6.1 Antenatal Care, Pre-eclampsia & Gestational Diabetes

Antenatal Care, Pre-eclampsia & Gestational Diabetes

Antenatal care (ANC) is a systematic program of risk assessment, clinical screening, and education aimed at optimizing maternal and fetal health outcomes. In the context of primary care and general practice, understanding the screening timelines, diagnostic thresholds, and prevention protocols for major pregnancy-related complications is vital for passing the licensing exams and ensuring patient safety.

1. Antenatal Screening Timeline

Comprehensive antenatal care involves routine visits that follow a standardized screening schedule to detect maternal conditions, infectious diseases, and fetal anomalies.

First Prenatal Visit (Booking Visit: 8–12 Weeks)

The initial visit focuses on establishing gestational age, obtaining a detailed medical and obstetric history, and performing baseline screening.

• Routine Laboratories: Complete Blood Count (CBC) to screen for anemia, blood typing and Rhesus (Rh) factor screening, antibody screening, rubella immunity, varicella immunity, and screening for infectious diseases including Syphilis (RPR or VDRL), HIV, and Hepatitis B surface antigen (HBsAg).
• Urinalysis and Urine Culture: Performed to screen for asymptomatic bacteriuria. Asymptomatic bacteriuria occurs in 2-10% of pregnancies and, if left untreated, progresses to acute pyelonephritis in up to 30% of cases due to progesterone-induced ureteral dilation and urinary stasis. First-line treatments include oral nitrofurantoin (avoid near term due to hemolytic anemia risk in the newborn), cephalexin, or amoxicillin-clavulanate.
• Cervical Cancer Screening: Pap smear if not up to date.
• Chlamydia & Gonorrhea Screening: Recommended for all pregnant women under 25, and older women at high risk.

First Trimester Screening (11–13 Weeks)

• Combined Test: Assesses the risk of trisomies 21, 18, and 13. It includes a maternal serum screening for Pregnancy-Associated Plasma Protein-A (PAPP-A, which is decreased in aneuploidies) and free Beta-hCG (which is elevated in Trisomy 21 and decreased in Trisomy 18/13), combined with a transvaginal ultrasound measuring fetal Nuchal Translucency (NT). An increased NT thickness (> 3.0 mm) is associated with aneuploidy and congenital heart defects.
• Cell-Free DNA (cfDNA) Screening: Also known as Non-Invasive Prenatal Testing (NIPT). Can be performed anytime after 10 weeks of gestation. It analyzes fetal DNA circulating in maternal blood and has a detection rate > 99% for Trisomy 21, with a very low false-positive rate (< 0.1%). It is recommended for high-risk patients (maternal age ≥ 35, abnormal serum screen, or personal history).

Second Trimester Screening (15–20 Weeks)

• Quad Screen: Performed if first-trimester screening was missed or to assess for open neural tube defects. It measures:
  1. Maternal Serum Alpha-Fetoprotein (MSAFP): Elevated in open neural tube defects (e.g., anencephaly, spina bifida) and abdominal wall defects (gastroschisis, omphalocele); decreased in Down syndrome.
  2. Human Chorionic Gonadotropin (hCG): Elevated in Down syndrome.
  3. Unconjugated Estriol (uE3): Decreased in Down syndrome and Trisomy 18.
  4. Inhibin A: Elevated in Down syndrome.
• Anatomy Scan (18–22 Weeks): A detailed structural ultrasound to evaluate fetal anatomy, placental location (to rule out placenta previa), and amniotic fluid volume.

Gestational Diabetes Screening (24–28 Weeks)

• All pregnant women not previously diagnosed with diabetes should be screened between 24 and 28 weeks using a glucose load challenge.

Group B Streptococcus (GBS) Screening (35–37 Weeks)

• Vaginal-Rectal Culture: A swab is collected to screen for GBS colonization.
• Management: If positive, or if the patient has a history of GBS bacteriuria during the current pregnancy or a previous infant with invasive GBS disease, intrapartum antibiotic prophylaxis is indicated. Penicillin G (5 million units IV load, then 2.5 million units IV every 4 hours until delivery) is the first-line agent. Ampicillin is an alternative. For penicillin-allergic patients with low risk of anaphylaxis, cefazolin is used. For those at high risk of anaphylaxis, clindamycin or vancomycin is administered depending on susceptibility testing.

