Pregnancy

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.

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)	Genopathies: injury to the gene locus Chromosomal aberrations (e.g., trisomy) Occur before conception
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.	Blastopathies Occurrence: up to 14 days after conception Congenital anomalies: very complex congenital anomalies with double malformations or missing body parts High risk of abortion Multiple pregnancy: conjoined twins especially
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	Formation of the uteroplacental unit The trophoblast further divides into the syncytiotrophoblast, which is involved in the development of the placenta, and the cytotrophoblast, which forms the chorionic cavity, which surrounds the embryoblast. Syncytiotrophoblast begins secreting hCG The maternal circulation is connected with the placental circulation The bilaminar embryonic disc develops (2 layers): epiblast and hypoblast
Week 3	Gastrulation: formation of the trilaminar embryonic disc (ectoderm, mesoderm, endoderm) The neural plate begins to form from the neuroectoderm.	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.	Fetopathies: anomalies Etiology Infections: fetopathies caused by infectious agents or pathogens Antibodies: Rh incompatibility Metabolic: diabetes mellitus

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

References:^[2][3]

• 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]

Confirmation of pregnancy

• Pregnancy test: measurement of human chorionic gonadotropin (beta-hCG)
  • Urine beta-hCG test (e.g., home pregnancy test)
    • Qualitative test; less sensitive than serum pregnancy test
    • hCG may be detected in urine 14 days after fertilization
  • Serum beta-hCG test (quantitative, high sensitivity)
    • Detectable 6–9 days (on average) after fertilization
    • Findings
      • Normal pregnancy: beta-hCG concentration doubles every 2.5 days in early pregnancy
        • Peaks at 10 weeks of gestation (peak value: ∼100,000 mlU/mL) and then declines
      • Beta-hCG level of 1,500–2,000 mlU/mL → pregnancy visible with transvaginal ultrasound (if beta-hCG < 1000 mlU/mL, repeat beta-hCG and transvaginal ultrasound in 2–3 days)
      • Low values or slow rise in the value: may indicate ectopic pregnancy, abortion
      • High values or fast rise in the value: may indicate beta-hCG secreting tumors (hydatidiform mole, choriocarcinoma), twin pregnancy
      • False-positive test results:
        • Recent mononucleosis infection or IgA deficiency due to heterophilic antibody formation, crossreacts with HCG testing
        • Perform urine HCG as antibodies do not cross glomerular membrane
• Ultrasound findings in normal pregnancy (abdominal or transvaginal)
  • At 5–6 weeks of pregnancy: detection of the embryo
  • At 10–12 weeks of pregnancy: detection of fetal heartbeat with Doppler ultrasound
  • At 18–20 weeks of pregnancy: fetal movements

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	17000Determining 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]}

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	↑ Oxygen consumption (by ∼ 20%) The diaphragm is displaced upwards → ↓ total lung capacity, residual volume, functional residual capacity, and expiratory reserve volume; increased intra-abdominal pressure through uterine growth → dyspnea Progesterone stimulates the respiratory centers in the brain → physiological, chronic compensated respiratory alkalosis ↑ Tidal volume (by ∼ 40%) → ↑ minute ventilation ↓ PCO2 (∼ 30 mm Hg)
Renal	↑ GFR → ↓ BUN and creatinine ↑ Aldosterone → ↑ plasma volume + hyponatremia ↑ Glucose levels in urine Pollakiuria
Endocrine	↑ Insulin ↑ Triglycerides and cholesterol
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	↑ Salivation ↓ Motility → constipation Hemorrhoids
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	Vaginal discharge Formation of varicose veins

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]

• 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]

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
  • Nulliparity
  • Migraine
  • Multiple gestation
  • Hydatidiform mole
  • GERD
• Clinical features
  • Nausea and/or vomiting
  • Normal vital signs, lab findings, and normal physical examination
• Treatment
  • Rehydration
  • Nausea management:
    • Adapt diet and avoid triggers
    • First-line: ginger and/or pyridoxine (vitamin B₆)
    • Second-line: add doxylamine
    • Third-line: administer antiemetics (e.g., dimenhydrinate or diphenhydramine)

