Pregnancy

Pregnancy begins with the fertilization of the ovum and its subsequent implantation into the uterine wall. The duration of pregnancy is counted in weeks of gestation from the first day of the last menstrual period and on average lasts 40 weeks. Presumptive signs of pregnancy include amenorrhea, nausea and vomiting, and breast enlargement and tenderness. Preconception counseling assists in the planning of pregnancy through education and risk assessment to help ensure best possible outcomes. Pregnancy can be confirmed definitively via positive serum or urine hCG tests and detection of the embryo on ultrasound. Ultrasound is also used to determine the gestational age and date of delivery. Women experience several physiological changes during pregnancy (e.g., increased plasma volume, venous stasis, increased insulin secretion, increased oxygen demand), which can lead to symptoms and conditions that may require treatment (e.g., peripheral edema, insulin resistance, hypercoagulability, dyspnea). Regular check-ups should be performed to detect potential high-risk pregnancies as well as fetal and maternal complications.

See also “Prenatal care” and “Maternal complications during pregnancy.”

Gravidity, parity, and duration of pregnancy ^[1]

• Gravidity: the number of times a woman has been pregnant, regardless of pregnancy outcome
  • Nulligravidity: no history of pregnancy
  • Primigravidity: history of one pregnancy
  • Multigravidity: history of two or more pregnancies
• Parity: the number of pregnancies that a woman carries beyond 20 weeks of gestation and ends with the birth of an infant weighing > 500 g
  • Nulliparity: no history of a completed pregnancy that reached beyond 20 weeks' gestation or ended with a birth weight of > 500 g
  • Primiparity: a history of one completed pregnancy that reached beyond 20 weeks' gestation or ended with a birth weight of > 500 g
  • Multiparity: a history of more than one pregnancy that reached beyond 20 weeks' gestation or ended with a birth weight of > 500 g
• Fetal age ^[2]
  • Counted as completed weeks of gestation and completed days (0–6) of the current week of pregnancy
  • Gestational age: estimated fetal age (in weeks and days) calculated from the first day of the last menstrual period
  • Conceptional age: the age (in weeks and days) of the fetus calculated from the day of conception (fertilization)
• Duration of pregnancy
  • Normal duration of pregnancy: 40 weeks (280 days)
  • Postterm pregnancy: a pregnancy that extends beyond 42 weeks' gestation or the estimated date of delivery plus 14 days
  • Periviable birth: live birth occurring between 20–25 weeks of pregnancy
  • Preterm birth: live birth before the completion of 37 weeks (< 37 0/7) of pregnancy
  • Postterm birth: live birth after 42 weeks (> 42 0/7) of pregnancy
• Trimesters of pregnancy
  • First trimester (weeks 1–13)
  • Second trimester (weeks 14–26)
  • Third trimester (weeks 27–40)

Recording systems

General principles

• Fertile women of reproductive age should be asked about their intention to become pregnant by their healthcare provider (all those planning to become pregnant should receive counseling).
• Preconception counseling aims to:
  • Identify and address any modifiable factors that may negatively affect pregnancy and childbirth.
  • Educate women and men about options for risk reduction and elimination.

