OB/GYN Pharm

Depression

Depression occurs in 10% to 16% of pregnant women. Maternal depression is associated with greater risk for premature birth, low birth weight, and fetal growth restriction. In addition to the potential impact of maternal depression on obstetric complications, untreated depression may have long-term implications for normal infant development.

Asthma

Asthma control may stay the same, worsen, or improve with pregnancy. The likelihood of each scenario is equal. Exacerbations are common, particularly in the second trimester and likely due to hormone changes, cessation or reduction of medications because of perceived risks, and increased susceptibility to respiratory illness (e.g. influenza) during this time.

Transplacental Drug Transfer

At one time, it was believed that the placenta acted as a barrier between mother and fetus. However, the placenta is an organ of exchange for a number of substances including nutrients, gases, antibodies and some medications. There are certain chemical properties of medications that influence the rate of transfer across the placenta.

Polio

Avoid vaccination of pregnant women

1st line/prevention constipation

Nonphar, Light physical exercise, dietary fiber 25-30 grams/day, fluids ( 8 - 8oz servings/day)

1st line/prevention anticoag

Nonpharm???

1st line (Mild N/V) Prevention

Nonpharmacologic options Light snack 15 - 20 minutes before getting out of bed; avoidance of triggers and spicy/fatty foods, acupressure-Sea Bands, and ginger

1st Line

Nonpharmacologic options Relaxation, stress management, adequate sleep, biofeedback

1st line/prevention

Nonpharmacologic options Small meals, food avoidance before bedtime, elevate head of the bed

Influenza (LAIV)

Not recommended for use in pregnancy

Measles, mumps, rubella (MMR)

Not recommended for use in pregnancy

Not recommended diabetes

Older sulfonylureas Chlorpropamide, tolbutamide

3rd line constipation

Osmotic laxatives Stimulants Polyethylene glycol, lactulose, magnesium, sulfate Bisacodyl, senna

Estrogens and progesterones may decrease activity of CYP1A2, 2C19

Decreased metabolism of substrates May need to decrease dose of substrates 1A2 Substrates: Theophylline, caffeine 2C19 Substrates: Omeprazole, esomeprazole, lansoprazole, pantoprazole

Medication Dose Management in the Pregnant Patient

Because of the array of physiologic changes that occur during a pregnancy and the resultant pharmacokinetic effects, it is critical to ensure that medication dosing is appropriate, with careful follow up and periodic reassessment.

Patients with pyelonephritis usually present with bacteriuria and systemic symptoms of

*fever, flank pain, nausea, and vomiting*. Complications of pyelonephritis include premature delivery, low infant birth weight, hypertension, anemia, bacteremia, and transient renal failure. Therefore, hospitalization is the standard of care for pregnant women since many require intravenous hydration.

Weeks 1 & 2 Blastogenesis

"All-or-nothing" effect: Teratogen could destroy the embryo leading to a terminated pregnancy; likely unknown to the mother. Alternatively, exposure may cause no problems.

Alternative oral agents diabetes

2nd generation sulfonylureas Biguanide Glyburide Metformin

Gestational or pregnancy induced

>140/90 mmHg after 20 weeks gestation - Low risk if BP not severe - C-section rate increased

Chronic

>140/90 mmHg diagnosed prior to pregnancy or <20 weeks gestation; or if hypertension persists beyond 12 weeks postpartum Intrauterine growth restriction, low birth weight, target organ damage

Fasting

< 105 mg/dL < 90 mg/dL

2 hour postprandial

<130 mg/dL <120 mg/dL

1 hour postprandial

<155 mg/dL <130-140 mg/dL

Preeclampsia

>140/90 mmHg plus one of the following: • Proteinuria: ≥300 mg per 24 hour urine collection; protein/creatinine ratio ≥0.3; or dipstick reading of 1+ • Thrombocytopenia: platelet <100,000 • Renal insufficiency: SCr >1.1 mg/dL or a doubling of SCr • Impaired liver function: LFTs ≥ 2xULN • Pulmonary edema • Cerebral or visual symptoms Headache, visual disturbance, oliguria, upper quadrant pain, LFTs, HELLP syndrome (Hemolysis, ELevated liver enzymes, Low Platelet counts) Æ life-threatening variant of preeclampsia

2nd line for GERD

Antacids Protectant Histamine-2 receptor blockers Tums, Mylanta, Maalox, MoM Sucralfate Ranitidine, cimetidine - evidence to support use; famotidine, nizatadine - limited data but presumably safe

Contraindicated HTN meds

ACE-inhibitors, angiotensin receptor blockers, aliskiren Category D but with fetal renal toxicity and death reported

Insufficient data to recommend • Atazanavir • Darunavir • Fosamprenavir • Tipranavir

ATZ - theoretical concern of increased bilirubin may impact neonate. Insufficient data to recommend dosing. DRV - Insufficient data to recommend dosing. FAMP- Insufficient data to recommend dosing. TPV - Insufficient data to recommend dosing.

2nd Line

Acetaminophen Codeine Other narcotic analgesics Preferred agent in those that do not respond to non-pharm +/- acetaminophen Typically Categories C or D (other narcotic)

Gastric secretion decreases by appx 40%, causing gastric pH to increase

Altered absorption of medications that require an acidic environment for absorption Patients may need to take affected drugs with food or acidic beverage (OJ) or switch to a different formulation (solution) Iron (commonly used in pregnancy for anemia) Digoxin Ampicillin Ketoconazole

Avoid

Aspirin (+/- caffeine and butalbital Ergotamines, dihydroergotamines PDA narrowing, bleeding, decreased uterine contractility Sudden fetal death

Management of Acute Severe Hypertension in Preeclampsia

BP ≥ 160 mmHg SBP and/or ≥ 105 mmHg diastolic if sustained

Pharmacokinetics in Pregnancy

Because the FDA Categories are variable and there is not always detailed information available for specific medications, it is important to understand and apply the physiologic changes that take place during pregnancy that potentially affect medication use. The changes begin in the first trimester and peak during the second. The following tables outline adjustments and alterations that occur in a pregnant patient.

Generally safe HTN meds

Beta blockers Hydralazine With the exception of atenolol Æ intrauterine growth restriction

Gastroesophageal Reflux Disease (GERD)

Between 40 - 80% of women experience heartburn or reflux symptoms. Lifestyle and dietary modifications should first be addressed, as in non-pregnant patients. If symptoms are not relieved, antacids or sucralfate are acceptable. Histamine 2 receptor blockers can be used for patients unresponsive to lifestyle changes and antacids. There is more data to support the use of ranitidine and cimetidine than other H2 blockers. Less data is available for proton pump inhibitors. Most PPIs are Category B (omeprazole Category C) but are still reserved for those patients that do not respond to other therapies.

