Novel First-Trimester Prediction Model for Any Type of Preterm Birth Occurring before 37 Gestational Weeks in the Absence of Other Pregnancy-Related Complications Based on Cardiovascular Disease-Associated MicroRNAs and Basic Maternal Clinical Characteristics
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Cohort
2.2. Combined First-Trimester Risk Analysis
2.3. Processing of Samples
2.4. Statistical Analysis
3. Results
3.1. Clinical Characteristics of Preterm Birth and Control Pregnancies
3.2. The First-Trimester Prediction Model for Preterm Birth before 37 Gestational Weeks Based on the Combination of Six MicroRNA Biomarkers and a Minimal Number of Maternal Clinical Characteristics
3.3. The First-Trimester Prediction Model for Preterm Birth before 37 Gestational Weeks Based on the Combination of 12 MicroRNA Biomarkers and a Minimal Number of Maternal Clinical Characteristics
3.4. The First-Trimester Prediction Model for Preterm Birth before 37 Gestational Weeks Based on the Combination of Six MicroRNA Biomarkers and the Maximal Number of Maternal Clinical Characteristics
3.5. The First-Trimester Prediction Model for Preterm Birth before 37 Gestational Weeks Based on the Combination of 12 MicroRNA Biomarkers and the Maximal Number of Maternal Clinical Characteristics
4. Discussion
5. Conclusions
6. Patents
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Normal Term Pregnancies (n = 80) | Preterm Birth (n = 106) | PTB (n = 41) | PPROM (n = 65) | p-Value 1 (95% CI) | p-Value 2 (95% CI) | p-Value 3 (95% CI) | |
---|---|---|---|---|---|---|---|
Maternal characteristics | |||||||
Autoimmune diseases (SLE/APS/RA) | 0 (0%) | 2 (1.89%) 1 RA 1 SLE | 0 (0%) | 2 (3.08%) 1—RA 1—SLE | 0.386 OR 3.852 (0.182–81.354) | 0.742 OR 1.940 (0.038–99.526) | 0.236 OR 6.339 (0.299–134.403) |
Other autoimmune diseases | 0 (0%) | 5 (4.72%) 4—AIT 1—systemic scleroderma | 2 (4.88%) 1—AIT 1—systemic scleroderma | 3 (4.61%) 3—AIT | 0.145 OR 8.724 (0.475–160.124) | 0.137 OR 10.190 (0.478–217.368) | 0.148 OR 9.016 (0.457–177.791) |
Diabetes mellitus (T1DM) | 0 (0%) | 5 (4.72%) | 3 (7.32%) | 2 (3.08%) | 0.145 OR 8.724 (0.475–160.124) | 0.078 OR 14.636 (0.737–290.480) | 0.236 OR 6.339 (0.299–134.403) |
Diabetes mellitus (T2DM) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0.889 OR 0.756 (0.015–38.505) | 0.742 OR 1.940 (0.038–99.526) | 0.918 OR 1.229 (0.024–62.787) |
Any kind of autoimmune disease (SLE/APS/RA/other/T1DM) | 0 (0%) | 12 (11.32%) 1—RA 1—SLE 1—SS 5—T1DM 4—AIT | 5 (12.20%) 3—T1DM 1—AIT 1—SS | 7 (10.77%) 1—RA 1—SLE 2—T1DM 3—AIT | 0.035 OR 21.296 (1.241–365.357) | 0.032 OR 24.260 (1.307–450.452) | 0.040 OR 20.641 (1.156–368.625) |
Trombophilic gene mutations | 0 (0%) | 6 (5.66%) | 1 (2.44%) | 5 (7.69%) | 0.112 OR 10.413 (0.578–187.625) | 0.278 OR 5.963 (0.238–149.670) | 0.071 OR 14.636 (0.794–269.823) |
Parity | |||||||
Nulliparous | 41 (51.25%) | 56 (52.83%) | 14 (34.15%) | 42 (64.61%) | 0.831 OR 1.065 (0.596–1.905) | 0.076 OR 0.493 (0.226–1.076) | 0.107 OR 1.737 (0.888–3.399) |
Parous—previous preterm delivery(ies) before 37 gestational weeks | 0 (0%) | 17 (16.04%) | 11 (26.83%) | 6 (9.23%) | 0.017 OR 31.480 (1.863–531.988) | 0.005 OR 60.705 (3.470–1062.101) | 0.052 OR 17.588 (0.972–318.358) |
Parous—previous term delivery(ies) after 37 gestational weeks | 39 (48.75%) | 33 (31.13%) | 16 (39.02%) | 17 (26.15%) | 0.015 OR 0.475 (0.260–0.867) | 0.310 OR 0.673 (0.313–1.447) | 0.006 OR 0.372 (0.184–0.754) |