Patient medical history

• Medical conditions: review history and identify chronic medical conditions that may affect pregnancy (e.g., hypothyroidism, diabetes mellitus, chronic hypertension)
  • Hypothyroidism
    • Screen women with a desire to conceive with risk factors for thyroid disease (e.g., age > 30 years, obesity, history of head or neck radiation). ^[3]
    • Treat women with a desire to conceive with elevated TSH with L-thyroxine until TSH levels are normal.
  • Diabetes mellitus
    • Educate affected women about the importance of maintaining normal glycemic levels before and during pregnancy.
    • Assess for complications of diabetes (e.g., retinopathy, nephropathy).
    • Aim for an HbA1c < 6.5%. ^[4]
  • Hypertension
    • Assess for retinopathy, renal disease, and ventricular hypertrophy.
    • Avoid using ACE inhibitors and angiotensin receptor blockers, as they are teratogenic.
• Family history of inherited conditions: assess family history of genetic conditions and cancer (e.g., breast cancer, endometrial cancer, colon cancer) and refer couples with a positive history for counseling.
• Communicable diseases
  • HIV-infection
    • Screen all women for HIV.
    • Initiate antiretroviral therapy in all women with HIV.
    • Counsel women with HIV regarding the risk of vertical transmission.
  • Other infections: STIs, tuberculosis (screen women at high risk and manage as appropriate)
• Medications
  • Review current medications, including alternative medicine preparations (e.g., herbal medicine, naturopathy) and nutritional supplements.
  • Discontinue teratogenic drugs and switch to safer medications, if possible.
  • Adjust the regimen of necessary medications and consider using the lowest dose possible for potentially harmful agents.
• Immunizations and pregnancy
  • Before pregnancy
    • Measles, mumps, rubella (MMR vaccine), and varicella vaccine
      • Screen all women for immunity with antibody titers.
      • Nonimmune women should receive vaccination.
      • Counsel to avoid conceiving for 28 days after the last vaccine dose.
  • During pregnancy
    • Influenza: Women who wish to conceive should receive the annual inactivated influenza vaccine.
    • Tetanus, diphtheria, and pertussis (Tdap vaccine): Women who wish to conceive should receive the Tdap vaccine according to the guidelines.
    • Hepatitis B vaccine: Vaccinate women with high risk for hepatitis B.
• Mental disorders
  • Review history of psychiatric disorders.
  • Inform about the risks of medication during pregnancy.
  • Screen women with no history of mental health conditions for anxiety and depression.

The administration of MMR vaccine, varicella vaccine, and zoster vaccine is contraindicated during pregnancy.

Lifestyle modifications

• Recommend maintaining a normal body weight prior to conception.
• Encourage regular moderate-intensity exercise.
• Nutrition
  • Screen for sufficient intake of macronutrients and micronutrients (calcium, iron, vitamin B12, vitamin B, vitamin D).
  • Ensure vitamin A is not taken in excess
  • Recommend intake of 0.4 mg of folic acid daily, ideally 4 weeks prior to conception, and continue for at least the first 2–3 months of pregnancy.
• Substance use
  • Screen all women for alcohol, tobacco, and recreational drug use.
  • Educate about associated adverse effects of substance use on maternal and fetal pregnancy outcomes.
  • Provide assistance and/or refer to the proper specialists for tobacco, alcohol, and recreational drug use cessation.

Management of exposures ^[5][6]

• Exposure to harmful agents
  • Advise patients to assess workplace and household for potentially harmful agents (e.g., heavy metals, solvents, chemicals).
  • Educate the patient about the avoidance of harmful agents and refer them to occupational medicine programs as needed.
• Exposure to violence
  • Screen for family violence at each visit.
  • If ongoing abuse is identified, providers should:
    • Provide community resources to the patient
    • Report the case as appropriate

• Presumptive signs
  • Amenorrhea
  • Nausea and vomiting
  • Breast enlargement and tenderness
  • Linea nigra: darkening of the midline skin of the abdomen
  • Hyperpigmentation of the areola
  • Abdominal bloating and constipation
  • Increased weight gain
  • Cravings for or aversions to certain foods
  • Increased urinary frequency
  • Fatigue

Human chorionic gonadotropin (hCG)

