Pregnancy-Related Complications in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study
Abstract
:1. Introduction
2. Methods
2.1. Subjects and Study Design
2.2. Definitions and Inclusion/Exclusion Criteria—Data Collection and Handling
2.3. Statistical Analysis
3. Results
3.1. Clinical Characteristics of Study Women
3.2. Pregnancy Complications in Women with RPL and in Control Women
3.3. Specific Features of Pregnancy Complications in Women with RPL
4. Discussion
- (1)
- By increasing the number of previous losses, the rates of women who became pregnant decreased, however the rates of women with pregnancy complications have the tendency to increase. Since the number of previous losses is considered an indicator of the severity of the RPL condition [3,32], it is possible that the biological factors underlying multiple pregnancy losses can continue to act by impairing the successive pregnancies, even though they have the strength to evolve towards advanced gestational ages. Further research is needed to check this hypothesis. A clear effect of the gravity of RPL condition, in terms of number of previous losses, has been shown in the case of selected pregnancy complications (Table 4).
- (2)
- When the women with RPL were stratified according to the two major diagnostic categories, explained and unexplained, the rates of overall pregnancy complications were similar. However, the analysis carried out by specific complication revealed that the risk of preeclampsia and abruptio placentae was higher in women with unexplained RPL. A possible, plausible explanation for this finding—taken into account that the above conditions are linked since preeclampsia is a known major risk factor for abruptio placentae—is that in some or several women with unexplained RPL a disorder in the placentation could occur.
- (3)
- When the women with RPL were stratified according to the other two major diagnostic categories, primary and secondary RPL, the rates of overall pregnancy complications were similar. However, the analysis carried out by specific complication revealed that the risk of GDM was higher in women with secondary than in women with primary RPL. A possible explanation for this finding could be that women with secondary RPL have been more exposed than women with primary RPL to the well-known diabetogenic effect of pregnancy that is exerted mainly in the second half of pregnancy, making them more susceptible for GDM in a successive pregnancy. This possibility is also supported by recent observation showing the association between high numbers of pregnancies and the increased prevalence of GDM [33].
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Complication | Definition |
---|---|
Threatened miscarriage | An abnormal vaginal bleeding and abdominal pain occurring before the 24 weeks in an otherwise ongoing pregnancy |
Miscarriage | A spontaneous PL occurring before the 24 weeks gestation |
Cervical insufficiency | CL < 25 mm by transvaginal ultrasound, or cervical changes detected on physical examination before 24 weeks of gestation [14] |
Chromosomal abnormalities | Any detected alteration of the fetal karyotype and/or DNA |
Fetal anomalies | Any structural/morphological abnormality detected by ultrasound |