Postpartum For infant

Birth to 6 weeks Term infant >35 weeks: • 2 mg/kg every 6 hours orally (ZDV syrup), started as close to birth as possibly (by 6-12 hours). <35 weeks but >30 weeks: • 2mg/kg every12 hours orally advance to every 8 hours at 2 weeks of age. <30 weeks: • 2mg/kg every 12 hours orally advance to every 8 hours at 4 weeks of age. For all scenarios give IV dose if unable to take PO: 1.5 mg/kg/dose

Diabetes Management during Lactation:

Breast feeding should be encouraged in women with diabetes. It is appropriate to continue insulin therapy during lactation. Recent studies have proven the safety of both metformin and glyburide in breastfeeding. In 3 randomized trials no clinically significant amounts of metformin were found in breast milk, while no glyburide was detected in breast milk.

Levetiracetam (LEV) C

C No protein binding. 30% metabolized in blood (hydrolysis) and 70% eliminated unchanged in urine. Case studies have shown incrased clearance during pregnancy with [LEV] ↓ 50%.

Zonisamide (ZNS)

C No studies during pregnancy published

Lamotrigine (LTG)

C Not a highly protein bound drug. Undergoes extensive metabolism; glucuronidation. Clearance in last trimester increased, [LTG] reduced 40% to 60%. Less affected if coadministered with enzyme inducing or inhibiting drug. Oral clefts

Gabapentin (GBP) pregabalin (PGB)

C Not metabolized, eliminated unchanged through kidneys. Suspect increased clearance related to GFR, however, not well studied.

Oxcarbazepine (OXC)

C Required metabolism to active form (MHD-OXC), which is eliminated by glucuronidation. Low protein binding. In 2 small studies [MHD-OXC] ↓ 36% during pregnancy.

Topiramate (TPM)

C Small amount metabolized. Possible increased clearance related to increased renal blood flow leading to a decline in [TPM]. No studies on pK during pregnancy published.

Alternate agents • Indinavir/ritonavir • Nelfinavir • Ritonavir • Saquinavir/ritonavir

C B B B IND - theoretical concern of increased bilirubin may impact neonate. Must use boosted regimen. NLF - no evidence of human teratogenicity. Extensive experience with use in pregnancy. RIT - limited experience with full dose in pregnancy (mainly used as booster) SQV - short term safety demonstrated for mother and infant.

Limited data HTN meds

Calcium channel blockers Clonidine No known increase in teratogenicity; nifedipine is commonly use

IV antibiotics for pyelonephritis

Cephalosporins (ceftriaxone, cefazolin) • Ampicillin + gentamicin • Ampicillin/sulbactam After the patient is noted to be afebrile for 48 hours, transition to equivalent oral antibiotics and discharge from hospital when stable. *The total antibiotic treatment duration (IV and oral) should be 10 - 14 days.*

Alternatives for prevention of perinatal transmission in women who have not received ART prior to labor

Combination ZDV + single dose nevirapine • Woman: ZDV given as described above plus single-dose nevirapine 200 mg at onset of labor. Consideration should be given to adding lamivudine during labor and maternal ZDV/lamivudine for 7 days postpartum which may reduce development of nevirapine resistance. • Infant: single dose nevirapine (2 mg /kg given at 2 to 3 days of age if mother received intrapartum, or given at birth if mother did not receive) plus ZDV for 6 weeks as described above.

Choice of Anticoagulant:

Complications of anticoagulant use during pregnancy include teratogenicity, bleeding, and loss of pregnancy, therefore choice of medications is crucial. Unfractionated heparin, low-molecular-weight heparin and danaparoid do not cross the placenta and are safe to use in pregnancy. Warfarin does cross the placenta and is teratogenic to the fetus with a high risk of early miscarriage.

Constipation

Constipation in pregnancy is prevalent, affecting 25-40% of women. This is likely due to the hormone progesterone which is increased in pregnancy and slows movement through the intestines. Increased dietary fiber, adequate hydration and light physical exercise are typically the first-line approaches to treatment. If additional treatment is warranted, supplemental fiber and/or stool softener is appropriate. Osmotic and stimulant laxatives can be used occasionally. Castor oil and mineral oil should be avoided because they cause stimulation of uterine contractions and impairment of maternal fat-soluble vitamin absorption, respectively.

Unfractionated heparin

Continuous infusion of IV heparin adjusted to maintain therapeutic aPTT or subcutaneous heparin every 12 hours in doses adjusted to target a midinterval activated partial thromboplastin time (aPTT) into the therapeutic range

Alternate agents • Didanosine • Emtricitabine • Stavudine • Abacavir

DDI & stavudine - cases of lactic acidosis, some fatal, reported in pregnant women receiving these together. Emtricitabine- No studies in human pregnancy. Abacavir - hypersensitivity reaction occurs in 5% - 8% of nonpregnant persons. Rate in pregnancy unknown.

Carbamzepine (CBZ)

D ↓ [CBZ] by 40% or more, but unbound drug may be less affected. Only ~ 70% bound. Usually changes are not clinically significant Facial dysmorphisms, neural tube defects, hypoplasia of distal phalanges

Phenobarbital (PB)

D ↓ [PB] up to 55% with greatest decline during first trimester. Not highly protein bound. Neonatal withdrawal, neonatal coagulopathy

Valproic Acid (VLP

D ↓ total [VPA] by about 50%. Highly protein bound and influenced by changes in albumin; increasing free fraction of VPA. Thus there is potential for side effects due to excess [VPA] or subtherapeutic effects. Facial dysmorphisms, neural tube defects, dose dependent effect on verbal IQ

Phenytoin (PHT)

D ↓total [PHT] from start of pregnancy and may fall by > 60% in third trimester. As PHT is highly protein bound, pregnancy related changes in albumin may affect free fraction. Change in unbound [PHT] may only ↓ by 18%. Recommend monitor free [PHT]. Fetal hydantoin syndrome Facial clefting, hypoplasia of distal phalanges, hypertelorism, neonatal coagulopathy

Probably safe HTN meds

Diuretics Not first line. Theoretically lower the increase in plasma volume during pregnancy but have been used successfully

2nd line

Dopamine Antagonist Metoclopramide (Category B) Promethazine, Prochlorperazine (Category C)

Severe hypertension (defined as BP >160/110) can cause maternal complications, hospital admission, and potential premature delivery.

Drug therapy is indicated for all women with a blood pressure of 160/100 mmHg or above. Treatment of nonsevere hypertension (SBP 140 - 159 mmHg or DBP 90 - 109 mmHg) reduces the risk of severe hypertension by 50% but does not substantially affect fetal outcomes. There is no consensus on when to initiate treatment of nonsevere hypertension and treatment goals vary. In the US, recommendations for treatment initiation include SBPs of 150 - 160 and DBPs of 100 - 110 mmHg, with the goal of treatment <150/100. However, some physicians have a lower threshold of treatment and feel comfortable targeting lower goals (ie <140/90 mmHg).

