Counseling of Female Veterans 

about Risks of 

Medication-Induced Birth Defects 

Eleanor Bimla Schwarz, MD, MS
 

Director, Womens Health Services Research Unit
 

Center for Research on Health Care
 

Departments of Medicine, Epidemiology,
 

Obstetrics, Gynecology and Reproductive Sciences
 

Magee-Womens Research Institute
 

University of Pittsburgh
 
 

Disclosures
 

NONE
 Funding from:
 

• NICHD -W.K. Kellogg Foundation
 

• AHRQ -American Diabetes Association 

• VA -Society of Family Planning 

• FDA -Hewlett Foundation 

• USAID 
Objectives
 

•	 Review recent data on Female Veterans’ use of 

medications that can cause birth defects. 

• Examine Veterans’ reports of the counseling they 

receive about medication-induced birth defects 

•	 Discuss best practices for safe-prescribing to women 

of childbearing potential. 
 

 

What is your role within VA? 

(choose all that apply) 

• Primary care provider 

• Women’s health specialist 

• Nurse 

• Social worker 

• Behavioral health specialist 

• Researcher 

• Other 
 

Vision 

1. Healthy moms 

2. Healthy babies 

3. Comfortable clinicians
 
 

 

Each year in the US...
	

62 million women of reproductive age
 

6 million pregnancies
 

4 million births
 

150,000 babies with birth defects
 

March of Dimes Perinatal Data Center, 2014
 
 

Each year in the US...
	

62 million women of reproductive age
 

Maternal
 

Illness
 

6 million pregnancies 

4 million births
 

150,000 babies with birth defects
 
 

 

Each year in the US...
	

62 million women of reproductive age
 

Maternal Medication 

Illness Use 

6 million pregnancies 

4 million births
 

120,000 babies with birth defects
 

March of Dimes, 2014
 
 

 

 

 

 

 

 

Teratogenic Medications
 

Medicines that can cause birth defects
 

thalidomide, 

isotretinoin, 

phenytoin, 

warfarin, 

methotrexate, 

lithium...

...more than 100 different drugs!
 
FDA Classification System 

• Class A: Fetal harm appears remote 

Class B: Animal studies revealed no evidence 

 of fetal harm 

Class C: No adequate studies in women. 

Class D: Evidence of human fetal risk 

– Use in pregnant women may be acceptable 

for serious disease when no safer drugs exist 

Class X: Contraindicated in women who are or 

may become pregnant 

•	 

•

•

•	 
 

Are women of reproductive age 

using class D and X Medications?
 
YES!!
 
 

 

 

 

Schwarz EB,et al. Am J Med 2005 

Nationally, how often are potentially teratogenic 

meds prescribed? 

Annually: 

11.7 million teratogenic Rx	 = 1 of every 25 Rx 

283 million prescriptions 

for women age 14-44 years who were not pregnant 

11.7 million teratogenic Rx = 1 of every 13 visits 147 million outpatient visits 

for women age 14-44 years who were not pregnant 
 

1/6 women filled 

a class D or X Rx 

In a large HMO in 2001...

Schwarz EB,et al. Ann Intern Med. 2007 
0. 

0. 

0. 

0. 

1. 

4. 

1. 

0. 

1. 

 

 

for ?
 

What are these 11.7 million prescriptions 

54

40

40

76

38

06

42

21

Accutane
 

Warfarin 

Anti-Seizure 

Anxiolytics 

Lithium 

Methotrexate 

Statins 

Tetracyclines 

Others 

Schwarz EB,et al. Am J Med 2005
 

67 
0 1 2 3 4 5

Cardiologists

Neurologists

Gynecologists

Rheumatologists

Dermatologists

Psychiatrists

GENERALISTS

Millions

 

 

 

Who’s writing these prescriptions? 

Family Practitioners General Internists 

Millions of Visits/year with a teratogenic Rx 

Schwarz EB,et al. Am J Med 2005 
 

49% of female Vets 

who received an Rx from a 

VA pharmacy received a 

potentially teratogenic Rx

Our Female Vets...

