Predictors of unfavorable perinatal outcomes in premature rupture of membranes

Introduction. One out of 10 patients with preterm labor exhibits signs of intra-amniotic inflammation, which often occurs subclinically and results in increased risk of premature rupture of membranes (PROM).

Aim: to identify predictors of unfavorable perinatal outcomes associated with PROM.

Materials and Мethods. The single-center retrospective cohort study was conducted from January 1 to November 1, 2023 by enrolling patients between 28 0/7 and 36 6/7 weeks of gestation with PROM. A total of 176 maternal and neonatal medical records were analyzed. Two groups of neonates were identified:Group 1 – neonates with favorable outcomes at the time of hospital discharge; Group 2 – fetuses or neonates with unfavorable outcomes at discharge (including antenatal fetal death, neonatal death, grade 3 intraventricular hemorrhage, periventricular leukomalacia, severe bronchopulmonary dysplasia, or surgical-stage necrotizing enterocolitis). There were analyzed maternal medical histories, pregnancy and delivery data, amniotic fluid index (AFI), maximum vertical pocket of amniotic fluid, severity of respiratory failure and central hemodynamic disturbances in premature neonates, as well as incidence rates for those born to mothers with PROM. Multivariate analysis was conducted to identify factors associated with neonatal outcomes.

Results. Antenatal fetal death was recorded in 7 of 176 cases (3.9 %), and neonatal mortality among live-born infants comprised 7 of 169 (4.1 %). Median gestational age at delivery in Group 2 was 193.0 days [IQR: 180.0–198.0], significantly lower than in Group 1 (238.0 days [IQR: 223.5–247.0], p < 0.001). Chorioamnionitis (p < 0.001) and anhydramnion (p = 0.003) were significantly more frequent in Group 2. Neonates in Group 2 required tracheal intubation (p < 0.001), surfactant therapy (p < 0.001), mechanical ventilation (p = 0.029), and high-frequency oscillatory ventilation (p < 0.001) more often within the first 72 hours of life. NEOMOD (Neonatal Multiple Organ Dysfunction) scores were significantly higher in this group (p < 0.001). In Group 2, Ureaplasma parvum in nasopharyngeal swabs was more frequently found by using polymerase chain reaction (p = 0.015).

Conclusion. Predictors of adverse outcomes in fetuses and preterm neonates with PROM consisted of anhydramnios, chorioamnionitis, lower gestational age and birth weight, cesarean delivery, elevated maternal C-reactive protein (CRP) and white blood cell count prior to delivery, an AFI ≤ 32.0 mm, higher NEOMOD scores, presence of diffuse ecchymosis at birth, detection of neonatal Ureaplasma parvum, lower hemoglobin levels, as well as increased procalcitonin and CRP levels within the first 72 hours of life.

1. Davey M.A., Watson L., Rayner J.A., Rowlands S. Risk scoring systems for predicting preterm birth with the aim of reducing associated adverse outcomes. Cochrane Database Syst Rev. 2011;(11):CD004902. https://doi.org/10.1002/14651858.CD004902.pub4. Update in: Cochrane Database Syst Rev. 2015;(10):CD004902. https://doi.org/10.1002/14651858.CD004902.pub5.

2. Ancel P.-Y., Lelong N., Papiernik E. et al.; EUROPOP. History of induced abortion as a risk factor for preterm birth in European countries: results of the EUROPOP survey. Hum Reprod. 2004;19(3):734–40. https://doi.org/10.1093/humrep/deh107.

3. Healthcare in Russia. 2021. Statistical Digest. [Zdravoohranenie v Rossii. 2021. Statisticheskij sbornik]. Moscow: Rosstat, 2021. 171 p. (In Russ.).

4. 2022 exceptional surveillance of preterm labour and birth (NICE guideline NG25) [Internet]. London: National Institute for Health and Care Excellence (NICE), 2022 Aug 4. Available at: https://www.ncbi.nlm.nih.gov/books/NBK591661/. [Accessed: 25.02.2025].

5. Romero R., Miranda J., Chaiworapongsa T. et al. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol. 2014;72(5):458–74. https://doi.org/10.1111/aji.12296.

6. Gomez-Lopez N., Romero R., Panaitescu B. et al. Inflammasome activation during spontaneous preterm labor with intra-amniotic infection or sterile intra-amniotic inflammation. Am J Reprod Immunol. 2018;80(5):e13049. https://doi.org/10.1111/aji.13049.

