1. Methyldopa

Mechanism of Action: Centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow from the central nervous system.

Dosage: 250-500 mg orally 2-3 times daily; maximum 3g/day

Efficacy: Moderate antihypertensive effect with excellent long-term safety data in pregnancy

Side Effects: Sedation, depression, orthostatic hypotension, hepatic dysfunction (rare)

Nursing Considerations:

• Monitor liver function tests during prolonged therapy
• Assess for excessive sedation that may interfere with activities
• Alert patient that urine may darken upon standing

2. Labetalol

Mechanism of Action: Combined alpha and beta-adrenergic receptor blocker with greater effect on beta receptors than alpha receptors.

Dosage:

• Oral: 100-400 mg twice daily; maximum 2400 mg/day
• IV (for severe hypertension): 10-20 mg IV, then 20-80 mg every 10-30 minutes; maximum 300 mg total

Efficacy: Effectively lowers blood pressure without significantly reducing cardiac output or uterine blood flow

Side Effects: Bradycardia, bronchospasm, dizziness, scalp tingling

Nursing Considerations:

• Monitor maternal heart rate and blood pressure
• Contraindicated in patients with asthma, heart block, or heart failure
• Position patient in left lateral position for IV administration

3. Nifedipine

Mechanism of Action: Calcium channel blocker that decreases peripheral vascular resistance.

Dosage: Extended-release 30-60 mg once daily; maximum 120 mg/day

Efficacy: Rapidly effective for acute blood pressure control

Side Effects: Headache, flushing, peripheral edema, tachycardia

Nursing Considerations:

• The immediate-release (sublingual) form should be avoided due to risk of precipitous hypotension
• Should not be administered with magnesium sulfate due to potential for hypotension
• Monitor for significant hypotension

1. Hydralazine

Mechanism of Action: Direct vasodilator that acts primarily on arterial smooth muscle.

Dosage: 5-10 mg IV every 20-40 minutes; maximum 20 mg per dose or 30 mg total

Efficacy: Effective for acute management of severe hypertension

Side Effects: Tachycardia, headache, flushing, lupus-like syndrome with prolonged use

Nursing Considerations:

• Administer slowly over 2 minutes
• Monitor blood pressure every 5 minutes for 30 minutes after administration
• May cause reflex tachycardia; monitor maternal heart rate

2. Diuretics

Mechanism of Action: Increase sodium and water excretion, reducing plasma and extracellular fluid volume.

Usage in Pregnancy: Generally avoided as first-line therapy due to potential for reduced placental perfusion; may be continued if patient was on therapy prior to pregnancy.

Side Effects: Electrolyte disturbances, volume depletion, hyperglycemia

Nursing Considerations:

• Monitor electrolytes, especially potassium
• Assess for signs of dehydration
• May be particularly useful in women with pulmonary edema

1. ACE Inhibitors and ARBs

ACE inhibitors (e.g., lisinopril, enalapril) and Angiotensin II Receptor Blockers (e.g., losartan, valsartan) are contraindicated throughout pregnancy.

Potential Adverse Effects:

• First trimester: Potential increased risk of congenital malformations
• Second and third trimesters: Fetal renal dysfunction, oligohydramnios, pulmonary hypoplasia, growth restriction, skull hypoplasia, and fetal or neonatal death

2. Atenolol

While other beta-blockers may be used, atenolol has been associated with fetal growth restriction and should be avoided.

Examples: Enoxaparin (Lovenox), Dalteparin (Fragmin)

Mechanism of Action: Enhances antithrombin activity, primarily inhibiting factor Xa and, to a lesser extent, factor IIa (thrombin).

Advantages:

• Does not cross the placenta
• Predictable dose response
• Lower risk of heparin-induced thrombocytopenia (HIT)
• Lower risk of osteoporosis with prolonged use
• Once-daily or twice-daily dosing
• Less need for monitoring compared to unfractionated heparin

Dosage:

Indication	Enoxaparin	Dalteparin
Prophylaxis	40 mg SC once daily	5,000 units SC once daily
Treatment	1 mg/kg SC twice daily or 1.5 mg/kg once daily	100 units/kg SC twice daily or 200 units/kg once daily
Mechanical heart valve	1 mg/kg SC twice daily with anti-Xa monitoring	100 units/kg SC twice daily with anti-Xa monitoring

Monitoring: Anti-Xa levels (4-6 hours post-dose) may be measured for therapeutic dosing or in certain situations (renal impairment, extremes of body weight, mechanical heart valves).