Not recommended for constipation

Emooliant Stimulant Mineral oil Castor oil

Asthma Exacerbation during Labor and Delivery

Exacerbations during labor are rare but can be induced by hyperventilation during labor. The optimal treatment strategy is the administration of SABAs. A side effect of high doses of beta-agonists is neonatal hypoglycemia, particularly in preterm babies. Blood glucose levels should be monitored during the first 24 hours after birth if high doses were used 48 hours prior to delivery.

2nd line constipation

Fiber Supplements Stool Softener Psyllium (Metamucil), polycarbophil (Fibercon), wheat dextran (Benefiber) Docusate

Recommended Agents • Nevirapine

No evidence of human teratogenicity. Increased risk of symptomatic rash and potentially fatal liver toxicity among women with CD4 counts > 250 when first starting therapy (unclear if pregnancy impacts this risk); thus should be clear benefit to outweigh risk if starting in such a pregnant woman. Women who become pregnant while on nevirapine and are tolerating it, may continue therapy regardless of CD4 count

Chronic Conditions in Pregnancy

For many women, pregnancy is a new consideration for a previously diagnosed health condition. For women of reproductive age (15-44 years) some of the most common chronic conditions include depression, hypertension, diabetes and asthma (among others). In the majority of situations, medications used to the treat the chronic illness can be continued throughout the pregnancy and even during breast-feeding. However, others require special considerations and alternative medication regimens.

>60 Days Growth & Maturation

For the remainder of the pregnancy, exposure to teratogens may result in growth retardation, CNS abnormalities or, in extreme cases, death.

Labor and Postpartum Management

GDM is not itself an indication for cesarean delivery or for delivery before 40 weeks of gestation. Unless other fetal or maternal indications are present women can be delivered at term, expectant management beyond due date is not recommended. Cesarean delivery should be considered if estimated fetal weight is greater than 4500 grams. Poorly controlled diabetic patients should have an amniocentesis for fetal lung maturity with delivery prior to 39 weeks. Corticosteroid administration to accelerate lung maturation will increase insulin or antidiabetic requirements for at least 5 days following steroid administration.

Vaccinations in Pregnancy

Generally, live vaccines are contraindicated for pregnant women because of theoretical risk of transmission of the vaccine virus to the fetus. Whether live or inactivated vaccines are used, vaccination of pregnant women should be considered on the basis of risk vs. benefit. Vaccination should be part of preconception planning, if applicable, and addressed when pregnancy is detected in those that do not take part in preconception planning. The main question to ask is: What is the risk of vaccination versus the benefits of protection in a particular circumstance?

Anticoagulation Management during Breast Feeding

Heparin and LMWHs are not secreted into breast milk and can be safely given to breast feeding mothers. Warfarin can once again be resumed postpartum and continued during breastfeeding. It is polar, non-lipophilic, and highly protein bound, properties which make it less likely to enter breast milk. Fondaparinux should be avoided as there is no published data to support its safety in breastfeeding. Additionally, lactating women were also excluded from clinical trials evaluating the new oral anticoagulants. The manufacturers advise against their use in this population.

Heparin (UFH):

Heparin has traditionally been the anticoagulant of choice during pregnancy because it does not cross the placenta and its safety for the fetus is clearly established. Risks of heparin therapy are to the mother only and include risks for bleeding, under- or over-anticoagulation, thrombocytopenia, and osteoporosis.

Hypertension

Hypertension affects approximately 10-15% of all pregnancies and the clinical spectrum can range from mild to severe. In most women, progression through this spectrum is slow, and the disease may never proceed beyond mild preeclampsia. In others, the disease can progress rapidly and become severe. There are different types of hypertension in pregnancy which can be categorized depending on onset, duration, and other clinical or laboratory findings.

Hypertension Management during Lactation:

Hypertension is not a contraindication to breast feeding. For a mother who wishes to breast feed for a couple of months, the clinician may consider withholding antihypertensive medications with close monitoring of blood pressure. For patients with more severe blood pressure elevation, medication is recommended.

Heparin induced Thrombocytopenia (HIT):

In pregnant women who develop HIT and require ongoing anticoagulant therapy, use of the heparinoid, danaparoid sodium, is recommended because it is an effective antithrombotic agent and has much less cross reactivity with UFH and therefore, less potential to produce recurrent HIT than LMWH. Fondaparinux, an antithrombotic agent, the first developed in a class selective factor Xa inhibitors is also suggested as possible treatment for pregnant women with HIT or history of HIT, however though studies show no placental passage deleterious potential effects cannot be excluded and it should be reserved for these cases only.

Hepatitis A

Inactivated virus Safety has not been determined Theoretical low risk

Increased body fat

Increased Vd of lipophilic drugs May consider increasing initial dose of lipophilic drugs Lipophilic medications: Trazodone; Diazepam; Opiates

Increased maternal plasma volume by 30-50%

Increased Volume of Distribution (Vd) or hydrophilic drugs May consider increasing initial dose of hydrophilic drugs Hydrophilic medications: Lithium

Increased hepatic blood flow

Increased amount of drug passes through liver resulting in increased metabolism May need to increase the dose The liver is the principle site of drug metabolism for many medications

Digoxin

Increased clearance Serum levels almost twofold lower in pregnancy; therapeutic drug monitoring essential

Phenytoin

Increased clearance; altered free and bound fractions May require higher doses; monitoring of free and total levels warranted

Decreased plasma albumin

Increased concentration of unbound (active) drug; particularly medications that are highly protein bound There will be an increase in active drug; total plasma concentrations will underestimate protein bound drugs Highly protein bound medications: Digoxin; Furosemide; Glyburide and glipizide; Naproxen and ibuprofen; Phenytoin

Estrogens and progesterones may increase activity of CYP3A4, 2D6, 2C9

Increased metabolism of substrates May need to increase the dose of substrates 3A4 Substrates: Felodipine, buspirone, midazolam, triazolam, (simvastatin, lovastatin- CatX in pregnancy) 2D6 Substrates: Desipramine, dextromethorphan, atomoxetine 2C9 Substrates: Tolbutamide, (warfarin - CatX)

Increased cardiac output GFR increases by 30-50%

Increased renal clearance of medications May need to increase the dose of renally cleared medications or dose more frequently (some of this effect is countered by the increase of free drug concentration secondary to dec. albumin) The kidneys are the principle site of drug elimination for many medications. Some notable medications: Diuretics, morphine, oxycodone, nitrofurantoin, lithium, ranitidine, glyburide

Asthma Management during Breastfeeding

Inhaled corticosteroids, theophylline, antihistamines, prednisone, cromolyn and beta 2 receptor agonists are not contraindicated during breastfeeding

2nd line diabetes

Insulin Novolin N (NPH), Humalog (lispro), Novolog (aspart), and Novolin R (regular).

