroid/hyperthyroid states in pregnancy
uric acid values are lower due to increased glomerular filtration rate
PIH- values increase to nonpregnant levels

urinalysis
albumin
elevations seen in preeclampsia and UTIs
chloride may slightly increase due to increased glomerular filtration rate
creatinine elevated due to increased glomerular filtration rate
ketones same
presence may indicate dehydration
starvation states
ketoacidosis in IDDM

glucose elevated due to increased glomerular filtration rate
WBCs same
often vaginal contamination
UTI if other indicators
RBCs same
may be due to violent exercise, kidney trauma, systemic or renal disease
bacteria
nonpregnant - >100,000 colonies/mL = infection
pregnant - >10,000 colonies/mL = infection

Pregnancy Basic Concepts

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