Side Effects: Bleeding, injection site reactions, rare HIT, osteoporosis with prolonged use

Nursing Considerations:

• Teach proper injection technique for self-administration
• Monitor platelet count periodically
• Assess for signs of bleeding
• Should be discontinued 24 hours before planned induction or cesarean section
• Cannot be reversed quickly with protamine sulfate (only partially effective)

Mechanism of Action: Binds to antithrombin, enhancing its inhibitory effects on thrombin (factor IIa) and factor Xa.

Advantages:

• Does not cross the placenta
• Shorter half-life (1-2 hours) than LMWH
• Can be fully reversed with protamine sulfate
• May be preferred in women with renal impairment
• May be preferred peripartum due to shorter half-life

Dosage:

Indication	Dosage	Monitoring Target
Prophylaxis	5,000-10,000 units SC every 12 hours	Not typically monitored
Treatment	Initial: 80 units/kg bolus, then 18 units/kg/hr continuous infusion	aPTT 1.5-2.5 × control
Adjusted-dose prophylaxis	Starting with 5,000-10,000 units SC every 12 hours	Mid-interval (6 hours post-dose) aPTT of 1.5-2.5 × control

Side Effects: Bleeding, HIT (more common than with LMWH), osteoporosis with prolonged use

Nursing Considerations:

• Monitor aPTT regularly for therapeutic dosing
• Check platelet count regularly (HIT risk)
• Teach proper injection technique for self-administration
• Assess for signs of bleeding
• Can be discontinued 4-6 hours before planned delivery

Warfarin

Mechanism of Action: Vitamin K antagonist that inhibits the synthesis of clotting factors II, VII, IX, and X.

Safety in Pregnancy: Generally contraindicated due to teratogenicity and fetal bleeding risk, but may be considered in specific situations (e.g., mechanical heart valves) during the second and early third trimesters.

Potential Adverse Effects:

• First trimester: Warfarin embryopathy (nasal hypoplasia, stippled epiphyses)
• Any trimester: Fetal intracranial hemorrhage, stillbirth, CNS abnormalities

Direct Oral Anticoagulants (DOACs)

Examples: Apixaban, Rivaroxaban, Dabigatran, Edoxaban

Safety in Pregnancy: Contraindicated due to limited data on safety and evidence of placental transfer.

Recommendation: Women on DOACs who become pregnant should be switched to LMWH as soon as possible.

Careful planning is required for anticoagulant management around delivery to balance the risk of thrombosis and hemorrhage.

General Recommendations:

Anticoagulant	Timing of Discontinuation Before Delivery	Timing of Resumption After Delivery
Prophylactic LMWH	24 hours before planned delivery or induction	12-24 hours after delivery if hemostasis is adequate
Therapeutic LMWH	24-36 hours before planned delivery	24 hours after delivery if hemostasis is adequate
Prophylactic UFH	12 hours before planned delivery	6-12 hours after delivery if hemostasis is adequate
Therapeutic IV UFH	4-6 hours before planned delivery	6-12 hours after delivery if hemostasis is adequate
Warfarin	Transition to LMWH/UFH at 36 weeks or earlier	Can be resumed day after delivery if good hemostasis

Two corticosteroids are commonly used for antenatal lung maturation:

Parameter	Betamethasone	Dexamethasone
Standard Dosing Regimen	Two doses of 12 mg IM given 24 hours apart	Four doses of 6 mg IM given every 12 hours
Half-Life	Longer (36-54 hours)	Shorter (16-36 hours)
Placental Transfer	Less metabolized by placenta	More metabolized by placenta
Onset of Action	24 hours	24 hours
Peak Effect	48 hours – 7 days	48 hours – 7 days
Duration of Benefit	Up to 7 days	Up to 7 days

Comparative Efficacy: Both betamethasone and dexamethasone are effective in reducing neonatal RDS and mortality. Some studies suggest betamethasone may be slightly more effective in reducing periventricular leukomalacia and infant mortality, but both are considered appropriate choices.

