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Pregnancy: Physiological Changes

    * Here we'll learn about physiological changes and common symptoms in pregnancy, which is a time of significant bodily adjustments to meet the demands of a growing fetus.
Hormonal Changes
  • Hormonal changes begin very early in pregnancy.
  • Human chorionic gonadotropin is a signal of pregnancy – in fact, many home pregnancy tests use this hormone to determine pregnancy status.
    • Human chorionic gonadotropin (hCG) is produced by the syncytiotrophoblast, which is a layer of placental tissue that forms during implantation (for more on the early and mature placenta, please see the links in our notes).
    • hCG triggers persistence of the corpus luteum and progesterone release until the mature placenta takes over progesterone production (recall that, in the absence of implantation and hCG stimulation, the corpus luteum regresses and progesterone levels fall).
  • Progesterone levels climb dramatically from ~30 mg/day during the pre-pregnancy luteal phase to up to 400 mg/day.
    • Progesterone has several roles during pregnancy:
It promotes smooth muscle relaxation, which is instrumental in maintaining uterine relaxation and preventing the conceptus from being pre-maturely expelled. And, it facilitates placental growth and development of uterine vasculature and breast development.
  • Estrogen levels also rise drastically over the course of pregnancy; it facilitates uterine growth and blood flow, and prepares the uterus for contraction during labor.
    • Estrogen also promotes development of breast ducts, and is important for fetal development and organ maturation.
  • Relaxin works with progesterone to inhibit uterine contractions, and also relaxes blood vessels and pelvic joints to accommodate the growing fetus and its passage through the birth canal.
  • Others
  • Prolactin, which is released from the posterior pituitary gland, promotes the enlargement of mammary glands and milk production.
  • Adrenal hormones (i.e., cortisol and aldosterone) and thyroid hormones also increase.
  • Related signs/symptoms:
As you can imagine, elevations in these hormone levels are associated with several symptoms of pregnancy.
  • The changes in the hypothalamic-pituitary-ovarian axis induce anovulation and amenorrhea; however, note that vaginal bleeding is common in the first 20 weeks of pregnancy, with about half of these pregnancies ending in spontaneous abortion.
  • Braxton-Hicks contractions are mild, irregular uterine contractions that feel like menstrual cramps in the low abdomen; they can be triggered by changes in position and dissipate with rest.
    • These contractions are usually felt beginning in the second trimester, though some people never experience them.
    • Importantly, Braxton-Hicks contractions are not associated with cervical changes of "true" labor contractions.
  • Breast tenderness is typical, and is the result of estrogen and progesterone's effects on duct and glandular development.
  • Seep disturbances are common during pregnancy, and may be related to hormonal changes – however, increased urine frequency and urgency, musculoskeletal discomfort, heartburn, and other factors also contribute to difficulty sleeping.
Cardiovascular and Hematological Changes
  • These changes, including increased cardiac output and increased blood volume, are necessary to maintain adequate maternal and fetal blood supply.
  • The maternal heart enlarges approximately 12%, due to increased venous filling; the heart is also displaced upwards and to the left, and rotates on its long axis.
  • Cardiac output, which is the product of heart rate and stroke volume, increases up to 60% during the course of pregnancy.
    • Cardiac output becomes sensitive to positioning, as the vena cava is compressed by the enlarged uterus and fetus in supine position.
  • The anatomical changes to the heart produce ECG changes:
A left axis shift, commonly with ST-segment depression and T-wave flattening and inversion. Be aware that sinus tachycardia or bradycardia are also common.
  • Total peripheral resistance (aka, systemic vascular resistance) decreases due to progesterone's vasodilation effects, and blood pressure falls.
    • Blood pressure reaches a nadir (lowest point) around 24-32 weeks, then begins to rise closer to term.
  • Changes in heart sounds are also common: the first heart sound becomes louder and splits early on, whereas the second heart sound may split around 30 weeks; a louder third heart sound is also common.
