Management of medical

conditions during pregnancyGrand Rounds, MAHC

May 29, 2019

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Disclosure of Affiliations, Financial Support, and Mitigating BiasPresenter: Dr Caroline Correia Date: May 29, 2019Presentation: Management of Medical Conditions during Pregnancy

Affiliations:

● I have no relationships with for-profit or not-for-profit

organizations.

Learning Objectives

1. To identify normal physiological changes in pregnancy and how they interact

with some common medical disorders.

2. To demonstrate confidence in assessing and adequately treating the

reviewed conditions in pregnant patients.

3. To practice this knowledge as it pertains to pre-pregnancy counseling and

postpartum follow-up.

Relevance in Primary Care

- Key role for primary care providers

- Management of medical disorders with implications for pregnancy in women

of childbearing age.

- Patient education, appropriate contraception, preconception counseling

- Collaboration with subspecialists and MFM’s.

- Recognition of tools to support decision making around drug safety: - Perinatology: Drugs in pregnancy and breastfeeding

- MotherRisk

- Reprotox

- MotherToBaby:

- LactMed

Relevance in Primary Care

- Rates of pregnancy have ↑ 65% in those >40yo from 1990-2008.

- Pregnancy may unmask occult chronic disease:- Glucose intolerance

- Renal dysfunction

- Hypercoaguable states

- Valvular heart disease

- Cerebral aneurysm

- Postpartum impacts- GDM → 75% chance of devel T2DM next 5y, 50% lifetime risk

- Preeclampsia → ↑ risk CVA & CAD

A trio of topics for today’s discussion

Hypothyroidism

Diabetes

Asthma

Hypothyroidism and Pregnancy

Hypothyroidism in Pregnancy

- Overt hypothyroidism ~2.5% of women. Subclinical 4-10%.

- Risks - OB: - Preeclampsia

- LBW

- Abruption

- Miscarriage

- perinatal mortality

- When treated: baseline risk of PTB, fetal anomalies, fetal demise, no

neurocognitive/motor deficits

- Risks - Neonatal/Long term - Behavioural (@ 3wk!)

- psychomotor development (@10mo)

- cog/motor delays (as early as 9-12mo;

↓ IQ @7yo)

- Deficits seem proportional to duration of pregnancy w/o

adequate fT4

Sutandar et al. Hypothyroidism in Pregnancy. JOGC 2007; 29(4):354-356.

Case 1

Jane 28yoF planning pregnancy

- Hypothyroidism

x 5y since hemithyroidectomy +

Hashimoto’s

- Takes 75mcg/d

- Last TSH 4.6 9mo ago

What would you advise?

What are your targets?

How often & what would you check?

What if not currently hypothyroid?

What if no hx thyroid disease - do you

include a TSH on your initial lab work?

Hypothyroidism - Physiological Changes in

Pregnancy- hCG stimulates TSH-Rc

- ↑ T4/3 during first 12w while ↑ hCG

- ↓TSH (15% can have suppressed TSH in T1; 10% in T2; 5% in T3)

- ~10-20% can have transiently low/undetectable TSH

- 2x ↑ TBG by 16wk, plateau ~20wk→ ↑ total T3/4, but not free

- Rapid reversal of changes postpartum. Normal by 4-6wks.

- Fetus - Does not produce own LT4 <12w = dependent on maternal LT4

- >12w less dependent

Soldin OP. Thyroid function testing in pregnancy and thyroid disease: trimester-specific reference intervals. Ther Drug Monit 2006;28(1):8–11.

Hypothyroidism - Screening?

- Universal screening is not recommended- SOGC

- Endocrine Society

- ATA

- Screen if symptoms or risk factors

Deshauer & Wyne. Subclinical hypothyroidism in pregnancy. CMAJ July 17, 2017 189 (28) E941; DOI: https://doi.org/10.1503/cmaj.161388

If internal or transferable pregnancy-

specific TSH reference ranges are

not available, an upper limit

reference range of 4.0 mU/L may be

used.

For most assays, this limit

represents a reduction in the

nonpregnant TSH upper reference

limit of 0.5 mU/L.

