508: Pregnancy & Lactation II - Management of Chronic Conditions in Pregnancy

What are complications of gestational diabetes in pregnancy?

• Fetal/Neonatal Complications

  • Macrosomia

  • Neonatal hypoglycemia

  • Hyperbilirubinemia

  • Shoulder dystocia

  • Other birth trauma

  • Childhood/adult obesity/diabetes

• Maternal Complications

  • Pre-eclampsia

  • Cesarean delivery

  • Preterm labor/delivery

  • Increased risk of T2DM

How do we screen for diabetes mellitus in pregnancy?

Oral Glucose Tolerance Test (OGTT) between 24-28 weeks gestation is recommended for ALL women

Who is oral glucose tolerance test indicated for?

Early OGTT indicated for overweight/obese (BMI >25) women with 1 additional risk factor:

• Physical inactivity

• First-degree relative with diabetes

• High-risk race or ethnicity

• Have previously given birth to an infant weighing 4,000g (approximately 9 lb) or more

• Previous gestational diabetes mellitus

• Hypertension (140/90 mm Hg or on therapy for hypertension)

• Women with polycystic ovarian syndrome

• A1c greater than or equal to 5.7%, impaired glucose tolerance, or impaired fasting glucose on previous testing

• History of cardiovascular disease

What types of OGTTs are used in pregnancy?

One Step OGTT

• 2 hour 75g OGTT

• Performed morning after over night fast

• Diagnosis made if any of the following are elevated:

  • Fasting: > 92 mg/dL

  • 1 hour: > 180 mg/dL

  • 2 hour: >153mg/dL

Two Step OGTT

• 1 hour 50g OGTT

  • If 1 hr >140 mg/dL ➔ perform 3 hour 100g OGTT

  • If 1 hr >200 mg/dL ➔ diagnosis made, no further testing required

• Diagnosis made if ≥ 2 readings are elevated for 3 hour 100g OGTT

  • Fasting: >95 mg/dL

  • 1 hour: >180 mg/dL

  • 2 hour: >155 mg/dL

  • 3 hour: >140 mg/dL

What are nonpharm ways to manage diabetes in pregnancy?

• Weight management

• Dietary modifications

  • Carb counting

• Light/moderate exercise as tolerated

• ~80% of women diagnosed with GDM can control BG with diet and exercise

What are our pharmacologic options to manage DM in pregnancy?

• 1st line: Insulin replacement

  • 0.7-1.0 units/kg/day divided ➔ dose depends on diagnosis

  • Insulin DOES NOT cross placenta

  • Maternal BG influence fetal BG

• 2nd line: Metformin (max dose: 2000mg daily)

  • Intolerance to insulin, good post-prandial BG with impaired fasting BG

  • Metformin DOES cross the placenta

What should we monitor pregnant pts with diabetes?

Antenatal Self Monitored Blood Glucose (SMBG)

• Testing at least 4x daily ➔ fasting and 2hr post-prandial

• Goals:

  • Fasting BG: 65-95 mg/dL

  • 2 hr PP: <120 mg/dL

Postpartum monitoring

• Screen for persistent DM at 6-12 wks postpartum

  • Place in therapy for the 2hr OGTT

• Screen for T2DM every 3 years in appropriate patients

• Counseling on continuing lifestyle modifications to prevent DM

How we do differentiate chronic HTN vs gestational HTN in pregnancy?

• Chronic HTN (cHTN)

  • HTN diagnosis prior to pregnancy or

  • BP >140/90 mmHg x 2 BEFORE 20 weeks gestation

• Gestational HTN (gHTN)

  • BP >140/90 mmHg x 2 on or after 20 weeks gestation

What are the BP cutoffs for indications of medications?

Severe: >160/110 ➔ meds indicated

Moderate: 150-159/100-109 ➔ meds considered

Mild: 140-149/90-99 ➔ meds considered

What are risk factors for pre-eclampsia (pregnancy complication marked by high blood pressure and signs of damage to another organ system)?

• History of pre-eclampsia in prior pregnancy

• Family history of pre-eclampsia

• Nulliparity or multi-order gestation

• Advanced maternal age ( >35 yo )

• Comorbidities: Diabetes, Hypertension, Obesity, CKD

How is pre-eclampsia diagnosed in pregnancy?