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
  • Clinical diagnosis
  • Laboratory analysis
    • Electrolyte disturbances (hypokalemia and hypochloremic metabolic alkalosis)
    • Signs of dehydration (e.g., ↑ hematocrit)
    • Ketonuria
• 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
  • Previous midtrimester pregnancy loss and/or preterm birth
  • Previous obstetric or gynecological trauma (e.g., termination of pregnancy, rapid delivery, multiple gestations, or cervical conization)
  • Cervical connective tissue weakness (e.g., Ehler-Danlos syndrome),
  • Diethylstilbestrol exposure
• 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
        • Preterm labor
        • Ruptured membranes
        • Chorioamnionitis or vaginal infection
        • ≥ 24 weeks' gestation
        • Unexplained vaginal bleeding
    • 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.
  • Venous return to the heart is disturbed and the cardiac output per minute decreases → fetal hypoxia → CTG shows ↓ FHR as a prolonged deceleration
  • After repositioning the mother in the left lateral position, the FHR recovers.
  • In the mother, supine hypotensive syndrome is characterized by tachycardia, dizziness, and nausea, and occasionally causes syncope.
• Peripheral edema
  • Very common, benign finding
  • Management:
    • Rule out DVT and preeclampsia
    • Monitoring; usually no treatment necessary
• Musculoskeletal condition
  • Lower back pain: increased lumbar lordosis caused by relaxation of the ligaments supporting the joints of the pelvic girdle in preparation for childbirth
  • Carpal tunnel syndrome (caused by peripheral edema; usually resolves after delivery)
• 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]}

Oligohydramnios

• Definition: amount of amniotic fluid < 500 mL in the third trimester
• 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
    • Late or post-term pregnancies (> 42 weeks of gestation)
    • Placental insufficiency
    • Preeclampsia
    • Premature rupture of membranes
  • Idiopathic
• Complications
  • Intrauterine growth restriction (diminished mobility of the fetus)
  • Intrauterine compression and decreased amniotic fluid ingestion → Potter sequence: pulmonary hypoplasia (cause of death due to severe neonatal respiratory insufficiency), craniofacial abnormalities, limb anomalies
  • Birth complications (e.g., umbilical cord compression)
• Diagnosis
  • Abdominal girth and uterine size small for gestational age
  • Ultrasound
    • Amniotic fluid index (AFI): semiquantitative tool to assess amniotic fluid volume (normal: > 5–24 cm)
      • Oligohydramnios: ≤ 5 cm
    • Assess for fetal anomalies
• Treatment
  • Amnioinfusion: infusion of fluid into the amniotic cavity through amniocentesis
  • Treat underlying cause (see preeclampsia, premature rupture of membranes, placental insufficiency for details)
  • Delivery is advised if the fetus is close to term.

Polyhydramnios

• Definition: excessive amniotic fluid volume (> 2000 mL in the third trimester) that results in uterine distention and is associated with an increased risk of fetal complications
• Etiology
  • Fetal anomalies
    • Gastrointestinal anomalies (e.g., esophageal atresia, duodenal atresia and stenosis)
    • CNS anomalies (e.g., anencephaly , meningomyelocele )
    • Chromosomal aberrations
    • Intrauterine infections (e.g., congenital TORCH infections)
    • Multiple pregnancy: twin-to-twin transfusion syndrome
  • Maternal conditions
    • Diabetes mellitus
    • Rhesus incompatibility: hemolytic disease of the newborn
• Complications
  • Fetal malposition
  • Umbilical cord prolapse
  • Premature rupture of membranes
  • Premature uterine contractions
  • Premature birth
• Diagnosis
  • Abdominal girth and uterine size large for gestational age
  • Ultrasound
    • AFI ≥ 24 cm
    • Assess for fetal anomalies
• Treatment
  • Amnioreduction: drainage of excess amniotic fluid
  • Treat the underlying cause
    • Glycemic control in diabetic mothers
    • Intrauterine exchange transfusion for newborns with hemolytic disease

References:^{[26][27][28][29]}