Hypothyroidism - Subclinical

- Similar risks at Hypothyroidism. - Adverse pregnancy outcomes (pregnancy loss - 2x base rate)

- Adverse perinatal outcomes (HDP, PTL)

- Neurocognitive effects (IQ)

- TPOAb +: Risk is ↑ & adverse outcomes occur at lower TSH levels- 2-2.5x ↑ rate SA (from baseline rates of 20-30%)

- To treat? - Nil (SOGC 2007)

- TPOAb+ should be treated. (Siobhan & Whyne. Subclinical hypothyroidism in pregnancy.

CMAJ. 2017)

- Treat at lower TSH thresholds when TPOAb+ ((ATA)

- ? LT4 ↓ risk of pregnancy loss in TPOAb+ euthyroid women who are newly pregnancy.

- May consider in women w/ hx of prior loss (R/B) - 25-50mcg starting

- 20,000 euthyroid, TPOAb+ women with a history of infertility or miscarriage

- 50 UK hospitals

- Random assignment to 50mcg LT4 vs Placebo

- Started prior to conception → end of pregnancy

- Results - no differences in: - Rates of conception

- Live birth (>34wks)

- Adverse events

Dhillon-Smith, Middleton, Sunner, Cheed. N Engl J Med 2019; 380: 1316-1325

TSH Reference Ranges:

- ATA: Because substantial differences exist in the upper reference limit for

TSH between different populations, each practitioner and hospital should

ideally seek to determine their own trimester- specific reference ranges,

obtained from analysis of healthy, TPOAb-negative, and iodine-sufficient

women.

However, the task force recognizes that this goal is frequently not feasible.

Hypothyroidism - Monitoring

- TSH, fT4 or TT4? - Most suggest TSH.

- SOGC: “up to indiv clinician.”

- ATA: TSH. fT4 immunoassays less reliable in pregnancy d/t flux of TBG & Albumin.

- Newer tandem Mass Spec. TT4 reliable in late pregnancy.

- TSH Treatment Targets - Trimester Specific. (also varies with multiples)- CTF - T1 <2.5; T2/3 <3.0

- ATA - Lower ½ of the Trimester-specific reference range. Or <2.5

- Frequency of monitoring: - Who: Overt, subclinical, at risk (TPOAb+, hemithyroidectomy, radioactive iodine)

- q4wk until 20w,, then once ~30wk.

- More frequently if dose changes required.

Soldin OP. Thyroid function testing in pregnancy and thyroid disease: trimester-specific reference intervals. Ther Drug Monit 2006;28(1):8–11.

Hypothyroidism - Management Principles

- Tx associated w/ improved outcomes - even if tx insufficient!

- Goal = euthyroid, early.

- Synthetic LT4 recommended. No evidence for teratogenicity

- Precarious absorption - Supplements (FeSulf + calcium carbonate) & food.

- 30 min prior or 4h postprandially

- Preexisting hypothyroidism: - Preconception: target TSH <2.5

- Dose often req 30-50% ↑ from pre-pregnancy dose - start w 2 extra doses/wk at recognition of

pregnancy.

- Postpartum, return to prepregnancy dose.

- R/a TSH 6wk postpartum.

Diabetes and Pregnancy

Case 2

28y F G1P0 T2DM BMI 34

- Planning pregnancy “next 6mo”

- Metformin 1g/d

- A1C 1y ago 8.6%

What do you advise her about her

risks?

What preconception

recommendations do you have for

her?

28yo F G2P1 BMI 34

- Early pregnancy LMP 8wk

- Prev SVD + vacuum 4200g male

2y ago

What testing or monitoring do you

offer?

Diabetes in Pregnancy

- Rates of both GDM (5.6%) & PGDM (2%) ↑ 1995-2010!

- ⇧ risks: proportional to glucose levels (Toronto Tri Hosp Study)- Miscarriage >> Stillbirth (up to 4 per 1000; 4-5x > non-DM patients)

- Macrosomia/LGA (& shoulder dystocia, C/S) > IUGR

- Preeclampsia (RR 3.7, 5-17%) - begin low dose ASA 12-16wk until 36wk

- Fetal malformations: neural tube (RR 10) (1mg Folic Acid), cardiac defects (3.9% < A1C 8.5%

< 8%)

- Goals: - Recognize

- Attain & Maintain glycemic control

- Involve multidisciplinary team to assist

- Monitor GDM pts postpartum for T2DM

Berger et al. Diabetes in Pregnancy. JOGC 2016. 38(7): 667-679.