Schwarz EB, et al Med Care Sept 2010 
 

 

 

 

 

 

 

 

 

 

 

 

 

Are these chronic meds?
 Women Veterans 

who filled 

>=1 Rx 

N=38,205 

N % 

Rx per woman 

per year 

Average # 

Days supply 

per woman 

Veteran 

per year 

Average 

Psychiatric 20155 52.8 4.2 133.5 

Antidepressant 5162 13.5 2.8 116.0 

Benzodiazepine 16430 43.0 3.9 112.5 

Antihypertensive 8115 21.2 2.7 195.5 

Statin 8790 23.0 2.1 153.5 

Neurologic 4687 12.3 3.4 134.0 

Tetracycline 6235 16.3 1.0 28.0 

Warfarin 547 1.4 4.9 164.5 

Retinoid 75 0.2 2.2 65.5 

Other 7562 19.8 1.3 34.5 

Schwarz EB, et al Med Care
 
 

 

 

Participating Female Vets
 

(OEF/OIF Vets, N=245) Total
 

Sexually active 86% 

Prior pregnancy 63% 

Unintended 72% 

pregnancy 

Prior abortion 29% 

Prior birth 66% 

Prior birth defect 6% 

† Infertility 11% 

Used contraception 

Condom with last sex 22% 

Hormonal method in last 12 months 48% 
 

 

 

Teratogenic Risk Counseling 

of Female Vets
 Received 

counseling
 

Sexually active 25% 

Prior pregnancy 25% 

Unintended 25% 

pregnancy 

Prior abortion 24% 

Prior birth 26% 

Prior birth defect 30% 

† Infertility 35% 

Used contraception 

Condom with last sex 15% 

Hormonal method in last 12 months 28% 
Schwarz EB, et al JGIM 2013 

Female Vets rarely report counseling 

about teratogenic risks 

•	 90% were confident that they would be 

told by their clinician if an Rx might cause a 

birth defect 

– 81% of women prescribed benzodiazepines
 

•	 But, only 24% of women with Rx had been 

warned of teratogenic risks 

– 22% of women prescribed benzodiazepines
 
 

 

 

 

Associated with
 

Teratogenic Risk Counseling? p-value 

Sexually active 0.15 

Prior pregnancy 0.27 

Unintended 0.61 

pregnancy 

Prior abortion 0.58 

Prior birth 0.96 

Prior birth defect 0.79 

† Infertility 0.12 

Used contraception 

Condom with last sex 0.06 

Hormonal method in last 12 months 0.16 
 

 

 

 

Any medication 24 % 90 % 

(n=286) 

ACE-inhibitor or 0 % 50 % 

ARB blocker (n=4) 

Benzodiazepine 22 % 81 % 

(n=37) 

Counseling by medication class
 

Confident they’d 

Received receive counseling 

counseling 

Statin (n=16) 19 % 81 %
 
 

 

 

Confidence Vet’d receive teratogenic 

risk counseling
 

•	 NOT associated with sociodemographics 

•	 Confidence decreased with: 

– Difficulty obtaining contraception in military 

78% vs. 91%, p=0.04 

–	 Pregnancy after MST, 67% vs. 91%, p=0.05
 

–	 History of drug use 

•	 Confidence increased with prior pregnancy 

affected by birth defects 
 

 

Does confidence matter?
 

Confidence associated with more likely to: 

•	 !gree that “VA provides good quality 

healthcare,” p=0.04 

•	 Plan to use VA as a primary source of 

healthcare in the future (85% vs 94%, p=0.04) 
 

 

 

 

 

 

 

 

Does FDA label affect
 

contraceptive counseling?
 

Apparently not Safe Rx 

Class A or B 

(95% CI) 

Risky Rx 

Class D or X 

(95% CI) 

p-value 

Nationally, visits with 

contraceptive counseling or 

Rx 

5.4% 4.1% p=0.24 

In Northern CA, Rx with 

contraceptive counseling or 

use 

39.4% 37.0% p<0.001 

Schwarz EB, et al. Am J Med 2005 

Schwarz EB, et al. Ann Intern Med. 2007 
Nationally... 

 <20% of US women receiving 

potentially teratogenic medications 

had documented receipt of family 

planning services 

Schwarz EB et al. Am J Med 2005;118:1240–9.
 
 

 

 

Among Female Vets
 

Receipt of family planning services 

(e.g. contraception, contraceptive counseling 

or pregnancy testing) was documented for 

• 36% of women filling only class A or B meds
 

• 52% of women who filled class C meds 

• 56% of those who filled class D or X meds 

Schwarz EB, et al Med Care
 
 

 

 

Does contraceptive method affect 

rates of positive pregnancy tests after filling a 

potentially teratogenic medication?
 

YES
 

Women 15-44 yo with + pregnancy test 

<3 months after filling a potentially teratogenic Rx % 

Overall 

Women with any contraceptive documentation 

1.0 

0.8 

Women with a most effective contraceptive 0.2 

Schwarz EB, et al Ann Intern Med 2007
 
 

 

 

 

 

What affects rates of safe prescribing to women
 

of reproductive age?
 

• Patient characteristics? 