Optimal Timing: Maximum benefit occurs when corticosteroids are administered at least 24 hours and less than 7 days before delivery.

Administration Considerations:

• Complete course when possible, but even incomplete courses provide benefit
• Administer deep IM injection, usually in the gluteal muscle
• Store according to manufacturer’s recommendations (some preparations require refrigeration)

1. Repeat Courses

While a single rescue course may be considered if the initial course was administered more than 7 days previously and gestational age is <34 weeks with imminent delivery risk, routine multiple courses are not recommended due to concerns about reduced fetal growth, reduced head circumference, and potential neurodevelopmental issues.

2. Late Preterm Corticosteroids

Evidence supports considering corticosteroids for women at risk of preterm birth between 34+0 and 36+6 weeks if they have not previously received a course of antenatal corticosteroids. Betamethasone is preferred in this situation.

3. Multiple Gestations

The same dosage regimen is used for multiple gestations as for singletons. There is no need to increase the dose.

Maternal Side Effects:

• Transient hyperglycemia (especially in diabetic patients)
• Leukocytosis
• Increased susceptibility to infection
• Injection site pain

Contraindications:

• Systemic maternal infection where delivery is indicated
• Chorioamnionitis (relative contraindication)

Key Nursing Responsibilities:

• Verify correct timing and dosage before administration
• Educate patients about the purpose, benefits, and potential side effects
• Document timing of each dose accurately
• Monitor maternal blood glucose in women with diabetes
• Monitor for signs of infection
• Coordinate timing with other interventions (e.g., tocolytics, magnesium sulfate)

Several classes of medications are used as tocolytics, each with a unique mechanism of action, efficacy profile, and side effect concerns:

Class	Mechanism	Examples	Efficacy	Key Concerns
Calcium Channel Blockers	Block calcium influx into myometrial cells	Nifedipine	Good, first-line in many centers	Hypotension, headache
NSAIDs/COX Inhibitors	Inhibit prostaglandin synthesis	Indomethacin	Moderate to good	Premature closure of ductus arteriosus, oligohydramnios
Beta-adrenergic Agonists	Stimulate β2 receptors in myometrium	Terbutaline	Moderate	Maternal cardiac effects, pulmonary edema
Oxytocin Antagonists	Block oxytocin receptors	Atosiban	Moderate	Limited availability in US, cost
Magnesium Sulfate	Decreases intracellular calcium	Magnesium Sulfate	Limited/controversial	Toxicity concerns at higher doses

Primary Agent: Nifedipine

Mechanism of Action: Blocks calcium influx through cell membranes, decreasing intracellular calcium concentration and reducing myometrial contractility.

Dosing Protocol:

• Loading dose: 10-20 mg orally, may repeat in 20-30 minutes if contractions persist (maximum 40 mg in first hour)
• Maintenance: 10-20 mg orally every 4-6 hours for 48-72 hours

Efficacy: Shown to be more effective than beta-mimetics with fewer side effects. Associated with decreased risk of respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage.

Side Effects:

• Maternal: Hypotension, headache, dizziness, flushing, nausea
• Fetal: Generally considered safe, minimal fetal effects

Contraindications:

• Hypersensitivity to nifedipine
• Hypotension (systolic BP <90 mmHg)
• Hepatic dysfunction
• Use caution with concurrent magnesium sulfate (risk of hypotension)

Nursing Considerations:

• Monitor blood pressure before administration and 15-30 minutes after each dose
• Observe for signs of hypotension
• Use with caution in women with diabetes (may affect glucose control)
• Do not administer sublingually due to risk of precipitous hypotension

Primary Agent: Indomethacin

Mechanism of Action: Inhibits cyclooxygenase enzyme, reducing prostaglandin synthesis, which is essential for uterine contractions.

Dosing Protocol:

• Loading dose: 50-100 mg orally or rectally
• Maintenance: 25 mg orally every 4-6 hours for up to 48 hours

Efficacy: Effective short-term tocolytic with comparable efficacy to other agents.