UtD

Pregestational DM - Preconception Care

- Counsel: reliable contraception, optimization prior to conception, impact of

BMI & glycemic control on pregnancy outcomes

- Optimize glycemic control (CDA & SOGC)- Prior to conception ≤ 7% (ideal ≤6.5%)

- During pregnancy ≤6.5% (ideal ≤6!)

- Recognize & educate- Engage the team (DEC). Early referral to Endocrine. Consider RD.

- Physical activity and weight gain

- Review meds - ACEi/ARBs, Statins. Insulin, Metformin, Glyburide ok. Others no.

- Begin folic acid 1mg/d

- Consider use of CGM

- Assess complications - * retinopathy (prior, T1, prn, <1yPP), *CKD/albuminuria (HDP).

- Postpartum - benefits of BF, contraception, planning another pregnancy.

Pregestational DM - During Pregnancy

- Care by a multidisciplinary team

- CBGM Targets: (↑ if hypoglycemia)- Fasting & Preprandial <5.3

- 1h postprandial <7.8

- 2h postprandial <6.7

- Monitoring - offer CGM

- Check A1C each trimester. Target ≤6.5%, ≤6% if possible.

- Discuss weight early and monitor weight gain regularly

- Ketones in T1DM with illness or CBG > 10.

Pregestational DM - Management

- Insulin preferred in T2DM over OHAs when inadequate glycemic control w/

lifestyle

- Insulin - Pump or MDI

- SA: lispro, aspart or glulisine.

- LA: detmir or glargine.

- ASA 81mg start 12-16wk to decr risk preeclampsia

- Assess comorbidites: - Renal function and uPCR

- TSH

- ECG if cardiac symptoms, HTN, or vascular disease

- Dilated eye exam q Trimester

Pregestational DM - Fetal Monitoring

- Visits- q2-4w T1/2 CBGM, team engagement, weight gain, fetal anatomy

- q1-2w in T3 CBGM, fetal monitoring to ↓ risk of IUFD, obst/medical complications, fetal growth

- Fetal surveillance: - Growth assessments q3-4wk beginning 28-32wk

- 34-36wk on: NST 2x/wk, BPP q1w

- Timing of delivery - typically 38-39wks.

Pregestational DM - Postpartum

- Insulin immediately ↓ below prepregnant doses & titrate gradually

- Monitor BG closely - risk of hypoglycemia

- Encourage breastfeeding to ↓ risk neonatal hypoglycemia, offspring obesity, ↓

risk of DM (4mo)

- Metformin & glyburide ok during lactation. Others no.

Gestational Diabetes.

- Between 3% to 20% of pregnant

women develop gestational

diabetes, depending on their risk

factors

- Counsel women at risk to prevent

- If multiple risk factors, perform

screening in T1, rpt at 24-28wk,

consider in T3

GDM - Screening

- Unrecognized or untreated → ↑

maternal & perinatal morbidity.

- Early A1C if suspect unrecognized

T2DM.

- Screening (CDA & SOGC) 2-step: - 50g OGCT 24-28wk

- <7.8mmol/L - neg screen

- 7.8-11.1 - move onto step 2

- ≥11.1 = GDM

- 2nd step: 75g OGTT. ≥ ⅓ results above cut

off = GDM.

GDM - Management During Pregnancy

- CBGM Targets: (↑ if hypoglycemia)- Fasting & Preprandial <5.3

- 1h postprandial <7.8

- 2h postprandial <6.7

- If on insulin, maintain >3.7

- Discuss appropriate wt gain & healthy interventions regularly

- Nutritional counseling

- Add insulin w/in 1-2 wks if not reaching glycemic targets with lifestyle mgmt

- If decline insulin, metformin or glyburide ok (counsel: cross placenta)

- Consider incr surveillance if poor glycemic control or comorbidities

- Can offer IOL 38-40wks.

GDM - Postpartum

- Strongly encourage Breastfeeding- ↓ neonatal hypoglycemia

- ↓childhood obesity

- ↓ DM in offspring

- ↓ T2DM & HTN in mother

- Ensure 75g OGTT b/w 6wks - 6mo (approx 8% will have T2DM)

- Encourage healthy diet & activity

- Screen annually with A1c - Risk correlates w/ dysglycemia & insulin need

- *Postnatal FBG strongest correlate

- Lean GDM <30y w/ insulin at risk for T1DM

- Recurrence 30-80%

Asthma in pregnancy

Asthma

- Affects 3-8% of women childbearing age.