History of miscarriage (spontaneous loss of a pregnancy before 22 weeks of gestation) | 16 (20.0%) | 26 (24.53%) | 12 (29.27%) | 14 (21.54%) | 0.465 OR 1.300 (0.643–2.629) | 0.255 OR 1.655 (0.695–3.941) | 0.820 OR 1.098 (0.490–2.459) |
History of perinatal death (the death of a baby between 22 weeks of gestation (or weighing 500 g) and 7 days after birth) | 1 (1.25%) | 3 (2.83%) | 3 (7.32%) | 0 (0%) | 0.474 OR 2.301 (0.235–22.543) | 0.118 OR 6.237 (0.628–61.962) | 0.581 OR 0.405 (0.016–10.099) |
ART (IVF/ICSI/other) | 2 (2.5%) | 8 (7.55%) | 1 (2.44%) | 7 (10.77%) | 0.150 OR 3.184 (0.657–15.423) | 0.984 OR 0.975 (0.086–11.081) | 0.059 OR 4.707 (0.943–23.496) |
Smoking during pregnancy | 2 (2.5%) | 5 (4.72%) | 3 (7.32%) | 2 (3.08%) | 0.439 OR 1.931 (0.365–10.218) | 0.229 OR 3.079 (0.493–19.208) | 0.833 OR 1.238 (0.170–9.038) |
Pregnancy details (first trimester of gestation) | |||||||
Maternal age (years) | 32 (25–42) | 32 (21–42) | 33 (21–42) | 32 (25–41) | 0.353 | 0.706 | 1.0 |
Advanced maternal age (≥35 years old) | 18 (22.5%) | 32 (30.19%) | 12 (29.27%) | 20 (30.77%) | 0.243 OR 1.489 (0.763–2.907) | 0.416 OR 1.425 (0.607–3.345) | 0.262 OR 1.531 (0.728–3.220) |
BMI (kg/m2) | 21.28 (17.16–29.76) | 22.05 (16.51–33.5) | 22.04 (17.96–31.83) | 22.14 (16.51–33.5) | 0.709 | 1.0 | 1.0 |
BMI ≥ 30 kg/m2 | 0 (0%) | 6 (5.66%) | 2 (4.88%) | 4 (6.15%) | 0.112 OR 10.413 (0.578–187.625) | 0.137 OR 10.190 (0.478–217.368) | 0.100 OR 11.780 (0.622–222.970) |
Gestational age at sampling (weeks) | 10.29 (9.57–13.71) | 10.14 (9.43–14.57) | 10.14 (9.43–12.86) | 10.14 (9.86–14.57) | 0.064 | 0.477 | 0.291 |
Screening—positive for spontaneous preterm birth (<34 weeks) with FMF algorithm | 5 (6.25%) | 25 (23.58%) | 12 (29.27%) | 13 (20.0%) | 0.003 OR 4.630 (1.686–12.714) | 0.002 OR 6.207 (2.009–19.174) | 0.018 OR 3.750 (1.260–11.158) |
Screening—positive for PE (<34 weeks) and/or FGR (<37 weeks) with FMF algorithm | 0 (0%) | 10 (9.43%) | 2 (4.88%) | 8 (12.31%) | 0.049 OR 17.518 (1.011–303.599) | 0.137 OR 10.190 (0.478–217.368) | 0.031 OR 23.800 (1.346–420.697) |
Aspirin intake during pregnancy | 0 (0%) | 7 (6.60%) | 1 (2.44%) | 6 (9.23%) | 0.089 OR 12.136 (0.683–215.714) | 0.278 OR 5.963 (0.238–149.670) | 0.052 OR 17.588 (0.972–318.358) |
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Hromadnikova, I.; Kotlabova, K.; Krofta, L. Novel First-Trimester Prediction Model for Any Type of Preterm Birth Occurring before 37 Gestational Weeks in the Absence of Other Pregnancy-Related Complications Based on Cardiovascular Disease-Associated MicroRNAs and Basic Maternal Clinical Characteristics. Biomedicines 2022, 10, 2591. https://doi.org/10.3390/biomedicines10102591
Hromadnikova I, Kotlabova K, Krofta L. Novel First-Trimester Prediction Model for Any Type of Preterm Birth Occurring before 37 Gestational Weeks in the Absence of Other Pregnancy-Related Complications Based on Cardiovascular Disease-Associated MicroRNAs and Basic Maternal Clinical Characteristics. Biomedicines. 2022; 10(10):2591. https://doi.org/10.3390/biomedicines10102591
Chicago/Turabian StyleHromadnikova, Ilona, Katerina Kotlabova, and Ladislav Krofta. 2022. "Novel First-Trimester Prediction Model for Any Type of Preterm Birth Occurring before 37 Gestational Weeks in the Absence of Other Pregnancy-Related Complications Based on Cardiovascular Disease-Associated MicroRNAs and Basic Maternal Clinical Characteristics" Biomedicines 10, no. 10: 2591. https://doi.org/10.3390/biomedicines10102591