7. Boyle A.K., Rinaldi S.F., Norman J.E., Stock S.J. Preterm birth: inflammation, fetal injury and treatment strategies. J Reprod Immunol. 2017;119:62–6. https://doi.org/10.1016/j.jri.2016.11.008.

8. Keelan J.A. Intrauterine inflammatory activation, functional progesterone withdrawal, and the timing of term and preterm birth. J Reprod Immunol. 2018;125:89–99. https://doi.org/10.1016/j.jri.2017.12.004.

9. Sim W.H., Araujo Júnior E., Da Silva Costa F., Sheehan P.M. Maternal and neonatal outcomes following expectant management of preterm prelabour rupture of membranes before viability. J Perinat Med. 2017;45(1):29–44. https://doi.org/10.1515/jpm-2016-0183.

10. Kenyon S., Pike K., Jones D.R. et al. Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial. Lancet. 2008;372(9646):1310–8. https://doi.org/10.1016/S0140-6736(08)61202-7.

11. Nabhan A.F., Abdelmoula Y.A. Amniotic fluid index versus single deepest vertical pocket as a screening test for preventing adverse pregnancy outcome. Cochrane Database Syst Rev. 2008;2008(3):CD006593. https://doi.org/10.1002/14651858.CD006593.pub2.

12. Weissmann-Brenner A., O'Reilly-Green C., Ferber A., Divon M.Y. Values of amniotic fluid index in cases of preterm premature rupture of membranes. J Perinat Med. 2009;37(3):232–5. https://doi.org/10.1515/JPM.2009.078.

13. Thomson A.J.; Royal College of Obstetricians and Gynaecologists. Care of women presenting with Suspected preterm prelabour rupture of membranes from 24+0 weeks of gestation: Green-top Guideline No. 73. BJOG. 2019;126(9):e152–e166. https://doi.org/10.1111/1471-0528.15803.

14. Weiner E., Barrett J., Zaltz A. et al. Amniotic fluid volume at presentation with early preterm prelabor rupture of membranes and association with severe neonatal respiratory morbidity. Ultrasound Obstet Gynecol. 2019;54(6):767–73. https://doi.org/10.1002/uog.20257.

15. Storness-Bliss C., Metcalfe A., Simrose R. et al. Correlation of residual amniotic fluid and perinatal outcomes in periviable preterm premature rupture of membranes. J Obstet Gynaecol Can. 2012;34(2):154–8. https://doi.org/10.1016/S1701-2163(16)35158-1.

16. Vermillion S.T., Kooba A.M., Soper D.E. Amniotic fluid index values after preterm premature rupture of the membranes and subsequent perinatal infection. Am J Obstet Gynecol. 2000;183(2):271–6. https://doi.org/10.1067/mob.2000.107653.

17. Bhagat M., Chawla I. Correlation of amniotic fluid index with perinatal outcome. J Obstet Gynaecol India. 2014;64(1):32–5. https://doi.org/10.1007/s13224-013-0467-2.

18. Chamberlain P.F., Manning F.A., Morrison I. et al. Ultrasound evaluation of amniotic fluid volume. I. The relationship of marginal and decreased amniotic fluid volumes to perinatal outcome. Am J Obstet Gynecol. 1984;150(3):245–9. https://doi.org/10.1016/s0002-9378(84)90359-4.

19. Manning F.A., Platt L.D., Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol. 1980;136(6):787–95. https://doi.org/10.1016/0002-9378(80)90457-3.

20. Phelan J.P., Ahn M.O., Smith C.V. et al. Amniotic fluid index measurements during pregnancy. J Reprod Med. 1987;32(8):601–4.

21. Phelan J.P., Smith C.V., Broussard P., Small M. Amniotic fluid volume assessment with the four-quadrant technique at 36-42 weeks' gestation. J Reprod Med. 1987;32(7):540–2.

22. Moore T.R., Cayle J.E. The amniotic fluid index in normal human pregnancy. Am J Obstet Gynecol. 1990;162(5):1168–73. https://doi.org/10.1016/0002-9378(90)90009-v.

23. Karpova A.L., Mostovoy A.V., Prutko E.E. et al. Interleukin-6 as an indicator for the severity of the multiple organ dysfunction syndrome in preterm infants weighing less than 1500 g: a retrospective cohort study. [Interlejkin-6 kak indikator tyazhesti poliorgannoj nedostatochnosti u nedonoshennyh detej s massoj tela menee 1500 g: retrospektivnoe kogortnoe issledovanie]. Pediatriya imeni G.N. Speranskogo. 2023;102(1):54–63. (In Russ.). https://doi.org/10.24110/0031-403X-2023-102-1-54-63.

