Medical Disorders in PregnancyDr. Brett VairObstetrics & GynecologyFamily Medicine Academic Half-Day

August 20, 2015

Outline

Obesity HypothyroidismPregestational diabetesChronic hypertensionSeizure disorders

I. Obesity

“One of the most blatantly visible, yet neglected, public-health problems that threatens to overwhelm both more and less developed countries.”

- WHO

Defining obesity in pregnancy

BMI should be calculated from prepregnancy height and weight

Those with a prepregnancy BMI >30 kg/m2 are considered obese

Other definitions: Women who are 110%-120% of their ideal body weight >91kg (>200 lbs)

• Maternal obesity results in in-utero programming and childhood obesity

A self-propagating phenomenon…

Q: What is the suggested weight gain in pregnancy for a woman who is obese (BMI 30.0-34.9)?

A. 10 kg

B. 3 kg

C. 7 kg

D. 15 kg

Suggested weight gain in pregnancy

• Women should be encouraged to enter pregnancy with a BMI <30, ideally <25

• All women without contraindications should participate in regular exercise

Exercise in pregnancy (SOGC Clinical Practice Guideline No. 129, June 2003)

All women without contraindications should be encouraged to participate in exercise as part of a healthy lifestyle during pregnancy

Reasonable goal: Maintain a good fitness level throughout pregnancy without reaching peak fitness or training for an athletic competition

Initiation of an aerobic exercise program in previously sedentary women: 15 minutes continuous exercise 3x/week

30 –minute sessions 4x/week

Exercise in pregnancyAbsolute contraindications:

Ruptured membranes Preterm labour Hypertensive disorders of pregnancy Cervical insufficiency IUGR Higher order multiple gestation (≥triplets) Placenta previa >28 weeks Persistent 2nd or 3rd trimester bleeding Uncontrolled type 1 diabetes, thyroid disease, or other serious

cardiovascular, respiratory, or systemic disorder

(SOGC Clinical Practice Guideline No. 129, June 2003)

Complications of obesity related to pregnancy

Infertility (OR 1.7-2) Spontaneous abortion (OR 2-3)

Increased risk of recurrent pregnancy loss

Prenatal risks: Hypertensive disorders in pregnancy (OR 2-3)

Increased likelihood of a woman experiencing severe complications from GHTN

Gestational diabetes (OR 1.4-20) Testing women with risk factors early in pregnancy is recommended

VTE (OR 2) OSA (OR 1.12)

Complications of obesity related to pregnancy Risks to the fetus/neonate:

Increased rate of fetal anomalies NTD (OR 1.7-2.2)

Protective effects of periconceptual folic acid to not appear to benefit obese women Recommended dose of 5mg daily (SOGC Clinical Practice Guideline No.

324, May 2015: 1.0 mg/day of folic acid recommended for those at “moderate risk”)

Also: Cardiac defects Orofacial clefts Ventral wall defects

Complications of obesity related to pregnancy

Risks to the fetus/neonate (continued)

Macrosomia (>4000g) (OR 2.1)

Birth injury, shoulder dystocia (OR 3.1)

Fetal death (OR 2.0-3.6) The most prevalent risk factor for unexplained stillbirth is prepregnancy

obesity Antepartum fetal testing may be considered

Childhood obesity (OR 1.9-2.2)

Complications of obesity related to pregnancy Intrapartum risks:

Macrosomia and shoulder dystocia Longer labour Difficulty with fetal monitoring Difficulty with uterine monitoring

Evidence of impaired uterine contractility Difficulty with regional anesthesia Anesthesia complications Cesarean delivery

Higher rate of complications Postoperative complications Lower likelihood of successful VBAC

Use of ultrasound in obese patients ~15% of normally visible fetal structures

will be suboptimally seen on the 18-22 week anatomic scan in women with a BMI >90th percentile Structures less commonly seen include:

heart, spine, kidneys, diaphragm, umbilical cord

Obstetric care providers should take BMI into consideration when arranging a fetal anatomic assessment in the 2nd trimester U/S at 20-22 weeks may be best

Error of ultrasound estimation of fetal weight: >10% difference from actual birth weight

Preconception Care

The preconception visit may be the single most important health care visit when viewed in the context of its effect on pregnancy

Identification and awareness by both patient and provider of obesity is the first step in management and prevention of pregnancy complications

Discussion and education about obesity and its poor perinatal outcomes should be provided

Important interventions: Weight reduction prior to conception Prevention of excessive gestational weight gain

