Measurement of Salivary Cortisol for Revealing Age-Specific Dependence of Cortisol Levels on Time, Feeding, and Oxygen Metabolism in Newborn Infants
Abstract
1. Introduction
2. Materials and Methods
2.1. Ethics Approval and Consent
2.2. Study Population
2.3. Data and Sample Collection
2.4. Cortisol Assay
2.5. Clinical Data
2.6. Data Analysis
3. Results
3.1. Crude Associations Between Clinical Backgrounds and Cortisol Levels
3.2. Influence of Postnatal Age to the Associations Between Clinical Backgrounds and Cortisol Levels
4. Discussion
4.1. Time of Day and Cortisol Levels
4.2. Maternal Condition, Exogenous Glucocorticoids, and Cortisol Levels
4.3. Age, Maturation, and Cortisol Levels
4.4. Feeding and Cortisol Levels
4.5. Blood Lactate and Cortisol Levels
4.6. Strength and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
HDP | Hypertensive Disorders of Pregnancy |
IUGR | Intrauterine Growth Restriction |
NICU | Neonatal Intensive Care Unit |
NIPS | Neonatal Infant Pain Scale |
PROM | Premature Rupture of Membranes |
Appendix A
Variables | Early (n = 22) | Medium (n = 45) | Late (n = 24) |
---|---|---|---|
Antenatal variables | |||
Maternal glucocorticoid | 4 (18.2%) | 18 (40.0%) | 22 (91.7%) * |
HDP | 2 (9.1%) | 13 (28.9%) | 3 (12.5%) * |
PROM | 5 (22.7%) | 8 (17.8%) | 15 (62.5%) |
Variables at birth | |||
Caesarean delivery | |||
All | 12 (54.5%) | 38 (84.4%) | 24 (100.0%) * |
Emergency | 5 (22.7%) | 33 (73.3%) | 24 (100.0%) * |
Male infants | 8 (36.4%) | 23 (51.1%) | 6 (25.0%) |
Gestational age (weeks) | 37.4 ± 1.9 | 34.2 ± 2.3 | 27.6 ± 1.5 |
Birth weight (g) | 2504 ± 419 | 1859 ± 448 | 978 ± 294 |
IUGR | 2 (9.1%) * | 10 (22.2%) | 4 (16.7%) |
Apgar score (1 min) | 8 (8, 8) | 7 (7, 8) | 4 (3, 6) |
Apgar score (5 min) | 9 (8, 9) | 8 (8, 9) | 7 (6, 8) |
Variables at the time of study | |||
Postconceptional age (weeks) | 38.3 ± 1.8 | 37.9 ± 1.5 | 40.4 ± 2.7 |
Feeding duration (hours) | 0.32 ± 0.21 | 0.34 ± 0.15 | 0.32 ± 0.17 |
Time elapsed from feeding to study (hours) | 1.46 ± 0.57 | 1.23 ± 0.59 | 1.19 ± 0.59 |
Morning studies | 13 (59.1%) | 36 (80.0%) | 23 (95.8%) * |
Blood pH ** | 7.36 ± 0.03 | 7.34 ± 0.05 | 7.33 ± 0.04 |
Blood lactate (mg/dL) ** | 22.8 ± 6.7 | 26.9 ± 9.4 | 23.0 ± 7.8 |
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Variables | Value |
---|---|
Antenatal variables (n = 77) | |
Maternal glucocorticoid | 28 (40.0%) |
Hypertensive disorders of pregnancy | 15 (21.4%) |
Premature rupture of membranes | 17 (24.3%) |
Variables at birth (n = 77) | |
Caesarean delivery | |
All | 53 (75.7%) |
Emergency | 44 (62.9%) |
Male infants | 27 (38.6%) |
Gestational age (weeks) | 34.2 (3.8) |
Body weight (grams) | 1916 (677) |
Intrauterine growth restriction | 14 (20.0%) |
Apgar score (1 min) | 7 (6, 8) |
Apgar score (5 min) | 8 (7, 9) |
