Dusen Maternal Fetal Medicine (PSMFM), Inc. eee a ee Philippine Obstetrical and Gynecological Society (POGS) CLINICAL PRACTICE GUIDELINES on PRETERM LABOR AND BIRTH Fourth Edition Tee) See ee toe Careeroy erase. 1 Be ligeine Society of a * Maternal Fetal Medicine (PSMFM), Inc. {rit MotiooF Poblete, MO end Carmela & Masiga Dy, 2) Pathogenic Spontanous Pte ith 20 ‘Recognized Affilate Subspecialty Society ofthe ‘ora Vicora A foe MO Philippine Obstetrical and Gynecological Society (POGS) A. Gilat rr a 26 Moe Seer ro Fopn Senet ab Gane Vee cr oe MO nd sa. Wa Bid sesso gets reseing Peter abo. 0 Vlon Ue, MO CLINICAL PRACTICE GUIDELINES on PRETERM LABOR AND BIRTH amen aa . Joeohd Ofer MO 9 Omega 3 and Fay Acids 8 Fourth Edition 10 Cervical Cerclage 00 Mane Catheeen Sone, bis November 2019 8. Gi tey —— 10s ‘SmerindeGurtover MO ont Anna Rosacs RC, Mo asone teres iss afeon, Bond eee 6 acoso 14. onocn Receptor Atagont 1 ‘Task Force on the Clinical Practice Guidelines ‘eta Ehomtuonemern Mi nd sph Gor Mca MO on Preterm Labor and Birth 15 Magnesium ate - nepotty PART I: MANAGEMENT OF PRETERM LABOR: ImMpaovinc NEONATAL OUTCOMES 18. Aneta Carkosteroise 2 ve ech Soca Her, 0 and acai Pre Pedrosa, a 17 Adages State for Nerapotetion 16 decay cenao-eomtelon Ml oes Pine Choe Us MD, ar Me, Cresta Por Salama Source, MO 19. Preterm iaborin pel remstances 170 op Geatiie Aragon Gavin MCs Ta MD Seer Ameoroe. Ute, hi ‘Ml zarogroibay. MD and hi Loodes A Siw pei a open c an open am Rane Epidemiology ee aloe P Tempo Guinto, MO, We, FPOGS, FPSMFN,FeSUOS Maya Domingo, ND, FPOGS, Feswy, FPsUOG The Works Hearth Organization, American Academy of Pecates (AAP) and ‘rican Collegeof Obstetrics and Gynecology (ACOG) define preterm bith As delivery of an infant before 37 completed weeks. before completion of 259 day from the fist day ofthe ast neeral menstrual period) Is further fenygoreed 19 (a) extremely preterm bith, whichis delivery at less than 28 fooks age of gestation (ACG); (0) very preterm birth, which i deivery Dbeweon 28 to 32 weeks AOG; ad () moderate toate preterm birth, which Ip delvery a 22 to 26 6/7 weeks age of gestation. The ACOG dines late preterm bith asthe delivery ofan infant between 2 0/7 weeks and 36 6/7, Weeks of gestation Le, 23910259 days ater the fist day ofthe LMP). Tiss Aonsidered important eategory because late pret infants stil have Digher mocbiity and mortality rates compare to ter infants because they ‘ie tl phlologealyané merabotealy immature deste having ase and ‘weight comparable to term newbs.” Preterm bith remains 2 global heath problem because tis stl he leading fase ef mortality in chien less than 5 years of age around the word Aetording to the atest global estimate, thera are 15 milion protorm births ‘nual, nating that out of 10 newborns are delivered before 37 weeks.”RE 5 GESTATIONAL AGE AND A rane ses Ca 2 0. a 9 te gn ererciny fon seam ro pena 200 0p 2 osongatsce, Hegel M8 ote gra en aio ene afc fet rin ma vend oi ens on eh 12010, WHo estates that at east 6% of preter births are fom Alia and South Asia (Figure 2), with lower income counres having higher rates eompared to higher income counties 12% vs 9%." A mew systeaticreview thowed tat in 201, Ason and sb: Saharon Nrian counties accounted for 78.9% of obits ad 81.1% of preterm bith wore The Philapines Tanks 8° among the top 10 countries with te highest amber of preterm bith, with reperted 348 900 preteen dalivanis i year (Table “TAB. TOP 30 COUNTRIES WITH HIGHEST NUMBER OF Pactgoa ant (OATA FROM WORLD HEALTH ORGANIZATION) Lids 3,5103000, 2G | nar 000 S.nigea Trg 5 Unies Seater 7. angedesh ‘Phippines 9. onrerte Hpi Cone oc dta rom the your 2014 to 2018 cllcted ram aeeracted puble and ivate training institutions of the Philppine Obstetrical and Gynecological Sodety [POGS) showed that preterm ne bith ate inthe Philppnes rages Worn 2% 0 27% The preterm sib at anges from 32.22% to as high 2= 95.65%, recorded in 2044. Preterm neonatal death rte Is fom 27.13% to 73785 (Tole 2}.