• Clinical science

Pregnancy

Abstract

Pregnancy begins with the fertilization of the ovum and 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. 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 benign, physiological changes during pregnancy (e.g., peripheral edema, dyspnea, increased urinary frequency). Regular check-ups should be performed to detect possible high-risk pregnancies as well as fetal and maternal complications.

Definition

  • Gravidity: the number of times a woman has been pregnant
  • Parity: the number of times a woman has given birth

Duration of pregnancy

  • The duration of pregnancy is counted in weeks of gestation from the first day of the last menstrual period
  • Normal duration of pregnancy: 40 weeks (280 days)
  • Preterm birth: live birth before the completion of 37 weeks (< 37 0/7) of pregnancy
  • Post-term birth: live birth after 42 weeks (> 42 0/7) of pregnancy

References:[1]

Stages of pregnancy

Pregnancy is divided into trimesters:

  • First trimester (week 1–13): highest risk of miscarriage
  • Second trimester (week 14–26)
  • Third trimester (week 27–40)
Day/week Stage Possible disorders
Day 0
  • Capacitation: maturation of the sperm in the female genital tract
  • Fertilization (conception): usually occurs in the upper end of the fallopian tubes (within 1 day of ovulation)
    • Consists of 2 phases: the acrosome reaction (dissolution of the spermatic cell membrane and the zona pellucida of the ovum) and impregnation (penetration of the sperm into the ovum)
  • Conjugation: fusion of the sperm and ovum to form the zygote (single cell)
Day 1–5
  • The zygote travels down the fallopian tube towards the uterus
  • Division of the zygote into the morula (16-cell mass) and then the blastocyst
  • The blastocyst consists of 2 cell layers: the outer trophoblasts and the inner embryoblasts.
Day 6
  • Implantation of the blastocyst (most commonly into the anterior or posterior wall of the uterus )
  • This may result in brief implantation bleeding.
Days 6–12
Week 3
  • Embryopathies: complex anomalies of individual organs
  • Particularly susceptible to teratogens
    • Infections
    • Drug toxicity
Weeks 3–8
  • Embryogenesis
  • Organogenesis: organ formation (chronological order)
    • CNS: The neural tube closes by week 4.
    • Heart: The heart begins to beat by week 4.
    • Ears and eyes
    • Upper and lower extremities
    • Teeth and gums
    • External genitalia (male/female characteristics)
From week 9
  • Fetogenesis: the fetus matures and grows.

The earlier disruptions take place during fetal development, the more complicated the resulting congenital anomalies!

References:[2][3]

Clinical signs of early pregnancy

  • Amenorrhoea
  • Nausea and vomiting
  • Breast enlargement and tenderness
  • Hyperpigmentation of the areola and formation of linea nigra
  • Increased urinary frequency
  • Fatigue
  • Cravings for or aversions to certain foods
  • Abdominal bloating and constipation
  • Livid discoloration of the vaginal introitus

References:[4][5]

Diagnosis of pregnancy

Confirmation of pregnancy

Transvaginal ultrasound findings
in normal pregnancy

Weeks after last menstruation β-hCG mlU/mL
Gestational sac 5 1500–2000
Yolk sac 6 2500
Fetal pole 7 5000
Fetal heartbeat 8 17000
  • Differential diagnosis: false pregnancy (pseudocyesis) → rare psychiatric condition with somatic symptoms
    • Women present with classic signs of pregnancy despite it being ruled out with ultrasound and a negative pregnancy test.

Determining the gestational age and date of delivery

The gestational age and date of delivery may be estimated using Naegele's rule or determined more accurately via ultrasound in the second and third trimester.

  • Gestational age: the age (in weeks and days) of the fetus calculated from the first day of the last menstrual period
  • Embryonic age: the age (in weeks and days) of the fetus calculated from the day of conception (fertilization)
  • Naegele's rule: used to calculate the 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.
  • Advanced Naegele's rule: first day of the last menstrual period + 7 days - 3 months + 1 year +/- variation of the regular 28 day menstrual cycle
  • Ultrasound: more accurate than Naegele's rule
    • Measurement of the crown-rump length (CRL) in the first trimester
    • Measurement of biparietal diameter, femur length, and abdominal circumference (starting at 14 weeks)
  • Fundal height during pregnancy: correlates with the gestational age

References:[1][6][4][7][8]

Physiological changes during pregnancy

Numerous physiological changes occur during pregnancy in order to support fetal growth and prepare for delivery.

