Case 1: Claire McFadden - High-Risk Pregnancy + Preterm Labour

Placenta: Placentation

1. Fertilization

2. Zygote (1 cell) divide into morula (16 cells) into blastocyst (32 cells)

• Fallopian tube → Uterus

3. Blastocyst implant into uterine wall (endometrium)

Placenta: Anatomy

1. Basal Plate (decidua basalis)

2. Intervillous space + villous tree

3. Chorionic plate

Placenta: Basal Plate

Maternal component

Contain:

• Maternal decidua: Transformed endometrium

• Embryonal cells: Cytotrophoblast, syncytiotrophoblast, trophoblast

Placenta: Intervillous Space + Villous Trees

Fetomaternal zone

Intervillous Space: Contact zone between maternal + fetal structures

• Gas + nutrient exchange

• Contain maternal blood

Villous Trees: Branching villi in intervillous space

• Contain fetal blood

Placental Barrier: Between maternal + fetal circulation

• Control gas + nutrient exchange

Placenta: Chorionic Plate

Fetal component

Contain:

• Embryonal Cells: Syncytiotrophoblast, cytotrophoblast, extraembryonic mesoderm

Connected to umbilical cord

• 3 blood vessels with fetal blood

  • 2 Umbilical Arteries: Carry de-O2 blood from fetus → Placenta

  • 1 Umbilical Vein: Carry O2 blood from placenta → Fetus

Placenta: Physiology

Hormone production

Gas, waste, nutrient exchange

Placenta Physiology: Hormone Production

hCG

Human placental lactogen

CRH

Relaxin

Estrogen

Progesterone

Placenta: hCG

Maintain pregnancy

Stimualte progesterone + estrogen production

Placenta: Human Placental Lactogen

Fetal growth + development

Increase insulin production

Decrease maternal insulin sensitivity → Induce gestational DM

Placenta: CRH

Produce surfactant

Placenta: Relaxin

Prevent uterine contraction

Dilate afferent arteriole in kidneys = Increase filtration rate

Placenta: Estrogen

Fetal growth

Endometrial proliferation

Mammary gland development

Placenta: Progesterone

Increase maternal basal body temp

Prevent menstruation + maintain pregnancy

Close cervix

Prevent uterine contractions

Placenta Physiology: Gas, Waste, Nutrient Exchange

Across chorionic villi

Passive: O2, CO2, urea, bilirubin, water, drugs, glucose, lactate

Active: Macronutrients, micronutrients, hormones, antibodies (IgG)

Preconception Care

Optimize maternal health+ prevent teratogenic exposures

• Genetic counseling

• Conception timing

• Vaccines

• Lifestyle

• Diet

Preconception Care: Genetic Counseling

Test for…

• Spinal muscular atrophy

• CF

• Major congenital anomalies (fragile X syndrome, familial adenomatous polyposis)

• Hereditary cancers

Preconception Care: Conception Timing

Delay if…

• Live vaccine

• Recent travel

• Recent teratogenic medication use

• Bariatric surgery

• Recent live birth

Preconception Care: Vaccines

MMR

Varicella

Preceonception Care: Lifestyle

Stop teratogenic medications

Maintain normal body weight + exercise

Preconception Care: Diet

Vit + mineral supplementation

• Folic acid

Decrease seafood

Antenatal Care

Diet

Lifestyle

Antenatal Care: Diet

Increase calories

Vit + mineral supplementation

• Folic acid

• Vit B12

• Vit D

Decrease caffeine

No alcohol + seafood

Antenatal Care: Lifestyle

Regular exercise

Travel precautions (vaccines, VTE)

Antenatal Care: 1st Trimester

GTPALS history

FMHx

Screening

US

Antenatal Care 1st Trimester: Screening

Comorbidities

• CBC: Anemia, thrombocytopenia, ABO, Rh factor

• Urine: Proteinuria, bacteriuria

• STIs: HIV, HBV, HCV, syphilis

Psychosocial

Genetic testing

Antenatal Care 1st Trimester: US

Confirm pregnancy + location

Evaluate embryo

• Anatomy

• Gestational age

Determine estimated delivery date

Antenatal Care: 2nd Trimester

Physical exam

Screening

US

Antenatal Care 2nd Trimester: Physical Exam

Weight

BP: < 140/90

Fundal height

• Normal: Correspond to gestational age > 20 weeks

Fetal heart

Antenatal Care 2nd Trimester: Screening

Comorbidities

• CBC: Anemia

• OGTT: Gestational DM

Antenatal Care 2nd Trimester: US

Biophysical profile (BPP)

