Pregnancy: Diagnosis, Maternal Physiology, and Routine Care

Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. There are numerous maternal adaptations to pregnancy, both anatomic and physiologic, which occur to help support the developing fetus and prepare the mother’s body for ultimate delivery. Pregnancy is not a pathologic condition, but good routine prenatal care can help achieve the best outcomes for both the mother and infant. Prenatal care includes appropriate lab and ultrasound testing, anticipatory guidance, and offering solutions or advice for common pregnancy discomforts.

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Overview

Definition

Pregnancy is defined as the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later.

Terminology

  • Gravidity: the number of times a woman has been pregnant
  • Parity: 
    • The total number of deliveries
    • More specifically, the total number of pregnancies reaching the age of viability regardless of the outcome (live birth, stillborn, cesarean delivery, etc.)
  • Abortion: 
    • Number of lost pregnancies prior to the age of viability
    • Includes both spontaneous abortions (i.e., miscarriages) and induced terminations of pregnancy
  • Last menstrual period (LMP): the 1st day of a woman’s LMP
  • Gestational age: the age of pregnancy calculated from the LMP
  • Embryonic age: the age of pregnancy calculated from the day of fertilization (not used in obstetric clinical practice)
  • Estimated date of delivery (EDD): also known as the estimated date of confinement

Sequence of events

  • Fertilization of the oocyte by a sperm → embryo
  • Implantation of the early embryo into the uterine wall
  • Fetal and placental differentiation, growth, and development
  • Concurrent changes occur in the mother’s body to support the developing fetus and prepare for delivery.
  • Labor and delivery of the infant
  • Puerperium: return of the mother’s body to the prepregnant state

Pregnancy duration

  • Pregnancy is counted by completed weeks + completed days of the current week since the LMP:
    • Known as weeks gestational age (wga)
    • E.g., 35 + 4 wga would indicate that an infant is 35 weeks and 4 days gestational age
  • Duration of normal pregnancy: 
    • Full-term pregnancy: 37–42 wga
    • Preterm pregnancy: < 37 wga
    • Post-term pregnancy: > 42 wga
    • Notes: Only about 5% of women deliver on their EDD.
  • Classified into trimesters:
    • 1st trimester: 0–13 + 6 wga 
    • 2nd trimester: 14 + 0 to 27 + 6 wga
    • 3rd trimester: 28 + 0 wga through delivery

Clinical Presentation

Individuals trying to get pregnant will typically present with a positive home pregnancy test. Many others may not know they are pregnant and will present with symptoms of early pregnancy, which may include:

  • Missed periods (amenorrhea)
  • Irregular bleeding (especially in cases of ectopic pregnancy and/or miscarriage)
  • Pelvic or abdominal pain/discomfort
  • Breast engorgement and tenderness
  • Nausea and vomiting
  • Fatigue
  • Frequent urination (typically later in pregnancy)

Diagnosis of Pregnancy and Establishing the EDD

Pregnancy is confirmed based on lab tests and obstetric ultrasound imaging. 

Laboratory

The major analyte used to establish pregnancy is β-hCG. 

  • β-hCG is a hormone produced early by the developing embryo.
  • The presence of β-hCG indicates pregnancy.
  • β-hCG tests may be:
    • Qualitative: to detect the presence or absence of β-hCG
      • Urine tests (available as over-the-counter kits) or a test at a medical lab
      • Reliable approximately 2 weeks after fertilization
    • Quantitative: to determine serum β-hCG levels
      • Serum tests
      • More sensitive, reliable 6–10 days after fertilization 
      • Can be used to track β-hCG levels when there is a concern for an abnormal pregnancy (e.g., ectopic pregnancy or miscarriage)
      • Levels should roughly double every 24–48 hours during the 1st month.