24. Karpova A.L., Mostovoy A.V., Bagaeva Z.E. et al. The NEOMOD scale in predicting the outcomes in newborns with birth weigh less than 1500 grams: a retrospective cohort study. [Shkala NEOMOD v prognozirovanii iskhodov u novorozhdennyh detej s massoj tela menee 1500 grammov: retrospektivnoe kogortnoe issledovanie]. Anesteziologiya i reanimatologiya. 2024;(2):49–57. (In Russ.). https://doi.org/10.17116/anaesthesiology202402149.

25. Karpova A.L., Mostovoi A.V., Dudkina E.A. et al. Early neonatal sepsis in COVID-19 era. [Rannij neonatal'nyj sepsis v epohu COVID-19]. Obstetrics, Gynecology and Reproduction. 2023;17(3):284–98. (In Russ.). https://doi.org/10.17749/2313-7347/ob.gyn.rep.2023.389.

26. Karpova A.L. Complete blood count: reference intervals for full term and late premature infants in the first day of life (part I). [Obshchij analiz krovi: referensnye intervaly dlya donoshennyh i pozdnih nedonoshennyh novorozhdennyh detej v pervye sutki zhizni (chast' I)]. Pediatriya imeni G.N. Speranskogo. 2022;101(1):62–70. (In Russ.). https://doi.org/10.24110/0031-403X-2022-101-1-62-70.

27. Karpova A.L., Mostovoi A.V., Borodich A.V. et al. General blood test: reference values for full-term and late preterm newborns in the first day of life (part II). [Obshchij analiz krovi: referensnye intervaly dlya donoshennyh i pozdnih nedonoshennyh novorozhdennyh detej v pervye sutki zhizni (chast' II)]. Pediatriya imeni G.N. Speranskogo. 2025;104(1):24–33. (In Russ.). https://doi.org/10.24110/0031-403X-2025-104-1-24-33.

28. Mustafin T.A., Karpova A.L., Mostovoi A.V., Kolesnikov A.N. Clinical and laboratory indicators of lethal outcome in premature newborns with body weigh less than 1500 grams. [Kliniko-laboratornye indikatory letal'nogo iskhoda u nedonoshennyh novorozhdennyh s massoj tela menee 1500 g]. Neonatologiya: novosti, mneniya, obuchenie. 2021;9(3):9–15. (In Russ.). https://doi.org/10.33029/2308-2402-2021-9-3-9-15.

29. Mostovoi A.V., Karpova A.L., Kharitonova N.R. et al. Morbidity and predictors lethal outcome in premature infants who received poractant alfa with gestational age of less than 32 weeks. [Zabolevaemost' i prediktory letal'nogo iskhoda u nedonoshennyh novorozhdennyh s gestacionnym vozrastom menee 32 nedel', poluchivshih poraktant al'fa raznymi metodami. Pediatriya imeni G.N. Speranskogo. 2022;101(1):27–38. (In Russ.). https://doi.org/10.24110/0031-403X-2022-101-1-27-38.

30. Younge N., Goldstein R.F., Bann C.M. et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Survival and neurodevelopmental outcomes among periviable infants. N Engl J Med. 2017;376(7):617–28. https://doi.org/10.1056/NEJMoa1605566.

31. Buscicchio G., Giannubilo S.R., Bezzeccheri V. et al. Computerized analysis of the fetal heart rate in pregnancies complicated by preterm premature rupture of membranes (pPROM). J Matern Fetal Neonatal Med. 2006;19(1):39–42. https://doi.org/10.1080/14767050500361505.

32. Vandenbroucke L., Doyen M., Le Lous M. et al. Chorioamnionitis following preterm premature rupture of membranes and fetal heart rate variability. PLoS One. 2017;12(9):e0184924. https://doi.org/10.1371/journal.pone.0184924.

33. Cataño Sabogal C.P., Fonseca J., García-Perdomo H.A. Validation of diagnostic tests for histologic chorioamnionitis: Systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2018;228:13–26. https://doi.org/10.1016/j.ejogrb.2018.05.043.

34. Okonek E.J., Schulz E.V., Belzer K. et al. Neonatal survival and outcomes following periviable rupture of membranes. Am J Perinatol. 2025;42(5):649–59. https://doi.org/10.1055/a-2414-1006.