• Site of production: placental syncytiotrophoblast
• Structure
  • α-subunit: common to hCG, FSH, LH, and TSH
  • β-subunit: specific to the placenta (pregnancy tests measure the β-hCG levels)
• Function
  • Maintenance of the corpus luteum during the first 8–10 weeks of pregnancy (LH has a similar function)
  • Luteal-placental shift: levels decrease after corpus luteum involution (placenta starts synthesizing its own estriol and progesterone)
• Pregnancy test: measurement of human chorionic gonadotropin (β-hCG)
  • Urine β-hCG test (e.g., home pregnancy test)
    • Qualitative test (less sensitive than serum pregnancy test)
    • β-hCG can be detected in urine 14 days after fertilization
  • Serum β-hCG test
    • Quantitative test (high sensitivity)
    • Detectable 6–9 days (on average) after fertilization

Ultrasound findings in normal pregnancy (abdominal or transvaginal) ^[10]

• Confirms pregnancy
• At 5 weeks of pregnancy: detection of the gestational sac (corresponds with a serum β-HCG level of 1500–2000 mIU/mL)
• At 5–6 weeks of pregnancy: detection of the yolk sac
• At 6–7 weeks of pregnancy: detection of the fetal pole and cardiac activity with transvaginal ultrasound
• At 10–12 weeks of pregnancy: detection of fetal heartbeat with doppler ultrasound
• At 18–20 weeks of pregnancy: fetal movements
• See POCUS for early pregnancy for more details.

Gestational age and estimated date of delivery

• Naegele rule: used to calculate the expected date of delivery (due date)
  • First day of the last menstrual period + 7 days + 1 year - 3 months
  • Inaccurate if:
    • The date of the last menstrual period is uncertain or unknown
    • The patient has irregular menstruation cycles
    • The patient conceived while taking contraceptive pills
• Ultrasonography
  • More accurate than Naegele rule
  • Measurement of the crown-rump length (CRL) in the first trimester
  • Measurement of biparietal diameter , fetal femoral length , and abdominal circumference in the second and third trimesters (can be used for determining gestational age starting at 13 weeks) ; ; ; ; ^[11]
• Symphysis fundal height: the length from the top of the uterus to the top of the pubic symphysis
  • Used to assess fetal growth and development from approx. 20 weeks' gestation onwards
  • Development is approx. 1 cm/week after 20 weeks
  • Correlates with gestational age

Cardiovascular system ^[12][13]

• ↑ Progesterone → ↓ vascular tone → ↓ peripheral vascular resistance (↓ afterload)
  • ↑ Cardiac output by up to 40% (↑ preload)
  • ↑ Stroke volume (by 10–30%)
  • ↑ Heart rate (by ∼ 12–18 bpm) → ↑ uterine perfusion
  • ↓ Mean arterial pressure
• Innocent systolic murmur
• The apex beat is displaced upward.
• ↑ Plasma volume → ↓ oncotic pressure → edema of lower limbs
• Varicosities
• Aggravation of preexisting valvular diseases

A physiological systolic murmur may be heard due to increased cardiac output and increased plasma volume.

Respiratory system ^[14]

• ↑ Oxygen consumption (by approx. 20%)
• ↑ Intraabdominal pressure through uterine growth → dyspnea (the diaphragm is displaced upwards → ↓ total lung capacity, residual volume, functional residual capacity, and expiratory reserve volume)
• Progesterone stimulates the respiratory centers in the brain → hyperventilation (to eliminate fetal CO₂ more efficiently) → physiological, chronic compensated respiratory alkalosis
  • ↑ Tidal volume → ↑ minute ventilation
  • ↓ PCO₂ (∼ 30 mm Hg)

Renal system ^[13][15]

• ↑ Renal plasma flow → ↑ GFR → ↓ BUN and creatinine
• ↑ Aldosterone → ↑ plasma volume and hypernatremia
• ↑ Progesterone and intraabdominal pressure → dilation of kidney, pelvis, and calyceal systems → reduced tone and peristalsis
  • Hydronephrosis and hydroureter
  • Urinary stasis → pyelonephritis
  • ↑ Urinary frequency
• ↑ Glucose levels in urine: Increased glomerular filtration results in overload of the glucose carrier responsible for its resorption.
• Mild proteinuria: Increased GFR and glomerular permeability to albumin increases protein excretion.

