Usos del pesari cervical en gestacions amb alt risc de part prematur i cèrvix curt

Abstract

CONTEXT: El part prematur (PP) segueix éssent la causa principal de morbimortalitat neonatal. En la població general, la taxa de PP és del 8-12%; malgrat això, diversos subgrups de gestants configuren poblacions de risc elevat de PP, com les dones amb antecedents de PP, les gestacions múltiples, o les dones que, durant la gestació, presenten episodis d’amenaça de part prematur (APP). Una longitud cervical (LC) ecogràfica curta s’ha convertit en el principal factor predictor de PP en pacients assimptomàtiques al segon trimestre, tant en gestacions úniques com gemel.lars. La taxa de PP és 5-6 vegades més gran en bessons, arribant al 50%. Entorn un 15% de gestacions gemel-lars presenten un cèrvix curt al segon timestre; la progesterona vaginal ha demostrat eficàcia en la prevenció del PP en aquestes pacients, mentre que el cerclatge cervical sembla empitjorar-ne els resultats. Les gestants que presenten APP durant la gestació també conformen un grup d’alt risc de PP: fins un 45% presentaràn novament APP, i un 25-30% pariràn preterme. La LC és un factor de risc independent pel PP després d’una APP. Cap intervenció s’ha mostrat eficaç en reduïr la taxa de PP en aquestes pacients. En un estudi randomitzat (RCT) multicèntric conduït pel nostre grup, el pesari cervical va mostrar una reducció significativa de la taxa de PP en gestacions úniques assimptomàtiques amb cèrvix curt al segon trimestre. OBJECTIU I DISSENY: Vam voler avaluar la utilitat del pesari cervical en la disminució de la taxa de PP en dues poblacions d’alt risc: vam dissenyar dos RCT en gestants assimptomàtiques amb cèrvix curt: un en gestacions gemel.lars (PECEP-Twins Trial), i l’altre en gestacions úniques després d’una APP (PECEP-Retard). Ambdós han estat publicats a la literatura científica i composen aquesta tesi per comendi de publicacions. El PECEP-Twins Trial fou un RCT multicèntric. L’objectiu principal era la taxa de PP <34 setmanes. La morbimortalitat neonatal també fou avaluada. RESULTATS: 137 gestacions gemelars amb LC ≤25mm foren randomitzades entre pesari cervical i conducta expectant. La taxa de PP <34 setmanes fou significativament menor en el grup pesari (16.2% vs 39.4%), així com la taxa de pes en néixer <2500g. No s’observaren diferències en la taxa de morbimortalitat neonatal. Tampoc s’observaren efectes adversos materns seriosos amb l’ús del pesari. El PECEP-Retard Trial fou un RCT incloent 357 gestacions úniques que romangueren assimptomàtiques i amb un cèrvix curt (≤25mm < 30 setmanes; ≤15mm de 300 a 336 setmanes) després d’un episodi d’APP, que foren randomitzades entre pesari cervical i conducta expectant. L’objectiu principal era la taxa de PP <34 setmanes; el PP <28 i <37 setmanes, i la morbimortalitat neonatal també fóren avaluades. RESULTATS: No es varen demostrar diferències en la taxa de PP <34 setmanes (10.7% vs 13.7%), en canvi, la taxa de PP <37 setmanes fou significativament menor en el grup pesari (14.7% vs 25.1%), així com la taxa de ruptura prematura de membranes preterme (RPMP) (2.3% vs. 8.0%), i la taxa de reingrés per nova APP (4.5% vs. 20.0%). No s’observaren efectes adversos materns seriosos; la taxa de morbimortalitat neonatal va ser equiparable en ambdós grups. CONCLUSIÓ: La inserció d’un pesari cervical s’associà a una reducció significativa del PP <34 setmanes en gestacions gemel.lars amb cèrvix curt. Si bé el pesari no va disminuïr la taxa de PP <34 setmanes en les gestac¡nts amb cèrvix curt deprés d’una APP, sí que en va disminuïr la de PP <37 setmanes, la taxa de reingrés per APP i la de RPMP. Proposem l’ús del pesari cervical en la prevenció del PP en aquestes dues poblacions d’alt risc de prematuritat.