‘ARLE. CENCE OF PRETERM BIRTHS ACCORDING To Poss FRoM 7044 TO 2018 ee aoa eae ee ae ay fone dh a sa aes aot rien mal Fm 035 amet Peta ais 0208 = [ anzaw | egy looking at Uie date from a tertiary ‘eter canter, University of the Fhlpines-Pikppine General Hosa (UP-PGH), a higher preterm Sve bith ‘ate of 280% t 25.29% sen, Likewise, the peter neonatal death rae ls ‘tao higher, ranging from 683% 1 80.5% (Tate 3). This may be attiouted to 8 higher incidence of preterm bith in pregrancis complated by other ‘madi or surgel co-morbiites, leita see Te saz [ ia Teli Sa ion | 94 Tell eos Dea | waa fa ora bas 9 tas ‘ua etalon ae “|| sata {RP nen he Ps ioe Ga yong the pretermnconatl deaths national date showed that approximately ae infonts born under te category of moderate fo late preterm 4) On the other hand, data rom UP-PGH showed that 20% of neonatal hs are seen amonginfants born very preterm (Table). Itcan be infeed this data that improvements in heslth care faites, equipment and nce of well-trained specialists may imorove survival f preterm ifort, lly those who ae under the category of moderate folate peter, cae oe foe ime a ge, Aap T wa "TAOLES. PRETERNA NEONATAL DEATHS ACCORDING TO AGEOF GESTATION dene} — st Pi Si 7 =a i ny pi Pp TD 2 —| a oking tho global and tca data, its evident that preterm beth remains 2 Imsjor heath risk because It fs asiodated with poor perinatal eutcames Furteemore, it predisposes survivors to long term sequalee, including Ievrocogntve deloy, physical lsbilties and higher sik of metabolic Asorders. Al ofthese complications impose socal and economic bude,hence causing 2 significant impact to the Solty. Further local studies are heeded t6 demonstrate the actal cost of treatment for preterm bith Moraover, theresa neod to core up ith better data cllection methods show a more acurate statics and have better analyse ofthe actual oc Situation This can aid in heath systern anaysis and can hela publi heakh lesers idenify any gaps in the exiting antenal cae protocl. These gaps, if ‘dented, can assist in designing guidelines or protecal to achieve the ‘ileum sustainable goal ef creasing preterm bits References 1 ffl 8 (201, eptember 23. Lt Par fins. rat Update le baile 2, Ufo Spots cen antares der morn 000 36:0 ‘pias setae sas vith angen rte Sone Omens Cone Gre snronnz 3. Stren 5.2012) Raton eal a weed timate of rar Gr roan 4 Ghanepateon Ne Meter AB tl rena wl mton erates smal eterna spent mao on mang sa et Chapter? Individualizing Risk Indicators for Preterm Birth Pita Mata F.Pobete, MO, FPOGS, PSMA, FPSUOG ones G. Madigak-Dy, MO, FPOGS, PSM, FPSLOG Hdertiicaton of women whose pregnancies are at higher than average isk of Peter Iabor and delivery would slow the possi of providing the women Usithigher level antnatal care withthe ah of preventing te preterm birth. ‘The purpose of this chapter isto provide an overview of current knowledge oat sk indicators for spontaneous preterm bith However it must be emphasized that approximately 45-50% of all preterm bint are iicpathic, occurring among wornen with no entfable sk factors. Inadton, the droct causality of risk factors hasbeen aii to establish > ‘some fotos may show an stocation but may no ncezsarly be causative, nd ‘may involve cofactors to exert thei effect, thus complicating the chain of causality Dewethles, with promising progres inthe realm of prevetion, partly Yegardng the cole of progesterone among women with short cerwe at ei fregnaney, identification of sk feerors curren known tobe (ar not to) fysouated wth preterm bith provdes a meaningful sep inte right decton Towards curbing trend nthe incidence of preter bith da wal may avo limecessary cost interventions or proibitons for unprowen rks ‘What information in the lineal story would Increase the kelhood of preterm bith? RECOMMENDATION The skactors enumerated ia Tables 1 and 2 increase the lkelhood of preterm bith and shoule be considered In the preconceptional counseling ane prenatal management of women,TT) yal ooueemimemnnt) label | © a | 5 i] ondaTp 2{TABLE2 ASK FACTORS STRATIFIED ACCORDING TO DEGREE OF MODINABHTY Non medMable Antenatal aeons Demographic Obstet ‘emt story re preterm bith age stor ofnleate preterm ith Marital ator story of medi nest preterm ‘Store atonal eight ith Incense of pregnany Pregnancy resulting rm sete Inter prepneny inten eprodion eoge aie gencer tasty of ror detaton ad curetage Modinabe Factors = 5 ehowerat etction W ‘Sinking uring pregnancy Watealundarweieht Pssre materalsrcing acne | Mater best ards) tow sega) wel ah mek rg 8 seal arom Deven dre pregnancy ‘cool consul unt) Vann Odefocney ew maternal ome fat ed sttas Lew consumption of ruts nd ‘egeables aaa nee oe ie arenicmtnrenne teinyoretnste pert ete towers Steogettenra ieee scence Infections (chlamydia, bacterial atin, asymptomatic bacteria pedo) “4 "SUMMARY IMony ofthe previously recognized risk actors for preterm