Trimester zero (Part 1 of 2)

Preconception care is primary prevention. The goal is to affirm pregnancy intention, reduce any potential harm, and recognize modifiable risk factors related to pregnancy while stratifying pregnancies on a continuum of low- to high-risk. The Centers for Disease Control and Prevention (CDC) has defined preconception care as “a set of interventions that aim to identify and modify medical, behavioral, and social risks to a woman’s health or pregnancy outcome through prevention and management.”¹

A recent consensus statement from the National Preconception Health and Health Care Initiative defined 9 specific preconception wellness measures to confirm high-quality preconception care: 1) pregnancy intention; 2) access to care; 3) preconception multivitamin with folic acid; 4) tobacco avoidance; 5) absence of uncontrolled depression; 6) healthy weight; 7) absence of sexually transmitted infections (STIs); 8) optimal glycemic control in women with pregestational diabetes; and 9) teratogenic medication avoidance.²

Recommended: Should women with intrahepatic cholestasis of pregnancy be delivered early?

By the time most women realize they are pregnant, organogenesis has begun and many prevention strategies (such as folic acid to prevent neural-tube defects (NTDs) or glycemic control to prevent diabetic embryopathy) are suboptimal in effect even if promptly initiated.³ Women who were given preconception counseling demonstrated a 50% greater likelihood of their subsequent pregnancies being intended.⁴

Several organizations have focused on optimizing health before conception, which resulted in development of clinical recommendations and educational materials for providers and patients (Table 1).

Components of preconception counseling

The first step in preconception care is reproductive counseling, including counseling about contraceptive options because nearly half of all pregnancies in the United States are unplanned.⁵ Following confirmation of pregnancy intention, a thorough history is indicated. Several questionnaires and forms are available for this purpose (Table 2).

NEXT: Family history

Family history

The United States Surgeon General’s Family History Initiative was launched to educate healthcare providers and patients about the value of using family history as a screening tool for inherited medical conditions and single-gene disorders.⁶ A family history is indicated for both partners⁷ and positive responses are followed up by risk assessment, testing, and genetic counseling. Completing genetic counseling and testing before conception is beneficial.⁸

Maternal genetic conditions

Precise identification of maternal genetic conditions is important when reviewing maternal risks and offspring morbidities associated with pregnancy, counseling about mode of inheritance, partner carrier screening, and risk of genetic condition in the offspring, and determining which prenatal diagnostic or preimplantation genetic screening or testing to recommend (Table 3).

Infections and immunizations

Immunization outside of pregnancy is generally preferable and live-virus vaccines are contraindicated in pregnancy because of their theoretical risk to the fetus.

Two vaccinations, however, are of particular importance antepartum: influenza and pertussis. Influenza can cause significant morbidity and mortality in pregnancy and all clinicians who care for women of reproductive age should encourage them to be vaccinated for influenza every year.⁹ Women planning pregnancy should also receive tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines during each pregnancy, between 27 and 36 weeks’ gestation.¹⁰

Increased understanding of the link between Zika virus and fetal neurological effects adds another discussion to preconception counseling. Because the rate of vertical transmission is unknown, the CDC recommends that women who have been diagnosed with Zika and those who may have been exposed wait at least 8 weeks after their exposure or onset of symptoms before attempting conception. The CDC website should be reviewed for the most up-to-date recommendations because they change regularly. Male partners should wait at least 6 months after their symptoms resolve to have unprotected intercourse.¹¹ Women who reside in endemic areas should discuss reproductive life planning with a physician knowledgeable about Zika. The current recommendation is that they delay pregnancy.¹²

Chronic medical conditions

Physicians should ascertain chronic medical conditions as a part of preconception care. Some common medical conditions that have an effect on or are affected by pregnancy are briefly discussed below. All preexisting chronic medical conditions should be optimized preconceptionally with a multidisciplinary team.