Organ system Changes
Cardiovascular
  • Progesterone↓ vascular tone↓ peripheral vascular resistance
    • ↑ Cardiac output (by up to 40%)
    • Stroke volume (by ∼ 10–30%)
    • Heart rate (by ∼ 12–18 bpm)
    • ↓ Mean arterial pressure
  • Innocent systolic murmur
  • The apex beat is displaced upward.
  • Varicosity and edema of lower limbs
Respiratory
Renal
Endocrine
Hematologic
  • Hematocrit particularly towards the end of pregnancy (30–34th week of gestation); dilutional anemia ; minimal value is 11 g/dL)
  • RBC count (increases from 8–10th week of gestation until the end of pregnancy by approx. 15–30%)
  • Platelet count
  • WBC count
  • Albumin
  • Fibrinogen and factor VII, VIII, decreased protein S → reduced prothrombin and partial thromboplastin times
  • ↑ Alkaline phosphatase (placental isoenzyme)
Gastrointestinal
Musculoskeletal
  • Increased lumbar lordosis; relaxation of the ligaments supporting the joints of the pelvic girdle in preparation for childbirth → can cause lower back pain
Skin
  • Spider angioma
  • Palmar erythema
  • Striae gravidarum
  • Hyperpigmentation: chloasma, linea nigra, hyperpigmentation of the nipples
Mammary glands
  • ↑ Size
Uterus
  • ↑ Size
Vulva and vagina

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

Physiological hypercoagulability during pregnancy leads to an increased risk of thrombosis! Patients suffering from thrombophilia should receive adequate thrombosis prophylaxis!

References:[9][10]

Nutrition during pregnancy

Basic principles

  • Nutritional intake needs to be adapted to meet both the demands of the mother and the fetus.
  • Dietary recommendations:
    • Limit caffeine intake: daily recommended dose < 200 mg
    • Avoid alcohol and tobacco use throughout pregnancy
    • Avoid unwashed or uncooked foods
  • Supplementation of vitamins and minerals is recommended.
Supplementation Reason for increased demand Consequences of deficiency
Folic acid
  • Folic acid 0.4–0.8 mg/day: Ideally, women should begin intake 4 weeks prior to pregnancy and continue with this dose for at least the first 2–3 months of pregnancy.
Vitamin B12
  • Recommended for pregnant women who adhere to a vegan diet
Iron
  • 30–60 mg/day
  • 120–240 mg/day for pregnant women with insufficient or no iron stores
Calcium
  • 1000–1300 mg/day (50% increase)
  • Increased fetal demand
  • Lactation
Iodine
  • 250 μg/day
  • Increased metabolism and excretion

Recommended weight gain during pregnancy

  • The recommendations are determined by the BMI prior to the pregnancy:
    • BMI < 18.5 (underweight): 28–40 lb
    • BMI 18.5–24.9 (normal weight): 25–35 lb
    • BMI 25–29.9 (overweight): 15–25 lb
    • BMI ≥ 30 (obese): 11–20 lb
  • Average recommended daily calorie intake:
    • Non-pregnant woman: 2000–2100 kcal
    • First trimester: 2200 kcal
    • Second and third trimester: 2500 kcal
  • Regular physical activity is recommended (contact sport should be avoided).

References:[11][12][13][14][15]

Physical activity during pregnancy

  • Regular physical activity (i.e., 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 any exercise program.
  • Modifying normal exercise routines may be necessary; activities considered unsafe should be avoided.
Safe and unsafe activities during pregnancy
Safe activities*
  • Walking
  • Running or jogging***
  • Swimming
  • Stationary cycling
  • Pilates
  • Yoga**
  • Racquet sports***
  • Strength training***
Unsafe activities
  • Contact sports (e.g., soccer, basketball)
  • Activities associated with a high risk of falling (e.g., snow skiing, water skiing, gymnastics, surfing)
  • Hot yoga
  • Hot Pilates
  • Skydiving
  • Scuba diving

* In pregnancies without complications as determined by an obstetrician

** Avoid positions associated with ↓ venous return

*** May be considered safe in women who took part in these exercises before the pregnancy and as determined by an obstetrician

Physical activity should be discontinued if the patient presents with any 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!