Imaging

  • Ultrasound is the obstetric imaging modality of choice to diagnose and date a pregnancy.
  • Purpose of early ultrasounds:
    • Viability: to establish if a viable pregnancy is present
    • To determine the number of fetuses
    • To establish the location of the pregnancy (e.g., rule out ectopic pregnancy)
    • Dating
  • 1st-trimester findings: 
    • Presence of a gestational sac:
      • 1st visible finding of pregnancy is seen around 4.5–5 wga.
      • A hypoechoic circle within the uterine cavity, surrounded by hyperechoic endometrium
      • Should be visible in the uterus if quantitative serum β-hCG is > 2,000
    • Presence of a yolk sac: 
      • A thin hyperechoic ring within the gestational sac
      • 1st seen approximately 5–6 wga and disappears around 10 wga
    • Presence of a fetal pole with a heartbeat: seen around 5.5–6 wga
  • Dating a pregnancy using ultrasound:
    • 1st trimester: measuring the crown-rump length of the fetal pole 
    • 2nd and 3rd trimesters: calculated using a formula by considering measurements of biparietal diameter, abdominal circumference, and femur length

Establishing the EDD

Establishing the EDD is one of the most important factors to accomplish after diagnosing a pregnancy. Dating a pregnancy is usually done by calculating the EDD from the LMP and comparing that date with the EDD obtained from early ultrasound measurements.

  • Calculating the EDD from the LMP:
    • The date that falls exactly 40 weeks after the LMP
    • Calculated by adding 280 days (or 9 months and 7 days) to the LMP
  • Dating by ultrasound:
    • Measure the crown-rump length and look up the associated date in a table (most ultrasound machines will show this along with the measurement).
    • Ultrasound dating is most accurate in the 1st trimester before genetic variation and the effects of intrauterine environment begin to have greater effects on fetal growth.
  • Establishing the final EDD:
    • Use the EDD obtained from the LMP if the EDD obtained from the crown-rump length measurement is within:
      • 5 days of the LMP-EDD for pregnancies < 9 wga
      • 7 days of the LMP-EDD for pregnancies 9–13 + 6 wga
      • Approximately 2 weeks in the 2nd trimester
      • Approximately 3 weeks in the 3rd trimester
    • Use the EDD obtained from ultrasound if the EDDs are further apart from each other than the dates listed above.
  • Calculating the EDD from the LMP is the most accurate method to date a pregnancy if that EDD is consistent with the dates obtained from the ultrasound.
  • If the LMP is unknown, a 1st-trimester ultrasound is the next most accurate way to date a pregnancy.

Physiological Changes During Pregnancy

To support fetal growth and development and prepare the mother’s body for eventual delivery, numerous anatomic and physiologic changes occur within a woman’s body during pregnancy.

Reproductive tract

Uterus:

  • Increased uterine size:
    • Mass ↑ from approximately 70 grams to 1100 grams
    • Volume capacity ↑ from approximately 10 mL to 5 L
    • Hypertrophy of the uterine wall with an accumulation of fibrous and elastic tissue
    • Growth is initiated through ↑ estrogen levels
    • By 28 wga, uterine growth slows and the uterus continues to stretch and become thinner.
  • Blood flow: ↑ from 50 mL/min to 450–750 mL/min at term 
  • Muscle contraction:
    • Uterus is maintained in a passive noncontractile state through ↑ levels of progesterone (a smooth muscle relaxant)
    • Braxton-Hicks contractions: 
      • Irregular contractions that do not cause cervical change
      • More noticeable as the pregnancy progresses 
  • Uterine involution: return of the uterus to its pre-pregnant state in the 1st several weeks postpartum

Cervix:

  • Cervix softens and can become bluish due to:
    • Edema
    • Increased vascularization
    • Hypertrophy and hyperplasia of the cervical glands
  • May undergo eversion:
    • Glandular cells normally lining the cervical canal become visible on the surface of the cervix.
    • Can cause benign bleeding (all bleeding in pregnancy should be fully worked up)
  • Endocervical mucosal cells produce a mucus plug, an immunological barrier for uterine contents.

Ovaries:

  • Ovulation and follicle development are suppressed by ↑ estrogen levels
  • The corpus luteum supplies progesterone during the 1st part of pregnancy until the placenta is developed enough to take over this function.