Variables at the time of study (n = 91) | |
Postconceptional age (weeks) | 38.7 (2.2) |
Postnatal glucocorticoid | 23 (25.3%) |
Time since the final administration (days) * | 28.5 (22.5) |
Administration within 14 days of study | 3 (3.3%) |
Administration within 28 days of study | 7 (7.7%) |
Feeding duration (hours) | 0.33 (0.17) |
Time elapsed from feeding to study (hours) | 1.27 (0.59) |
Morning studies | 72 (79.1%) |
Neonatal Infant Pain Scale before saliva collection | 0.6 (1.5) |
Blood pH ** | 7.34 (0.04) |
Blood lactate (mg/dL) ** | 25.1 (8.6) |
Cortisol (nmol/L) | 20.0 (18.5) |
Ln cortisol (nmol/L) | 2.70 (0.76) |
Variables | Ln Cortisol (nmol/L) | Regression Coefficient | p | |
---|---|---|---|---|
Antenatal glucocorticoid | Yes | 2.73 (0.64) | 0.06 (−0.270, 0.369) | 0.723 |
No | 2.67 (0.13) | Reference | ||
HDP | Yes | 2.28 (0.56) | −0.524 (−0.839, −0.210) | 0.001 |
No | 2.80 (0.77) | Reference | ||
PROM | Yes | 2.79 (0.71) | 0.137 (−0.227, 0.500) | 0.461 |
No | 2.65 (0.79) | Reference | ||
Caesarean delivery | ||||
All | Yes | 2.64 (0.73) | −0.309 (−0.780, 0.162) | 0.198 |
No | 2.92 (0.90) | Reference | ||
Emergency | Yes | 2.57 (0.67) | −0.414 (−0.787, −0.041) | 0.030 |
No | 2.97 (0.88) | Reference | ||
Male infants | Yes | 2.66 (0.69) | −0.068 (−0.395, 0.259) | 0.683 |
No | 2.72 (0.81) | Reference | ||
Gestational age (weeks) | 0.015 (−0.032, 0.061) | 0.535 | ||
IUGR | Yes | 2.54 (0.81) | −0.189 (−0.618, 0.240) | 0.389 |
No | 2.73 (0.75) | Reference | ||
Apgar score (5 min) | 0.029 (−0.166, 0.224) | 0.772 | ||
Postconceptional age (weeks) | −0.009 (−0.077, 0.059) | 0.793 | ||
Postnatal glucocorticoid | Yes | 2.74 (0.74) | 0.061 (−0.341, 0.462) | 0.768 |
No | 2.68 (0.78) | |||
Feeding duration (hours) | 0.476 (−0.394, 1.347) | 0.284 | ||
Time elapsed from feeding to study (hours) | −0.260 (−0.557, 0.037) | 0.086 | ||
Morning studies | Yes | 2.55 (0.67) | −0.691 (−1.108, −0.273) | 0.001 |
No | 3.24 (0.86) | Reference | ||
Neonatal Infant Pain Scale | −0.037 (−0.165, 0.091) | 0.569 | ||
Blood pH | −0.047 (−0.096, 0.003) | 0.064 | ||
Blood lactate (mg/dL) | 0.019 (−0.004, 0.043) | 0.106 | ||
Postnatal age (days) | ||||
Early ≤ 10 | 2.83 (0.83) | Reference | ||
10 < Medium ≤ 56 | 2.68 (0.75) | −0.153 (−0.574, 0.267) | 0.475 | |
56 < Late | 2.61 (0.68) | −0.224 (−0.728, 0.280) | 0.384 |
Variables | Regression Coefficient | p | |
---|---|---|---|
Premature rupture of membranes | 0.069 (−0.594, 0.733) | 0.838 | |
Interaction with postnatal age | Early | Reference | |
Medium | 0.051 (−0.853, 0.955) | 0.911 | |
Late | 0.357 (−0.536, 1.251) | 0.433 | |
Male infants | 0.428 (−0.180, 1.035) | 0.168 | |
Interaction with postnatal age | Early | Reference | |
Medium | −0.598 (−1.347, 0.152) | 0.118 | |
Late | −0.845 (−1.764, 0.073) | 0.071 | |
