BlueCross and BlueShield of Montana Medical Policy/Codes
Salivary Testing
Chapter: Medicine: Tests
Current Effective Date: October 25, 2013
Original Effective Date: July 18, 2013
Publish Date: October 25, 2013
Revised Dates: October 11, 2013
Description

For several decades, there has been interest in testing various hormone levels using saliva as the specimen rather than blood plasma or urine. Salivary testing has been viewed as potentially more advantageous due to its noninvasive nature and the relative ease and convenience of sample collection, which can be done in the home.

Consumers now have the ability to order home saliva tests over the Internet for some hormones such as estrogen, progesterone, testosterone, melatonin, cortisol, and dehydroepiandosterone (DHEA). A physician’s prescription is not required for these saliva tests, which are primarily promoted for the evaluation of menopause and aging.

Preterm birth is considered a major healthcare problem worldwide. The National Center for Health Statistics reports that approximately 11% of the estimated 4 million births in the United States annually are preterm, incurring significant morbidity and mortality. Therefore, identification of women at risk for preterm labor has been a research focus for many years, with the hope that early intervention can prevent the progression from preterm labor to preterm birth. Current techniques include a scoring system based on a patient’s past medical history (the Creasy system), home uterine activity monitoring, and measurements of fetal fibronectin collected on a cervical swab. It has also been observed that salivary estriol levels surge several weeks before the onset of spontaneous preterm labor. Therefore, measurement of salivary estriol has been explored as a risk predictor for preterm labor. SalEst™ is a laboratory technique approved by the U.S. Food and Drug Administration (FDA) for measuring salivary estriol as a risk assessment marker of preterm labor and delivery. The SalEst™ system is indicated for use every 1 to 2 weeks in pregnant women with singleton pregnancies between their 22nd and 36th weeks of pregnancy.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coverage

Salivary hormone testing is considered experimental, investigational and unproven including, but not limited to, serial monitoring of salivary estriol levels as a technique of risk assessment for preterm labor or delivery.

Policy Guidelines

There is no specific CPT code for this laboratory test. The unlisted chemistry CPT code 84999 is most commonly used. CPT code 82677 describes the measurement of estriol levels may also be reported. In the past this code has been used to describe measurement of estriol in the blood or urine, but the CPT code does not limit the site of collection. Also, there are 2 HCPCS “S” codes available that are specific for estriol, S3650 (menopause) and S3652 (preterm labor).

Rationale

Currently, the Creasy system is one of the most commonly used initial risk assessment tools for predicting preterm labor. This system (and other risk-scoring systems) is based on a woman’s obstetric history and other anatomic factors, but fails to identify half of the women destined to experience preterm labor. Home uterine activity monitoring is another technique used to predict preterm labor by monitoring the pattern of uterine contractions. However, this device is typically used in women already identified at increased risk based on the Creasy system. In addition, controversy persists as to the clinical effectiveness of this approach. Fetal fibronectin measurements are used to predict preterm labor in women already experiencing symptoms suggestive of preterm labor. In contrast, measurement of salivary estriol has been investigated as a technique that can be potentially used as an ongoing assessment of preterm labor risk in asymptomatic women. The scientific rationale for this approach is based on the observation that a rise in estriol typically occurs prior to delivery at term and prior to preterm birth. The convenience of measuring estriol in the saliva creates the opportunity of routine monitoring of pregnant women to identify women at risk of preterm labor.

The following clinical applications of the test have been proposed.

  • Monitoring of salivary estriol may be used as a component of the clinician’s assessment or risk for preterm labor and delivery.
  • In the event of an initial positive test, further monitoring for other risk factors for preterm birth, including a repeat salivary estriol test, may be performed. If the repeat test is also positive, high-risk care should be maintained.
  • A negative test predicts the likelihood of not delivering within the ensuing 2 weeks.

However, no clinical studies are available that demonstrate that treatment decisions based on salivary estriol testing result in beneficial health outcomes. Beneficial outcomes for those correctly identified to have preterm labor might include a reduction in the incidence of preterm labor or birth, or both; decrease in the incidence of hospitalization in the neonatal intensive care unit (NICU); or degree of cervical dilation at the time of diagnosis of preterm labor.

However, appropriate interventions for asymptomatic women with positive salivary estriol tests are ill defined. Possible interventions include education regarding the early signs and symptoms of preterm labor, increased office visits for monitoring, use of a home uterine activity monitoring for prompt detection of preterm labor, increased bed rest or the use of prophylactic tocolytics, or hospitalization for monitoring. It could be argued that education regarding the early signs and symptoms of preterm labor is appropriate for all pregnant women. There are no data regarding the value of increased office visits, and, as mentioned, the role of home uterine activity monitoring remains controversial. While tocolytics have an established role in the acute treatment of patients with preterm labor, the use of prophylactic or maintenance tocolysis is not supported by the literature.

Negative salivary estriol tests might permit physicians to confidently withhold treatment in asymptomatic women considered high risk based on the Creasy system. Relevant outcomes may be a decrease in the number of office visits, cervical exams, or ancillary tests, such as intravaginal ultrasound. However, there are no data reporting such outcomes. Early symptoms of preterm labor may be subtle or vague. High-risk patients reporting such symptoms present a diagnostic dilemma to physicians, who may consider corticosteroid therapy or hospitalization. However, at present, no published studies address the outcomes associated with the use of a salivary estriol testing in symptomatic patients.