  • We'll often hear systolic murmurs, too, due to increased heart flow past the cardiac valves.
  • Swelling and edema in the lower extremities due to increased venous pressure.
  • Hematological changes include a 20-30% increase in red blood cell volume with a 50% increase in plasma volume; this uneven change produces dilutional anemia with reduced hematocrit.
  • Pregnancy is a hypercoagulable state with higher rates of thromboembolic events. Along with hypertension, thromboembolic events are a top cause of maternal mortality.
Respiratory System Changes
  • Changes in the respiratory system are necessary to ensure adequate oxygenation of mother and fetus and removal of metabolic wastes; studies show that maternal oxygen consumption increases by up to 40% during pregnancy.
  • Increased progesterone levels alter respiratory centers in the brain, increasing maternal sensitivity to carbon dioxide and driving hyperventilation, which helps raise maternal arterial oxygen tension.
  • Tidal volume, minute ventilation, and alveolar ventilation are increased by approximately 50%; functional residual capacity is reduced. Review Lung Volumes & Capacity.
These respiratory changes produce compensated respiratory alkalosis with lower partial pressure of carbon dioxide and higher partial pressure of oxygen; this shift optimizes waste exchange between the fetal and maternal blood supplies.* Review hemoglobin curves. Anatomical changes of pregnancy include upward displacement of the diaphragm and increases in the subcostal angle and transverse rib cage diameter.*
    • Overall, chest wall compliance decreases, but lung compliance stays the same.
  • In the upper respiratory tract, hormonal changes produce tissue swelling and increased mucus secretion that lead to nasal stuffiness and rhinitis.
  • Overall, these changes produce dyspnea in up to 75% of pregnant patients, often beginning as early as the first trimester.
Musculoskeletal Changes
  • Musculoskeletal changes and symptoms are caused by weight gain, a shift in the center of gravity, and hormonal factors.
  • Lordosis and stretching of the abdominal muscles are associated with back strain and pain.
  • Increased joint and ligament laxity in the lumbar spine and pelvis can also cause discomfort and pain.
Metabolic Changes
  • Metabolic changes during pregnancy enable the mother's body to keep up with the increasing demands of a developing fetus; these changes facilitate the transfer of glucose to the fetus.
  • Basal metabolic rate and caloric needs are increased; basal metabolic rate increases up to 20% by the third trimester.
  • People with singleton pregnancies can expect to gain 25-35 lbs (approximately 11-16 kilograms), more or less, depending on their prepregnancy weight.
    • Be aware that acute excess weight gain can indicate fluid retention, and that low weight gain is associated with fetal growth restrictions.
  • During pregnancy, hormones shift metabolism to favor insulin resistance: pregnancy is characterized by fasting hypoglycemia, postprandial hyperglycemia, and hyperinsulinemia.
  • Gestational Diabetes:
    • 6-8% of pregnant people in the U.S. develop gestational diabetes.
    • In the mother, elevated high blood glucose increases the risk of preeclampsia.
    • In the fetus, excess glucose availability can lead to macrosomia (larger than average fetal size), and, because fetal insulin levels are elevated, hypoglycemia can occur after birth.
GI Changes
  • Nausea and vomiting, so-called "morning sickness," is common (and not limited to the morning hours).
    • In most cases, nausea and vomiting begins as early as 4 weeks gestational age, and ends after the first trimester.
    • Patients are advised to eat smaller, more frequent meals, and to avoid foods that slow gastric emptying (such as high fat, high protein foods); beware of safety concerns with some antiemetics.
    • Gastric reflux and epigastric pain are also common, and patients are advised to eat frequent small meals to aid digestion.
    • Over-the-counter anti-gastric reflux medicines that do not contain salicylates are recommended; if severe or refractory, proton-pump inhibitors may be useful.
  • Pegnancy is associated with changes in bowel movements; constipation is common due to progesterone's relaxation effects on smooth muscle.
