Chronic Disease

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• Chronic health conditions are common in women of reproductive age. The prevalence for selected diseases is as follows (Kaiser Family Foundation, Women’s Health Care Chartbook, 2011):
  • Arthritis – 9%
  • Asthma/other respiratory – 14%
  • Diabetes mellitus – 5%
  • Heart disease – 2%
  • Hypercholesterolemia – 9%
  • Hypertension – 11%
  • Thyroid – 8%
• More than 50% of all women of reproductive age have one or more risks for developing a chronic disease:
  • The most common risk factor is obesity

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• In every pregnancy there are (at least) two patients — the woman and the fetus(es).
• Medical conditions and treatments may affect the pregnant woman and her embryo(s)/fetus(es) differently.
• Pregnancy may have an impact on the course of the medical condition. In some cases, it may worsen the condition or result in delay in needed treatment.
• Specific chronic diseases can, themselves, prove teratogenic (e.g. diabetes mellitus, epilepsy) as can the medications used to treat them.

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• As with every primary care patient, a thorough history to identify chronic diseases and current therapies is appropriate for all women of childbearing age.

[/symple_toggle][symple_toggle title="Risk Reduction Strategies" state="closed"]

A number of pre-pregnancy strategies have the potential to minimize risks and are, therefore, appropriate for all women of childbearing potential:

• Optimize disease control in preparation for pregnancy;
• Change potentially teratogenic treatments to ones with the safest profile for embryonic development;
• Educate the woman about how pregnancy might affect her own short- and long-term health;
• Encourage contraceptive use until the chronic disease(s) and treatment(s) are most favorable to a healthy pregnancy and infant;
• Assure that all women, irrespective of pregnancy desires, are supplementing their diet with 400 mcg of folic acid daily in combination with a healthy diet of folate rich foods.
  • In addition, women with high risk factors for pregnancies including those with insulin-dependent diabetes mellitus or a diagnosis of epilepsy (particularly if treated with valproic acid or carbamazepine) should be advised that higher doses of folic acid are recommended around the time of conception.
    • The precise dose required to reduce the risk of NTDs in high risk women is unknown but the most consistent recommendation is 4 mg starting one month prior to attempting pregnancy and continued through the first 3 months of gestation.
    • This high dose requires a prescription and should not be recommended if the woman is not at risk of pregnancy.
• Seek appropriate consultation and work to coordinate care across specialists interacting with the woman.
• A framework for systematically approaching the preconception considerations of chronic diseases is presented as a free CME module on this website. The module is titled “Maximizing Prevention: Targeted Care for Those with High Risk Conditions”.

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• Women with chronic diseases can have healthy pregnancies and healthy infants but the likelihood is greatly increased by good pre-pregnancy disease control with the fewest and safest medicines possible.
• It is especially important for women with chronic diseases to plan their pregnancies and to work with their providers to achieve the highest level of wellness possible before stopping their method of contraception.
• A woman with chronic disease should be specifically cautioned to never stop a prescription medicine without medical consultation — even if she thinks she has become pregnant.

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[symple_toggle title="Asthma" state="closed"]

• Prevalence: 9.4% of women of reproductive age in US, 8.2% of pregnant women
• Key Points:
  • Approximately 30% of women will have asthma severity worsen during pregnancy. Those who are poorly controlled prior to pregnancy are most at risk.
  • Poorly controlled asthma during pregnancy is associated with serious maternal and fetal complications (preeclampsia, hypertension, hyperemesis gravidarum; stillbirth and infant death, neonatal hypoxia, IUGR, premature birth and low birth weight).
  • Women whose asthma is well controlled during pregnancy have perinatal outcomes similar to those of non-asthmatic women.
• Medication Issues:
  • Most inhaled asthma medications are safe during pregnancy.
  • Women should be counseled to not discontinue medications during pregnancy.
  • The preferred inhaled corticosteroid is budesonide due to FDA category B rating; all others are category C.
  • Oral corticosteroids have been associated with reduced birth weight, increased risk of preeclampsia, and increased risk of oral clefts (1st trimester use). However, when indicated for management, the risks of oral corticosteroids are probably less than the risks of severe uncontrolled asthma.
• Family Planning (timing of conception):
  • Educate women on the advantages of using contraception until their asthma is under good control.