– Age= 

• at KP: 25-34 yrs > 15-24 yrs > 35+ yrs
 

• at VA: 18-25 yrs > 26-34 yrs > 35+ yrs
 

• at UPMC: 18-29 yrs > 30+ yrs 

• Provider characteristics? 

– Gyn > non-gyn; NPs/PAs/CNMs > MDs
 

– Not gender, age, race, or years in practice 

Schwarz EB, et al. Am J Med 2005
 

Schwarz EB et al. Med Care 2010
 
 

 

 

 

What affects rates of safe prescribing to women
 

of reproductive age? 

Clinic characteristics 

• VA Women’s clinic OR=1.96* 

• At KP and UPMC some clinics 2x others 

Provider characteristics 

• Not gender, age, race, or tenure 

• Gyn > non-gyn 

• NPs/PAs/CNMs > MDs 

Schwarz EB, eAt QAAal. Am J Med 2005 

Schwarz EB, et al. Ann Intern Med 2007 

Schwarz EB et al. Med Care 2010 2010 
 

 

 

Clinical Indication?
 

• Isotretinoin better than all others
 

• Coumadin worse than others
 

Schwarz EB, et al. Am J Med 2005
 

Schwarz EB et al. Med Care 2010
 
 

 

 

Barriers & Facilitators
 

Barriers 

Electronic decision 

Facilitators 

Limited PCP visit time support tools 

Lack of ∆ reimbursement 

reimbursement structure 

Difficulty identifying Education resources for 

teratogenic risk providers and patients 

Schwarz EB et al. Birth Defects Res A Clin Mol Teratol. 2009 85(10): 858–863. 

Eisenberg DL et al. J Gen Intern Med. 2010;25(4):291-7. 
 

 

 

Electronic Decision Support?
 

Simple Alerts 

“Concern has been raised about 

use of this med during pregnancy.” 

Multifaceted Alerts 

“Concern has been raised about 

use of this med in pregnancy.” 

Plus links to: 

•Info on meds 

•Order for pregnancy testing 

•Orders for contraception 

•Refer to specialist 

41 primary care physicians 

randomized 
Hypotheses
 





Simple alert would be good 

Multifaceted alert would be better 
 

 

Clinical Decision Support
 

Schwarz EB, et al
 

JGIM 2012 
 

 

Clinical Decision Support
 

Schwarz EB, et al
 

JGIM 2012 
25.2*

27.2*

30.2*

23.3 25.9

27.4

15

20

25

30

35

T0 T1 T2 % of Terato w/ FamilyPlanning

Simple Multifaceted/Control

Visits with Teratogenic Rx & 
 

Family Planning Services
 

* p = 0.04 for improvement over time 

+3.0% 

+2.0% 

+1.5% 

+2.6% 
 

Results
 

● 3 types of patients: 

 Contraception on all visits = 26% 

NO contraception on any visits = 69% 

No contraception before intervention, with 

contraception after alert = 5% 
 

 

Challenges
 

● Doctors who received multifaceted alerts 

accessed links only 16% of time. 

● Alerts fired only once per visit: 

 14% doctors who received alert cancelled Rx, 

AND unknowingly Rx’d another teratogen! 

 Limited visible effect of intervention. 
Limitations
 

Electronic medical record data incomplete 

Vasectomy, sterilization, condoms 

Contraceptive counseling ICD-9 codes rarely used 

because no reimbursement provided 

Should not differ between groups 
 

Not just poor documentation
 

Counseling about risk of birth defects and/or 

contraception was reported by Women 

• 41% if no potentially teratogenic Rx
 

• 45% if pot’ly teratogenic Rx, no CDS
	

• 57% if pot’ly teratogenic Rx and CDS
	

Schwarz EB, et al J Womens Health 2013
 
 

 

 

Conclusions
 

Computerized alerts can be helpful, 

but refinement is needed. 

Alerts need to re-fire if Rx another teratogen. 

Routine documentation of fertility and 

contraception is important for safe Rx to women 

of childbearing age. 
 

Safe prescribing to women of 

childbearing potential
 

Risks of teratogenic exposure 

greatest in early pregnancy
 

49% of US pregnancies 

unintended 

6% of US pregnancies exposed to 

potentially teratogenic medication 

Andrade SE et al. Am J Obstet Gynecol 2004;191:398–407.
 
 

 

 

 

 

Proactive counseling
 

•	 Risks are greatest in early pregnancy 

–	 Before most receive prenatal care 

–	 Before many know they are pregnant
 

•	 Perception (or misperception) of risks 

impact behavior 

–	 Discontinue needed medication 

–	 Abortion 

Koren G et al Can J Pub Health 1991 May-Jun;82(3):S11-4, S33-7 

Jasper JD, et al Lancet. 2001 Oct 13;358(9289):1237-8 
 

 

 

“Scares” can have long-term effects
 

After a false-positive screen 

for congenital Is my child normal? hypothyroidism... 