Gestational age (weeks) | −0.085 (−0.199, 0.029) | 0.143 | |
Interaction with postnatal age | Early | Reference | |
Medium | 0.130 (−0.030, 0.290) | 0.110 | |
Late | −0.074 (−0.299, 0.150) | 0.516 | |
Apgar score (5 min) | 0.113 (−0.228, 0.455) | 0.516 | |
Interaction with postnatal age | Early | Reference | |
Medium | 0.006 (−0.428, 0.440) | 0.978 | |
Late | −0.296 (−0.736, 0.144) | 0.188 | |
Postconceptional age (weeks) | −0.102 (−0.215, 0.01) | 0.074 | |
Interaction with postnatal age | Early | Reference | |
Medium | 0.057 (−0.125, 0.239) | 0.54 | |
Late | 0.167 (0.012, 0.322)) | 0.035 | |
Feeding duration (hours) | 0.796 (−0.134, 1.727) | 0.093 | |
Interaction with postnatal age | Early | Reference | |
Medium | 0.239 (−1.720, 2.198) | 0.811 | |
Late | −1.498 (−2.644, −0.351) | 0.010 | |
Time elapsed from feeding to study (hours) | −0.748 (−1.275, −0.221) | 0.005 | |
Interaction with postnatal age | Early | Reference | |
Medium | 0.524 (−0.139, 1.187) | 0.122 | |
Late | 0.677 (0.045, 1.309) | 0.036 | |
Blood pH | −4.719 (−10.933, 1.496) | 0.137 | |
Interaction with postnatal age | Early | Reference | |
Medium | 4.800 (−3.839, 13.439) | 0.276 | |
Late | −5.606 (−12.854, 1.641) | 0.130 | |
Blood lactate (mg/dL) | 0.086 (0.048, 0.124) | <0.001 | |
Interaction with postnatal age | Early | Reference | |
Medium | −0.064 (−0.111, −0.016) | 0.008 | |
Late | −0.104 (−0.154, −0.054) | <0.001 |
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Suzuki, T.; Iwata, S.; Hanai, C.; Fukaya, S.; Watanabe, Y.; Nakane, S.; Okamura, H.; Saitoh, S.; Iwata, O. Measurement of Salivary Cortisol for Revealing Age-Specific Dependence of Cortisol Levels on Time, Feeding, and Oxygen Metabolism in Newborn Infants. Biosensors 2025, 15, 420. https://doi.org/10.3390/bios15070420
Suzuki T, Iwata S, Hanai C, Fukaya S, Watanabe Y, Nakane S, Okamura H, Saitoh S, Iwata O. Measurement of Salivary Cortisol for Revealing Age-Specific Dependence of Cortisol Levels on Time, Feeding, and Oxygen Metabolism in Newborn Infants. Biosensors. 2025; 15(7):420. https://doi.org/10.3390/bios15070420
Chicago/Turabian StyleSuzuki, Tomoko, Sachiko Iwata, Chinami Hanai, Satoko Fukaya, Yuka Watanabe, Shigeharu Nakane, Hisayoshi Okamura, Shinji Saitoh, and Osuke Iwata. 2025. "Measurement of Salivary Cortisol for Revealing Age-Specific Dependence of Cortisol Levels on Time, Feeding, and Oxygen Metabolism in Newborn Infants" Biosensors 15, no. 7: 420. https://doi.org/10.3390/bios15070420
APA StyleSuzuki, T., Iwata, S., Hanai, C., Fukaya, S., Watanabe, Y., Nakane, S., Okamura, H., Saitoh, S., & Iwata, O. (2025). Measurement of Salivary Cortisol for Revealing Age-Specific Dependence of Cortisol Levels on Time, Feeding, and Oxygen Metabolism in Newborn Infants. Biosensors, 15(7), 420. https://doi.org/10.3390/bios15070420