Pennsylvania Academy of Family Physicians Foundation & UPMC 43rd Refresher Course in Family Medicine

CME Conference March 10-13, 2016

Medical Conditions During Pregnancy Karen Moyer, MD

Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices.

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Medical Complications of Pregnancy

Karen Moyer, MD

March 12, 2016

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Disclosure

The speaker has no conflict of interest, financial agreement, or working affiliation with any group or organization.

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More than 90% of pregnant women take some type of medicaton during their pregnancy

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Medical complications of pregnancy are common and something that a family practitioner should feel comfortable managing.

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Goals

Review common medical problems that occur during pregnancy.

Understand what medications may be used when treating these conditions.

Be more comfortable managing medical complications during pregnancy in your office.

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(8.1) includes information for a pregnancy exposure registry for the drug when one is available.. Information in the Pregnancy sub-section includes a Risk Summary, Clinical considerations, and Data

(8.2), and provides information about using the drug while breastfeeding, such as the amount of drug in breast milk and potential effects on the breastfed infant.

(8.3), new to the labeling, includes information, when necessary, about the need for pregnancy testing, contraception recommendations, and information about infertility as it relates to the drug.

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Aches and Pains

General aches and pains

Tylenol up to 3g/ day Considered safe and effective

NSAIDs can be used in certain situations... Second trimester

1st trimester associations with orofacial clefts & cardiac defects

3rd trimester (early closure of the ductus)

Tylenol based products are not working.

In lieu of narcotics

Pregnancy prolongation in early preterm labor (Indocin)8

Aches and Pains

Aspirin Avoid during organogenesis

Gastroschisis O.R. 2.37

Used for certain medical indicaitons preeclampsia prevention – start at 12-13 weeks

Narcotics can be used but must be informed. No risk for birth defects, but ….

Must discuss fetal exposure risk and potential for withdrawal after delivery - Neonatal abstinence syndrome

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URI

24 yo G1P0 at 7 weeks gestation presents with runny nose, congestion, cough, sore throat x 7 days and is asking what she can take. Her 1st appointment with her OB provider is in 2 weeks.

A) Psudoephedrine

B) Guaifenesin

C) Tea with honey, netty pot & nasal strips

D) Phenylephrine

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Lower Respiratory infection

Penicillins & Cephalosporins – first line

Macrolides Risk for infantile hypertrophic pyloric stenosis

Highest risk if given directly to the infant in first 2 weeks of life (AR 24.4), followed by week 2-4 of life (AR 3.24)

If given in pregnancy week 0-27 (AR 0.01), week 28- birth (AR 0.67)

AmiNOglycosides – fetal renal and ototoxicity

FloroquiNOlones – fetal arthropathy

Tetracyclines – stains developing teeth 11

OTC topical antifungals, antibacterials and low dose steroid creams all considered safe

By the way, I also have

a rash.

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Nausea / Vomitting

Avoid triggers

Small meals often – complex carbs & protein

“crackers” by the bedside

Forget the iron initially

Consider other causes if severe

Ginger – 1 -1.5g daily Capsules, lollipops, candies, tea Improves nausea but not episodes of emesis

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Nausea / Vomitting

B6 (pyridoxine) 25mg TID Decreases nausea but not emesis

Doxylamine (unisom) 10 mg daily Combo with B6 sold as Diclegis

Antihistamines (Benadryl, Meclizine, Dramamine)

Reglan 10mg = Phenergan 25mg = Zofran 4mg ODT

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GERD

Avoid triggers,

Small meals often

Remain upright after meals

Antacids (calcium or aluminum)

H2 Blockers

PPI’s

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Asymptomatic Bacteriuria & Urinary Tract Infections

>100,000 cfu of bacteria Treat 3-7 days and f/u with a test of cure

PCN, cephalosporins, quinolones 1st line

Nitrofurantoin in 1st trimester not associated with increased risk of malformations (OR 0.79) Increased risk for neonatal jaundice when given 3rd

trimester.