II. Hypothyroidism

Thyroid Physiology and Pregnancy

Moderate glandular hyperplasia and increased thyroid vascularity are physiologic Thyroid volume by U/S increases a mean of 18%

Returns to normal postpartum Any significant goiter should be worked up

TBG increases 200%

High levels of hCG have some TSH-like activity and stimulate thyroid hormone secretion Suppresses TSH

Throughout pregnancy there is a 30-50% increase in T4 requirement

Maternal thyroid hormone is transferred to the fetus throughout pregnancy Important for fetal brain development Fetus is entirely dependent on maternal thyroid hormones prior to 12 weeks

Hyperemesis gravidarum & gestational thyrotoxicosis

Many women with hyperemesis gravidarum have abnormally high thyroxine levels and low TSH levels Results from thyrotropin receptor stimulation from BhCG Transient condition called gestational thyrotoxicosis Antithyroid drugs are not warranted, even if associated with

hyperemesis TSH and FT4 levels will become more normal by midpregnancy

Complications of hypothyroidism in pregnancy

Untreated or partially treated clinical hypothyroidism is associated with: Infertility Miscarriage Preeclampsia Abruption Preterm birth Low birth weight Fetal death Impaired psychomotor function in infants whose mothers have

serum fT4 <10th %ile

Possibility of lower IQ in children of women with untreated subclinical hypothyroidism

Thyroid screening in pregnancy Universal screening for maternal hypothyroidism is not

recommended

Women at high risk for hypothyroidism should be screened Symptomatic Previous therapy for hyperthyroidism History of high-dose neck irradiation Goiter/palpable thyroid nodule FHx of thyroid disease Type I DM Suspected hypopituitarism Hyperlipidemia Medications (amiodarone, lithium, dilantin)

Role of TPO Antibodies

Present in: 90% of women with Hashimoto’s thyroiditis 10% of euthyroid women

Crosses the placenta May increase risk of:

Spontaneous abortion Placental abruption

Increases incidence of postpartum thyroid dysfunction

Routine testing of TPO antibodies during pregnancy is not recommended

Serial levels of TPO in women treated for hypothyroidism are not indicated because treatment does not alter them

Management of hypothyroidism in pregnancy

Approximately 45-85% of women with preexisting hypothyroidism need up to 45% increase in thyroxine replacement dose during pregnancy Increased metabolism of thyroxine Weight gain Increased T4 pool High serum TBG Placental deiodinase activity Transfer of T4 to the fetus

Management of hypothyroidism in pregnancy

Ferrous sulfate and calcium carbonate interfere with T4 absorption and should be taken at a different time of day from thyroxine therapy

Pregnant women should space their levothyroxine and prenatal vitamin by at least 2-3 hours

Q: How much time does it take for thyroxine therapy to alter TSH level?

A. 48 hours

B. 1 week

C. 2 weeks

D. 4 weeks

Management of hypothyroidism in pregnancy TSH and FT4 levels should be checked:

Preconception At the first prenatal visit in the first trimester 4 weeks after altering the dose of thyroxine replacement

q4weeks until TSH is normal At least every trimester in pregnancy

FHR should be assessed at each visit to rule out fetal bradycardia

Increased ultrasound surveillance is not recommended if euthyroid May consider monthly ultrasounds for fetal growth, thyroid

assessment, and fetal heart rate if clinically hypothyroid

Postpartum thyroiditis

Transient autoimmune thyroiditis occurs in 5-10% of women during the first year after childbirth

Up to 25% of women with DM Type I develop postpartum thyroid dysfunction

Diagnosed infrequently Typically develops months after delivery Vague signs and symptoms

Postpartum thyroiditis

Two recognized clinical phases:

(1) Thyrotoxicosis 1-4 months Small, painless goiter Fatigue, palpitations Treatment: B-Blocker for symptom management Sequelae: 2/3 become euthyroid, 1/3 become hypothyroid

(2) Hypothyroidism 4-8 months Goiter (more prominent) Fatigue, inability to concentrate Treatment: Thyroxine for 6-12 months Sequelae: 1/3 permanently hypothyroid

Overall, women who experience postpartum thyroiditis have a ~30% risk of eventually developing permanent hypothyroidism

III. Pregestational Diabetes

Complications in pregnancy Incidence of complications is inversely proportional to

glucose control

Poorly controlled DM is associated with: Spontaneous abortion Congenital anomalies IUFD Preterm birth Preeclampsia Macrosomia Operative delivery Birth injury Delayed lung maturity, RDS Neonatal jaundice, hypoglycemia, hypocalcemia