• Movement

• Tone

• Breathing

• Amniotic fluid volume

  • Normal: Deepest fluid pocket = 2-7cm

Fetal HR

• Normal: 110-160 BPM

Placenta location

• Low-Lying

• Previa: Covering internal os

High-Risk Pregnancy: Description

1+ risk factors present

High-Risk Pregnancy: Epidemiology

Risk factors…

• Maternal 

  • ≥ 35 years

  • Medical conditions

    • Metabolic: HTN, DM, obesity

    • Resp: Asthma, pulmonary HTN

    • Structural heart condition

    • Anemia

    • CKD

    • Infection: HIV, Zika, chorioamnionitis, toxoplasmosis, CMV

    • Myasthenia gravis

    • Antiphospholipid syndrome

  • Gynecological conditions

    • Uterine leiomyoma: Benign fibroids

    • Uterine surgery

  • Substance use

• Fetal

  • Multiple gestation

  • Placental abnormalities

  • Vasa previa: Blood vessels over birth canal

  • Abnormal amniotic fluid levels

  • Chromosomal abnormalities

High-Risk Pregnancy: Investigations

Screening

• Fetal aneuploidy + neural tube defect

• OGTT

• Routine blood tests

• Urinalysis + culture

Imaging: US

High-Risk Pregnancy Screening: Fetal Abnormalities

Enhanced 1st trimester screening (eFTS)

Multiple marker screening

Non-invasive prenatal testing (NIPT)

Fetal Abnormalities Screening: eFTS

Serum Analysis:

• Beta-hCG: Tumor marker

  • Increased

• PAPP-A (pregnancy-associated protein A): Placental protein

  • Increased

• AFP (alpha-fetoprotein): Tumor marker

  • Decreased

US: Nuchal translucency

Fetal Abnormalities Screening: Multiple Marker Screening

Serum Analysis:

• Beta-hCG

• AFP

• Unconjugated estriol: Weak estrogen

  • Decreased

• Inhibin A: Placental protein

  • Increased

Fetal Abnormalities Screening: NIPT

Serum Analysis: Cell-free fetal DNA (genetic testing)

High-Risk Pregnancy Screening: OGTT

Gestational DM

Earlier at < 15 weeks

High-Risk Pregnancy Screening: Routine Blood Tests

Blood type + Rh

CBC

Rubella/varicella immunity

STI screening

High-Risk Pregnancy Investigation: US

1st Trimester: ≤ 13 weeks

• Confirm pregnancy

• Estimate gestational age

2nd Trimester: 18-22 weeks

• Anatomy survey

• Limitation: Low sensitivity for cardiac, GI, MSK, and facial features

3rd Trimester: ≤ 36 weeks

• Routine fetal surveillance

• Limitation: User error

High-Risk Pregnancy: OTC Medications

AVOID:

Ginger: After 1st trimester

• Nausea/vomiting

Sodium bicarbonate

• GERD

NSAIDs

• Pain

Oral stimulate decongestants (pseudoephedrine)

• Rhinitis

Retinoids

• Acne

Teratogenic Prescriptions

ACE inhibitors/ARBs

Warfarin

Anticonvulsants

• Valproate

• Phenytoin

• Carbamazepine

Lithium

Tetracyclines

Aminoglycosides

• Streptomycin

Teratogens: ACE Inhibitors/ARBs

Alternative: Labetalol

Adverse Effects:

• Affect renal + skull development

• Growth restriction

• Increase amniotic fluid

Teratogens: Warfarin

Alternative: Heparin

Adverse Effect: Fetal warfarin syndrome

• Affect nasal development

• CNS defects

• Growth restriction

• Fetal bleeding

Teratogens: Anticonvulsants

Alternative: Lamotrigine

Adverse Effects:

• Neural tube defects

• Congenital heart defects

• Cleft lip/palate

• Developmental delay

Teratogens: Lithium

Alternatives:

• Atypical antipsychotics

  • Quetiapine

  • Olanzapine

  • Aripiprazole

  • Risperidone

• Lamotrigine

Adverse Effects: Cardiac anomalies (Ebstein)

Teratogens: Tetracyclines + Aminoglycosides

Alternative: Beta-lactams

Adverse Effect: Ototoxicity

High-Risk Pregnancy: Complications

Diabetes

UTI

Pregnancy Diabetes: Investigations

Gestational DM: 24-28 weeks

• OGTT

Pregestational DM:

• HbA1c < 15 weeks

• Fasting blood glucose

Pregnancy Diabetes: Treatment/Management

Nonpharmacological

Pharmacological

Pregnancy Diabetes Management: Nonpharmacological

Patient education

• Nutrition

• Physical activity

Glycemic control

• Diet changes

• HbA1c monthly

• Self glucose monitoring

Fetal monitoring: US

Delivery planning

• Cesarean: Fetal weight > 4500 g

• Early delivery: Poor glycemic control

Pregnancy Diabetes Management: Pharmacological

Insulin: First-line

• During pregnancy

• Infusion during delivery

Low dose ASA

Oral antihyperglycemics

• Metformin: Preferred

• Glyburide (sulfonylurea)