Side Effects:

• Maternal: Nausea, heartburn, gastritis, platelet dysfunction
• Fetal: Premature constriction/closure of the ductus arteriosus, oligohydramnios, necrotizing enterocolitis, intraventricular hemorrhage

Restrictions on Use:

• Limited to pregnancies <32 weeks gestation due to risk of premature ductal closure
• Duration should not exceed 48-72 hours
• Fetal echocardiography should be considered for treatment exceeding 48 hours

Contraindications:

• Gestational age >32 weeks
• Renal or hepatic dysfunction
• Active peptic ulcer disease
• Platelet dysfunction or bleeding disorder
• Oligohydramnios
• Known ductal constriction

Nursing Considerations:

• Monitor amniotic fluid volume
• Educate patient about GI side effects and provide prophylaxis if needed
• Monitor for maternal oliguria
• Consider fetal echocardiography for prolonged therapy

Primary Agent: Terbutaline

Mechanism of Action: Stimulates β2-adrenergic receptors in the myometrium, leading to decreased intracellular calcium and myometrial relaxation.

Dosing Protocol:

• Acute: 0.25 mg subcutaneously every 20-30 minutes for up to 4 doses
• IV: 2.5-10 μg/min, titrated to uterine quiescence (rarely used now)

Efficacy: Effective in delaying delivery for 48 hours but with significant maternal side effects.

Side Effects:

• Maternal: Tachycardia, palpitations, tremor, headache, nausea, vomiting, hyperglycemia, hypokalemia, pulmonary edema (rare but serious)
• Fetal: Tachycardia, hyperinsulinemia, hyperglycemia

Contraindications:

• Cardiac disease
• Poorly controlled diabetes
• Hyperthyroidism
• Uncontrolled hypertension
• Use with caution in multiple gestations (increased risk of pulmonary edema)

Nursing Considerations:

• Monitor vital signs (especially pulse and respiratory rate)
• Maintain strict fluid balance
• Monitor for signs of pulmonary edema (dyspnea, tachypnea, crackles)
• Monitor electrolytes and blood glucose
• Limit fluid intake to reduce risk of pulmonary edema

1. Oxytocin Antagonists (Atosiban)

Mechanism: Competitively inhibits oxytocin receptors in the myometrium, preventing oxytocin-induced contractions.

Status: Approved in Europe but not available in the United States.

Advantages: Fewer cardiovascular side effects than beta-mimetics.

2. Magnesium Sulfate as Tocolytic

Mechanism: Competes with calcium at the cellular level, leading to decreased intracellular calcium and reduced myometrial contractility.

Dosing for Tocolysis:

• Loading: 4-6 g IV over 20-30 minutes
• Maintenance: 2-3 g/hour IV

Efficacy: Limited evidence supports its efficacy as a tocolytic; some studies suggest it is no more effective than placebo. Currently not recommended as a first-line tocolytic.

Side Effects: Similar to those described in magnesium sulfate section.

Combining tocolytics from different classes has been studied as a potential strategy to improve efficacy or reduce individual drug dosages.

Current Evidence:

• Limited data showing improved efficacy over single-agent therapy
• Increased risk of maternal adverse effects
• Generally not recommended in routine practice

Insulin remains the gold standard treatment for gestational diabetes when diet and exercise fail to maintain adequate glycemic control. It does not cross the placenta and has no known teratogenic effects.

Types of Insulin Used in Pregnancy:

Insulin Type	Onset	Peak	Duration	Primary Use in GDM
Rapid-acting (Lispro, Aspart)	10-15 min	1-2 hours	3-5 hours	Mealtime coverage
Short-acting (Regular)	30-60 min	2-4 hours	6-8 hours	Mealtime coverage
Intermediate-acting (NPH)	1-2 hours	4-8 hours	12-18 hours	Basal coverage
Long-acting (Detemir)*	1-2 hours	Minimal	20-24 hours	Basal coverage

*Insulin detemir is FDA pregnancy category B; glargine has less data but is increasingly used.

Insulin Regimens:

• Starting Dosage: 0.7-1.0 units/kg/day total daily dose in divided doses
• Distribution:
  • 50% as basal insulin (NPH or detemir)
  • 50% as prandial insulin (rapid or short-acting)
• Adjustments: Based on blood glucose patterns, typically increased throughout pregnancy due to progressive insulin resistance

Common Regimens:

1. Single injection: For fasting hyperglycemia only – bedtime intermediate-acting insulin
2. Multiple daily injections: Basal-bolus regimen with NPH at bedtime and rapid-acting before meals
3. Intensive therapy: Basal insulin (1-2 times daily) plus prandial insulin with each meal

Side Effects:

• Hypoglycemia (most significant risk)
• Weight gain
• Injection site reactions

Nursing Considerations:

• Educate on proper injection technique and storage
• Teach hypoglycemia recognition and management
• Emphasize importance of regular blood glucose monitoring
• Provide guidance on insulin dosage adjustments based on patterns
• Coordinate with dietary education

1. Metformin

Mechanism of Action: Decreases hepatic glucose production and increases peripheral glucose uptake.