Preconception Care Associated with better outcomes Multidisciplinary approach

All women with DM type 1 and 2 should receive information on reliable birth control and importance of good glycemic control prior to conception Hgb A1C ≤7.0%

Folic acid supplementation 5mg (SOGC Clinical Practice Guideline No. 324, May 2015: 1.0 mg/day of

folic acid recommended for those at “moderate risk”)

Discontinue potentially harmful medications ACE Inhibitors ARBs Statins

Preconception care

Lifestyle modification Efforts should be made to

reduce body weight

Women with DM type 2 who are planning pregnancy should switch from oral antihyperglycemic agents to insulin for glycemic control

Assessment and management of diabetic complications

Women with preexisting vascular complications are more likely to have poor pregnancy outcomes

Retinopathy Women with DM type 1 and 2 should have opthalmalogical

assessments: Preconception During the first trimester As needed during pregnancy Within the first year postpartum

Risk of progression is increased with poor glycemic control in pregnancy

Assessment and management of diabetic complications

Hypertension Incidence of hypertension complicating pregnancy is 40%-45% in

women with DM type 1 and 2 Type 1 DM more often associated with preeclampsia Type 2 DM more often associated with chronic hypertension

Poor glycemic control in early pregnancy is a risk factor

Assessment and management of diabetic complications

Chronic kidney disease Diabetic women should be screened for chronic kidney disease

prior to conception Estimation of GFR

During pregnancy, random albumin:creatinine and serum creatinine should be measured each trimester

In women with an elevated serum creatinine, pregnancy can lead to a permanent deterioration in renal function

Management of diabetes in pregnancy

Multidisciplinary care

Glycemic control: Fasting PG <5.3 1-hour post-prandial <7.8 2-hour post-prandial <6.7

Increased risk of hypoglycemia in pregnancy, particularly in the first trimester Hypoglycemic unawareness due to loss of counterregulatory

hormones Glycemic targets may have to be raised

Management of diabetes in pregnancy

Frequent self-monitoring of blood glucose is essential Pre- and post-prandial

Pharmacologic therapy: Insulin

Basal bolus therapy Continuous subcutaneous insulin infusion

Oral antihyperglycemic agents (DM Type 2) No evidence to show increased risk of

congenital anomalies with glyburide or metformin

Use of oral agents is not currently recommended in pregnancy Large RCT currently underway

Q: Insulin crosses the placenta…

TrueFalse

Management of diabetes in pregnancy

Postpartum: Metformin and glyburide can be considered for use during

breastfeeding Long-term data are lacking

High risk of hypoglycemia Careful monitoring

Women with DM Type 1 should be screened for postpartum thyroiditis TSH 6-8 weeks postpartum

Breastfeeding should be encouraged

IV. Chronic Hypertension

Definitions Chronic hypertension:

Either a history of hypertension preceding pregnancy or a blood pressure ≥140/90 prior to 20 weeks’ gestation

Severe hypertension: sBP ≥160 mmHg or dBP ≥110 mmHg

Other disorders… GHTN, preeclampsia, superimposed preeclampsia, HELLP….

Recall maternal physiologic changes in pregnancy…

Increased blood volume Decreased colloid oncotic

pressure Overall decrease in total

peripheral resistance

Physiologic decrease in BP in 1st and 2nd trimester may mask chronic HTN

A BP of ≥ 120/80 mmHg in the 1st or 2nd trimester is not normal

Risk factors and associations

Renal disease Collagen vascular disease Antiphospholipid syndrome Diabetes Thyrotoxicosis Cushing’s disease Hyperaldosteronism Pheochromocytoma Coarctation of the aorta

Maternal Fetal

Complications in pregnancy

Worsening HTN Superimposed preeclampsia

(20%) Eclampsia HELLP syndrome Cesarean delivery Pulmonary edema Hypertensive encephalopathy Retinopathy Cerebral hemorrhage AKI

IUGR (8-15%) Oligohydramnios Placental abruption (0.7-

1.5%; ~2-fold increase) PTB (12-34%) Perinatal death (2- to 4-fold

increase)

Q: Which of the following antihypertensive drugs are safe for use in pregnancy?