Anatomic and physiologic changes in pregnancy by system

Table: Anatomic and physiologic changes in pregnancy
System Parameters that ↑ in pregnancy Parameters that ↓ in pregnancy Symptoms and anatomic changes
Cardiovascular system
  • CO
  • HR
  • Stroke volume
  • Venous pressure
  • Peripheral vascular resistance
  • Blood pressure
  • Varicose veins
  • Hemorrhoids
  • Increased risk for congestive heart failure in at-risk individuals
Hematologic system
  • Plasma volume (↑ 40%‒50% due to water retention)
  • RBC mass (↑ 15%‒30%)
  • WBC count:
    • Up to 29,000/µL can be physiologic
    • Work-up if > 20,000/µL
  • Coagulation factors: II, VII, VIII, X, and XII
  • Fibrinogen
  • Hemoglobin and hematocrit concentrations
  • Platelets
  • Anticoagulants: protein S
  • Fibrinolysis
  • Blood viscosity (improves placental perfusion)
  • PT and aPTT may be slightly ↓
  • Hypercoagulability → risk of DVT/PE
  • Dilutional anemia → fatigue, shortness of breath
  • Edema
Respiratory system
  • Tidal volume
  • Minute ventilation (↑ 50%)
  • Oxygen consumption
  • FRC
  • Expiratory residual volume
  • Pulmonary vascular resistance
  • Diaphragm rises by approximately 4 cm due to uterine expansion.
  • Physiologic respiratory alkalosis
GI system Intraabdominal pressure
  • GI motility (delayed emptying)
  • Lower esophageal sphincter tone
  • Stomach and intestines are displaced upward.
  • Heartburn
  • Constipation
  • Nausea and vomiting
Renal system
  • Kidney size (due to ↑ blood volume)
  • GFR (↑ approximately 50%)
  • Renal plasma flow
  • Creatinine clearance
  • Proteinuria
  • Bicarbonate excretion (compensatory mechanism for respiratory alkalosis)
  • Serum creatinine (should be < 0.8 mg/dL in pregnancy)
  • Serum BUN
  • Serum sodium
  • Plasma osmolality
  • Glucose reabsorption
  • ↑ Urinary frequency
  • Nocturia
  • Urinary incontinence
  • Hydronephrosis in the 3rd trimester (due to ureteral compression)
  • ↑ Risk for UTI
  • Glucosuria may be physiologic (seen in 50% of individuals).
  • Compensatory metabolic acidosis
Endocrine and metabolic systems
  • Basal metabolic rate
  • Total T3 and T4 (thyroid hormones
  • Glucose intolerance
  • Cortisol
  • Anterior pituitary volume
  • Progesterone and estrogen
  • Prolactin
  • Oxytocin
  • Relaxin
  • Renin and aldosterone
  • Erythropoietin
  • TSH
  • FSH and LH
  • ↑ Caloric needs
  • ↑ Volume of the anterior pituitary
  • Breast enlargement and tenderness
  • Pain from stretching of ligaments (e.g., pelvic pain, round ligament pain)
DVT/PE: deep vein thrombosis/pulmonary embolism
GFR: glomerular filtration rate
UTI: urinary tract infection
TSH: thyroid stimulating hormone
FSH: follicle stimulating hormone
LH: luteinizing hormone

Skin changes

  • Stretch marks
  • Hyperpigmentation of:
    • Face (known as melasma, or the “mask of pregnancy”)
    • Nipples
    • Perineum
    • Abdominal line (known as the linea nigra)
    • Umbilicus
  • Spider angiomata
  • Palmar erythema
Linea nigra

Linea nigra and hyperpigmentation of the umbilicus in pregnancy

Image: “Linea nigra” by Daniel Lobo. License: CC BY 2.0

Normal Prenatal Care

Appointment schedule

The typical schedule of prenatal visits for low-risk individuals:

  • Every 4 weeks up through 28 wga
  • Every 2 weeks from 28–36 wga
  • Every week from 36 wga until delivery

Prenatal visits

Parameters to measure/monitor for healthy, uncomplicated individuals at routine prenatal visits:

  • 1st visit:
    • Ultrasound to confirm the estimated date of confinement (either in-office or ordered)
    • Full physical exam, including a pelvic exam
    • Recommend supplements: 
      • Folic acid (best if started prior to pregnancy)
      • Multivitamins with iron
  • All visits:
    • Weight
    • Blood pressure
    • Fetal HR (using doppler auscultation)
    • Ask the mother about:
      • Abnormal bleeding
      • Contraction-like or cramping abdominal pain
      • Abnormal loss of fluid
  • Starting at 20 wga: fundal height measurements
  • Starting at 28 wga, ask the mother about: 
    • Fetal movements:
      • Should experience 10 movements in a 2-hour period at least once daily
      • Individuals who report decreased fetal movement should be evaluated.
    • TDaP immunization (once)
    • Rh immunoglobulin to Rh-negative women
  • Starting at 34–36 wga: Assess fetal presentation (vertex or breech).