Neurologic

Seizure disorders: Seizure disorders are the most common neurologic diseases in pregnancy. One-third of women with a seizure disorder will experience more frequent seizures while pregnant. Seizure disorders increase the risk of congenital anomalies, whether or not the woman is taking antiepileptic drugs (AEDs).¹³ Women should be managed on the most effective AED, ideally monotherapy at the lowest effective dose, with the exception of valproate, which should be avoided. Given the increased rate of NTDs associated with AEDs, supplementation with 4 mg of folic acid (versus 0.4 mg) should be initiated before conception.

More: The role of IVF with PGS in recurrent miscarriage

Cardiovascular

Hypertension: Chronic hypertension (cHTN) affects 3% to 5% of women of reproductive age.¹⁴ cHTN in pregnancy is associated with higher rates of preterm birth, placental abruption, intrauterine growth restriction, preeclampsia, and fetal demise. Women with cHTN are at risk of worsening hypertension and end organ damage, and 20%–25% develop superimposed preeclampsia.¹⁵ Treating severe-range blood pressures improves pregnancy outcomes.¹⁶ Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are considered Category C in the first trimester and Category D in the second and third trimesters, and should be discontinued before conception. Labetalol, nifedipine, and methyldopa are the optimal agents to use during pregnancy; however, other agents can also be used with caution and in coordination with a maternal-fetal medicine (MFM) specialist.¹⁵ Women with long-standing hypertension should be assessed for retinopathy, renal disease, and ventricular hypertrophy.

Congenital cardiac disease: As more women with congenital cardiac disease, both corrected and uncorrected, reach reproductive age, preconception counseling for them becomes increasingly important. Pregnancy and its associated changes in cardiovascular physiology can pose significant risks. These women require a multidisciplinary approach with cardiology and MFM. The New York Heart Association Functional Classifications and World Health Organization Classification of Maternal Risk should be used.¹⁷

NEXT: Pulmonary and gastrointestinal concerns

Pulmonary

Asthma: Asthma complicates approximately 4%–8% of pregnancies.¹⁸ Women with poorly controlled asthma before pregnancy are more likely to experience worsening symptoms during pregnancy. The goal of treatment in pregnancy is to maintain adequate oxygenation of the fetus by preventing hypoxic episodes in the mother.¹⁹ Preconception care should focus on medically optimizing asthma control and identifying and reducing exposure to allergens.

Asthma self-management skills- including self-monitoring with peak flow monitors, correct use of inhalers, and prompt handling of signs of worsening asthma-enhance asthma control. Inhaled corticosteroids are first-line controller therapy for persistent asthma during pregnancy.

Gastrointestinal

Inflammatory bowel disease: Inflammatory bowel disease (IBD) does not decrease fertility; however, fertility in patients with IBD is possibly affected by active disease, medications, and prior surgeries. Women with IBD experience worse obstetrical and pregnancy-related outcomes compared to the general population, even with disease remission.²⁰

The course of IBD during pregnancy is determined by how active the disease is at conception. Women in remission at conception are likely to remain in remission during pregnancy. In contrast, up to 70% of women with active disease at conception will have continued or worsening symptoms.²¹

Stopping medications that are maintaining remission can induce relapse or flare. Methotrexate and diphenoxylate are contraindicated in pregnancy, whereas sulfasalazine, 5-aminosalicylates, and corticosteroids are considered safe. Many immunomodulators (ie, azathioprine and 6-mercaptopurine) and biologic agents (ie, infliximab) are safe during pregnancy but their use should be managed in coordination with MFM and an IBD specialist.

Renal

Lupus nephritis: Women with systemic lupus erythematosus (SLE) have better pregnancy prognoses if their disease has been quiescent for at least 6 months prior to pregnancy and they have normal or near-normal renal function. Active SLE at conception is a strong predictor of adverse maternal and obstetrical outcomes.

Next: Recurrent pregnancy loss

Disease flares with pregnancy are difficult to decouple from the physiologic changes of pregnancy and from preeclampsia. Most SLE medication can be continued during pregnancy, but these drugs should be reviewed prior to conception. Medications contraindicated in pregnancy include cyclophosphamide, mycophenolate, methotrexate, and leflunomide. Other SLE drugs that are reasonably safe for use during pregnancy (with certain limitations beyond the scope of this review) are nonsteroidal anti-inflammatory drugs, glucocorticoids, azathioprine, rituximab, belimumab, and some antihypertensive medications.