---

2. Gestational Diabetes Mellitus (GDM)

Gestational Diabetes Mellitus (GDM) is defined as carbohydrate intolerance resulting in hyperglycemia with onset or first recognition during pregnancy. The metabolic changes of pregnancy, primarily mediated by Human Placental Lactogen (hPL), progesterone, cortisol, and prolactin, induce progressive peripheral insulin resistance to ensure adequate glucose delivery to the growing fetus. When maternal pancreatic beta-cell compensation is inadequate, GDM develops.

Diagnostic Criteria (Two-Step Approach)

The two-step method is widely recommended by the ACOG (American College of Obstetricians and Gynecologists):

1. Step 1: 50g Glucose Challenge Test (GCT):
   • Non-fasting screening test. Maternal blood glucose is measured 1 hour after ingestion of a 50g oral glucose load.
   • A value ≥ 130 mg/dL (7.2 mmol/L) or ≥ 140 mg/dL (7.8 mmol/L) (depending on institutional threshold) is positive and requires the diagnostic second step.
2. Step 2: 100g 3-Hour Oral Glucose Tolerance Test (OGTT):
   • Performed in a fasting state (minimum 8 hours). Blood glucose is measured at fasting, 1 hour, 2 hours, and 3 hours post-ingestion of a 100g glucose load.
   • Carpenter-Coustan Diagnostic Thresholds:
     • Fasting: ≥ 95 mg/dL (5.3 mmol/L)
     • 1-Hour: ≥ 180 mg/dL (10.0 mmol/L)
     • 2-Hour: ≥ 155 mg/dL (8.6 mmol/L)
     • 3-Hour: ≥ 140 mg/dL (7.8 mmol/L)
   • A diagnosis of GDM is confirmed if two or more values are met or exceeded.

Glycemic Targets and Management

• First-Line: Nutritional counseling, carbohydrate restriction (typically 33-40% of complex carbohydrates), and moderate physical activity (e.g., walking 30 minutes daily).
• Glycemic Targets:
  • Fasting: < 95 mg/dL (5.3 mmol/L)
  • 1-hour postprandial: < 140 mg/dL (7.8 mmol/L)
  • 2-hour postprandial: < 120 mg/dL (6.7 mmol/L)
• Pharmacotherapy: Initiated if ≥ 10-20% of capillary blood glucose readings exceed target thresholds within 1-2 weeks.
  • Insulin is the gold standard and first-line pharmacotherapy because it does not cross the blood-placenta barrier. A typical starting regimen is 0.7-2.0 units/kg/day, combining intermediate/long-acting (NPH/Detemir) and rapid-acting (Novorapid/Humalog) insulins.
  • Metformin can be used as an alternative or if a patient refuses insulin, but it crosses the placenta. Oral sulfonylureas (e.g., glyburide) are associated with higher rates of neonatal hypoglycemia and macrosomia and are generally not recommended.

---

3. Hypertensive Disorders of Pregnancy & Pre-eclampsia

Hypertensive disorders complicate up to 10% of pregnancies. Accurate classification is critical:

• Chronic Hypertension: Blood pressure ≥ 140/90 mmHg predating pregnancy or diagnosed before 20 weeks of gestation.
• Gestational Hypertension: New-onset systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg after 20 weeks of gestation in a previously normotensive patient, in the absence of proteinuria or severe features.
• Pre-eclampsia: New-onset hypertension after 20 weeks of gestation AND either proteinuria or severe multi-organ dysfunction.

Diagnostic Criteria for Pre-eclampsia

• Hypertension: SBP ≥ 140 mmHg or DBP ≥ 90 mmHg on two occasions at least 4 hours apart.
• Proteinuria: Defined as:
  • ≥ 300 mg per 24-hour urine collection (gold standard).
  • Protein-to-creatinine ratio ≥ 0.3.
  • Dipstick reading of 2+ (used only if quantitative methods are unavailable).
• Diagnosis in the Absence of Proteinuria: In a patient with new-onset hypertension, pre-eclampsia can still be diagnosed if any of the following severe features are present:
  • Thrombocytopenia: Platelet count < 100,000/μL.
  • Renal Insufficiency: Serum creatinine > 1.1 mg/dL or a doubling of baseline creatinine.
  • Impaired Liver Function: Liver transaminases (AST/ALT) elevated to twice the upper limit of normal, or severe persistent right upper quadrant/epigastric pain.
  • Pulmonary Edema.
  • Cerebral or Visual Symptoms: New-onset headache unresponsive to medication, photopsia, scotoma, or cortical blindness.
  • Systolic BP ≥ 160 mmHg or Diastolic BP ≥ 110 mmHg on two occasions at least 4 hours apart (or minutes apart if antihypertensives are initiated immediately).