Dosage: Initial 500 mg once or twice daily, increased gradually to maximum of 2000-2500 mg daily in divided doses.

Efficacy: Multiple studies including the MiG trial (Metformin in Gestational Diabetes) have demonstrated efficacy comparable to insulin for glycemic control. Benefits include:

• Less maternal weight gain
• Lower rates of maternal hypoglycemia
• Potential reduction in gestational hypertension and preeclampsia

Limitations:

• Approximately 30-40% of women require supplemental insulin
• Crosses placenta (concentration in fetal circulation approaches maternal levels)

Side Effects: Gastrointestinal disturbances (nausea, diarrhea, bloating), vitamin B12 deficiency with long-term use

Long-term Effects: Follow-up studies of children exposed to metformin in utero suggest no adverse effects on growth, motor, or social development. Some studies show potential benefits in reducing childhood obesity.

2. Glyburide (Glibenclamide)

Mechanism of Action: Sulfonylurea that stimulates pancreatic insulin secretion.

Dosage: Initial 2.5 mg once or twice daily, increased as needed to maximum 20 mg daily.

Efficacy: Studies show varying degrees of efficacy compared to insulin, with some suggesting:

• Higher rates of maternal hypoglycemia compared to insulin or metformin
• Higher rates of neonatal hypoglycemia
• Greater maternal weight gain compared to metformin
• Higher rates of treatment failure than previously thought (up to 20-30%)

Placental Transfer: Initially thought to have minimal placental transfer, newer data suggest significant transfer (up to 70% of maternal concentrations).

Side Effects: Hypoglycemia, weight gain, allergic skin reactions

3. Other Oral Agents

Other classes of oral hypoglycemic agents (DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors) have limited data on safety in pregnancy and are not recommended.

Factors Influencing Medication Choice:

• Severity of hyperglycemia
• Patient preferences (injection vs. oral medication)
• Risk factors (obesity, previous macrosomia)
• Patient reliability/compliance
• Resource availability (ability to monitor glucose, cost)

Current Recommendations (Based on Evidence):

1. First choice: Insulin (especially for more severe hyperglycemia)
2. Acceptable alternative: Metformin (with patient counseling about potential need for supplemental insulin)
3. Less preferred: Glyburide (due to concerns about increased adverse neonatal outcomes)

Special Considerations:

• Pre-existing conditions (e.g., PCOS may respond well to metformin)
• Obesity (metformin may have advantages due to less weight gain)
• Patient adherence issues (oral medications may improve compliance)
• Risk of hypoglycemia (metformin has lower risk than insulin or glyburide)
• Gestational age at initiation of therapy

Key Nursing Responsibilities:

• Teach blood glucose monitoring technique and target ranges
• Educate about medication administration (injection technique for insulin)
• Provide dietary counseling in coordination with dietitian
• Educate about symptoms and management of hypoglycemia
• Encourage appropriate physical activity
• Monitor for signs of complications
• Educate about the importance of postpartum diabetes screening

Two primary formulations of progesterone are used for preterm birth prevention:

Formulation	Route	Dosage	Primary Indication
17α-hydroxyprogesterone caproate (17-OHPC)	Intramuscular injection	250 mg weekly	History of spontaneous preterm birth
Micronized progesterone	Vaginal (gel, suppository, or capsule)	90-200 mg daily	Short cervix (≤25 mm) in current pregnancy

Key Differences:

• 17-OHPC: Synthetic progestin, longer half-life, weekly administration, systemic effects
• Vaginal progesterone: Natural progesterone, daily administration, higher local uterine/cervical concentrations, fewer systemic effects

Indication: Women with a singleton pregnancy and history of spontaneous preterm birth before 37 weeks in a previous pregnancy.