This policy was based on a 1999 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment (1) that specifically focused on a 1999 report by Heine and colleagues that studied the use of biweekly salivary estriol determinations to evaluate the predictive value of salivary estriol for preterm labor compared to the Creasy system. (2) Of the original 714 patients with evaluable data, 113 were excluded, including 35 patients treated with betamethasone and 55 patients with preterm labor, but delivered at term. In the remaining patients, only 23 experienced preterm labor, and thus 4 times as many patients with preterm labor were excluded as were included. The incidence of preterm labor in the evaluated patients was only 4%, less than half the incidence commonly reported in other series. This low incidence falsely elevates the negative predictive value of salivary estriol testing, because the predictive value of a test depends on the incidence of the disease in the population studied. A negative salivary estriol test resulted in a minimal change in the negative predictive value, from a baseline of 96% for the whole study population to 98% for the subset with negative tests. In addition, the test is not very sensitive, ranging from 42% to 64%, depending on the subgroup studied and the criteria for a positive test.

In addition, this study did not present the data separately for asymptomatic patients and those with possible symptoms of preterm labor. Thus the sensitivity and specificity of salivary estriol testing is unknown in the context of the asymptomatic patient, the patient with some symptoms suggestive of preterm labor, or the patient who meets criteria for hospitalization and tocolysis. The data presented in Heine’s study apply to the average patient (both asymptomatic and symptomatic), and the estimates of preterm labor risk would undoubtedly be revised upward or downward based on the patient’s clinical status at the time of the test. Thus, the risk estimated by salivary estriol testing may be misleading or less accurate than a clinical assessment based on physical examination at the same time. Without this information, it is impossible to evaluate the use of testing in specific clinical situations where a positive or negative test might make an important difference in the management of the patient.

2006 Update

The literature was searched in December 2005 for studies published since the 1999 TEC Assessment. The 1999 study by Heine et al. (2), which was published in a supplemental issue of a journal, was published again in 2000 (3), with exactly the same data as reported in the TEC Assessment. No other studies were found that would change the results of the TEC Assessment or the medical policy.

In 2001, the American College of Obstetricians and Gynecologists (ACOG) issued a press release stating "ACOG … cannot recommend the Salivary Estriol (E3) test (SalEst™ )… because it produces a high percentage of false positive results and could potentially add significant costs and unnecessary interventions to prenatal care." (4)

The lack of additional published literature and the existing statement from ACOG suggest that there is declining interest in salivary estriol as a predictor of preterm labor.

2013 Update

A search of peer reviewed literature through June 2013 identified no new clinical trial publications or any additional information that would change the coverage position of this medical policy.

The American Association of Clinical Endocrinologists (AACE) guideline on management of menopause recommends against the use of salivary tests for sex hormone concentrations, and noted large intrasubject variability. The 2012 American College of Obstetricians and Gynecologists (ACOG) guidelines and the 2012 North American Menopause Society (NAMS) position statement both concurred with this conclusion; the NAMS stated that salivary hormone testing “has proven to be inaccurate and unreliable.” (9,10)

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

ICD-9 Codes

Experimental, investigational and unproven for all diagnoses.

ICD-10 Codes

Experimental, investigational and unproven for all diagnoses.

Procedural Codes: 82677, 84999, H1001, H1002, H1003, H1004, H1005, S3650, S3652
References
  1. Salivary estriol for the assessment of spontaneous preterm labor. Chicago, Illinois:  Blue Cross Blue Shield Association – Technology Evaluation Center (TEC) Assessment Program (1999 July) 14(10): 1-17.
  2. Heine RP, McGregor JA, Dullien VK. Accuracy of salivary estriol testing compared to traditional risk factor assessment in predicting preterm birth. Am J Obstet Gynecol 1999; 180(1 pt 3):S214-8.
  3. Heine RP, McGregor JA, Goodwin TM et al. Serial salivary estriol to detect an increased risk of preterm birth. Obstet Gynecol 2000; 96(4):490-7.
  4. American College of Obstetricians and Gynecologists (ACOG) press release. SalEst™ not recommended as a screening tool for predicting premature labor. Washington, DC; January 31, 2001. Available online at http://www.acog.org .
  5. Lawrence, Herenia P. Salivary Markers of Systemic Disease: Noninvasive Diagnosis of Disease and Monitoring of General Health. Journal of the Canadian Dental Association (2002 March) 68(3): 170-174.
  6. Medical Guidelines for Clinical Practice for Management of Menopause. American Association of Clinical Endocrinologists Endocrine Practice (1999 November/December) 5(6): 355-366. (Web site accessed 1/29/2004).  http://www.aace.com .
  7. Thiedke, C.C. Menopause. Clinics in Family Practice (2002) 4(4): 1-16.
  8. Hodgson, S.F., Watts, N.B., et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis. Endocrine practice: official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologist (2003 November-December) 9(6): 544-64.
  9. ECRI Institute. Accuracy of Salivary Hormone Tests Compared With Serum Hormone Tests. Plymouth Meeting (PA): ECRI Institute; 2013 Mar. 13p. (Hotline Response).
  10. ECRI Institute. Accuracy of Salivary Hormone Tests for Menopause. Plymouth Meeting (PA): ECRI Institute; 2012 Jul. 7p. (Hotline Response).
  11. Salivary Estriol as Risk Predictor for Preterm Labor-Archived. Chicago, Illinois:  Blue Cross Blue Shield Association Medical Policy Reference Manual (2006 January) Medicine 2.04.11.
History
May 2013  New 2013 BCBSMT medical policy.  Considered considered experimental, investigational and unproven. 
October 2013 Document updated with literature review. Coverage unchanged.  Added HCPCs codes H1001, H1002, H1003, H1004,  and H1005.
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Salivary Testing