Treatment Strategies for Pre-Existing Types I and 2 Diabetes in Pregnancy

Insulin is the preferred agent for management of diabetes in pregnancy because of the lack of long-term safety data for noninsulin agents. Frequent titration of insulin to match changing requirements is usually needed. In the first trimester, there is often a decrease in total daily dose of insulin. In the second trimester, rapidly increasing insulin resistance requires weekly or biweekly increase in insulin dose to achieve glycemic targets. In general, a small proportion of the total daily dose should be given as basal insulin and a greater proportion as prandial insulin. All insulins are pregnancy category B except for glargine and glulisine, which are category C.

Treatment Strategies for GDM

Lifestyle modification is considered the 1st-line therapy for all women with GDM and includes medical nutrition therapy, exercise and glucose monitoring. Many women can be successful with lifestyle modification alone. In those that are not, pharmacologic therapy should be initiated. Efficacy and short-term safety has been determined with glyburide and metformin. However, these oral medications do cross the placenta to some extend and long-term safety data is not yet available. Insulin has also been proven safe and effective. See table 17 below for additional information.

Recommended agents • Lopinavir/ritonavir

No evidence of human teratogenicity. Twice daily dosing regimen is recommended. Consider increasing dose in third trimester. C

Preprandial

No recommendation < 105 mg/dL

Acute Conditions in Pregnancy

Like all women, pregnant women can develop acute conditions, some of which are actually influenced or exacerbated by the pregnancy. In some cases, the risks associated with the acute illness are magnified during pregnancy, and early screening and treatment become critical. In other cases, such as during treatment of certain sexually transmitted diseases, the urgency regarding treatment comes from an increased likelihood of infection leading to preterm labor. Occasionally, common acute care issues, such as migraine headache, improve during pregnancy. Some of the most common acute conditions are outlined below.

Low Molecular Weight Heparins (LMWH):

Low-molecular-weight heparin has largely replaced unfractionated heparin for prophylaxis and treatment in pregnancy. Benefits of LMWH over UFH include improved bioavailability, longer plasma half-life, more predictable dose response and improved safety profile. These agents have potential advantages over UFH during pregnancy because they cause less heparin-induced thrombocytopenia (HIT), have the potential for once daily administration and probably result in a lower risk of heparin-induced osteoporosis. Studies have proved equal effectiveness of LMWH in treating VTE as well as prophylaxis in high risk patients during pregnancy as compared to UFH.

Potential Maternal Complications Bleeding:

Major bleeding for pregnant patients treated with UFH is 2%, which is consistent with the reported rates in nonpregnant patients. Administration of adjusted dose subcutaneous UFH can cause a persistent anticoagulant effect (28 hour post discontinuation of SQ dose) at the time of delivery. Bleeding complications are significantly less common with LMWH as compared to heparin. Both require cessation of therapy prior to scheduled labor as above. Postpartum therapy of both UFH and LMWH can be restarted within 12-24 hours of delivery, but should not be started sooner than within 2 hours after removing epidural catheter if for prophylactic reasons or within 24 hours after catheter for therapy. Warfarin can also be started postpartum within 24 hours of delivery. Treatment is generally continued until at *least 6 weeks postpartum, for a minimum of 6 months total therapy.*

Delayed gastric emptying by 30-50%; increased transit time (progesterone effect)

May increase or decrease medication absorption, depending on the medication's absorption site. Ex: if the site of action is the GI tract, absorption may be increased; absorption may be decreased it typically occurs past the gut May need to increase or decrease dose or change to a non-oral formulation Typically is only clinically important in situations where rapid onset of a medication is desired (ie, antihypertensives for hypertensive emergency/urgency, some pain medications).

Nausea and vomiting

May limit oral absorption; occurs most frequently during the first trimester Patients should be advised to take medications during times where nausea and vomiting is least pronounced. Typically this is "morning sickness" so evening dosing is recommended This can apply to any oral medication, particularly those that have a longer onset of action.

Preferred HTN meds

Methyldopa Labetalol Preferred due to safety shown in long term studies (but ↑↑ side effects) Increasingly preferred due to ↓ side effects

A woman's clinical condition and her free serum concentrations of antiepileptic drug should be the basis for dose adjustments.

Monitor antiepileptic drug levels monthly and, if possible, obtain free levels.

Nonpharmacologic options are first line when the nausea and vomiting are mild (see table 5). A number of pharmacotherapeutic approaches have been tried for treatment of nausea and vomiting.

Multivitamins, pyridoxine (vitamin B6), and antihistamines (including doxylamine) have shown efficacy. There is now a combination prescription medication with pyridoxine and doxylamine called Diclegis. It is a delayed release formulation and is dosed at bedtime. Phenothiazines and metoclopramide are widely used and generally considered safe if the symptoms are not well controlled with vitamins and antihistamines. Evidence of safety and efficacy with serotonin antagonists is limited, but ondansetron can be considered for hyperemesis gravidum or when other treatments fail. Corticosteroids are effective for hyperemesis gravidum but are associated with a small increase in the risk of *oral clefts* when used during the first trimester.

Caution

NSAIDs Safe in the first 2 trimesters but contraindicated in the 3rd trimester (premature PDA closure)

Nausea and Vomiting

Nausea and vomiting affect up to 90% of pregnant women, usually beginning during the fifth week of gestation and lasting through the first trimester. But 15% of women experience it throughout pregnancy. There is also a condition known as hyperemesis gravidum where unrelenting vomiting can cause weight loss, dehydration, and ketonuria.

Step 1: Mild Intermittent

No daily medications needed; Inhaled beta agonist prn

One-Step Strategy

Perform a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 and 2 h, at 24-28+ weeks of gestation in women not previously diagnosed with overt diabetes. • The OGTT should be performed in the morning after an overnight fast of at least 8 h. • The diagnosis of GDM is made when any of the following plasma glucose values are met or exceeded: o Fasting: 92 mg/dL o 1 hour: 180 mg/dL o 2 hour: 153 mg/dL

Postpartum Depression

Postpartum depression is differentiated from other forms of depression in terms of its timing. The DSM-IV-Text Revision defines postpartum depression as 'the onset of depressive symptoms within 4 weeks of giving birth'. In the clinical setting, however, postpartum depression is often diagnosed when symptoms occur within 12 months of child's birth. It is common for new mothers to experience mood swings or heightened emotions postpartum, often referred to as the 'baby blues'. These, however, are usually mild and resolve within the first 10 days of the infant's life.