Prevention and Management

• Aspirin Prophylaxis: Low-dose aspirin (81–150 mg/day) should be initiated at 12–16 weeks of gestation in women with high-risk factors (e.g., history of pre-eclampsia, chronic hypertension, pregestational diabetes, autoimmune disease, renal disease, multiple gestation).
• Antihypertensive Therapy: Indicated if BP is persistently ≥ 160/110 mmHg to prevent maternal stroke. First-line agents include:
  • Labetalol: Beta-blocker with alpha-blocking activity. Avoid in patients with asthma.
  • Hydralazine: Direct vasodilator. Can cause reflex tachycardia and headache.
  • Nifedipine (Extended-Release): Calcium channel blocker.
  • Note: ACE inhibitors, ARBs, and direct renin inhibitors are strictly contraindicated due to risks of fetal renal dysgenesis, oligohydramnios, and skull hypoplasia.
• Seizure Prophylaxis: Magnesium Sulfate is the drug of choice.
  • Dosing: IV loading dose of 4–6 g over 15–20 minutes, followed by a continuous IV infusion of 1–2 g/hour for 24 hours postpartum or post-delivery.
  • Monitoring Toxicity: Close clinical monitoring is essential:
    • Patellar reflex (deep tendon reflexes are lost at 8–10 mEq/L).
    • Respiratory rate (depression occurs at 12–15 mEq/L, and respiratory arrest at > 15 mEq/L).
    • Urine output (magnesium is cleared renally; output must be > 30 mL/hour to prevent drug accumulation).
  • Antidote: If toxicity is suspected, stop the infusion immediately and administer 1g of Calcium Gluconate 10% IV over 5–10 minutes.
• Delivery Timing:
  • Gestational hypertension or pre-eclampsia without severe features: Delivery at 37 0/7 weeks.
  • Pre-eclampsia with severe features: Delivery at 34 0/7 weeks (or earlier if maternal/fetal instability occurs), after administering corticosteroids (e.g., betamethasone 12 mg IM two doses 24 hours apart) for fetal lung maturity if under 37 weeks.

---

4. Rhesus (Rh) Prophylaxis

Rhesus (Rh) isoimmunization occurs when an Rh-negative mother is exposed to Rh-positive fetal red blood cells, triggering the production of maternal anti-D IgG antibodies. In subsequent pregnancies, these antibodies cross the placenta and target Rh-positive fetal red blood cells, causing Hemolytic Disease of the Fetus and Newborn (HDFN), which can lead to severe fetal anemia, hyperbilirubinemia, hydrops fetalis, and intrauterine death.

Clinical Protocol for Rh Prophylaxis

To prevent maternal sensitization, Anti-D Immunoglobulin (RhoGAM) must be administered to all Rh-negative, unsensitized (antibody-screen negative) women:

1. Routine Antepartum Prophylaxis: A standard dose of 300 mcg (1500 IU) is administered at 28 weeks of gestation.
2. Postpartum Prophylaxis: Within 72 hours after delivery of an Rh-positive infant. The infant's blood type is confirmed via cord blood typing at birth.
3. Indications for Potentially Sensitizing Events: Administer 300 mcg of Anti-D immunoglobulin (or a micro-dose of 50 mcg if gestational age is < 12 weeks) within 72 hours of:
   • Miscarriage (spontaneous or induced abortion)
   • Ectopic pregnancy
   • Chorionic villus sampling (CVS) or amniocentesis
   • External cephalic version
   • Abdominal trauma
   • Antepartum vaginal bleeding (e.g., placental abruption, placenta previa)

Determining the Required Dose

• A standard 300 mcg dose of Anti-D immunoglobulin neutralizes up to 30 mL of fetal whole blood (or 15 mL of fetal red blood cells).
• Rosette Test: A qualitative screening test performed on maternal blood postpartum to detect the presence of fetal-maternal hemorrhage.
• Kleihauer-Betke (KB) Test: If the Rosette test is positive, a quantitative KB test (acid elution technique) is performed to determine the percentage of fetal cells in the maternal circulation. This allows calculation of the exact volume of fetal-maternal hemorrhage and determines if additional doses of Anti-D immunoglobulin are required to prevent sensitization.
  • Calculation Formula: Volume of fetal bleed (mL) = (fetal cells / maternal cells) x 5000 mL Divide the volume by 30 to get the number of vials, and round up to the nearest whole number plus one vial for safety.