The most important aspect of preconception counseling in cases of SLE is to determine whether pregnancy may present an unacceptably high maternal or fetal risk, and to optimize preconception disease status.

References

1. Johnson K, Posner SF, Biermann J, et al. Recommendations to improve preconception health and health care-United States. A report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care. MMWR Morb Mortal Wkly Rep. 2006;55(RR-6):1-23.

2. Frayne DJ, Verbiest S, Chelmow D, et al. Health Care System Measures to Advance Preconception Wellness: Consensus Recommendations of the Clinical Workgroup of the National Preconception Health and Health Care Initiative. Obstet Gynecol. 2016;127(5):863-72.

3. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Number 60, March 2005. Pregestational diabetes mellitus. Obstet Gynecol. 2005;105(3):675-85.

4. Moos MK, Bangdiwala SI, Meibohm AR, Cefalo RC. The impact of a preconceptional health promotion program on intendedness of pregnancy. Am J Perinatol. 1996;13(2):103-8.

5. Henshaw SK. Unintended pregnancy in the United States. Fam Plann Perspect. 1998;30(1):24-9, 46.

6. Yoon P SM. The family history public health initiative Atlanta, GA: CDC; 2004.

7. Dolan SM, Moore C. Linking family history in obstetric and pediatric care: assessing risk for genetic disease and birth defects. Pediatrics. 2007;120 Suppl 2:S66-70.

8. JGDC. Jewish Genetic Disease Consortium. 2015 [cited 2015 November]; Available from: http://www.jewishgeneticdiseases.org/genetics-and-carrier-screening/

9. Committee opinion no. 608: influenza vaccination during pregnancy. Obstet Gynecol. 2014;124(3):648-51.

10. CDC. Pregnancy and Whooping Cough. 2016 [cited July 17, 2016]; Available from: https://www.cdc.gov/pertussis/pregnant/hcp/pregnant-patients.html

11. Petersen EE, Polen KN, Meaney-Delman D, et al. Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure – United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(12):315-22.

12. Simeone RM, Shapiro-Mendoza CK, Meaney-Delman D, et al. Possible Zika Virus Infection Among Pregnant Women - United States and Territories, May 2016. MMWR Morb Mortal Wkly Rep. 2016;65(20):514-9.

13. Hadar E, Ashwal E, Hod M. The preconceptional period as an opportunity for prediction and prevention of noncommunicable disease. Best Pract Res Clin Obstet Gynaecol. 2015;29(1):54-62.

14. SMFM Statement: benefit of antihypertensive therapy for mild-to-moderate chronic hypertension during pregnancy remains uncertain. Am J Obstet Gynecol. 2015;213(1):3-4.

15. American College of O, Gynecologists, Task Force on Hypertension in P. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-31.

16. Sibai BM, Anderson GD. Pregnancy outcome of intensive therapy in severe hypertension in first trimester. Obstet Gynecol. 1986;67(4):517-22.

17. Canobbio MM, Warnes CA, Aboulhosn J, et al. Management of Pregnancy in Patients With Complex Congenital Heart Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation. 2017; Published ahead of print.

18. Kwon HL, Belanger K, Bracken MB. Asthma prevalence among pregnant and childbearing-aged women in the United States: estimates from national health surveys. Ann Epidemiol. 2003;13(5):317-24.

19. Dombrowski MP, Schatz M. ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 90, February 2008: asthma in pregnancy. Obstet Gynecol. 2008;111(2 Pt 1):457-64.

20. Cornish J, Tan E, Teare J, et al. A metaanalysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007;56(6):830-7.

21. Getahun D, Fassett MJ, Longstreth GF, et al. Association between maternal inflammatory bowel disease and adverse perinatal outcomes. J Perinatol. 2014;34(6):435-40.