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Asthma in Pregnancy

8-9% of pregnant women

Treat to prevent maternal and fetal hypoxia

Two main predictors with regard to symptoms in pregnancy... Severity of symptoms in the year prior to

pregnancy

Medication compliance and treatment

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Asthma Treatment Goals and Meds

Similar to the non-pregnant state Treat allergy symptoms

Claritin, Zyrtec and Singulair all class B

Use asthma severity classification

to guide treatment. Goal is albuterol use < twice weekly

Start with budesonide if starting

inhaled steroid for the first time. If well controlled on current regimen, leave them

on it. 18

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Monitoring

If persistently poor control then monitor for IUGR with growth u/s Q3-4 weeks.

Goal Oxygen: sats >95% in pregnancyPaO2 >70

A “normal” CO2 level is not normal in a pregnant woman. Respiratory alkalosis occurs in pregnancy due to increased tidal

volumes, so if the CO2 is in the normal range, the patient is

already retaining. 19

Thyroid Disorders

Second most common endocrine disorder in women of reproductive age.

Incidence: overt hypothyroidism 0.4%

Subclinical hypothyroidism 2-3%

Hyperthyroidism 0.2%

Targeted screening with TSH, reflex free T4 Maintain TSH <2.5 mIU per L

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Who to screen?

Current thyroid disease

Current Type 1 DM

FHx of autoimmune thyroid disease

History of: high dose neck radiation

postpartum thyroid dysfunction

prior therapy for hyperthyroid

prior infant with thyroid dz21

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Hypothyroidism

Most Common Causes

Iodine deficiency

Hashimoto’s disease

Subacute thyroiditis

If left untreated leads to increased risk of...

Preterm birth

Low birth weight

Placental abruption

Gestational HTN

Fetal thyroid dysfunction

Miscarriage

Fetal cognitive defects

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Hypothyroidism Management

Rx: Levothyroxine

Women on a stable dose should increase by 2 additional doses/ week with a missed menses or + pregnancy test.

Monitor TSH every 4-6 weeks until stable

Once stable, monitor TSH at least each trimester.

Postpartum, return to pre-pregnancy dosing 23

Hyperthyroidism

Causes Graves’ disease

Toxic multinodular goiter

Subacute thyroiditis

Thyroid adenoma (hyperfunctioning)

Gestational trophoblastic disease

Effects Preterm delivery

Low birth weight

Fetal loss

Thyroid disease of infant

Preeclampsia

Heart failure

Miscarriage

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Hyperthyroidism Treatment

Treat with PTU 1st trimester, then switch to Methimazole for 2nd & 3rd trimester.

(risk of birth defects with Methimazole, risk of hepatotoxicity with PTU)

Goal: high normal free T4, low normal TSH

Monitor TSH, FT4 Q 4 weeks

Growth u/s Q4 weeks after 24 weeks

Weekly NST’s starting at 32 weeks.

No need to treat subclinical hyperthyroidism –no change in outcomes

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Postpartum Thyroid Dysfunction

Postpartum Thyroiditis 25% hyperthyroid hypothyroid recovery

43% hypothyroid only

32% hyperthyroid only B-blockers rather than antithyroid meds for symptomatic

tachycardia

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Depression

10-15% of pregnant women meet diagnostic criteria for depression

Up to 70% of pregnant women report symptoms of depression

Screen with PHQ 9, Edinburgh or Beck inventory scale.

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Depression

Think first before discontinuing antidepressants that are working well

Higher miscarriage rate in those stopping meds in first trimester

Can lead to worsening depression and poor self care, substance use, preterm birth, & low birth weight.

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Depression

Assess the severity of the symptoms

Review the reasons the woman was prescribed her particular medications.

Employ non- pharmacologic measures of treatment

Discuss with patient the risk of taking medication and the risk of not taking medication during pregnancy

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Depression

Higher doses of a single agent generally preferred over lower doses of multiple agents.

If you can adjust meds prior to pregnancy, rather than during pregnancy, that is preferred.