Dosage and Administration:

• 250 mg intramuscular injection weekly
• Initiated between 16+0 and 20+6 weeks gestation
• Continued until 36+6 weeks gestation or delivery

Evidence of Efficacy:

• Original Meis trial (2003) showed 34% reduction in recurrent preterm birth with 17-OHPC
• PROLONG trial (2019) failed to confirm benefit in a different population
• Meta-analyses suggest benefit, particularly in high-risk US populations

FDA Status: The FDA approved Makena (brand name 17-OHPC) in 2011 but recommended withdrawal in 2019 after PROLONG trial results. Currently, the medication remains available, and professional organizations continue to include it in treatment guidelines.

Side Effects:

• Injection site pain, swelling, and bruising
• Urticaria (hives) or pruritus
• Nausea
• Depression
• Glucose intolerance (rare)

Contraindications:

• Thrombophlebitis or thromboembolic disorders
• Known or suspected breast cancer or other hormone-sensitive cancer
• Undiagnosed abnormal vaginal bleeding
• Liver dysfunction or disease
• Uncontrolled hypertension

Indications:

1. Singleton pregnancy with short cervical length (≤25 mm) before 24 weeks gestation
2. Alternative to 17-OHPC for history of spontaneous preterm birth

Formulations and Dosage:

• Vaginal gel: 90 mg daily (8% gel, Crinone)
• Vaginal suppository: 100-200 mg daily
• Vaginal capsule: 100-200 mg daily

Timing:

• Typically started after identification of short cervix (often around 20-24 weeks)
• Continued until 36+6 weeks gestation or delivery

Evidence of Efficacy:

• Multiple randomized controlled trials have demonstrated efficacy in women with short cervix
• Meta-analyses show 40-45% reduction in preterm birth in women with short cervix
• Associated with reduction in neonatal morbidity and mortality

Side Effects:

• Vaginal irritation or discharge
• Minimal systemic side effects
• Less injection site pain compared to 17-OHPC

Clinical Scenario	Recommended Approach	Evidence
Singleton pregnancy with prior spontaneous preterm birth	17-OHPC or vaginal progesterone	Strong evidence for 17-OHPC; increasing evidence for vaginal progesterone
Singleton pregnancy with short cervix (≤25 mm)	Vaginal progesterone	Strong evidence for efficacy
Multiple gestation	Not routinely recommended	No consistent evidence of benefit
Preterm premature rupture of membranes	Not recommended	Insufficient evidence
Arrested preterm labor	Not routinely recommended	Insufficient evidence
Short cervix in twin pregnancies	May consider vaginal progesterone	Limited evidence of possible benefit

Current Professional Organization Recommendations:

• ACOG (American College of Obstetricians and Gynecologists): Offers progesterone supplementation for women with singleton pregnancy and prior spontaneous preterm birth or short cervical length.
• SMFM (Society for Maternal-Fetal Medicine): Recommends offering 17-OHPC to women with singleton pregnancy and history of spontaneous preterm birth, and vaginal progesterone for women with singleton pregnancy and short cervical length.

Current Controversies:

• 17-OHPC efficacy: Conflicting results between Meis trial and PROLONG study
• Optimal formulation: Whether vaginal progesterone may replace 17-OHPC for prior preterm birth
• Optimal dosing: Variations in dose and formulation of vaginal progesterone
• Role in multiple gestations: Some subgroups may benefit, but evidence is inconsistent
• Starting earlier: Whether initiating therapy before 16 weeks offers additional benefits

Key Nursing Considerations:

• Patient Education:
  • Explain purpose and expected benefits
  • Teach proper administration technique for vaginal progesterone
  • Discuss importance of adherence to weekly injection schedule for 17-OHPC
  • Review potential side effects and when to contact healthcare provider
• Administration of 17-OHPC:
  • Use proper technique for IM injection (Z-track method recommended)
  • Rotate injection sites to minimize local reactions
  • Consider use of longer needles for women with higher BMI
• Monitoring:
  • Assess for signs of preterm labor at each visit
  • Monitor for side effects and compliance
  • Document cervical length measurements if performed

1. Seizure Prophylaxis:

• CNS depressant effect
• Blocks N-methyl-D-aspartate (NMDA) receptors
• Decreases acetylcholine release at motor nerve terminals
• Vasodilation of cerebral blood vessels reduces cerebral ischemia
• May reduce cerebral edema by stabilizing endothelial cells