- Severity may change antenatally - rule of 1/3s

- ↑ complications by 15-20% - perinatal mortality

- preeclampsia

- PTB

- LBW

- GDM

- Severe asthma - 30-100% ↑ risk

- No association with fetal malformations

Kwon HL, et al. Asthma prevalence among pregnant and childbearing-aged women. Ann Epidemiol. 2003;13(5):317

Kallen, B, et al. Asthma During Pregnancy - a population based study. Eur J Epidem 2000; 16:167.

Asthma and Pregnancy. Ontario Lung Association

Case 3

- 23yo non-smoker, G1P0 at 12w.

- PMHx asthma x 8y, worsened over the past year. Smokes 1/2ppd.

- Symptoms of cough & wheeze daily. Salbutamol ~ 3x/d.

- Nocturnal cough disrupting her sleep.

- PEFR is 65% of predicted and incr to 85% post SABA.

What do you do?

a) Continue current

b) Add budesonide

c) Add theophylline

d) Add salmeterol

e) Add inhaled cromolyn

Anything else?

Respiratory Changes- Elevation of the diaphragm (4cm), chest

diameter incr 2+cm, rib flaring (T1)

- Decr FRC and stable FEV1 & FEV1/FVC

- Progesterone - a respiratory stimulant - ↑

Sn of central resp centre to CO2 → ↑ RR &

Minute Volume 20-50%

- Compensated resp alk. ↑ PaO2 and lower

PaCO2 (contrib to diffusion gradients

between mother & fetus) 7.43 | 29 | 100

- ↑ arterial O2 tension 2ndary to ↑ ventilation

20% ↑ O2 demand (metabolic needs of

fetus, plac, ut & d/t incr WOB, CO)

Up To Date

Derangedphysiology.com

Asthma - Management

- Same as for non-pregnant patients.

- Avoid triggers. - Emphasize prevention - flu shot.

- Smoking cessation.

- Inhaler technique

- Take regular medications.

- Monitor PEFR. Kick counts >28w. Growth ax >32w if not well controlled.

- Postpartum: review meds. If severity changed, will likely revert.

- OK to BF w/ all asthma rx, except theophylline (neonatal irritability)

Asthma - Medical Management

- Tx same as non-pregnant. Achieve control asap.

- B2 agonists:- Safe in pregnancy, growing experience w/ LABA salmerterol.

- ICS: - Inhaled - minimal absorption, no evidence for fetal malform’ns or effects. Budesonide

(Pulmicort)/fluticasone (Flovent).

- Oral - should not be withheld in acute attacks. *GDM. *PPROM

- Anticholinergics: no adverse fetal effects.

- LTRA: monoleukast (Singulair)

- Don’t start, but may continue if tolerated & benefit- Immunotherapy for allergies

- Anti-IgE - omalizumab (Xolair)

Asthma - Acute Exacerbation

- Manage as in non-pregnant patients:

- IVF, O2

- SABA - inh preferred.

- Anticholinergics - ipratropium. LAMAs not commonly used, but data suggests ok.

- PO/IV steroids (same doses as non-pregnant patients)

- ? incr cleft palate <12w, preeclampsia, LBW. Benefits >> Risks.

- If not improving:

- IV B2 agonists - terbutaline rather than epi (ut art vasoconstriction)

- MgSO4

Take Home Points - control for improved outcomes

Asthma

- Rule of thirds

- Monitor control w/ PEFR

- Mgmt largely same as for

non-pregnant population

Thyroid

- 9 doses/wk for preexisting

- No universal screening

- Consider risk factors

- Check TPOAb if TSH >2.5

- Treat:

- All TSH >10

- TSH >4 if TPOAb+

- Consider Rx:

- TSH >4 w/ TPOAb -

- TSH >2.5 w/ TPOAb+

Diabetes

- Preconception counseling

- Screening & recognition of

GDM

- Early glycemic control &

wt mgmt

- Fetal surveillance

- Postpartum follow up