Routine pregnancy laboratory and imaging studies

All pregnant individuals should have certain labs done at different points during their pregnancy. These include:

  • At their 1st obstetrics appointment:
    • CBC
    • Blood type and screen (may indicate future compatibility issues with fetal blood type)
    • Urinalysis
    • Rubella immunity status
    • HIV
    • Hepatitis B surface antigen
    • Rapid plasma reagin test for syphilis
    • Gonorrhea and chlamydia testing
    • Pap smear (only if due for routine Pap screening)
    • Screening for inherited diseases based on ethnicity (e.g., hemoglobinopathies, cystic fibrosis)
  • Screening for fetal aneuploidy (e.g., trisomy 21):
    • Multiple options available
    • Options include different combinations of multiple serum analytes and ultrasound.
    • A common option used is a test assessing the cell-free fetal DNA found in maternal serum (often referred to as noninvasive prenatal testing (NIPT)).
  • Other tests:
    • Full anatomic assessment of the fetus, placenta, and uterus/cervix at 18–22 wga 
    • 1-hour glucose tolerance test (GTT) at 24–28 wga
    • CBC is often repeated with GTT.
    • Group B Streptococcus culture at 35–37 wga
    • Bedside ultrasound to check fetal presentation (vertex/head down, breech/buttocks down) around 35 wga

Diet, exercise, and weight gain

Table: Safe and unsafe diets in pregnancy
Safe Unsafe
  • Moderate caffeine intake
  • Artificial sweeteners
  • Fish: limit to < 12 oz/week
  • Excess caffeine intake
  • Saccharine
  • Unpasteurized foods, especially dairy (risk of listeria)
  • Swordfish, shark, king mackerel, or raw fish (risk of mercury poisoning)

Weight gain:

The recommended weight gain during pregnancy is based on the individual’s prepregnancy BMI. Normal weight-gain recommendations:

  • Underweight (BMI < 18.5): 28–40 lbs
  • Normal weight (BMI 18.5–24.9): 25–35 lbs
  • Overweight (BMI 25–29.9): 15–25 lbs
  • Obese (BMI > 30): 11–20 lbs
  • Note: Weight loss is not recommended during pregnancy.

Exercise:

  • Purpose: controls weight gain, improves delivery, improves weight loss after pregnancy
  • Recommendation: moderate exercise for 30 minutes on most days of the week
  • In general, women can continue performing exercises they were doing prior to pregnancy at the same level of intensity (goal: maintain fitness level rather than increasing exercise intensity).
  • Avoid contact sports and/or activities associated with the risk of falling or abdominal trauma (e.g., soccer, horseback riding, downhill skiing).
  • Avoid exercising in hot weather.

Safety

  • Air travel is safe for up to 36 weeks (after which, the risk of labor or complications on board ↑).
  • Precautions to prevent deep vein thrombosis during long trips (both flights and road trips):
    • Compression stockings
    • Frequent hydration
    • Frequent ambulation in the airplane or at rest stops (every 1–2 hours)
  • Frequent handwashing
  • Avoid kitty litter (to ↓ risk of toxoplasmosis).

Common Discomforts of Pregnancy

Pain

  • Pregnancy hormones (e.g., progesterone, relaxin) cause ligaments to stretch more easily and ↑ water retention
  • Common pains:
    • Pelvic pain from stretching at the pubic symphysis and sacroiliac joints → maternity support belts can help
    • Round ligament pain (described subsequently)
    • Foot pain
    • Low back pain (from shifting center of gravity)
    • Carpal tunnel syndrome
  • Round ligament pain: 
    • Round ligaments attach the uterus to the pelvic sidewall.
    • As the uterus grows, the round ligaments can stretch and cause pain.
    • Differentiating round ligament pain (benign) from more concerning pain:
      • Round ligament pain is often unilateral.
      • On exam, push the uterus toward the painful side; if this maneuver relieves pain, it is likely round ligament pain.
  • Analgesics:
    • Acetaminophen is the safest analgesic.
    • Try and avoid NSAIDs due to their effects on the fetal kidneys.