Multidisiplinary, team approach to treatment

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Medications

SSRI’s Low risk of fetal anomalies (even with Paxil)

6-12/1,000 risk of PPH

increased risk for neonatal adaptation syndrome and admission to the NICU

TCA’s - Low risk for congenital malformations

Valproate – risk for neural tube defects

Carbamazepine – facial dysmorphism, fingernail hypoplasia

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References

ACOG Executive Summary: Hypertension in pregnancy. Obstet Gynecol2013;122:1122-31.

ACOG Practice Bulletin #137: Gestational diabetes mellitus. Obstet Gynecol. 2013; 122: 406-16.

Asthma in Pregnancy. ACOG Practice Bulletin No.90. American College of Obstetricians and Gynecologists. Obstet Gynecol, 2008; 111: 457-64.

Belanger K, et al. Effect of pregnancy on maternal asthma symptoms and medication use. Obstetrics & Gynecology. 2010; 115 (3), 559-67.

Carney, et al. Thyroid disease in pregnancy. American Family Phsician. 2014; 89(4): 273-278.

Crump WJ. The pregnant patient with hypertension. Family Practice Recertification. 2001; 23(14): 39-43.

Elimian A, Figueroa R, Spitzer AR, et al. Antenatal corticosteroids: Are Incomplete courses beneficial? Obstetrics & Gynecology. 2003; 102 (2): 352-355.

Fontaine P, Sabourin ME. Medical Complications of Pregnancy. ALSO 2013

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Garner L, et al. First trimester A1C as a tool to predict the development of gestational diabetes in high risk women. Obstetrics & Gynecology. 123():52S, May 2014.

Irgens et al Long term mortality of mothers and fathers after pre-eclampsia: population based cohort studyBMJ 2001; 323: 1213-7

Isler CM, Barrilleaux PS, Rinehart BK, et al. Postpartum seizure prophylaxis: Using maternal Clinical Parameters to Guide Therapy. Obstetrics & Gynecology.2003; 101: 66-69.

Kaaja, Greer Manifestations of Chronic Disease During PregnancyJAMA 2005;294:2751-2757

Lain KY, Roberts JM. Contemporary Concepts of the pathogenesis and management of preeclampsia. JAMA. 2002; 287 (24): 3183-3186.

Lund et al, Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study. BMJ. 2014; 348;g1908doi.

Patel, BN et al. Antidepressant use during pregnancy. American Family Physician. 2011; 83 (10): 1213-1215.

Reif MC. How to identify and manage preeclampsia. Women’s Health in Primary Care. 2003; 6:235-243.

Roberts JM, Pearson G, Cutler J, et al. Summary of the NHLBI working group on research on hypertension during pregnancy. Hypertension. 2003; 41(3): 437-445.

Roberts, Gammill Preeclampsia, Recent Insights Hypertension 2005; 46:1243-1249.

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Screening and diagnosis of gestational diabetes mellitus. Committee Opinion No. 504. Obstet Gynecol 2011;118:751–3

Servey, J., Chang, J. Over-the-Counter Medications in Pregnancy. American Family Physician. 2014; 90(8); 548-555.

Sibai BM, Akl S, Fairlie F, et al. A protocol for managing severe preeclampsia in the second trimester. American Journal of Obstetrics & Gynecology. 1990; 163 (3): 733-738.

Sibai BM, Mercer BM, Schiff E, et al. Aggressive versus expectant management of severe preeclampsia at 28-32 weeks’ gestation: A randomized controlled trial. American Journal of Obstetrics & Gynecology. 1994; 171(3): 818-822.

Skjaerven et al Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort

BMJ, doi:10.1136/bmj.38555.462685.8f Thyroid disease in pregnancy. ACOG Practice Bulletin No 148: American

College of Obstetricians and Gynecologists. Obstet Gynecol 2015; 125: 996-1005.

Use of psyciatric medications during pregnancy and lactation. ACOG Practice Bulletin No 92: American College of Obstetricians and Gynecologists. ObstetGynecol. 2008; 111: 1001-20.