Endocrine system ^[13][16][17]

• Progesterone
  • Responsible for pregnancy maintenance
  • Produced by the corpus luteum until the 10–12 weeks of gestation, after which it is produced by the fetoplacental unit
• Human placental lactogen: a hormone synthesized by syncytiotrophoblasts of the placenta, which promotes the production of insulin-like growth factors.
  • Increases insulin levels
  • Causes insulin resistance
  • Increases serum glucose levels and lipolysis to ensure sufficient glucose supply for the fetus
  • Maternal insulin resistance begins in the second trimester and peaks in the third trimester.
• Thyroid hormones
  • ↑ hCG → ↓ TSH levels during the first part of the first trimester
  • ↑ TBG → ↑ T₄ and T₃ → slightly increased free T₄ and T₃ levels during first trimester
  • Free T4 and T3 levels decrease during the second and third trimesters
• ↑ SHBG and corticosteroid-binding globulin
• ↑ Triglycerides and cholesterol (due to increased lipolysis and fat utilization)
• Hyperplasia of lactotroph cells in the anterior pituitary → physiological enlargement of the pituitary gland (up to 40% increase from pregestational volume)

Hematologic system ^[13][18][19]

• ↑ Plasma volume → ↓ hematocrit, especially towards the end of pregnancy (30–34^th week of gestation) → dilutional anemia (hemoglobin value rarely drops below 11 g/dL)
• ↑ RBC mass (increases from 8–10^th week of gestation until the end of pregnancy)
• ↓ Platelet count ^[20]
• ↑ WBC count
• ↓ Albumin
• Hypercoagulability is due to an increase in fibrinogen, factor VII, and factor VIII and a decrease in protein S; (reduces the risk of intrapartum blood loss).
• ↑ Alkaline phosphatase (placental isoenzymes)
• ↓ Iron and folate levels due to increased vitamin and mineral requirements

Physiological hypercoagulability during pregnancy leads to an increased risk of thrombosis. Patients with thrombophilia should receive adequate thrombosis prophylaxis.

Gastrointestinal system ^[13]

• ↑ Salivation
• ↓ Lower esophageal sphincter tone → gastroesophageal reflux
• ↓ Motility → constipation
• Gallbladder stasis → gallstones
• Hemorrhoids

Musculoskeletal system ^[13]

Pelvic girdle pain ^[21]

• Etiology: increased pressure from the uterus, lumbar lordosis, and relaxation of the ligaments supporting the joints of the pelvic girdle
• Clinical features: lower back pain
  • Particularly between the posterior iliac crest and the gluteal fold and in the area of the sacroiliac joint
  • May radiate to the thighs and hips
  • Worsens with weight-bearing
• Diagnosis: positive pelvic pain provocation tests (e.g., posterior pelvic pain provocation test, FABER test, active straight leg raise)
• Management
  • Nonpharmacological: heat therapy, manual therapy (e.g., massage, spinal manipulation), braces, physical therapy
  • Pharmacological: acetaminophen

Round ligament pain

• Etiology: stretching of the round ligament of the uterus as the uterus expands
• Epidemiology: one of the most common conditions during pregnancy
• Clinical features
  • Typically manifests in the second and third trimester
  • Sharp pain in the lower abdomen and groin area (most often right-sided)
  • Triggered by sudden and/or rapid movements (e.g., rolling over in bed, sneezing, vigorous physical activity)
• Diagnosis: based on clinical history
• Management: usually no treatment required; resolves after delivery

Skin

• Spider angioma
• Palmar erythema
• Striae gravidarum: scarring that manifests as erythematous, violaceous, and/or hypopigmented linear striations on the abdomen
• Hyperpigmentation: chloasma, linea nigra, hyperpigmentation of the nipples