2. Fetal Neuroprotection:

• Blocks NMDA receptors, preventing excessive calcium influx into neurons
• Reduces inflammatory cytokine production
• Prevents excitatory amino acid-induced damage
• Stabilizes cell membranes
• Anti-apoptotic effects
• May improve cerebral blood flow

3. Other Physiological Effects:

• Mild tocolytic effect (reduces uterine contractility)
• Peripheral vasodilation (reduces blood pressure)
• Increased renal blood flow
• Reduces platelet aggregation
• Bronchodilation

Indications:

• Eclampsia (treatment of seizures)
• Severe preeclampsia (prevention of eclampsia)
• Some cases of preeclampsia without severe features (controversial, varies by institution)

Dosing Regimen:

Indication	Loading Dose	Maintenance Dose	Duration
Severe preeclampsia	4-6 g IV over 20-30 minutes	1-2 g/hour IV continuous infusion	24 hours postpartum or until resolution of severe features
Eclampsia (after seizure)	6 g IV over 15-20 minutes	2 g/hour IV continuous infusion	24 hours after last seizure

Evidence of Efficacy:

• The Magpie Trial (2002) demonstrated that magnesium sulfate reduced the risk of eclampsia by more than 50% compared to placebo
• Superior to phenytoin, diazepam, or nimodipine for seizure prevention
• NNT (Number Needed to Treat) approximately 63-69 women with preeclampsia to prevent one case of eclampsia
• NNT approximately 36 women with severe preeclampsia

Indications:

• Women at high risk for delivery before 32 weeks gestation
• Preterm labor with intact membranes
• Preterm premature rupture of membranes
• Planned preterm birth for maternal or fetal indications

Dosing Regimen:

Loading Dose	Maintenance Dose	Duration
4 g IV over 30 minutes	1 g/hour IV continuous infusion	Until delivery, or Maximum 24 hours if delivery does not occur, or Discontinued if preterm birth no longer imminent

Evidence of Efficacy:

• Meta-analyses demonstrate 30-45% reduction in cerebral palsy risk
• Most effective when given within 24 hours of birth
• Number needed to treat: approximately 63 women to prevent one case of cerebral palsy
• Benefit observed primarily for deliveries before 30-32 weeks gestation

Timing Considerations:

• Ideally administered at least 4 hours prior to anticipated birth
• Still beneficial even if delivery occurs sooner
• If imminent delivery is delayed, consider discontinuing after 24 hours
• May be repeated if preterm birth becomes imminent again after previous course

Clinical Monitoring:

• Vital signs (blood pressure, heart rate, respiratory rate)
• Urine output (maintain >30 ml/hour)
• Deep tendon reflexes (DTRs)
• Level of consciousness
• Respiratory assessment

Laboratory Monitoring:

• Serum magnesium levels (therapeutic range: 4-8 mEq/L or 4.8-9.6 mg/dL)
• Renal function (creatinine)

Signs of Magnesium Toxicity by Level:

Serum Level (mEq/L)	Clinical Manifestations
4-8	Therapeutic range
8-10	Loss of patellar reflexes
10-12	Respiratory depression
15-20	Cardiac arrest, respiratory paralysis

Common Side Effects:

• Flushing
• Nausea/vomiting
• Headache
• Lethargy or confusion
• Muscle weakness
• Diplopia (double vision)
• Slurred speech
• Sensation of warmth
• Hypotension (especially with rapid administration)
• Pulmonary edema (rare)

Renal Impairment:

• Magnesium is primarily excreted by the kidneys
• Dose reduction required in women with renal insufficiency
• More frequent serum level monitoring recommended
• Consider starting at 0.5-1 g/hour for women with renal impairment

Concurrent Calcium Channel Blocker Use:

• Combined use can lead to exaggerated hypotension
• Careful blood pressure monitoring required
• Consider using alternative tocolytic if magnesium already in use

Effects on Labor and Delivery:

• May mildly decrease the strength of contractions
• May prolong labor slightly
• Does not preclude use of oxytocin augmentation if needed

Neonatal Effects:

• Transient hypotonia or lethargy may occur
• Respiratory depression (rare with therapeutic maternal levels)
• Decreased intestinal motility
• Hypocalcemia