RESOURCES

National Heart, Lung, and Blood Institute: Guidelines for the Diagnosis and Management of Asthma (2007).http://www.nhlbi.nih.gov/guidelines/asthma/index.htm

Agency for Healthcare Research and Quality Guideline: Asthma in pregnancy (2008). http://www.guideline.gov/content.aspx?id=12630.

American College of Obstetricians and Gynecologists (2008). Asthma in Pregnancy ACOG Practice Bulletin 90, Obstetrics & Gynecology 111(2 Pt 1), 457-64.

[/symple_toggle][symple_toggle title="Autoimmune Disorders (e.g. Lupus)" state="closed"]

• Autoimmune disorders are 6-10 times more common in women than men
• Autoimmune disorders most likely have their onset during the reproductive years.
• Key Points:
  • Some autoimmune diseases have significant impact on the outcome of pregnancy (e.g. systemic lupus erythematosis and presence of anti-Ro/SS-A or SS-B antibodies, antiphospholipid syndrome).
  • Disease quiescence in the 6 months prior to conception is associated with improved pregnancy outcome for some autoimmune conditions (e.g. lupus)
  • Pregnancy may accelerate disease progression in women with evidence of significant end organ dysfunction as a result of their disease (e.g. lupus nephritis).
  • Preconception consultation with a maternal-fetal medicine specialist should be considered.
• Medication Issues:
  • Many medications used to control autoimmune diseases are either contraindicated in pregnancy (e.g. methotrexate) or may pose risk, particularly with prolonged exposure (e.g. NSAIDs).
  • Glucocorticoids are the mainstay of therapy during pregnancy.
• Family Planning (timing of conception):
  • Given the significant risks of autoimmune diseases in pregnancy, women should be encouraged to develop a reproductive life plan that minimizes the risk of unplanned pregnancy.
  • Timing of conception may have a significant impact on pregnancy outcome.
  • Women with autoimmune diseases should be encouraged to achieve optimal control of their condition on the least teratogenic regimen before attempting to conceive.

RESOURCES

American College of Obstetricians & Gynecologists (2012). Antiphospholipid Syndrome, ACOG Practice Bulletin #132. Obstetrics & Gynecology 120 (6), 1514-1521.

American College of Rheumatology Guidelines for Screening, Treatment, and Management of Lupus Nephritis, 2012.http://www.rheumatology.org/Practice/Clinical/Guidelines/Lupus_Nephritis/

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**Content currently being updated: Refer to 2018 ACOG Practice Bulletin 197 for updated information**

• Prevalence varies substantially with ethnicity
• Up to 10% of Caucasians have an inherited thrombophilia, responsible, at least in part, for up to 50% of maternal VTE
• Factor V Leiden mutation may be present in as many as 1:20 Caucasians but very uncommon in Asian populations
• Antiphosplipid antibody syndrome is the most common acquired thrombophilia of pregnancy and is more common in blacks
• Key Points:
  • Consider screening women of reproductive age for a personal or family history of VTE or recurrent or severe adverse pregnancy outcomes. Offer genetic counseling and testing for those who may be at risk.
  • Women of reproductive age with a history of thrombophilia should be counseled on increased maternal and fetal risks which include maternal VTE, arterial thrombosis, severe preeclampsia, placental abruption, recurrent miscarriage, fetal growth restriction, fetal stroke, and death.
• Medication Issues:
  • Although treatment is controversial, current ACOG guidelines recommend offering treatment in pregnancy for women with certain inherited thrombophilias.
  • Warfarin is teratogenic and, whenever possible, should be transitioned to heparin or LMWH prior to and during pregnancy.
• Family Planning (timing of conception):
  • Estrogens promote hypercoagulable states and are contraindicated in women with thrombophilias.
  • There are no contraindications to progestin-only methods, intrauterine devices, or barrier methods.

