Improving Ambulatory Saliva-Sampling Compliance in Pregnant Women: A Randomized Controlled Study

Abstract

ObjectiveNoncompliance with scheduled ambulatory saliva sampling is common and has been associated with biased cortisol estimates in nonpregnant subjects. This study is the first to investigate in pregnant women strategies to improve ambulatory saliva-sampling compliance, and the association between sampling noncompliance and saliva cortisol estimates.MethodsWe instructed 64 pregnant women to collect eight scheduled saliva samples on two consecutive days each. Objective compliance with scheduled sampling times was assessed with a Medication Event Monitoring System and self-reported compliance with a paper-and-pencil diary. In a randomized controlled study, we estimated whether a disclosure intervention (informing women about objective compliance monitoring) and a reminder intervention (use of acoustical reminders) improved compliance. A mixed model analysis was used to estimate associations between women's objective compliance and their diurnal cortisol profiles, and between deviation from scheduled sampling and the cortisol concentration measured in the related sample.ResultsSelf-reported compliance with a saliva-sampling protocol was 91%, and objective compliance was 70%. The disclosure intervention was associated with improved objective compliance (informed: 81%, noninformed: 60%), F(1,60) = 17.64, p<0.001, but not the reminder intervention (reminders: 68%, without reminders: 72%), F(1,60) = 0.78, p = 0.379. Furthermore, a woman's increased objective compliance was associated with a higher diurnal cortisol profile, F(2,64) = 8.22, p<0.001. Altered cortisol levels were observed in less objective compliant samples, F(1,705) = 7.38, p = 0.007, with delayed sampling associated with lower cortisol levels.ConclusionsThe results suggest that in pregnant women, objective noncompliance with scheduled ambulatory saliva sampling is common and is associated with biased cortisol estimates. To improve sampling compliance, results suggest informing women about objective compliance monitoring but discourage use of acoustical reminders.

Nonadherence with ambulatory saliva sampling is associated with biased salivary testosterone estimates

“…Such a pattern has been observed in prior studies estimating the association between ambulatory saliva-sampling nonadherence and salivary cortisol, another well-known and frequently used biomarker with a circadian rhythm (Kudielka et al, 2003;Broderick et al, 2004;Kudielka et al, 2007;Moeller et al, 2014). However, to our knowledge, studies on the association between saliva-sampling nonadherence and sT estimates are lacking.…”

“…After the samples were returned to us, we froze them at -20°C until biochemical analysis. It should be noted that participants were also instructed to collect saliva samples 30, 45, and 60 min after awakening (see Moeller et al, 2014). These samples were intended to estimate circadian awakening responses in biomarkers if required (e.g.…”

“…Recruitment took place in the context of a previously published study (Moeller et al, 2014). We applied the following exclusion criteria: week of gestation <12 or >32, presence of diseases potentially affecting the neuroendocrine system, high-risk pregnancy, human immunodeficiency virus (HIV) infection, the use of hormone-containing medication, insufficient German language skills, and the absence of regular antenatal visits at the outpatient service.…”

“…Particularly relevant for large-scale studies, this procedure is noninvasive, ecologically valid, and relatively inexpensive Shiffman et al, 2008;Giltay et al, 2012;Kudielka et al, 2012). However, a disadvantage of ambulatory saliva sampling is that nonadherence with scheduled sampling times is common and often not selfreported by participants-as observed in prior studies using covert electronic adherencemonitoring systems (Kudielka et al, 2003;Broderick et al, 2004;Jacobs et al, 2005;Moeller et al, 2014). Due to the circadian decline of sT concentrations over the course of the day (Dabbs, 1990), nonadherence with scheduled saliva sampling may bias the estimation of sT concentrations and hence cause unreliable and invalid sT data.…”

“…Such strategies have been successfully used in ambulatory salivary cortisol research (e.g. electronic adherence-monitoring systems; see Adam and Kumari, 2009;Granger et al, 2012;Kudielka et al, 2012;Moeller et al, 2014) but are associated with additional study costs and study burden for participants.…”