Use peak expiratory flow rate (PEFR) to detect deterioration of asthma and make therapy recommendations related to severity of airway obstruction.

Predicted PEFR values are 380-550 L/min

Eclampsia

Preeclampsia + seizures As above for preeclampsia

Step 4: Severe Persistent

Preferred: Anti-inflammatory agent: inhaled corticosteroid (high dose)* + long acting inhaled beta 2 agonist (salmeterol) + oral corticosteroid** if needed Alternative: Inhaled corticosteroid (high dose) + theophylline (serum level 5-12 mcg/ml) + oral steroids** if needed *Budesonide is the preferred inhaled corticosteroid for use during pregnancy, however there are no studies showing any others are unsafe for use* **Oral steroids up to 2 mg/kg/day, max 60 mg/day

tep 2: Mild Persistent

Preferred: Anti-inflammatory agent: inhaled corticosteroid (low dose) Alternative: Cromolyn, leukotriene receptor antagonist or theophylline (serum level 5-12mcg/ml) Inhaled beta agonist prn

Step 3: Moderate Persistent

Preferred: Anti-inflammatory agent: low-dose inhaled corticosteroid and salmeterol or medium dose inhaled corticosteroid or if needed medium-dose inhaled corticosteroid plus salmeterol Alternative: Low dose or if needed medium-dose inhaled corticosteroid and either leukotriene receptor antagonist (monteleukast, zafirlukast) or theophylline (serum level 5-12mcg/ml) Note: Theophylline for nocturnal asthma not routinely recommended.

Diabetes

Pregnancy is a hyperinsulinemic state characterized by a decrease in insulin sensitivity. This insulin resistance is at least partly explained by the presence of "diabetogenic" hormones, such as human placental lactogen, progesterone, cortisol, prolactin, placental growth hormone and recent studies involve tumor necrosis factor and leptin. Fasting plasma glucose levels are generally lower in pregnancy than in the nonpregnant state, but postprandial values tend to be higher, particularly in persons who cannot adequately augment their insulin response.

Tetanus and Diptheria (Td)

Pregnant woman should receive Td vaccine if indicated (previously vaccinated pregnant women who have not received a Td vaccination within the past 10 year should receive a booster). May be reasonable to wait until the 2nd trimester to administer. Lack of data with Tdap in pregnant women. Pregnancy is not a contraindication, providers may choose when protection against pertussis outweighs vaccine risk.

Headaches

Primary headaches in pregnant women are the most common types of headache. The majority of pregnant women with a history of migraine headaches actually experience symptom improvement during pregnancy.

Low-molecular weight heparins

Prophylactic LMWH • dalteparin 5,000 units subcutaneously every 24 h • tinzaparin 4,500 units subcutaneously every 24 h • enoxaparin 40 mg subcutaneously every 24 h (although at extremes of body weight, modification of dose may be required) Intermediate-dose LMWH • dalteparin 5,000 units subcutaneously every 12 h • enoxaparin 40 mg subcutaneously every 12 h Adjusted-dose LMWH: weight-adjusted or full-treatment doses of LMWH given once daily or bid • dalteparin 200 units/kg • tinzaparin 175 units/kg once daily • dalteparin 100 units/kg every 12 h • enoxaparin 1 mg/kg every 12 h

3rd line gerd

Proton pump inhibitors Dopamine antagonist All are Category B, except omeprazole (possibly because mostly widely used and more available data) metoclopramide

Human Papillomavirus

Quadrivalent virus is not recommended for use in pregnancy

Nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs)

Recommended agents • Zidovudine • Lamivudine ZDV - No evidence of human teratogenicity. Preferred agent for use in ART in pregnancy based on efficacy studies and extensive use. LMV - Extensive experience in combination with ZDV in pregnancy. No evidence of human teratogenicity.

Influenza (inactive)

Recommended for all pregnant women during influenza season (unless otherwise contraindicated)

Ampicillin

Reduced serum half-life; increased clearance Dosing at higher end of spectrum appropriate

Epilepsy

Seizure frequency does not change with pregnancy in most women with epilepsy. Studies have demonstrated no frequency change in 54% to 80% of women with epilepsy, while decreased frequency ranges between 3% and 24% and increased frequency ranges from 14% to 32%. It is thought that seizures may increase in frequency due to changes in hormones, sleep deprivation, medication nonadherence due to perceived risks, and changes in free serum concentrations of antiepileptic drugs secondary to the pharmacokinetic changes associated with pregnancy.

3rd line

Serotonin Antagonist Corticosteroids (avoid 1st trimester) Ondansetron (Category B) Methylprednisolone, dexamethasone, prednisolone

Anitepileptics and Breastfeeding

Significant amounts of some antiepileptic drugs may reach the infant through breast feeding. Primidone and phenobarbital are secreted into breast mild. Metabolism is reduced in infants which can lead to drug accumulation, sedation and withdrawal when breastfeeding is discontinued. The infant should be carefully observed and drug monitoring in the infant is recommended. Lamotrigine is highly distributed in breast milk and should not be used. Benzodiazepines can be sedating to the infant and result in respiratory depression. Phenytoin, carbamazepine, oxcarbamazepine and valproic acid are compatible with breastfeeding.

Not Recommended • Efavirenz

Significant malformations (cleft palate, anencephaly) were observed in 15% (n=20) of infants born to monkeys who received during 1st trimester. Three case reports of neural tube defects in humans after 1st trimester exposure. Use should be avoided in first trimester. Use after second trimester may be considered if other alternatives are not available. Women of childbearing potential should be counseled about contraception.

Not recommended in GERD

Sodium bicarbonate; bismuth products Alka-seltzer; pepto-bismol

Infant born to HIV infected woman who has not received ART prior to labor

Some clinicians may choose to use ZDV in combination with additional drugs. As above for preeclampsia

Two-Step Strategy

Step 1: • Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at 24-28+ weeks of gestation in women not previously diagnosed with overt diabetes. • If the plasma glucose level measured 1 h after the load is ≥140 mg/dL* (7.8 mmol/L), proceed to a 100-g OGTT. Step 2: • The 100-g OGTT should be performed when the patient is fasting. he diagnosis of GDM is made if at least two of the following four plasma glucose levels (measured fasting and 1 h, 2 h, 3 h after the OGTT) are met or exceeded: o Fasting: 95 mg/dL o 1 hour: 180 mg/dL o 2 hour: 155 mg/dL o 3 hour: 140 mg/dL

18-60 Days Organogenesis

Structural anomalies: organ systems are developing during this stage; teratogenic exposures may result in organ system abnormalities (ie heart or neural tube defects).

Insufficient data to recommend • Tenofovir

Studies in monkeys show decreased fetal growth and reduction in fetal pone porosity within w months of starting maternal therapy. Clinical studies in humans (children) show bone demineralization with chronic use. Significant fetal passage. Lack of data in humans and concern regarding potential fetal bone effects, should not be used unless last alternative.