•	 78% reported strong 

emotional reaction 

•	 After one year, 18% had 

persistent insecurity about 

their child’s health

•	 Some without concerns at 

1 year, reported insecurity 

after 4 years 

• At 4 years, 80% reported
 persistent insecurity
 Fyro K and Bodegard G Four-year follow-up of psychological reactions to 

false positive screening tests for congenital hypothyroidism. 

Acta Paediatr Scand. 1987 Jan;76(1):107-14 
Behringer T, et al 2011 

Clinician counseling is important
 

96 women with a h/o Anxiety requiring meds 

• In pregnancy? 29% “likely” to continue meds
	

• If FD! warning? 5% “likely” to continue meds 

• If clinician counseled med was safe (despite FDA 

warning)? 41% switched to “likely” 

Prim Care Companion CNS Disord
 
 

Know her plans
 

•	 When, if ever, would you like to have a baby 

in the future? 

•	 What are you doing to delay or avoid 

pregnancy? 

– 50% of female Veterans have no documented use 

of prescription contraception 
 

 

 

What are your plans for pregnancy?
 

trying to

conceive

wouldn't mind

conceiving

don't know

wouldn't mind

avoiding

trying to avoid

High SES clinic Low SES clinic 

Schwarz et al Prevalence and Correlates of
 

Ambivalence towards Pregnancy Contraception 2007
 
 

 

Discuss Absolute Risks
 

Twice a very, very, small risk
 

is still a very small risk
 

Relative Risk Baseline risk Absolute risk
 

2 1/100 2/100
 

2 1/million 2/million
 
 

 

 

 

FIGURE 1. Graphical representation of risks in pregnancy. The risk of major congenital malformations of 

most of the drugs is at base line risk level (1% to 3%). Only few drugs are documented teratogens with a 

risk between 20% and 30%. VPA indicates valproic acid. 

From: 
OTIS Mother to Baby
 

Benzodiazepines 

http://www.mothertobaby.org/files/benzodiazepines.p 

df 

• Paroxetine 

http://www.mothertobaby.org/files/paroxetine.pdf 

• Fluoxetine 

http://www.mothertobaby.org/files/fluoxetine.pdf 
 

 

 

 

Voluntary Risks in Perspective
 

IUD (per year) 

Vasectomy 

Legal abortion < 9 wks 

BCP, nonsmoker < 35 

Sexual intercourse (PID) age 15-24 

Laparoscopic BTL 

BCP, nonsmoker > 35 

Football 

Continued pregnancy 

Auto driving 

Motorcycling 

0 20 40 60 80 100 120 

1/5000 1/1000 

Annual Deaths per 100,000 Women 

Hatcher et al. Contraceptive Technology, 1998
 
 

Unfortunately
 

• Unintended pregnancy is common 

– 49% of US pregnancies 

– 5% of US women each year 

• Even more common among military women
 

Frindlay K et al Obstet Gynecol 2013
 

The Alan Guttmacher Institute, 2010
 
 

 

 

 

 

3 Simple Ways to Prevent
 

Medication-induced Birth Defects
 

• Nexplanon® 

® 

® 

Sivin I. Contraception. 2007;Ronnergdag Acta Obstet Gynecol Scand. 1999 ;Inki P Contraception. 2007; 

Power J 2007; PMID: 17636668;Darney P 2009; PMID: 18423453;Steiner MJ 2010; PMID: 20159174 

etonogestrel (2006) 

– Labeled use for 3 years 

– Lighter menses 

• Mirena levonorgestrel (2001) 

– Labeled for 5 years, Studied to 7 yrs 

– Lighter menses/Amenorrhea 

• ParaGard “copper T” (1988) 

– Labeled use for 10 years 

– Effective in studies for 12-20 yrs 

– May have heavier cramping/menses 
Real world effectiveness
 

5% 

8% 

9% 

Winner B et al, NEJM 2012
 
 

 

Complicated patient?
 

Guidance is available! 

•	 the CDC “US Medical Eligibility Criteria”

–	 http://www.cdc.gov/mmwr/pdf/rr/rr59e0528.pdf 

•	 the WHO Medical Eligibility Criteria for 

Contraceptive Use, 4th edition 

–	 http://whqlibdoc.who.int/publications/2010/9789241563888_eng.pdf 
 

 

 

 

 

 

 

 

 

 

Medical Eligibility Criteria
 

Category Interpretation 

1 

No restriction for use 

Use method for any circumstance 

2 Advantages outweigh theoretical/proven risks 

Generally use the method 

3 

Theoretical/proven risks outweigh advantage 

Generally not recommended unless no other 

method available or acceptable 

4 Unacceptable health risk 

Do not use 

WHO MEC, 4rd Edition, 2008
 
Do YOU know?
 