RESOURCES

American College of Obstetricians and Gynecologists (2013). Inherited Thrombophilia, ACOG Practice Bulletin # 138. Obstetrics & Gynecology 122 (3), 706-717.

Centers for Disease Control and Prevention (2010). U.S Medical Eligibility for Contraceptive Use.http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm

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• One of the most common medical conditions encountered during pregnancy
• The prevalence of pregestational diabetes in pregnancy is approximately 2-5%.
• The prevalence of diabetes prior to conception and during pregnancy is increasing with increasing rates of obesity, older maternal age at the time of conception, and decreasing rates of physical activity.
• Key Points:
  • Poor glycemic control prior to pregnancy is associated with pregnancy loss and birth defects in the newborn.
  • Pregnancy may accelerate disease progression in women with diabetic nephropathy and retinopathy
  • Underlying coronary artery disease poses a 5-15% risk of maternal mortality during pregnancy.
  • Increased incidence of congenital anomalies related to glycemic control. Achieving optimal glycemic control prior to pregnancy improves outcomes. Goal is HgbA1C <6%, fasting glucose 60-90, 1 hr postprandial <140, 2 hr postprandial <120.
  • Risks for neural tube defects may be further reduced by supplementing with high dose folic acid. The precise dose required to reduce the risk of NTDs in high risk women is unknown.
    • The most consistent recommendation is 4 mg starting one month prior to attempting pregnancy and continued through the first 3 months of gestation.
    • This high dose requires a prescription and should not be recommended if the woman is not at risk of pregnancy.
  • Preconception consultation with a maternal-fetal medicine specialist should be considered.
• Medication Issues:
  • In order achieve optimal glycemic control, patients on oral hypoglycemic may require conversion to insulin
  • ACE-inhibitors and statins are considered teratogenic and should be discontinued prior to conception.
  • There is limited data on oral hypoglycemic agents.
• Family Planning (timing of conception):
  • Woman should be counseled on using an effective contraceptive method until her blood sugars have reached optimal levels and appropriate consultations and evaluations have been completed.
  • No specific contraindications to any contraceptive method in women who do not have end organ dysfunction.
  • Women with evidence of vascular disease or other end organ dysfunction should avoid estrogen containing contraceptives.

RESOURCES

Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline, (2013). Login required (free).

http://www.endocrine.org/education-and-practice-management/clinical-practice-guidelines/

National Heart, Lung, and Blood Institute: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (2003).http://www.nhlbi.nih.gov/guidelines/hypertension/index.htm

Centers for Disease Control and Prevention (2010). U.S Medical Eligibility for Contraceptive Use.http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm

[/symple_toggle][symple_toggle title="HIV Infection" state="closed"]

See Infectious Diseases.

[/symple_toggle][symple_toggle title="Hyperlipidemia" state="closed"]

• Prevalence: 9% of women of reproductive age
• Key Points:
  • Consideration of comorbidities is most important, e.g. diabetes, HTN, and coronary artery disease. Education and understanding of risks of these conditions and importance of adequate control prior to conception is vital.
• Medication Issues:
  • Statins are considered teratogenic and should be stopped prior to and during pregnancy.
• Family Planning (timing of conception):
  • No specific contraindications to any contraceptive method in women who do not have end organ dysfunction.
  • Consideration of comorbidities should lead the preconception planning discussion.
  • Women with evidence of vascular disease or other end organ dysfunction should avoid estrogen containing contraceptives.