Cough and Cold

Symptoms related to the common cold are usually mild and self-limited, and generally do not require or respond well to intervention. However, many pregnant women with the common cold will seek advice and symptomatic therapy from their clinician. Women with the common cold can be reassured that their symptoms will generally resolve within a week.

Not studied diabetes

TZDs, meglitinides, GLP-1 agonists, DPP4 inhibitors Pioglitazone, nateglinide, liraglutide, sitagliptin

Delivery Options anticoag

The delivery options in women using anticoagulants are best considered by a multidisciplinary team. Several options are possible, including spontaneous labor and delivery, induction of labor, and elective cesarean section. The plan for delivery should take into account obstetric, hematologic, and anesthetic issues. In order to avoid an unwanted anticoagulant effect during delivery (especially with neuraxial anesthesia) in women receiving adjusted-dose subcutaneous UFH or LMWH who have a planned delivery; twice-daily subcutaneous UFH or LMWH should be discontinued 24 h before induction of labor or cesarean section, whereas patients taking once-daily LMWH should take only 50% of their dose on the morning of the day prior to delivery.

Urinary Tract Infections (Asymptomatic bacteriuria, acute cystitis, and pyelonephritis)

The most common infections in pregnant and nonpregnant women are urinary tract infections. However, the treatment between these two groups is quite different. Asymptomatic bacteriuria, meaning that a urine culture shows an infection but the patient has no symptoms, is not treated in a healthy, non-pregnant female. However, in the pregnant population, we screen for asymptomatic bacteriuria between *12 and 16 weeks gestation*. We do this because untreated, bacteriuria is more likely to progress to pyelonephritis in pregnant women than non-pregnant.

New Oral Anticoagulants:

The new oral anticoagulants (dabigatran, rivaroxaban, apixaban) are not available as treatment options for pregnant patients. Pregnant women were excluded from participating in these clinical trials. Also, animal reproductive toxicity has been described with dabigatran and rivaroxaban. The human reproductive risk of these medications remains unknown at this time.

Use a first choice antiepileptic drug for seizure type.

The prevention of tonic-clonic seizures is of upmost importance, as this form of epilepsy is potentially the most harmful to mother and fetus.

Screening and Diagnosis of gestatoinal diabetes

The recommendations for screening and diagnosis of diabetes in pregnancy vary between organizations and experts. Different diagnostic criteria will identify different degrees of maternal hyperglycemia and maternal/fetal risk. The American Diabetes Association (ADA) concludes that GDM diagnosis can be accomplished with either of the two strategies outlined in Table 12.

HIV Management during Breastfeeding

The recommendations related to breastfeeding by HIV-positive mothers differ between various organizations as research continues to emerge. The CDC recommends that women with HIV in the United States refrain from breastfeeding in order to avoid postnatal transmission of HIV to the infant. These recommendations also exist in order to prevent infant exposure to antiretrovirals. Zidovudine, lamivudine and nevirapine have been detected in the breast milk of women.

Human Immunodeficiency Virus (HIV)

The use of antiretroviral medication during pregnancy has two critical objectives: treatment of the HIV infected woman and reduction of vertical transmission of HIV to the fetus.

Factors that affect drug concentration in the infant

Timing of feeds • Frequency and duration of feeds • Volume of milk consumed • Infant's ability to metabolize the drug

Hepatitis B

Vaccine contains noninfectious HbsAg particles Based on limited experience, no apparent risk to fetus (CDC) Neither pregnancy nor lactation are contraindications for the vaccine Vaccine should be considered if indicated

1st line (Moderate to Severe N/V)

Vitamins Antihistamines Combination Vitamin B6 25mg q8 ̊; multivitamins Doxylamine, diphenhydramine, meclizine Diclegis (pyridoxine/doxylamine)

Warfarin

Warfarin crosses the placenta and therefore poses significant risk for both bleeding in the fetus and teratogenicity. An embroyopathy similar to chondrodysplasia punctata (stippled epiphyses and nasal and limb hypoplasia) has been reported in at least 5-10% of infants exposed to warfarin between 6 and 12 weeks of gestation. Although prevention of first trimester exposure may avert skeletal embryopathy, the risk for fetal bleeding persists throughout gestation, resulting in a high rate of fetal loss. Fetal CNS abnormalities that are most likely secondary to bleeding may result from warfarin exposure at any point in gestation. These conditions present as microcephaly, optic atrophy, or mental retardation. Warfarin is further contraindicated toward term, when the combination of delivery induced trauma and anticoagulation can cause serious bleeding in the neonate.

Encourage non-pharmacologic options

When appropriate, non-pharmacologic options are first-line. For acute conditions that are typically pregnancy-influenced (ie nausea, constipation, GERD) and some chronic conditions (ie diabetes) there are modalities for acquiring symptom relief without utilizing medications. When non-pharmacologic methods fail, medications should be considered.

Osteoporosis

When heparin is administered for greater than one month, there is a risk of osteoporosis developing. In general, symptomatic vertebral fractures have been reported to occur in about 2-3% of the patient population, and significant reductions in bone density (5-10%) have been reported in up to 30% of patients receiving long term UFH therapy. Evidence now shows that LMWHs have a lower risk of osteoporotic fracture at only 0.04%.

Depression Management during Breastfeeding

When treating postpartum depression, the mother can continue (and should be encouraged) to nurse if appropriate. Sertraline is a preferred pharmacologic option due to its low secretion into breast milk. Likewise, paroxetine also exhibits minimal excretion into breast milk, but it has been linked increased risk of cardiac defects in the developing fetus and is therefore used as a second-line agent. Nortriptyline is also used as a second-line agent. Non-pharmacologic options should also be considered and include psychotherapy, exercise, acupuncture, and massage.

HIV infected woman who is receiving ART and becomes pregnant

Woman • Continue current ART regimen if successfully suppressing HIV RNA, except avoid use of efavirenz or other potentially teratogenic drugs in the first trimester and drugs with known adverse potential for the mother (d4T/ddI combination) • Drug resistance testing is recommended if the woman has detectable viral load • Generally if woman requires treatment, ART should not be stopped during the first trimester. • Continue ART regimen during intrapartum period and post partum. ZDV is also given as described in Table 30 during labor. • Schedule cesarean delivery at 38 weeks gestation if HIV RNA >1000 copies/mL near time of delivery Infant • ZDV as described in Table 20 within 6 to 12 hours of birth.