Pregnancy Diabetes: Complications

Maternal

• HTN

• UTI

• Polyhydramnios: Increased amniotic fluid

• Preterm labour

Diabetic embryopathy

• Congenital heart disease

• Neural tube defects

• Small left colon

• Renal disorders

• Caudal regression: Loss of scrum + lower lumbar spine

Diabetic fetopathy

• Macrosomia

• Postnatal hypoglycemia

• Polycythemia: High RBC

Pregnancy UTI: Pathophysiology

Progesterone (uterine relaxation) + in-utero fetal pressure on bladder = Urinary stasis

Pregnancy UTI: Investigations

Screening: 1st trimester

Urinalysis

Urine culture

Pregnancy UTI Investigations: Urinalysis

Pyuria: 

• WBC

• Leukocyte esterase

Bacteriuria: Urinary nitrites

Leukocyte casts: Pyelonephritis

Pregnancy UTI Investigations: Urine Culture

Bacteriuria: ≥ 10⁵ CFU/mL

Pregnancy UTI: Treatment

Empiric antibiotics

Repeat culture: 1 week

Pregnancy UTI Treatment: Empiric Antibiotics

Indications:

• Asymptomatic bacteriuria

• Lower UTI

Agents:

• Fosfomycin

• Beta-lactams

  • Cephalosporin

  • Aminopenicillins + beta-lactamase inhibitor (amox/clav)

• Nitrofurantoin: Avoid close to delivery

• TMP/SMX: Avoid during 1st trimester + > 32 weeks

AVOID: Fluoroquinolones, aminoglycosides

Pregnancy UTI: Complications

Pyelonephiritis

Preterm labour

HTN + preeclampsia

Chorioamnionitis

Pyelonephritis: Description

Infection in renal pelvis + parenchyma

Pyelonephritis: Clinical Presentation

Fever

Flank pain

CVA tenderness

UTI symptoms

Pyelonephritis: Investigations

Urinalysis

Urine culture

Blood culture

Blood tests

• CBC: Leukocytosis

• Inflammatory markers: Elevated

Pyelonephritis: Treatment/Management

Empiric antibiotics

Analgesics

Pyelonephritis Treatment: Empiric Anitbiotics

Ampicillin + gentamicin: First-line

TMP/SMX

Amox/clav

Cefpodoxime

Preterm Labour: Description

Labour between 20 and < 37 weeks’ gestation

Preterm Labour: Epidemiology

Risk factors…

• Nonmodifiable

  • Preterm birth hx

  • Cervical insufficiency: Cervical dilation in 2nd trimester

  • Multiple gestations

• Modifiable

  • Smoking

  • Substance + cannabis use

  • Maternal age

    • ≤ 18 years

    • > 35 years

  • Infection

    • Chorioamnionitis

    • UTI

    • Bacterial vaginosis

    • STIs

  • Abdominal trauma

Preterm Labour: Treatment/Management

37 Weeks: Deliver

< 34 Weeks: Tocolytics, steroids

< 32 Weeks: Magnesium sulfate, steroids

Antibiotics

Preterm Labour Treatment: Tocolytics

Inhibit uterine contractions

Types:

• Nifedipine

• Indomethacin

• Terbutaline

• Magnesium sulfate

Tocolytics: Nifedipine

Class: CCB

Adverse Effects:

• Maternal

  • Hypotension

  • Dizziness

Tocolytics: Indomethacin

Class: NSAID

Adverse Effects:

• Maternal

  • Esophageal reflux

  • Gastritis

  • Nausea/vomiting

• Fetal

  • Renal dysfunction

  • Premature ductus arteriosus closure

Tocolytics: Terbutaline

MOA: Beta-2 adrenergic agonist

Adverse Effects:

• Maternal

  • Tachycardia

  • Hypotension

  • Hypokalemia

  • Hyperglycemia

• Fetal

  • Tachycardia

  • Hypoglycemia

Tocolytics: Magnesium Sulfate

Fetal neuroprotection

Class: CCB

Adverse Effects:

• Maternal: Mg2+ Toxicity

  • Hypocalcemia

• Respiratory depression

• Pulmonary edema

Preterm Labour Treatment: Steroids

Promote surfactant production + fetal lung maturity

Ex: Betamethasone, dexamethasone

Preterm Labour Treatment: Antibiotics

GBS prophylaxis

• Penicillin G

• Ampicillin

• Penicillin allergy

  • Cefazolin

  • Clindamycin

PPROM prophylaxis

• 7 days ampicillin + erythromycin → 5 days amoxicillin + erythromycin