RESOURCES

2013 ACC/AHA Blood Cholesterol Guideline available at:

https://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a.full.pdf

Cardiovascular Risk Calculator:

https://my.americanheart.org/professional/StatementsGuidelines/Prevention-Guidelines_UCM_457698_SubHomePage.jsp

[/symple_toggle][symple_toggle title="Seizure Disorders" state="closed"]

• Epilepsy is the most common neurologic disorder in pregnancy
• Estimated to be present in 0.2-0.5% of pregnancies
• Key Points:
  • Increased incidence of congenital malformations in women with seizure disorder regardless of whether they are taking anticonvulsants.
  • Goal is to keep the woman seizure free on the simplest medication regimen.
  • Is the diagnosis of a seizure disorder well established? Should the woman be on anticonvulsants?
  • Being seizure free for at least 9 months prior to pregnancy is probably associated with a high rate (84%–92%) of remaining seizure-free during pregnancy.
• Medication Issues:
  • Anticonvulsants may be associated with birth defects, particularly valproate.
  • Women on multidrug regimens may be able to simplify them or switch to a regimen that is less potentially teratogenic prior to conception.
  • Advise all women to ingest 0.4 mg (400 mcg) of synthetic folic acid daily from supplements and/or fortified food sources (such as highly-fortified breakfast cereals) AND to consume folate-rich foods daily (e.g., green, leafy vegetables).
    • Folic acid supplementation is of special significance for women on anticonvulsants since some (e.g. valproate, carbamazepine) are associated with reductions in levels of folic acid and increased rates of NTDs
    • The most consistent recommendation is supplementation with 4 mg of folic acid daily in women on anticonvulsant therapy starting 1 month prior to anticipated conception and continued for the first three months of pregnancy.
    • This dose requires a prescription.
  • Women should be counseled NOT to stop or change their medication regimen without clinical supervision, even if they think they have become pregnant.
• Family Planning (timing of conception):
  • Timing of conception should be planned for after the woman is on a stable medication regimen that controls her seizure disorder and has been on high doses of folic acid for at least one month.
  • To achieve seizure control with the safest drug regimen possible may take time so contraception may be needed in the short term.
    • Hormonal contraceptives may have a higher failure rate in women on certain anticonvulsants that induce the hepatic cytochrome P450 system.

RESOURCES

Practice Parameter update: Management issues for women with epilepsy: Focus on pregnancy (an evidence-based review) (2009). Teratogenesis and perinatal outcomes. American Academy of Neurology and Epilepsy Society.http://www.neurology.org/content/73/2/133.full.html

Practice Parameter update: Management issues for women with epilepsy: Focus on pregnancy (an evidence-based review) (2009). Obstetrical complications and change in seizure frequency. American Academy of Neurology and Epilepsy Society.http://www.neurology.org/content/73/2/126.full.html

Centers for Disease Control and Prevention (2010). U.S Medical Eligibility for Contraceptive Use.http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm

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**Content is in process of being updated: Refer to 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum. **

• 2^nd most common endocrinopathy affecting pregnancy
• Hyperthyroidism affects approximately 0.2% of pregnancies; Grave’s disease most common (95%)
• Overt hypothyroidism affects approximately 2.5% of pregnancies
• Subclinical hypothyroidism affects approximately 2 to 5% of pregnant women
• Key Points:
  • Uncontrolled hyperthyroidism is associated with increased incidence of preeclampsia, CHF, thyroid crisis and placental abruption
  • Uncontrolled hypothyroidism is associated with intellectual impairment in the offspring as well as pregnancy complications of hypertension and preeclampsia, placental abruption, anemia, postpartum hemorrhage, preterm birth, low birthweight, and fetal death
  • Control in the euthyroid state improves outcomes
  • Thyroid hormone requirements increase in pregnancy (by about 30-50%) , especially in the 1^sttrimester.
• Medication Issues:
  • Goal is to achieve euthyroidism on the lowest possible dose possible since the medications can cross the placenta.
  • Methimazole is preferred treatment for hyperthyroidism in pregnancy although it does have a teratogenic risk. Propylthiouracil may be preferred in the first trimester.
  • Levothyroxine dose should be increased as early in pregnancy as possible and monitored throughout
  • Goal TSH in pregnancy is lower than in non-pregnant women, exact target is controversial
  • Treatment of subclinical hypothyroidism remains controversial.
• Family Planning (timing of conception):
  • It is customary to avoid pregnancy 6 months after radioactive iodine treatment.
  • Women should be receiving optimal replacement therapy and be in a euthyroid state prior to conception
  • Be aware that treatment of thyroid disease may increase fertility as women who have uncontrolled hypothyroidism are often anovulatory.