Oligohydramnios | AFV < 5% for GA, or AFI < 5 cm or MDP < 2 cm [15] |
Polyhydramnios | A deepest vertical pocket of >8 cm or an AFI > 24 cm [16] |
Fetal growth restriction | Fetus with an UEFW 5–10th percentile for GA, calculated using the IGC according to Snijders and Nicolaides [17] |
Intrauterine fetal death | Fetal death at 24 weeks gestation or late |
GDM | GDM was defined following WHO criteria [18] |
Preeclampsia | Preeclampsia was defined according to ACOG 2013 [19] |
Placenta previa/low-lying placenta | Defined according to the criteria of RCOG [20] |
Placental abruptio | The premature separation of the placenta before delivery [21] |
Pregnancy-related liver disorders | (a) HG; (b) ICP; (c) AFLP; (d) HELLP syndrome; (e) ALE; (f) BO |
Preterm PROM | Premature rupture of the membranes before 37 weeks gestation |
Group 1 Women with RPL in Pregnancy (n) | Group 2 (Controls) Healthy Pregnant Women (n) | |
---|---|---|
Subjects | 431 | 661 |
Age (years) | 35.83 ± 5.95 * | 31.70 ± 5.82 |
BMI (Kg/m2) | 24.51 ± 4.66 * | 23.41 ± 4.78 |
Cigarette smoking | 56 (13%) ** | 126 (19%) |
Ethnicity Caucasian | 378 (87.7%) | 551 (83.3%) |
Asiatic | 23 (5.4%) | 47 (7.1%) |
Hispanic | 9 (2%) | 24 (3.6%) |
African | 21 (4.9%) | 39 (6%) |
Number of pregnancy losses | 1247 | - |
Miscarriages per women | 2.89 ± 1.15 | - |
Women with 2 losses (%) | 209 (48.5%) | - |
Women with ≥3 losses (%) | 222 (51.5%) | - |
Women with RPL explained | 259 (60.1%) | - |
Women with RPL unexplained | 172 (39.9%) | - |
Women with primary RPL | 284 (65.89%) | - |
Women with secondary RPL | 147 (34.11%) | - |
Years of follow-up | 2.58 ± 1.8° | 2.51 ± 1.6 |
Type of Complication | Women with RPL (%) | Healthy Pregnant Women (C) (%) | OR (95%CI) | p-Value | Δ% by Age (RPL vs. C) * | Δ% by BMI (RPL vs. C) * |
---|---|---|---|---|---|---|
Threatened miscarriage | 51 (11.8%) | 26 (3.9%) | 3.278 (2.01–5.34) | <0.0001 | −0.9 | 1.9 |
Spontaneous miscarriage | 55 (12.7%) | 17 (2.5%) | 5.541 (3.17–9.68) | <0.0001 | 4.8 | 3.3 |
Cervical insufficiency | 21 (4.9%) | 5 (0.75%) | 6.72 (2.54–17.96) | <0.0001 | −0.1 | 2.3 |
Chromosomal abnormalities | 12 (2.8%) | 3 (0.4%) | 6.28 (1.76–22.39) | <0.005 | 1.4 | 3.3 |
Fetal anomalies | 19 (4.24%) | 12 (1.8%) | 2.49 (1.19–5.19) | <0.01 | −0.9 | 2.1 |
Oligohydramnios | 13 (3%) | 7 (1%) | 2.90 (1.15–7.43) | <0.05 | 0.3 | 0.2 |
Polyhydramnios | 4 (1%) | 1 (0.15%) | 6.18 (0.68–55.5) | NS | −0.8 | 1.5 |
Fetal growth restriction | 14 (3.2%) | 4 (0.6%) | 5.51 (1.80–16.86) | <0.005 | 1.8 | 3.1 |
Intrauterine fetal death | 5 (1.2%) | 1 (0.15%) | 7.74 (0.9–66.53) | <0.005 | −0.1 | 0.9 |
Gestational diabetes mellitus | 43 (10%) | 29 (4.3%) | 2.41 (1.48–3.93) | <0.0001 | 0.9 | 6.6 |
Preeclampsia | 46(10.7%) | 35 (5.3%) | 2.13 (1.35–3.37) | <0.005 | −2.5 | 8.9 |
Placenta previa | 11 (2.5%) | 5 (0.75%) | 3.43 (1.18–9.95) | <0.05 | 0 | 1.5 |
Abruptio placentae | 24 (5.6%) | 19 (2.8%) | 1.99 (1.07–3.69) | <0.05 | 0.5 | 0.4 |
Pregnancy-related liver disorders | 32 (7.6%) | 8 (1.2%) | 6.54 (2.98–14.34) | <0.0001 | 1.5 | 1.6 |
Preterm PROM | 28 (6.49%) | 9 (1.36%) | 51.4 (26.17–100.98) | <0.0001 | 0.9 | 3.6 |
Type of Complication | Women with 2 Losses OR (95% CI) p-Value | Women with 3 Losses OR (95% CI) p-Value | Women with >3 Losses OR (95% CI) p-Value |