MethyldopaDiureticsACE inhibitorsARBsLabetalolAtenololCalcium channel blockers

Preconception counseling

Appropriate counseling regarding possible complications Discontinuation of ACE inhibitors and ARBs Consider work-up for associated causes if not previously

done

Management Early pregnancy investigations (if not previously documented):

Creatinine Fasting blood glucose Serum potassium Urinalysis EKG

Baseline GHTN labs Transaminases CBC Creatinine Urine protein:creatinine ratio Urate LD

Consider IM consult New dx of HTN, investigation of associated causes

Management

Home BP monitoring

ASA 81 mg initiated after diagnosis of pregnancy but <16 weeks gestation Consider for continuation until delivery

Calcium supplementation (at least 1g/d) in women with low calcium intake

Lifestyle modification Insufficient evidence to make recommendations regarding:

Dietary salt restriction Exercise Workload reduction, stress reduction Bed rest

Management Antihypertensive drugs

Methyldopa Labetalol Nifedipine

Insufficient evidence to conclude that one antihypertensive is better than the other

Antihypertensive agents should probably be started (or increased, or modified) in pregnancy when sBP ≥160 mmHg or dBP ≥110 mmHg on two occasions

A woman’s natural BP may be necessary for adequate placental perfusion Goal of maintaining BP around 130-155/80-105 mmHg

<140/90 mmHg with end-organ damage, renal disease, diabetes

V. Seizure disorders

Q: In pregnancy, there is evidence to support a risk of increased seizure frequency…True

False

Complications in pregnancy

Maternal complications: Insufficient evidence to support or refute a change in seizure

frequency in pregnancy or an increased risk of status epilepticus in pregnant women with epilepsy

Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84-92%) of remaining seizure free during pregnancy

90% of women with epilepsy have successful pregnancies and deliver healthy babies

Complications in pregnancy

Fetal complications: GTC seizures increase the risk of hypoxia and acidosis as well as

injury from blunt trauma May cause fetal heart rate abnormalities

Risks associated with in utero exposure to AEDs: Fetal loss (1.3-14%) Perinatal death (1.3-7.8%) Congenital malformations (4-7%; ~twice the baseline risk)

Most common: cardiac, NTDs, craniofacial, fingers, etc. Low birth weight (7-10%) Prematurity (4-11%) Developmental delay Childhood epilepsy

AEDs and congenital anomalies

Antiepileptic drug Rate of major malformations

Valproate 10.7%

Phenobarbital 6.5%

Lamotrigine 2.7%

Carbamazepine 2.5%

Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry:

Effect of pregnancy on disease Concentrations of some AEDs fall

Increase in hepatic cytochrome P450 enzyme activity Increased renal clearance Changes in volume distribution

Decreased protein binding results in higher levels of unbound biologically active AEDs May cause toxicity

Preconception counseling Conception should be deferred until seizures are well

controlled on minimum dose of medication Monotherapy is preferable Good compliance with AEDs is essential

Inform women about risk of congenital malformations in infants exposed to AEDs in utero 4-8% risk

Avoid category D drugs if possible in the first trimester Carbamazepine Phenobarbital Phenytoin Valproate Topiramate

Preconception counseling Neurologic consultation

regarding possibility of tapering off and stopping AEDs if the patient has been seizure free for >2 years and EEG is normal Observe for 6-12 months before

attempting conception

Preconception folic acid 5 mg (SOGC Clinical Practice

Guideline No. 324, May 2015: 1.0 mg/day of folic acid recommended for those at “moderate risk”)

Enzyme-enhancing AEDs enhance the metabolism of OCPs

Postpartum

Breastfeeding is not contraindicated

For most AEDs, the pharmacokinetics in the mother will return to prepregnancy levels within 10-14 days postpartum Monitor AED levels 8 weeks postpartum and adjust doses

accordingly to avoid toxicity

Sleep deprivation may exacerbate seizures

Counsel patients regarding seizure precautions

Referral options in Calgary

OB MFM MDIP DIP ACCP

Suggested References Obesity in pregnancy. SOGC Clinical Practice Guideline No. 239,

February 2010.

Exercise in pregnancy and the postpartum period. SOGC Clinical Practice Guideline No. 129, June 2003.

Diabetes and pregnancy. Canadian Diabetes Association Clinical Practice Guideline. Can J Diabetes 37(2013), S168-S183.

Diagnosis, evaluation, and management of hypertensive disorders of pregnancy: executive summary. SOGC Clinical Practice Guideline No. 307, May 2014.

Pre-conception folic acid and multivitamin supplementation for the primary and secondary prevention of neural tube defects and other folic acid-sensitive congenital anomalies. SOGC Clinical Practice Guideline No. 324, June 2015.

Questions?