RESOURCES

Guidelines of the American Thyroid Association For The Diagnosis And Management Of Thyroid Disease During Pregnancy And Postpartum, (2011).http://thyroidguidelines.net/pregnancy

Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline, (2012). Login required (free).

http://www.endocrine.org/education-and-practice-management/clinical-practice-guidelines

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Centers for Disease Control and Prevention (2016). U.S Medical Eligibility for Contraceptive Use.
http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm

National Heart, Lung, and Blood Institute: Guidelines for the Diagnosis and Management of Asthma (2007).
http://www.nhlbi.nih.gov/guidelines/asthma/index.htm

ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy, Obstetrics & Gynecology: July 2018 – Volume 132 – Issue 1 – p e18-e34
https://journals.lww.com/greenjournal/Abstract/2018/07000/ACOG_Practice_Bulletin_No__197__Inherited.55.aspx

2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum. https://www.liebertpub.com/doi/full/10.1089/thy.2016.0457

American Academy of Neurology: Management issues for women with epilepsy — Focus on pregnancy: Vitamin K, folic acid, blood levels, and breastfeeding (2009).
http://www.neurology.org/content/73/2/142.full.pdf

American Academy of Neurology: Management issues for women with epilepsy — Focus on pregnancy: Obstetrical complications and change in seizure frequency (2009).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475195/pdf/znl126.pdf

American Academy of Neurology: Fact Sheet on Antiepileptic Medications during Pregnancy (2009).
https://www.aan.com/Guidelines/Home/GetGuidelineContent/337

In Spanish:https://www.aan.com/Guidelines/Home/GetGuidelineContent/386

American Academy of Neurology: Women with Epilepsy: Drug Risks and Safety during Pregnancy (2009)  https://www.aan.com/Guidelines/Home/GetGuidelineContent/338

Also in Spanish!

https://www.aan.com/Guidelines/Home/GetGuidelineContent/385

Centers for Disease Control and Prevention. Preconception Health and Health Care: Women (2013). Offers content on a number of chronic diseases and on preconception health, in general, for men and women.
http://www.cdc.gov/preconception/women.html.

FamilyDoctor.org: Epilepsy and Pregnancy (2010).
http://familydoctor.org/familydoctor/en/diseases-conditions/epilepsy/epilepsy-and-pregnancy.html.

March of Dimes: Preexisting Diabetes. https://www.marchofdimes.org/complications/preexisting-diabetes.aspx 

ACOG FAQ: A Healthy Pregnancy for Women with Diabetes: http://www.acog.org/Patients/FAQs/A-Healthy-Pregnancy-for-Women-with-Diabetes

American College of Obstetricians and Gynecologists (2007). Guidelines for Women’s Health Care: A Resource Manual (3rd ed). Washington, DC: ACOG.

American Academy of Pediatrics and American College of Obstetricians and Gynecologists (2013). Guidelines for Perinatal Care (7th ed.). Evansville, Ill: AAP/ACOG.

Dunlop, A.L., Jack, B.W. Bottalico, J.N. (2008). The clinical content of preconception care: women with chronic medical conditions. American Journal of Obstetrics and Gynecology 199 (6B) 310-327.