References:[16]

High-risk pregnancies

Early identification of high-risk pregnancies is vital in order to prevent the occurrence of maternal and fetal complications, which are associated with high morbidity and mortality rates. High-risk pregnancies require regular prenatal care to monitor and support the pregnant mother (see prenatal care).

Risk factors for a complicated pregnancy

References:[17]

Maternal complications during pregnancy

Nausea and vomiting of pregnancy

Uncomplicated nausea and vomiting (“morning sickness”)

  • Epidemiology: occurs in up to 90% of pregnancies; onset at 5–6 weeks' gestation, peaking at 9 weeks' gestation, usually abating by 16–20 weeks' gestation
  • Risk factors
  • Clinical features
    • Nausea and/or vomiting
    • Normal vital signs, lab findings, and normal physical examination
  • Treatment

Hyperemesis gravidarum

  • Definition: : severe, persistent nausea and vomiting associated with a > 5% loss of pre-pregnancy weight and ketonuria with no other identifiable cause
  • Clinical features: nausea, vomiting, physical signs of dehydration, hypersalivation, orthostatic hypotension, malnourishment
  • Diagnosis
  • Treatment:
    • Same as treatment of uncomplicated nausea and vomiting;
    • Plus: IV rehydration with supplementation of electrolytes and ondansetron and, if these prove ineffective, glucocorticoids

Cervical insufficiency

  • Definition: painless cervical dilation, in the absence of uterine contractions; and/or labor, in the second trimester of pregnancy
  • Etiology: Most cases are idiopathic.
  • Risk factors
  • Clinical features
    • Painless cervical dilation with or without prolapsed membranes
    • Nonspecific findings
      • Pelvic cramps or back ache
      • ↑ Volume, changed color (yellow or blood-stained), and/or thinner consistency of vaginal discharge
  • Diagnosis
    • Clinical diagnosis typically before 24 weeks' (may be up to 28 weeks') gestation; or
    • History of ≥ 2 previous midtrimester pregnancy losses or ≥ 3 preterm births; not explained by any other cause, and a transvaginal ultrasound cervical length < 25 mm before 24 weeks' gestation
    • Treatment
      • Serial cervical ultrasound monitoring should be commenced in high-risk women (i.e., previous preterm birth) between 16–24 weeks' gestation.
      • Cervical cerclage
        • Definition: placement of a supportive suture in the cervicovaginal junction to prevent early pregnancy loss or preterm birth
        • Methods: McDonald cerclage , Shirodkar cerclage
        • Indications
          • Current singleton pregnancy, previous preterm birth at < 34 weeks' gestation, and a short cervical length at < 24 weeks' gestation
          • Current singleton pregnancy with a clinical diagnosis of cervical insufficiency at < 24 weeks' gestation
          • Prior cerclage due to cervical insufficiency at < 24 weeks' gestation
        • Contraindications
      • Vaginal progesterone supplementation: indicated for a short cervical length at < 24 weeks' gestation in the absence of a previous preterm birth
      • Strict bed rest is not recommended.

A shortened cervical length alone is not sufficient to diagnose cervical insufficiency.

Further complications

  • Supine hypotensive syndrome: compression of the vena cava and pelvic veins by the uterus may occur during the third trimester of pregnancy as a result of the mother lying in a supine position.
  • Peripheral edema
    • Very common, benign finding
    • Management:
  • Musculoskeletal condition
  • Hypertensive pregnancy disorders
  • Gestational diabetes
  • Pregnancy pyelonephritis (most common pregnancy complication)
  • Gastrointestinal reflux
  • Bleeding during pregnancy
  • Placenta praevia
  • Cephalopelvic disproportion: the fetal size is disproportionately large for the maternal pelvis
    • Can result in a prolonged second state of labor
  • Polymorphic eruption of pregnancy
  • Maternal conditions during pregnancy (e.g., malignancy, infections, trauma)

References:[18][1][19][20][21][22][23][24][25]

Fetal complications during pregnancy

Oligohydramnios

Polyhydramnios

References:[26][27][28][29]