BP ≥ 140/90 × 2 at least 20min apart + ONE of the following:

• (+) Proteinuria → 300+mg protein in 24 urine

  • > 0.3 alb/cr ratio

  • ≥ 1+ protein on urine dipstick

• (+) Thrombocytopenia → Plt <100,000/microL

• (+) Renal → SCr > 1.1 or doubling from baseline

• (+) Hepatic → AST/ALT 2 x ULN

• (+) Pulonary edema

• (+) Cerebral/Visual symptoms

• BP ≥160/110 mmHg x 2 at lest 1-2 minutes apart sufficient for BP target

When is eclampsia diagnosed?

Preeclampsia + seizures (grand mal seizures)

What are goals of therapy for preeclampsia?

• Decrease BP to goal

  • <140/90 mmHg for most patients with gHTN / cHTN

  • <130/80 mmHg for cHTN and pre-existing DM

• Prevent pre-eclampsia/eclampsia

• Prevent complications (target organ damage, pre-term labor/delivery, low birth weight)

• Deliver a viable, health infant

• Maternal morbidity/mortality prevention

What is HELLP syndrome?

Hemolysis

Elevated liver enzymes

Low platelets → may be sevre form of pre-eclampsia, but could be present independent of BP elevations and proteinura

What are pharmacotherapy options for cHTN vs gHTN?

• cHTN

  • if medication controlled prior to pregnancy, either continue medication OR change to preferred agent

• gHTN

  • initiate therapy when BP >150/100 OR when BP >140/90 if preexisting cardiac hx, vascular dx, or DM

What are our 1st line options for HTN in pregnancy?

• Labetalol 100-1200mg BID (αβ Blockers)

  • Lower risk of IUGR than traditional beta blockers

  • No change in cardiac output

  • Caution: asthma, heart dx, CHF

  
  

• Nifedipine XR 30-120mg daily (Calcium Channel Blocker)

  • No teratogenicity est.

  • No change in cardiac output

  • Concern for reflex tachycardia and HAs

What are our 2nd line options for HTN in pregnancy?

2nd line agents

• Thiazide Diuretics

  • Theoretic concerns for intravascular volume depletion ➔fetal growth restriction

  • Concerns for electrolyte abnormalities

• Non-DHP CCB - Increased risk for CV defects

Which HTN meds do we AVOID during pregnancy?

• ACE-inhibitor / ARB:

  • 1st trimester CV/CNS defect

  • 2nd & 3rd trimester nephrotoxic (renal failure / anuria)

• Atenolol: increased fetal/neonatal mortality

How do we manage Preeclampsia / Eclampsia?

• Delivery is the only cure → Deliver if severe or near term

• Consider betamethasone if 24-34 weeks

  • Fetal lung maturation

• Treat HTN acutely → IV labetalol or hydralazine

• Prevent seizures → IV magnesium

Clinical risk assessment for Preeclampsia (recommendations for aspirin use)

***LOOK OVER***

What preeclampsia risk factors would constitute the use of low dose aspirin? (High risk factors)

• History of preeclampsia, especially when accompanied by an adverse outcome

• Multifetal gestatio

• Chronic HTN

• Type 1 or 2 diabetes

• Renal disease

• Autoimmune disease (SLE, antiphospholipid syndrome)

How do we manage asthma in pregnancy?

What is our product of choice?

Pregnancy clinical pearls

• Short acting product of choice → Albuterol

• ICS preferred – budesonide (category B) and all others (category C) but can be used

• Montelukast preferred over others in class bc more info

• Systemic steroids – highest risk of fetal abnormality (cleft palate) during wks 0-9 ➔ prednisone is preferred steroid

What are risk factors for VTE in pregnancy?

• Physiologic changes during pregnancy

• Personal history of VTE (DVT or PE)

• Obesity

• Age

• Hypertension

• Smoking

How do VTEs complicate pregnancy?

Pregnancy is considered a hypercoagulable state

• Increased clotting factors (VII, VIII, IX, X, and XII)

• Decreased antithrombin III, protein S

• Increased platelet function

• Venous stasis

What’s our drug of choice for VTE management?

1st line: LMWH and unfractionated heparin (do not cross placenta)

• LMWH (category B) preferred < 36wga and preferred in outpatient setting

  • Enoxaparin

    • Prophylaxis – 40mg SC once daily

    • Intermediate dosing (often 40mg SC q12h)

    • Therapeutic – 1mg/kg SC q12h

    • BID dosing preferred when possible, because of PK

Heparin (category C) preferred if ≥36 wga

What do we generally AVOID for VTEs in pregnancy?