Reproductive system

• Uterus: increase in size
• Vulva and vagina
  • Vaginal discharge
  • Formation of varicose veins
• Mammary glands increase in size

Basic principles

• Nutritional intake: must be adapted to meet the demands of both the mother and the fetus
• Dietary recommendations
  • Limit caffeine intake: daily recommended dose < 200 mg (this equals about 1–2 cups of coffee or 2–4 cups of caffeinated tea)
  • Avoid alcohol and tobacco use throughout pregnancy. ^[22]
  • Avoid unwashed or uncooked foods.
    • Fish (contamination with parasites and bacteria)
    • Milk products: high risk of congenital listeriosis
    • Meat: high risk of congenital toxoplasmosis
  • Avoid fish with possibly high levels of methylmercury, esp. tilefish, swordfish, shark, mackerel, and tuna.

Recommended weight-gain during pregnancy ^[33]

• Recommended weight-gain is determined by BMI prior to pregnancy
  • BMI < 18.5 (underweight): 28–40 lb (12–18 kg)
  • BMI 18.5–24.9 (normal weight): 25–35 lb (11–16 kg)
  • BMI 25–29.9 (overweight): 15–25 lb (7–11 kg)
  • BMI ≥ 30 (obese): 11–20 lb (5–9 kg)
• Average recommended daily calorie intake
  • First trimester: 2,200 kcal
  • Second and third trimester: 2,500 kcal
• Regular physical activity is recommended (see below).

• Regular physical activity (e.g., aerobic and strength-training exercise) is considered beneficial and is recommended before, during, and after pregnancy.
  • Careful evaluation of medical and obstetric disorders is necessary before recommending regular physical activity.
  • Contraindications to aerobic exercise
    • Severe anemia
    • Restrictive lung disease
    • Hemodynamically significant heart disease
    • Cervical insufficiency
    • Premature rupture of membranes
    • Gestational hypertension and preeclampsia
  • Exercise routines that are considered unsafe during pregnancy should be avoided or modified accordingly.

Physical activity should be discontinued in the event of the following: antepartum or postpartum hemorrhage, uterine contractions, amniotic fluid leakage, chest pain, dyspnea before exertion, dizziness, headaches, calf pain/swelling, and/or muscle weakness with impaired balance.

Early identification of high-risk pregnancies is vital in order to prevent the occurrence of maternal and fetal complications. They require regular prenatal care to monitor and support the pregnant mother (see “Prenatal care”).

Risk factors for a complicated pregnancy ^[35][36]

• Family history (medical and obstetric) of complicated pregnancies
• Personal history
  • Advanced maternal age (> 35 years)
  • First pregnancy
  • Multiple pregnancies
  • Multiparity (> 5 births)
  • Medical conditions (e.g., antiphospholipid syndrome, hypertension, diabetes mellitus, epilepsy, malignancies)
  • Social and environmental factors (e.g., drug use, stress)
  • Preexisting gynecological conditions (e.g., uterine leiomyoma, history of uterine surgery)
  • Prior complicated pregnancies
    • Premature delivery (< 38 weeks), baby with low birth weight, or a baby born with congenital defects
    • Prior cesarean delivery
    • Rhesus incompatibility
    • History of > 2 abortions or placental abruption
    • Use of assisted reproductive technologies: in vitro fertilization, ICSI
  • Complications that arise during pregnancy: See “Maternal complications during pregnancy” and section below.