---|---|---|---|
Threatened miscarriage | 3.31 (1.87–5.88) p < 0.0001 | 2.39 (1.15–4.99) p < 0.02 | 4.36 (2.22–8.56) p < 0.0001 |
Spontaneous miscarriage | 2.30 (1.08–4.91) p < 0.05 | 4.47 (2.11–9.47) p < 0.0005 | 16.47 (8.64–31.38) p < 0.0001 |
Cervical insufficiency | 3.21 (0.92–11.21) p = 0.06, NS | 7.91 (2.47–25.36) p < 0.001 | 13.12 (4.30–40.01) p < 0.0001 |
Chromosomal abnormalities | 2.11 (0.35–12.76) p = 0.06, NS | 9.29 (2.19–39.41) p < 0.005 | 11.07 (2.60–47.07) p < 0.002 |
Fetal anomalies | 3.58 (1.61–7.98) p < 0.002 | 1.35 (0.37–4.86) p = 0.64, NS | 1.69 (0.46–6.09) p = 0.42, NS |
Oligohydramnios | 3.23 (1.12–9.34) p < 0.05 | 2.33 (0.59–9.15) p = 0.22, NS | 0.95 (0.11–7.93) p = 0.96, NS |
Polyhydramnios | 6.37 (0.57–70.68) p = 0.13, NS | 5.40 (0.33–87.07) p = 0.23, NS | 6.73 (0.41–108.55) p = 0.17, NS |
Fetal growth restriction | 4.85 (1.35–17.37) p < 0.02 | 4.10 (0.90–18.57) p = 0.06, NS | 8.73 (2.30–33.11) p < 0.002 |
Intrauterine fetal death | 9.61 (0.99–92.90) p = 0.05, NS | 5.50 (0.34–88.53) p = 0.22, NS | 6.73 (0.41–108.55) p = 0.17, NS |
Gestational diabetes mellitus | 2.39 (1.35–4.23) p < 0.005 | 2.14 (1.03–4.40) p < 0.05 | 2.17 (0.99–4.75) p = 0.05, NS |
Preeclampsia | 2.76 (1.63–4.67) p < 0.0002 | 1.93 (0.97–3.83) p = 0.05, NS | 1.15 (0.47–2.21) p = 0.75, NS |
Placenta previa | 5.90 (1.95–17.81) p < 0.002 | 2.16 (0.41–11.30) p = 0.35, NS | 0.59 (0.03–10.93) p = 0.73, NS |
Abruptio placentae | 1.17 (0.48–2.82) p = 0.72, NS | 3.31 (1.53–7.16) p < 0.05 | 2.18 (0.84–5.59) p = 0.10, NS |
Pregnancy-related liver disorders | 4.97 (2.00–12.33) p < 0.001 | 9.64 (3.90–23.81) p < 0.0001 | 6.21 (2.20–17.52) p < 0.001 |
Preterm PROM | 3.26 (1.27–8.32) p < 0.05 | 3.71 (1.29–10.63) p < 0.02 | 10.95 (4.54–26.37) p < 0.0001 |
Women with RPL (n = 431) (%) | Healthy Pregnant Women (n = 661) (%) | OR (95% CI) | p-Value | |
---|---|---|---|---|
Women with 1 complication | 138 (32%) | 101 (15.27%) | 2.611 (1.948–3.500) | <0.0001 |
Women with 2 complications | 54 (12.52%) | 31 (4.61%) | 2.910 (1.838–4.609) | <0.0001 |
Women with 3 complications | 26 (6.03%) | 6 (0.9%) | 7.008 (2.859–17.174) | <0.0001 |
Women with 4 complications | 11 (2.55%) | - | NA | |
Women with 5 complications | 2 (0.46%) | - | NA |
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Ticconi, C.; Pietropolli, A.; Specchia, M.; Nicastri, E.; Chiaramonte, C.; Piccione, E.; Scambia, G.; Di Simone, N. Pregnancy-Related Complications in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study. J. Clin. Med. 2020, 9, 2833. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092833
Ticconi C, Pietropolli A, Specchia M, Nicastri E, Chiaramonte C, Piccione E, Scambia G, Di Simone N. Pregnancy-Related Complications in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study. Journal of Clinical Medicine. 2020; 9(9):2833. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092833
Chicago/Turabian StyleTicconi, Carlo, Adalgisa Pietropolli, Monia Specchia, Elena Nicastri, Carlo Chiaramonte, Emilio Piccione, Giovanni Scambia, and Nicoletta Di Simone. 2020. "Pregnancy-Related Complications in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study" Journal of Clinical Medicine 9, no. 9: 2833. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092833