BACKGROUND: Preterm birth (SPB) remains the leading cause of neonatal morbidity and mortality. Delivery before 37 weeks occurs in 8-12% of cases; however, various subgroups of patients are at high risk for spontaneous preterm birth (SPB) viz women with previous SPB, multiple gestations or those with threatened preterm labour (TPL). Sonographic cervical length (CL) ≤25mm is the main risk factor for SPB in asymptomatic women mid-trimester in both twin and singleton pregnancies. The preterm birth rate in twins is 5-6 times higher, rising to 50%. Around 15% of twin pregnancies present a short cervix mid-trimester; vaginal progesterone has proved effective in preventing SPB in these patients. Cervical cerclage has been reported to increase the adverse outcome rate. Women with a previous TPL episode comprise another subgroup at high risk for SPB. Around 45% are readmitted with subsequent TPLTPL episodes, and 25-30% deliver before 37 weeks. Shorter CL is a specific risk factor for SPB after a TPLTPL episode. Despite No intervention has proved effective in reducing the SPBSPB rate in these patients. In a case-control study of asymptomatic pregnant women with CL ≤25mm mid-trimester, cervical pessary reduced the SPB rate in both singleton and twin pregnancies. Cervical pessary was effective in preventing SPB in asymptomatic singleton pregnancies with mid-trimester short CL in a multicentre, randomised controlled trial (RCT) by our group, the PECEP-Trial. OBJECTIVE AND STUDY DESIGN: We aim to ascertain whether cervical pessaries reduced SPB in two high-risk-for-SPB populations. Two RCT were designed to evaluate the pessary effect on the SPB rate: 1) in asymptomatic women with short CL carrying twins (PECEP-Twins Trial), and 2) in singleton pregnancies remaining asymptomatic and with short CL after a TPL episode (PECEP-Retard). Both were published in a high-impact scientific journal and comprise this article-based thesis. PECEP-Twins: An open-label, multicentre, RCT was conducted in 5 hospitals. The primary outcome was SPB <34 weeks. Neonatal morbidity and mortality were also evaluated. RESULTS: 137 twin pregnancies with CL ≤25mm were randomly assigned to pessary or expectant management. SPB <34 weeks was significantly lower in the pessary group (16.2% vs 39.4%). Pessary use was associated with a significant reduction in the rate of birthweight <2500 g. No significant differences were observed in other neonatal morbidity outcomes. No serious adverse effects associated with pessary use were observed. PECEP-Retard: An open RCT was conducted in 357 pregnant women who had not delivered 48h after a TPL episode and had a short cervix remaining (≤25 mm before 30 weeks and ≤15mm from 300 to 336 weeks). Patients were randomly assigned to pessary or routine management. Primary outcome was SPB rate <34 weeks; SPB <28 and <37 weeks and neonatal morbidity and mortality were also evaluated. RESULTS: No significant differences in the SPB rate <34 weeks between groups were observed (10.7% vs 13.7%). SPB <37 weeks was significantly lowered in the pessary group (14.7% vs 25.1%). The premature preterm rupture of membranes (PPROM) rate was also significantly lower in pessary carriers (2.3% vs. 8.0%) as was the readmission rate for new TPL episodes (4.5% vs. 20.0%). No serious adverse maternal events occurred; neonatal morbidity and mortality were similar in both groups.

CONCLUSION: Cervical pessary was associated with a significant reduction in SPB <34 weeks in women with twin pregnancies and a short cervix. Pessary use did not significantly lower the SPB rate before 34 weeks in women with a short cervix remaining after a TPL but did significantly reduce the SPB rate before 37 weeks, TPL recurrence and PPROM rate. We propose the use of a cervical pessary for preventing SPB in these two high-risk-for-SPB populations.