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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.
1
Medical Complications of Pregnancy
Karen Moyer, MD
March 12, 2016
1
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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2
Medical complications of pregnancy are common and something that a family practitioner should feel comfortable managing.
4
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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3
(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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4
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.
12
5
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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6
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
7
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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9
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.
27
10
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.
28
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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11
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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15
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
57
20
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++
60
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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
23
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
69
24
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
71
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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