If 100 fertile women are sexually active, how many would 

you expect to become pregnant within one year if they use 

no form of contraception? 

• 5% 

• 25% 

• 50% 

• 85% 
Do YOU know?
 

If 100 fertile women are sexually active, how many would 

you expect to become pregnant within one year if they use 

no form of contraception? 

• 5% 

• 25% 

• 50% 

• 85% 
 

Cumulative failure rates
 

“During a lifetime of use of 

reversible methods, the 

typical woman will experience 

1.8 contraceptive failures”

Trussell J & Vaughan B, Fam Plann Perspect 1999
 
POLL: Have you been trained to 

place nexplanon?
 

• Yes 

• No, I’d like help getting trained 

• No, I’m not a clinician 

• No, I’m a clinician but not interested 
 

 

NuvaRing You place in vagina; 
 • Lighter periods 

replace monthly. 92% • May decrease acne • Blood clots 53%
 

Method of 

Birth Control How to use it 

How well it 

works Benefits Risks 

% 

satisfied 

Nexplanon • Nothing to do or remember Placed under skin of 


 • Light or no periods Implant arm by a clinician. >99% • May decrease acne • Irregular periods 79%
 Works for 3 years. • No increased risk of clots 

Mirena IUD Placed in uterus by • Nothing to do or remember 

clinician. >99% • Light or no periods • Irregular periods 86% 

Works for 5 years. • No increased risk of clots 

Depo • Light or no periods • Irregular periods Provera Given every 3 months. 97%
 • May decrease acne • May cause weight gain 54%
 

shot • No increased risk of clots 

Evra You place on skin; • Lighter periods Patch replace weekly. 92%
 • May decrease acne • Blood clots 44%
 

Combined 

Swallow at the same 
 • Lighter periods Pill time daily. 92% • May decrease acne • Blood clots 54%
 

Progestin-only Swallow at the same • Lighter periods 

mini-pill time daily. 92%
 • No increased risk of clots • Irregular periods 54%
 

C Must use every time 
 • Protects from infections ondoms ou have sex. 85% and HIV • Allergy to latex 43%
 y

• Nothing to do or remember 

Placed in uterus by • No hormones • May cause heavier 

clinician. >99% • Periods remain regular periods and cramping 80% 

Works for 12 years. • Effective immediately 

ParaGard IUD • No increased risk of clots 
References
 •	 Counseling of female veterans about risks of medication-induced birth defects. PMID: 23807071 

Provision of potentially teratogenic medications to female veterans of childbearing age. 

PMID: 20706159 

Clinical decision support to promote safe prescribing to women of reproductive age: a clusterrandomized trial. PMID: 22297687 

Counseling about medication-induced birth defects with clinical decision support in primary care. 

PMID: 23930947 

Women's perspectives on counseling about risks for medication-induced birth defects. 

PMID: 19637252 

Prescription of teratogenic medications in United States ambulatory practices. PMID: 16271908 

Documentation of contraception and pregnancy when prescribing potentially teratogenic 

medications for reproductive-age women. PMID: 17876020 

Opportunities missed: improving the rate of contraceptive counseling or provision when prescribing 

reproductive-aged women potentially teratogenic medications in a family medicine resident clinic. 

PMID: 21920192 

Providing contraception for women taking potentially teratogenic medications: a survey of internal 

medicine physicians' knowledge, attitudes and barriers. PMID: 20087677 

Promoting safe prescribing in primary care with a contraceptive vital sign: a cluster-randomized 

controlled trial. PMID: 23149528 

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Thank You!
 

Questions?
 schwarzeb@upmc.edu 
 

Hepatic enzyme inducers
 

•	 Decrease effectiveness of hormonal 

contraceptives (including implants) 

–	 Carbamazepine 

–	 Barbiturates 

–	 Phenobarbital 

–	 Primidone 

–	 Effavirenz 

–	 St. John’s Wort 

•	 DMPA likely still ok 

• ParaGard® “copper T” still 

works really well 

Sivin I. Contraception. 2007;Ronnergdag Acta Obstet Gynecol Scand. 1999 ;Inki P Contraception. 2007; 

Power J 2007; PMID: 17636668;Darney P 2009; PMID: 18423453;Steiner MJ 2010; PMID: 20159174