Gastrointestinal symptoms

  • Nausea and vomiting:
    • Common especially in early pregnancy (colloquially, “morning sickness”)
    • More common in the mornings but may occur throughout the day
    • Often improves in the early 2nd trimester
    • Management:
      • Vitamin B6 supplementation
      • Dietary changes: eat 1st thing in the morning. Consume smaller meals more frequently.
  • Acid reflux/heartburn
  • Constipation

Differential Diagnosis

Oligomenorrhea/amenorrhea

The primary symptom of pregnancy is a “missed” menstrual cycle. Pregnancy must always be ruled out using a simple urine-pregnancy test in reproductive-aged women presenting with abnormal bleeding. Other common causes of abnormal uterine bleeding include:

  • Polycystic ovarian syndrome: a metabolic condition resulting in abnormally elevated androgen levels that can suppress menstruation. Polycystic ovarian syndrome is typically treated with oral contraceptive pills and lifestyle modifications to promote weight loss.
  • Hypothalamic amenorrhea: a condition in which the hypothalamus decreases gonadotropin-releasing hormone (GnRH) secretion, which in turn decreases the release of follicle-stimulating hormone (FSH), resulting in the suppression of ovulation and menstruation. Hypothalamic amenorrhea most commonly arises in the setting of eating disorders and/or women athletes. Management typically involves nutritional support and psychotherapy.
  • Premature ovarian insufficiency: a condition of premature menopause in which the ovarian follicles fail to ovulate starting at an abnormally young age. Management involves hormone replacement therapy and fertility treatments as desired.

Pelvic pain

Some individuals may present with pelvic pain and/or bleeding, which are symptoms that are more concerning for an abnormal pregnancy. Again, pregnancy should always be tested for in these individuals using a urine-pregnancy test. If the test is positive, the differential diagnosis includes:

  • Ectopic pregnancy: implantation of an embryo outside of the uterine cavity, most commonly in the fallopian tube. The growing embryo can lead to tubal rupture and internal hemorrhage, which is associated with a high rate of maternal morbidity and mortality when not treated promptly. 
  • Threatened, spontaneous, incomplete, or missed abortion (i.e., miscarriage): Spontaneous abortion (SAB) refers to the spontaneous loss of a pregnancy with complete expulsion of the fetal tissue. A threatened abortion means that symptoms are present (pelvic pain and bleeding), suggesting an SAB is possible. A missed abortion refers to a fetus that has died in utero but has not yet been expelled. An incomplete abortion refers to a fetus that has died but only a part of the fetal tissue has been expelled. Individuals are diagnosed and followed up with serial ultrasounds and, sometimes, by monitoring β-hCG levels.

References

  1. Bastian, LA., Brown, H.L. (2020). Clinical manifestations and diagnosis of early pregnancy. In Barss, V.A. (Ed.), UpToDate. Retrieved July 15, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-early-pregnancy 
  2. MacKenzie, A.P., Sephenson, C.D., Funai, E.F. (2021). Prenatal assessment of gestational age, date of delivery, and fetal weight. In Barss, V.A. (Ed.), UpToDate. Retrieved July 15, 2021, from https://www.uptodate.com/contents/prenatal-assessment-of-gestational-age-date-of-delivery-and-fetal-weight 
  3. Bauer, K.A. (2020). Maternal adaptations to pregnancy: Hematologic changes. In Barss, V.A., Tirnauer, J.S. (Eds.), UpToDate. Retrieved July 15, 2021, from https://www.uptodate.com/contents/maternal-adaptations-to-pregnancy-hematologic-changes 
  4. Thadhani, R.I., Maynard, S.E. (2020). Maternal adaptations to pregnancy: Renal and urinary tract physiology. In Chakrabarti, A. (Ed.), UpToDate. Retrieved July 15, 2021, from https://www.uptodate.com/contents/maternal-adaptations-to-pregnancy-renal-and-urinary-tract-physiology 
  5. Weinberger, S.E. (2021). Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes. In Barss, V.A. (Ed.), UpToDate. Retrieved July 15, 2021, from https://www.uptodate.com/contents/maternal-adaptations-to-pregnancy-dyspnea-and-other-physiologic-respiratory-changes 
  6. Foley, M.R. (2021). Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes. In Barss, V.A. (Ed.), UpToDate. Retrieved July 15, 2021, from https://www.uptodate.com/contents/maternal-adaptations-to-pregnancy-cardiovascular-and-hemodynamic-changes 
  7. Pascual, Z. (2021). Physiology, pregnancy. In StatPearls. Retrieved July 15, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/27194/ 
  8. The American College of Obstetricians and Gynecologists. How your fetus grows during pregnancy. Retrieved July 15, 2021, from https://www.acog.org/womens-health/faqs/how-your-fetus-grows-during-pregnancy

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