Anesthetic Considerations:

• Potentiates neuromuscular blocking agents
• May prolong recovery from anesthesia
• Anesthesia providers should be informed about magnesium administration

Administration Guidelines:

• Verify order and dose carefully (high-alert medication)
• Use infusion pump for IV administration
• Administer loading dose over appropriate time period (not too rapidly)
• Avoid subcutaneous extravasation (tissue necrosis risk)
• Ensure antidote (calcium gluconate) is readily available

Monitoring Schedule:

Parameter	Frequency	Target
Blood pressure	Every 5-15 min during loading, then every 30-60 min	Maintain SBP >90 mmHg
Heart rate	Every 30-60 min	60-100 bpm
Respiratory rate	Every 30-60 min	>12 breaths/min
Oxygen saturation	Continuous in high-risk patients	>95%
Deep tendon reflexes	Every 1-4 hours	Present (1+ to 2+)
Urine output	Hourly	>30 mL/hour
Serum magnesium levels	6-12 hours after initiation and dose changes	4-8 mEq/L

Patient Education:

• Explain purpose of medication (seizure prevention or neuroprotection)
• Prepare for sensation of warmth, flushing during administration
• Describe monitoring procedures
• Instruct to report difficulty breathing, chest pain, or severe headache
• Explain importance of maintaining bed rest with assistance

High-Risk Factors (One factor sufficient for LDA recommendation):

• History of preeclampsia, especially with adverse outcomes
• Multifetal gestation
• Chronic hypertension
• Type 1 or Type 2 diabetes
• Renal disease
• Autoimmune disease (systemic lupus erythematosus, antiphospholipid syndrome)

Moderate-Risk Factors (LDA recommended with ≥2 factors):

• Nulliparity
• Obesity (BMI >30 kg/m²)
• Family history of preeclampsia (mother or sister)
• Age ≥35 years
• Sociodemographic characteristics (African American race, low socioeconomic status)
• Personal history factors (previous adverse pregnancy outcome, >10-year pregnancy interval)

Additional Indicators:

• Abnormal uterine artery Doppler studies
• Elevated first-trimester markers (PAPP-A, PlGF)
• History of placental insufficiency

Recommended Dose:

• 81-150 mg daily (most common: 81 mg in US, 75-150 mg in Europe)
• Recent evidence suggests that 150 mg may be more effective than lower doses

Timing of Initiation:

• Optimally started between 12-16 weeks gestation
• May be initiated as early as after confirmation of pregnancy
• Still beneficial if started before 28 weeks, but efficacy decreases with later initiation
• Most recent data suggest maximum benefit when started before 16 weeks

Administration Recommendations:

• Take at bedtime (maximizes efficacy based on circadian rhythm of blood pressure)
• Take with food if GI upset occurs
• Use enteric-coated formulations to reduce GI irritation
• No need for monitoring of platelet function or aspirin levels

Duration:

• Continue until delivery
• May be discontinued at 36 weeks in some protocols to reduce theoretical bleeding risk
• No need to taper off; can be discontinued abruptly

Overall Effectiveness:

• Meta-analyses show 10-30% reduction in preeclampsia risk, with greater benefit in high-risk women
• 17% reduction in preterm birth
• 14% reduction in fetal/neonatal death
• 20% reduction in fetal growth restriction

Key Studies:

1. ASPRE Trial (2017): 150 mg aspirin started at 11-14 weeks reduced preterm preeclampsia by 62% in high-risk women identified by screening
2. US Preventive Services Task Force Meta-analysis (2014): 17% reduction in risk of preeclampsia across all women, with greater benefit in high-risk groups
3. CLASP Trial: Demonstrated safety of low-dose aspirin in pregnancy

Factors Affecting Efficacy:

Factor	Impact on Efficacy	Evidence
Dosage	Higher doses (≥100 mg) appear more effective	Multiple meta-analyses
Timing of initiation	Starting before 16 weeks more effective	ASPRE trial, meta-analyses
Time of day	Bedtime administration more effective	Chronotherapy studies
Risk level	Greater benefit in higher-risk women	Consistent across studies
Adherence	Regular daily use required	Compliance studies
Maternal weight	May need higher doses for obesity	Emerging evidence