Renal Changes
  • Glomerular filtration rate and renal plasma flow are increased
    • Urine frequency and urgency is increased - as we show in our diagram, this typically worsens as the fetus grows and puts pressure on the urinary bladder.
    • Sodium retention, which contributes to edema.
Dermatological Changes
  • Dermatological changes are also common in pregnancy.
  • Increased placental production of melanocyte-stimulating hormone (MSH) increases skin pigmentation.
    • This can lead to, for example, the "mask of pregnancy," a darkening of facial skin, and linea nigra, which is a darkened line down the mid-abdomen. Darkening of the areolas, axilla, and genitals is also common. These changes typically regress within a year after the pregnancy ends.
Summary of Signs and Symptoms of Pregnancy
This is not an exhaustive list, and there is variation in the presence and/or timing of the following phenomena.
  • In the first trimester, weeks 1-12, patients often experience:
    • Nausea/vomiting
    • Cravings for some foods, accompanied by strong distaste for other foods, and often disgust toward strong smells
    • Constipation
    • Increased urinary frequency
    • Increased heart and breathing rates
    • Heart burn
    • Weight changes (some patients actually lose weight in the first trimester)
    • Breast tenderness and nipple changes
    • Mood swings
    • Fatigue
  • In the second trimester, weeks 13-28, the following typically begin:
    • Sensations of fetal movements
    • Body aches
    • Skin darkening
    • Swelling in the extremities
    • Significant breast and belly growth
    • Braxton-Hicks contractions
  • In the third trimester, weeks 29-40, note the following:
    • Stronger fetal kicking
    • More pronounced dyspnea
    • Difficulty sleeping
    • Colostrum leaks
  • Postpartum period is associated with:
    • Lochia (vaginal discharge postbirth)
    • Fatigue
    • Breast tenderness and leaking
    • Risk of postpartum depression
References
  • Bernstein, Helene B. "Normal Pregnancy & Prenatal Care." In CURRENT Diagnosis & Treatment: Obstetrics & Gynecology, edited by Alan H. DeCherney, Lauren Nathan, Neri Laufer, and Ashley S. Roman, 12th ed. New York, NY: McGraw-Hill Education, 2019. accessmedicine.mhmedical.com/content.aspx?aid=1159952371.
CDC. "CDC Newsroom," January 1, 2016. https://www.cdc.gov/media/releases/2022/p0919-pregnancy-related-deaths.html.
  • "Endocrinology of Pregnancy - ClinicalKey." Accessed December 19, 2022. https://www-clinicalkey-com.proxy.ulib.uits.iu.edu/#!/content/book/3-s2.0-B9780323479103000103.
  • Gregory, David S, Velyn Wu, and Preyasha Tuladhar. "The Pregnant Patient:Managing Common Acute Medical Problems" 98, no. 9 (2018): 9.
  • Gupta, Keshav Kumar, and Shahram Anari. "Medical Management of Rhinitis in Pregnancy." Auris Nasus Larynx 49, no. 6 (December 1, 2022): 905–11. https://doi.org/10.1016/j.anl.2022.01.014.
  • Kazma, Jamil M., John van den Anker, Karel Allegaert, André Dallmann, and Homa K. Ahmadzia. "Anatomical and Physiological Alterations of Pregnancy." Journal of Pharmacokinetics and Pharmacodynamics 47, no. 4 (August 2020): 271–85. https://doi.org/10.1007/s10928-020-09677-1.
  • Lawson, Gerald Wightman. "Naegele's Rule and the Length of Pregnancy – A Review." Australian and New Zealand Journal of Obstetrics and Gynaecology 61, no. 2 (2021): 177–82. https://doi.org/10.1111/ajo.13253.
  • LoMauro, Antonella, and Andrea Aliverti. "Respiratory Physiology of Pregnancy." Breathe 11, no. 4 (December 2015): 297–301. https://doi.org/10.1183/20734735.008615.