HIV infected pregnant woman who is ART naïve and does NOT require treatment for her own health

Woman • Drug resistance testing is recommended prior to start of ART and if suboptimal suppression after initiation of ART • ART is recommended for prevention of perinatal transmission (even if not indicated for woman's own health): Consider delaying ART initiation until after first trimester completed. Use ZDV as a component of ART when feasible. Avoid efavirenz or other potentially teratogenic drugs in the first trimester and drugs with known adverse potential for the mother (d4T/ddI combination). Nevirapine can be used as part of ART for women with CD4 count < 250, but only used in women with higher CD4 count if benefit clearly outweighs the risk du to increased risk of severe hepatic failure. • Use of ZDV prophylaxis alone is controversial, but may be considered for women with HIV RNA < 1000 copies/mL on no therapy. • Continue ART during intrapartum period (ZDV given as IV infusion as described in Table 30) • Evaluate need for continued therapy postpartum; discontinue ART unless has indications for continued therapy. • Schedule cesarean delivery at 38 weeks gestation if HIV RNA >1000 copies/mL near time of delivery Infant • ZDV as described in Table 20 within 6 to 12 hours of birth.

HIV infected pregnant woman who is ART naïve AND has indications for ART

Woman • Drug resistance testing is recommended prior to start of ART and if suboptimal suppression after initiation of ART • Initiate ART: Use ZDV as a component of ART when feasible. Avoid efavirenz or other potentially teratogenic drugs in the first trimester and drugs with known adverse potential for the mother (d4T/ddIcombination). Nevirapine can be used as part of ART for women with CD4 count < 250, but only used in women with higher CD4 count if benefit clearly outweighs the risk due to increased risk of severe hepatic failure. • For women who require immediate start of therapy for their own health, treatment should be started as soon as possible, including the first trimester. • Continue ART during intrapartum period (ZDV given as IV infusion as described in Table 30) and postpartum. • Schedule cesarean delivery at 38 weeks gestation if HIV RNA >1000 copies/mL near time of delivery Infant • ZDV as described in Table 20 within 6 to 12 hours of birth.

HIV infected pregnant woman who is ART experienced but not currently receiving ART

Woman • Obtain full ART history and evaluate need for treatment for overall health. • Drug resistance testing is recommended prior to start of ART and if suboptimal suppression after initiation of ART • Initiate ART with regimen chosen based on resistance testing and prior therapy history. Use ZDV as a component of ART when feasible. Avoid efavirenz or other potentially teratogenic drugs in the first trimester and drugs with known adverse potential for the mother (d4T/ddI combination). Nevirapine can be used as part of ART for women with CD4 count < 250, but only used in women with higher CD4 count if benefit clearly outweighs the risk due to increased risk of severe hepatic failure. • Continue ART during intrapartum period (ZDV given as IV infusion as described in Table 30) and postpartum. • Evaluate need for continued therapy postpartum; discontinue ART unless has indications for continued therapy. • Schedule cesarean delivery at 38 weeks gestation if HIV RNA >1000 copies/mL near time of delivery Infant • ZDV as described in Table 20 within 6 to 12 hours of birth.

Maternal Intrapartum

ZDV 2 mg/kg IV over 1 hour, followed by a continuous infusion of 1 mg/kg/h Onset of labor until delivery of infant

HIV Perinatal Transmission

Zidovudine has been shown to reduce the risk of perinatal HIV transmission when administered according to a strict regimen (Table 20). This regimen was shown to reduce the risk of perinatal transmission by 70% when given alone in a randomized, double blind clinical trial, pediatric (P)-ACTG 076. ZDV reduces viral load in blood and genital secretions with antenatal drug administration. There are insufficient data available at present to justify the substitution of any other antiretroviral agent other then ZDV for the purpose of reducing perinatal HIV transmission. ZDV should be included in any antenatal regimen unless contraindicated due to severe toxicity. If a patient is using ZDV strictly for purpose of preventing fetal transmission a sole therapy of ZDV can be considered at patient request if maternal HIV RNA levels <1,000 copies/ml but is not optimal.

Acute cystitis is an infection with associated symptoms of

acute urgency, frequency, hematuria, or dysuria. The treatment of acute cystitis and asymptomatic bacteriuria are similar. E Coli is the most common pathogen in UTI, though other gram negative rods or Group B Strep could be the cause of infection. Oral antibiotics are typically sufficient treatment of asymptomatic bacteriuria and acute cystitis.

Protein binding

as outlined in table 2, maternal plasma albumin decreases while fetal albumin increases. As maternal albumin decreases, more free drug will be able to cross the placenta and bind to fetal albumin.

spontaneous labor occurs in women receiving anticoagulation, neuraxial anesthesia should not be used. Where the level of anticoagulation is uncertain and where laboratory support allows for rapid assessment of heparin levels, then testing can be considered to guide anesthetic and surgical management. In women receiving subcutaneous UFH, careful monitoring of the aPTT is required and, if it is markedly prolonged, protamine sulfate may be required to reduce the risk of

bleeding. If bleeding occurs that is considered secondary to LMWH rather than to an obstetric cause, protamine sulfate may provide partial neutralization.

The most common consequence of changes in maternal physiology during pregnancy is a

decrease in total serum drug concentrations; frequently associated with an increased volume of distribution. Thus, increased dosing or increased dose frequency may be required, in opposition to the clinician's first instinct, which is to minimize dosing during pregnancy (Table 3). Unfortunately, most drugs have not been studied in pregnant women, and therefore, the decision about whether to increase a dose will depend on the therapeutic window and on a careful clinical assessment of the patient's response. In very few cases do pregnant women require doses lower than those that are effective in non-pregnant patients.

Molecular weight

drugs with a small molecular weight (<500 daltons) will readily cross the placenta where larger molecules cross more slowly. Drugs with a MW > 1,000 daltons do not cross the placenta in significant amounts a. Drugs with MW > 1,000 - insulin, heparin

Specific risks of uncontrolled diabetes include

fetal anomalies, preeclampsia, macrosomia, intrauterine fetal demise, neonatal hypoglycemia, and neonatal hyperbilirubinemia, among others. In addition, diabetes in pregnancy increases the risk of obesity and type 2 diabetes in offspring later in life. These risks are generally greater in patients with pre-existing diabetes (type 1 or type 2) than GDM and thus, clinicians may choose manage pre-existing diabetes more aggressively in regard to glycemic targets. As with diagnosis, there is not one consensus recommendation among organizations regarding glycemic targets in pregnancy.

Ionization

fetal pH is slightly more acidic than maternal pH. This permits weak bases to cross the placenta. Once in fetal circulation, the drug molecule becomes ionized and will not readily diffuse back in to the maternal circulation. Ionized drugs will not cross the placenta readily.

Use monotherapy and/or minimize dosage -

if pharmacologic options are required, a simplified drug regimen is optimal. Trying to use one agent or the smallest number of agents, and additionally the lowest effective dose is generally in the patients' interests. However, close observation on disease or condition status is warranted as under-treating is equally dangerous in some scenarios.