Yonkers, KA, Vigod, S, Ross, LE. Diagnosis, Pathophysiology, and Management of Mood Disorders in Pregnant and Postpartum Women. American Journal of Obstetrics & Gynecology. 2011; 117(4); 961-977.

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Hypertensive Disorders of Pregnancy

Chronic Hypertension HTN that predates the pregnancy – look for secondary causes

Gestational Hypertension HTN begins after 20 weeks but no proteinuria or systemic symptoms BP’s return to normal within 12 weeks post partum

Preeclampsia with or without severe features & eclampsia HTN with proteinuria or systemic symptoms Beginning in pregnancy >20wks

Preeclampsia superimposed on chronic HTN HTN predating pregnancy with new or worsening proteinuria, symptoms

or end organ involvement and often worsening BP’s 35

Preeclampsia

A pregnancy specific syndrome of reduced organ perfusion related to vasospasm and activation of the endothelium.

Part of a spectrum of diseases which include HELLP and acute fatty liver of pregnancy (AFLP)

Incidence 5-7% of primigravidas

Risk of recurrence 20%36

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Preeclampsia…

Is a systemic process.

Is progressive by nature.

Is associated with later life cardiovascular

disease.

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Etiology/Pathophysiology

No one really knows. The theories are…… Poor Placentation

Spiral arteries incompletely invaded by trophoblast, do not dilate, develop atheromatous changes, lead to decreased placental perfusion

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OR...

Endothelial Cell DysfunctionReduced endothelial mediated relaxation

vasculature becomes a higher resistance system

increased blood pressures

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And……

Genetic factors Imbalance of vasoactive substances Immunologic reaction between mother and fetus

(host vs graft/ mother against placenta) Platelet activation and Coagulation abnormalities Obesity – leads to endothelial activation and

resultant inflammatory response. Vasculopathic (see diagram)

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Risk Factors

Nulliparous (6-8 x more common than in multiparous). New partner returns risk to nulliparous level

Age > 40 Race (more common in african american women) Increased placental size (multiple gestation,

hydatidaform mole, hydrops) Prior History Comorbid Medical problems (essential HTN, DM,

hyperthyroid, hypercoagulability, chronic renal disease, collagen vascular disease)

Obesity (13% when BMI > 35) Genetics – maternal and placental

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Preeclampsia Without Severe Features (Mild Preeclampsia)

SBP > 140 or DBP >90 that begins >20 weeks gestation need at least 2 readings > 4 hours

apart

AND

New proteinuria >300 mg in 24 hrs. (or SPOT >300, or 1+ on dipstick in two random specimens >4 hrs apart)

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Preeclampsia with Severe Features (severe preeclampsia)

SBP >160 or DBP >110On two occasions > 4 hours apart

Elevated creatinine (>1.1) Thrombocytopenia (<100,000) Elevated LFT’s (> 2x normal) Headaches, vision changes, RUQ pain) Pulmonary edema Microangiopathic hemolysis

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Changes in Diagnostic Criteria

5 grams protein removed

IUGR removed

Preeclampsia diagnosis can be made in the absence of proteinuria

There seems little association between the degree of proteinuria and pregnancy outcomes (maternal or fetal) once 300 mg/dl of proteinuria is reached.

IUGR treated similarly in preeclampsia vs. no preeclampsia

Preeclampsia is a systemic disease, if the kidneys are not affected other organs may be and this is just as significant

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Eclampsia

Seizures – in the setting of preeclampsia with no other identifiable causes

Treatment = Magnesium Sulfate

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Pearls for Diagnosis

Don’t discount the initial BP reading at any office visit.

If you think about preeclampsia get the labs.

Pay attention to the BP at the first prenatal appointment

If elevated, consider Dx of CHTN

Physiologic drop in BP in 2nd trimester so this may be the only abnormal value you’ll see until 3rd trimester.