Avoid warfarin

May use in 2nd/3rd trimester for mechanical valves

How do we monitor LWMH in pregnancy?

Consider monitoring anti-factor Xa levels

• Draw peak 4-6 hrs after last dose

• Prophylaxis – may check every 1-3 months

• Treatment – check monthly; may consider weight based dose adjustments

What levels of LMWH do we look for in pregnancy?

Levels for prophylaxis → 0.1-0.6 International units/mL

Levels for treatment → 0.6-1 International units/mL

How do thyroid disorders complicate pregnancy?

• ↑ thyroid binding globulin (TBG)

• ↓ iodide levels

• hCG and placental changes

  • hCG structurally similar to TSH

What are maternal/fetal complications of hyperthyroidism?

• Maternal risk: HF, pre-E, PTD

• Fetal risk: still birth, cleft lip, hydrops, craniosynostosis, etc

What are maternal/fetal complications of hypothyroidism?

• Maternal risk: HTN, pre-E, PTD, placental abruption

• Fetal risk: spontaneous abortion, LBW, low IQ, cretinism

What agents do we use for hyperthyroidism in pregnancy?

• 1st trimester

  • Propylthiouracil (D)

  • FR: fetal hypothyroidism, goiter

• 2nd/3rd Trimester

  • Methimazole (D)

  • FR: fetal hypothyroidism, goiter

What agents do we use for hypothyroidism in pregnancy?

Levothyroxine (A)

• Typically requires ~30% higher dose, may require titration through pregnancy

What do we monitor for thyroid disrorders?

• Symptoms c/w hyper/hypothyroidism

• Labs – trimester specific goals (per AAFP guidelines)

  • TSH

    • 1st trimester = 0.1 – 2.5

    • 2nd Trimester = 0.2 - 3

    • 3rd trimester = 0.3 – 3.0 respectively

      • Should see gradual return to pre-pregnancy TSH goals

  • Free T4

    • 1st trimester = 0.8-1.2

    • 2nd Trimester = 0.6-1.0

    • 3rd trimester = 0.5-0.8

What’s the physiology of lactation?

• Primarily controlled by prolactin (PRL)

  • PRL concentrations gradually increase during pregnancy

  • Lactogenesis inhibited by high estrogen and progestin concentrations during pregnancy

  • Lactation triggered by decrease in progestin following delivery

  • Once established, milk production is regulated by infant demand

• Breastfeeding provides maternal and infant health benefits

What are the Lactation Safety Categories?

• L1 - Safest

  • Drug taken by a large amount of lactating women and not shown ADR

  • Controlled studies in lactation do not show ADR

• L2- Safer

  • Drug studied in a limited number of lactating women and not shown ADR

  • Evidence shows risk for harm is remote

• L3 - moderately safe

  • No controlled studies in breastfeeding women OR controlled studies show only minimal nonthreatening risk

  • Risk is possible

  • Give if benefit outweighs risk

• L4 - possibly hazardous

  • Risk to breastfed infant or breastmilk but benefits may outweigh risks to infant (life-threatening situation, safer drugs cannot be used as alternative)

• L5 - hazardous

  • Studies documents significant risk or high risk medication with known infant damage.

  • Risk outweighs benefit.

  • Medication is contraindicated for breastfeeding.

How is medication transferred to milk during lactation?

• Simple Diffusion – most common method of transfer

  • Ionization

  • Lipophilic

  • Protein binding

  • Molecular weight

• Milk/Plasma ratio – Drugs excreted in breast milk

  • >1-5 indicates high level in milk

  • <1 indicates low levels in milk

What are some things to consider during lactation?

• Consider dose/route/frequency and duration of maternal use

  • In general - <1% of maternal dose will get to infant

• Infant specific considerations

  • Compare to usual dose if medication used for pediatrics

  • Age

  • Days postpartum

  • Feeding intervals

• Relative infant dose

  • RID = Infant dose / maternal dose (in mg/kg/d)

    • <10% is generally safe

How can we minimize infant exposure to medicaitons?

• Evaluate duration of treatment

• Avoid extended release formulations/medications with long half lives

• Consider feeding times