Solubility

lipophilic drugs cross the placenta more easily that hydrophilic medications a. Lipophilic drugs - opiates, some antibiotics

1st Line diabetes

nonpharm Nutritional interventions, caloric restriction for obese women, self glucose monitoring

Monotherapy is preferable

o Rates of major malformation for monotherapy with antiepileptic drugs is approximately 3% o Phenytoin, lamotrigine, and carbamazepine pose the risk of cleft palate o Phenobarbital has been associated with cardiac malformations o Polytherapy is associated with a greater risk of malformation

• Valproic acid should be avoided if possible.

o The risk of major malformation is approximately 8% o Major malformations include spina bifida, facial clefts and cognitive teratogenicity of the infant o Valproic acid associated malformations are dose dependent. Low doses (<800 to 1000 mg/day) may pose a similar risk to that of carbamazepine (4%) and phenobarbital (6%). o If valproic acid must be used, avoid high plasma levels and divide dose every 6 to 8 hours.

Preconception planning

patients that are thinking of becoming pregnant should be screened for potential problematic prescription and OTC medications as well as herbals supplements. Traditional herbal treatments are widely available and, as natural products, are often not perceived to have potential toxicities. However, herbal supplements are not FDA regulated and very little information pertaining to safety in pregnancy is available.

Discourage self-medication

patients that become pregnant should be encouraged to consult a physician or pharmacist before self-treating any condition. Again, this includes herbal supplements; patient should treat them as they would a prescription or OTC medication in pregnancy, seeking medical advice before continuing or initiating.

Non-pharmacologic options should be considered first-line and includes

relaxation, stress management, and biofeedback.

Blood pressure measurement:

the patient should be in the seated position, taken on *2 separate occasions at least 6 hours apart*, to assume diagnosis. Tobacco and caffeine should be avoided 30 minutes prior to the measurement.

Exacerbations and poor control are associated with poor outcomes for both the baby and the mother. Uncontrolled asthma increases the risk of perinatal mortality, preeclampsia, preterm birth, and low-birth-weight infants. Thus, it is important to maintain adequate control of asthma throughout pregnancy

to reduce maternal and fetal complications. The advantages of treating asthma in pregnancy markedly outweigh any potential risks. For the most part, the management of asthma in pregnancy is the same for non-pregnant patients in accordance with the following principles:

A reasonable starting place for dosing most drugs in pregnancy is to

use the lowest dose known to be effective in adults. However, the assumption that less is better for pregnant patients incorrectly leads to the use of doses far lower than those shown to be effective (example: levothyroxine requirements for hypothyroidism typically increase by at least 30% in pregnancy). The result is that the mother receives no benefit, yet she and the fetus are exposed to potential toxicity. Situations in which it is reasonable to increase or decrease doses relative to the standard dosing for a particular drug are best identified by considering the drug's pharmacokinetic profile and the way pregnancy can be expected to influence this profile.

Monitor serum drug concentrations -

when serum drug concentrations can be obtained and evaluated, this is advised, particularly for narrow therapeutic index medications (lithium, levothyroxine, anticonvulsants, digoxin). It is important to monitor frequently because pharmacokinetics are changing as the pregnancy progresses.

Factors that affect transfer across the breast

• Breast blood flow • Metabolism of drug within the breast • Degree of ionization of the drug • Solubility of the drug in water or lipids • Plasma and milk protein binding • pH

Oral antibiotics for asymptomatic bacteriuria or acute cystitis

• Cephalosporins -> cephalexin • Nitrofurantoin o Safe and effective throughout most of pregnancy. However, nitrofurantoin can cause hemolysis in patients with G6PD deficiency. There is concern that transplacental nitrofurantoin might cause fetal hemolytic anemia in the infant. Reports of risk are conflicting but sources suggest that *nitrofurantoin is contraindicated after week 37.* • Beta-lactams Æ amoxicillin o Safe but E. Coli resistance limits use

Factors that affect the concentration of drug in the mother

• Drug dose, route, frequency and compliance • Clearance rate • Plasma protein binding

The specific cause of postpartum depression remains unclear, but suggested mechanisms include changes in several different hormone and neurotransmitter levels. Risk factors often demonstrated in women diagnosed with postpartum depression include:

• Hx of depressive episodes or major depressive disorder • Gestational diabetes • Multiple gestation • Poor marital and social support

In cases where an exacerbation cannot be adequately controlled with SABA administration, oral or IV corticosteroids can be used:

• Hydrocortisone 100 mg q 8 hours during labor and delivery and for 24 hours after delivery to prevent adrenal crisis, if systemic steroids taken within 4 weeks • Methylprednisolone 40-60 mg IV q 1 hour during labor, delivery and immediately post-partum

HIV infected woman of childbearing potential but not pregnant and who had indications for initiating ART

• Initiate ART as per adult treatment guidelines • Avoid drugs with teratogenic potential in women of childbearing age unless adequate contraception ensured.

Anticoagulation in pregnancy may be required antepartum and/or postpartum in the following scenarios:

• Long term anticoagulation indications o E.g. prosthetic heart valves, two or more episodes of venous thromboembolism (VTE), atrial fibrillation with CHADS2 ≥ 1 • Prophylaxis for pregnant patients with other risk factors o E.g. previous single VTE with idiopathic cause, previous VTE with pregnancy or hormone related risk factor, certain thrombophilias • Acute VTE during pregnancy

Ideal medication characteristics to limit exposure during breastfeeding

• Short half life • Once daily dosing • Highly protein bound • Low oral bioavailability • Low lipid solubility

Pregnancy and Lactation Labeling

• The FDA recently made the decision to remove the pregnancy categories A, B, C, D, and X from all human prescription drug and biological product labeling. • The new labeling will include a summary of the risks of using a drug during pregnancy and lactation, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and lactation. • There is a new subsection called "Females and Males of Reproductive Potential" that provides information on pregnancy testing and contraception recommendations and information about a drug's effects on fertility when this information is needed.

Maternal hyperglycemia should be avoided during labor. Maternal circulating glucose levels should be assessed every 1 to 2 hours and continuous intravenous insulin should be given as needed to maintain plasma glucose <110. Following are suggestions for insulin administration during labor and delivery.

• Usual dose of insulin or oral medication at bedtime • Morning dose of medication held • IV normal saline initiated • Once active labor starts, or glucose levels decrease to less than 70mg/dl infusion is changed from saline to 5% dextrose and delivered at 100-150cc/hr (2.5mg/kg/min) to achieve level approx 100 mg/dl • Patient glucose levels should be monitored at bedside hourly and infusion adjusted accordingly • Regular insulin (short-acting) should be administered IV at 1.25U/h if glucose levels exceed 100-110 mg/dl