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Maternal Complications

Pulmonary Edema Decreased GFR

oliguria (U.O. <500cc/24hr) Renal insufficiency (CR >1.1)

Coagulopathy (HELLP, DIC) Hepatocellular damage, subcapsular hemorrhage Placental Abruption Cardiovascular disease: doubles with h/o preeclampsia

dx after 37 weeks, but increases 8-9 fold with severe disease or delivery < 34 weeks.

CNS (ischemia, hemorrohage, infarction, Seizure) Cerebral Hemorrhage (most common cause of death)

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Fetal Complications

IUGR (increased morbidity/mortality)

Hypoxia

Fetal demise

(The earlier and more preterm the preeclampsia develops, the worse the outcomes)

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Prediction / Prevention

No test to determine who will develop preeclampsia

Not Effective - vitamin C, Vitamin E, low salt diet, bed rest.

Slight effect Calcium – in populations with low calcium intake

may lessen severity.

Low dose ASA – in patients with prior early or severe preeclampsia & delivery < 34 weeks. May lessen incidence and adverse perinatal outcomes.

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Management of GHTN & Preeclampsia w/o severe features

The outcomes are very similar for these two diagnoses, so they are now managed in the same way.

Can consider outpatient management if normal fetus and reliable patient

Goal of monitoring is to detect progression to preeclampsia with severe features, which would be an indication for delivery sooner.

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Outpatient Management if Stable and Reliable Patient

Labs and 24 hour urine at diagnosis, then weekly if stable Weekly visits with BP, labs, symptom assessment Additional weekly measure of BP at home or in the office Daily kick counts by the mother NST and/or BPP at diagnosis and then 1 to 2 times/wk until

delivery Ultrasound at diagnosis and then Q3-4 weeks (growth &AFI) No BP meds unless consistently >high 150’s/ high 90’s Delivery at 37 weeks No Magnesium intrapartum

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Preeclampsia with Severe Features

Inpatient management Treat BP’s if > 160/110 Delivery at 34 0/7 wks

Mode of delivery to be determined by gestational age, fetal presentation, cervical status and maternal/ fetal condition.

Magnesium Sulfate during labor and up to 24 hours post partum

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To Delay or Proceed with Delivery

Steroids & Delay delivery for 48 hours

PPROM Labor (give tocolytics) Platelets < 100,000 LFT’s > 2x normal IUGR Oligohydramnios

1st dose Steroids

and deliver!

Uncontrollable hypertension

Pulmonary edema

Non-reassuring fetal status

Placental abruption

Eclampsia

Fetal Demise

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Chronic Hypertension

Home BP monitoring

Rule out secondary causes of HTN

Healthy weight and moderate exercise

Baseline preeclampsia labs

Early ultrasound for dating

Growth ultrasounds Q 4 weeks (starting at 28 weeks)

NST’s weekly starting at 32 weeks

Treat BP’s > 160/ 105

Drugs of choice = labetalol, aldomet, nifedepine

Delivery in 39th week54

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CHTN with Superimposed Preeclampsia

Without severe features Delivery at 37 weeks

With severe features Delivery at 34 weeks

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Admission/Intrapartum Management

Continuous fetal monitor

VS Q 15-30 minutes until stable

Bedrest

Strict I/O’s with Foley

NPO except ice chips

Labs Q6-8 hrs (CBC, BMP, LFT’s, uric acid)

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Control Blood Pressure

SBP >160 or DBP >110 Hydralazine (5mg IV + 5-10mg Q 15-

30min PRN)

Labetalol (20 mg IV, then 40 mg 10min later if needed, then 80 mg IV Q 10min PRN to max dose 220mg in 24 hrs)

Nifedipine (10 mg PO Q 20 min prn),

Nicardipine gtt (start at 5 mg/h, go up by 2.5 mg/h Q 15 min PRN to max 15 mg/h

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Monitor Fluid Status

Foley Strict I/O’sMaintain urine

output at about 30cc/hr Total fluids not to

exceed 125cc/hr

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Preventing Seizures& Mg++ Toxicity

Magnesium (for severe pre-E)

4-6g IV over 15-20 min, then 2-3g/hr gtt (Therapeutic range is 4-8 mg/dl)

Risk of seizure does notcorrelate to the blood pressure.