Oligohydramnios ^[37]

• Definition: amount of amniotic fluid is less than expected for gestational age
• Etiology
  • Fetal anomalies
    • Urethral obstruction (e.g., posterior urethral valves)
    • Bilateral renal agenesis
    • Autosomal recessive polycystic kidney disease (ARPKD)
    • Chromosomal aberrations (e.g., trisomy 18)
    • Intrauterine infections (e.g., congenital TORCH infections)
    • In multiple pregnancies: twin-to-twin transfusion syndrome
  • Maternal conditions
    • Placental insufficiency
    • Late or postterm pregnancies (> 42 weeks of gestation)
    • Premature rupture of membranes
    • Preeclampsia
  • Idiopathic
• Diagnosis ^[38]
  • Small abdominal girth and uterine size for gestational age
  • Ultrasound: determine amniotic fluid and assess for fetal anomalies
  • Amniotic fluid index (AFI): a semiquantitative tool used to assess amniotic fluid volume (normal range: 8–18 cm)
    • Determined by dividing the uterus into 4 quadrants, holding the transducer perpendicular to the patient's spine, and adding up the deepest vertical pocket of fluid in each quadrant.
    • Oligohydramnios: ≤ 5
    • In pregnancies < 24 weeks and multiple gestations, the single deepest pocket is used (normal range: 2–8 cm).
• Treatment
  • Amnioinfusion: infusion of fluid into the amniotic cavity through amniocentesis
  • Treat underlying cause: See “Preeclampsia,” “Premature rupture of membranes,” and “Placental insufficiency.”
  • Delivery is advised if the fetus is close to term.
• Complications
  • Intrauterine growth restriction (due to diminished mobility of the fetus)
  • Birth complications (e.g., umbilical cord compression)
  • Potter sequence
    • Etiology
      • Chronic placental insufficiency
      • ↓ Renal output (e.g., due to bilateral renal agenesis, ARPKD, obstruction of posterior urethral valves)
      • Chronic amniotic fluid leakage
    • Pathophysiology: oligohydramnios → intrauterine compression and decreased amniotic fluid ingestions → ↓ space for fetal development → internal and external deformations
    • Clinical features
      • Pulmonary hypoplasia (cause of death due to severe neonatal respiratory insufficiency)
      • Craniofacial abnormalities (e.g., prominent epicanthal and infraorbital folds, flattened nose, receding chin, low set ears)
      • Wrinkling of the skin
      • Limb anomalies (e.g., bowed legs, clubbed feet)

Potter babies cannot Pee.

POTTER sequence: Pulmonary hypoplasia (lethal), Oligohydramnios (origin), Twisted facies, Twisted skin, Extremity deformities, and Renal agenesis (classic form).

Polyhydramnios ^[39]

• Definition: excessive amniotic fluid volume expected for gestational age that results in uterine distention.
• Etiology
  • Typically idiopathic (∼ 70% of cases) ^[40]
  • Fetal anomalies
    • Gastrointestinal (e.g., esophageal atresia, duodenal atresia and stenosis): reduced swallowing and absorption of amniotic fluid
    • CNS: anencephaly; (leads to impaired swallowing of amniotic fluid, leakage of cerebrospinal fluid, and increased urination due to lack of fetal ADH), meningomyelocele (due to leakage of cerebrospinal fluid) ^[41]
    • Pulmonary: cystic lung malformations
    • Multiple pregnancy: twin-to-twin transfusion syndrome
    • Fetal anemia ^[42]
    • Chromosomal aberrations
    • Intrauterine infections (e.g., congenital TORCH infections)
  • Maternal conditions
    • Diabetes mellitus
    • Rh incompatibility (e.g., hemolytic disease of the newborn)
• Diagnostics
  • Physical examination: abdominal girth and uterine size large for gestational age
  • Ultrasound
    • AFI ≥ 25
    • Assess for fetal anomalies
  • Others
    • Rh screen
    • Blood glucose
• Treatment
  • Amnioreduction: drainage of excess amniotic fluid
  • Treat the underlying cause (e.g., glycemic control in diabetic mothers, intrauterine exchange transfusion in hemolytic disease of the newborn)
• Complications
  • Fetal malposition
  • Umbilical cord prolapse
  • Premature birth
  • Premature rupture of membranes
  • Premature uterine contractions

Other complications

• Hemolytic disease of the fetus and newborn
• Intrauterine growth restriction
• Teratogenic birth defects

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