  • "Maternal Adaptations to Pregnancy: Cardiovascular and Hemodynamic Changes - UpToDate." Accessed December 19, 2022.
  • "Maternal Adaptations to Pregnancy: Dyspnea and Other Physiologic Respiratory Changes - UpToDate." Accessed December 21, 2022.
  • "Maternal Mortality." Accessed December 6, 2022. https://www.who.int/news-room/fact-sheets/detail/maternal-mortality.
  • "Maternal Mortality Rates and Statistics - UNICEF DATA." Accessed December 6, 2022. https://data.unicef.org/topic/maternal-health/maternal-mortality/.
  • "Maternal Mortality Rates in the United States, 2020," November 7, 2022. https://www.cdc.gov/nchs/data/hestat/maternal-mortality/2020/maternal-mortality-rates-2020.htm.
  • "Maternal Physiology - ClinicalKey." Accessed December 7, 2022. https://www-clinicalkey-com.proxy.ulib.uits.iu.edu/#!/content/book/3-s2.0-B9780323608701000034.
  • Merck Manuals Professional Edition. "Evaluation of the Obstetric Patient - Gynecology and Obstetrics." Accessed December 6, 2022. https://www.merckmanuals.com/professional/gynecology-and-obstetrics/approach-to-the-pregnant-woman-and-prenatal-care/evaluation-of-the-obstetric-patient.
  • Merck Manuals Professional Edition. "Gynecology and Obstetrics." Accessed December 6, 2022. https://www.merckmanuals.com/professional/gynecology-and-obstetrics.
  • Merck Manuals Professional Edition. "Hyperemesis Gravidarum - Gynecology and Obstetrics." Accessed December 6, 2022. https://www.merckmanuals.com/professional/gynecology-and-obstetrics/abnormalities-of-pregnancy/hyperemesis-gravidarum.
  • Mulder, Eg, S de Haas, Z Mohseni, N Schartmann, F Abo Hasson, F Alsadah, Smj van Kuijk, J van Drongelen, Mea Spaanderman, and C Ghossein-Doha. "Cardiac Output and Peripheral Vascular Resistance during Normotensive and Hypertensive Pregnancy – a Systematic Review and Meta-Analysis." BJOG: An International Journal of Obstetrics & Gynaecology 129, no. 5 (2022): 696–707. https://doi.org/10.1111/1471-0528.16678.
  • "Naegele's Rule and the Length of Pregnancy - A Review - PubMed." Accessed December 7, 2022. https://pubmed.ncbi.nlm.nih.gov/33079400/.
  • "OECD Health Statistics 2022 - OECD." Accessed December 6, 2022. https://www.oecd.org/health/health-data.htm.
Pascual, Zoey N., and Michelle D. Langaker. Physiology, Pregnancy. StatPearls [Internet]. StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK559304/.
  • "Physiological Changes in Pregnancy - ClinicalKey." Accessed December 7, 2022. https://www-clinicalkey-com.proxy.ulib.uits.iu.edu/#!/content/book/3-s2.0-B9780702076381000037.
  • Sperling, Rhoda. Obstetrics and Gynecology. Newark, UNITED KINGDOM: John Wiley & Sons, Incorporated, 2020. http://ebookcentral.proquest.com/lib/iupui-ebooks/detail.action?docID=6261125.
  • Taranikanti, Madhuri. "Physiological Changes in Cardiovascular System during Normal Pregnancy: A Review." Indian Journal of Cardiovascular Disease in Women WINCARS 03, no. 02/03 (August 2018): 062–067. https://doi.org/10.1055/s-0038-1676666.
  • Troiano, Nan H., Patricia Witcher, and Suzanne Baird. AWHONN's High-Risk and Critical Care Obstetrics: Medical-Surgical Nursing. Philadelphia, UNITED STATES: Wolters Kluwer, 2018. http://ebookcentral.proquest.com/lib/iupui-ebooks/detail.action?docID=5829233.