Toxicity Lose patellar reflex 8-12

Somnolence 10-12

Resp Depression 15-17

Paralysis 15-17

Cardiac Arrest 30-35

Antidote is Calcium Gluconate

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If an Eclamptic Seizure Occurs…

DON’T PANIC Seizures are generally short lived

Protect airway

Place on left side

Supplemental oxygen

Give additional 2g Mg++

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Post Partum

Continue Mg++ for 24 hours Newer studies advocating use of clinical factors

to determine when to stop Mg++ Diuresis >100cc/h x 2 hrs

Sustained BP < 150/100

Absence of clinical symptoms (HA, vision changes, RUQ pain)

Avoid the use of NSAIDs for post partum pain control

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Post Partum

HTN should resolve within 12 weeks of delivery More severe disease takes longer to normalize post

partum Continue oral anti-hypertensives as needed to maintain

BP < 160/110 Note that all anti-hypertensive meds are excreted to some

degree in breast milk. Calcium channel blockers and diuretics do not appear to affect the baby.

You can still have seizures post partum (up to 6 weeks)

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Post Partum and Follow Up

For any woman with a hypertensive disorder of pregnancy BP should be monitored in the hospital for 72 hours (or outpatient equivalent surveillance), & then again in 7-10 days

All women should leave the hospital with information about the signs & symptoms of preeclampsia.

For women with a history of preeclampsia and preterm birth, yearly evaluation of BMI, BP, lipids & glucose is suggested.

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Gestational Diabetes

Carbohydrate intolerance diagnosed during pregnancy

6-7% of pregnancies

Incidence directly related to the prevalence of diabetes in the general population.

Increased risk in Hispanic, Native American, Asian and Pacific Islanders

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Complications

Maternal Increased risk of hypertensive

disorders of pregnancy

50% risk of developing Type 2 DM in 10 years

Increased risk of operative delivery

Fetal Macrosomia

Shoulder dystocia

Birth trauma

Hypoglycemia

Hyperbilirubinemia

Stillbirth

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Who to Screen and When?

Universal screening with 50 g (1 hour) OGTT for all pregnant women at 24-28 weeks 3 hour GTT if elevated

Screen early with 1hour OGTT or A1C if risk factors: Prior history of GDM

Known insulin resistance

Obesity (BMI >30)

Baby > 9 lbs

**If early screening is negative. Repeat at normal time.66

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Which Criteria for Diagnosis?

1 hour GTT > 135 or 140

3 hour GTT

Pick cutoffs for your institution and stick with them.

Carpenter Coustan

NationalDiabetes Group

Fasting 95 105

1 hour 180 190

2 hour 155 165

3 hour 140 145

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Benefits of Blood Sugar Control

Decreased risk of Perinatal death

Shoulder dystocia

Birth trauma

LGA infants

Preeclampsia

Cesarean delivery

Hypertensive disorders68

Blood Sugar Monitoring

Recommended 4 times / day Fasting (goal <95)

Either 1 or 2 hours post prandial - goal < 140 or 120 respectively

- 1 hour post prandial monitoring seems to lead to better control

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Which Agents to Use?

• Dietary education and carbohydrate control . Moderate exercise

• Glyburide or Metformin- widely used but not FDA approved

-More women fail metformin therapy alone

OR• Insulin

-does not cross the placenta 70

Antenatal Monitoring

Not indicated for GDMA1 (diet controlled) Delivery in the 40th week (by 41 0/7)

For GDMA2 Biweekly NST’s starting at 32 weeks

Growth ultrasound at 36 weeks Discuss option of delivery by cesarean if EFW >4500g

Delivery in 39th week if sugars well controlled

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Post Partum Follow Up

2 hour OGTT at 6-12 weeks post partum to detect evidence of insulin resistance or type 2 DM.

Screening at least every 3 years for diabetes.

- consider yearly screening as 50% will become diabetic in 10 years.

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