bith are now “being viewed ina now ight. Risk ratios provided by the most recent mot avis tudes eve more acurate slgicant estimates of risk compared to imply tng one or few tal, whee rks may have been aver or under ated, Factors receing ite attention can now be seen to confer risks Drevously recoerzed. Evidence is also beglaning to lay the ground fo many pieces of the complex and diverse pathways linking psychosocial tors to maternal an fetal outcome, Moaiableinicators sich as shor Interpregrancy interval, vagiral and periodontal infection deserve closer on in the lal eeting, With the knowledge ofthese inciators ana thelr Inaividual rsk rats, the clriian must be vigiant to screen fer ntl rks, even Inthe preconception period, so that they ean counsel fens early enaugh and may be able to provide not nly preventive ot rphilacic interventions, but psychosocial 2s wall as emotional suppert to er patents. ls Aa EM Oe Case CS CAL da, Sams 8 095 Rasen esecen ein lr rere thse th et teria Eate en on dna corbin aa) maison lowes ot heh 5, Sah Ps. roc cope and sien mh tamen. A Seemte.eicw ant mtaaipas Aa Otte! Opel Sad. 2012 dasoinupieooustrsoransox 1 nts te Poe, oem wenden nd dept n lon inhi Earn DOSIbL A reopen oy laters Hel Reortl Ferma aos esto notre 50042 Kimo Jen Pak Cio 5 ee Kets ogre with sn isin the Ute sue ane 212 secre wesc Ns elo steph 912.98, 1 brath Pak A iar yo cancer ptm ha ev sa fatten age ath weg angie gat atr Onane ogg from te Pipe td Eat Aon" oxputinbosed study. BW! Opt. 200 eto seep zoe cssa8 Intra tnd ane Rett Poadr Pent dom 2042 FOaO 331) 165 APR, Neb Pt AM, Dono Avena tema ap Adve tome Fremangy ametasnsns Ate edPot 239 sto 208 057 5 i3 Pathogenesis of Spontaneous Preterm Birth ‘arora Vieria Alin, MD, OGS, PSU FPSUOG Preterm births have been tadtionally classified into two based on the ‘Groumstances surrounding the delivery ‘+ Indicated preterm bith ~ resus fom either induction of labor oF arean section due toithera maternal or etal ines ‘Spontaneous preterm bin ~ occur itr due to preterm abor with intact membrones oF preterm pralabar rupture of membranes "Yn 2 ‘ecent study with » more encompassing terminology, ths may be "sssocited with atleast one of the flowin: 4) preterm abo, 2), preterm praaborruptire of membranes, and 3) cervicalinsutsency™ ‘This chapter focuses onthe development of spontaneous preterm births, This Iiwolvs three man processes known a5 the ial common pathway of labor 4 increased uterine contract, 2} membrane piu end 3) ean pening, ‘These are the same processes that occu in term bths, only that incase of 6 Preterm pregnancy, the activation ofthese is tonedered patheloye” These ‘racesses may occur inno patculr order and are intertwined snd led to one ‘another Rather than dictate recommendations, the chapter serves ara seri Bointor the encanto understand how common isk actors everualiy este Dreterm labora the molecular level, and hopefully ces in futur research on Prevention, diagnosis, and management. Preterm birth involves a numberof pathways of diferent pathologies that may ‘overep resulting In the aforementioned final common pathy. The move commonly mentioned are these four major processes: 3) sctivation of the hypothalame-pituitary adrenal (HPA) ans: 2) infection and an Inflammatory ‘response: 3} decdual hemerthage; 4) pathologies! uterine ditention™ These roceses are shownin Figure 1. 20 Laren ‘Aes fom mse of ese) conte ca Ung Peete he ky thay canes teva rer ears Pet Beh Coy Cees heer erie 7 nave creme: Po 200” 6 map Pay ee Pra Bh Ase fom: hs /ie vin garbecaOn@oey. ioe 8 Dare eae (Sry es bi Activation ofthe HPA) Aas Strat involes the production of orzo. Onthe mathe, this exhibits negating feedback on the hypothalamus but stimulstes placental production of ‘oticctopinrelesing hormone (CR, thereby further increasing the cotiol levels Stadies have shown that CRH modulates the production of eretarandins, Brogesterone and estroge, and affects myometrial contrat, na prospective Cohor study," it was shown that erased stress levels measured by 2 scoring {uestonnsite and sera measuvernats of cortisol reultedin9 12% Inetease ih preterm births. Placental CRM iso stimulates etal sorenal zone Inone study, Slafaet lM used Fetal adrenal gland sxe 36a raditar of preterm birth, Placenta! nsiiceney a‘S2conidry to chronic villous or wteroplacantaldzease which causes interne comoromise and decreased feta grows may alo lead t ectvation of he fetal HPA ans thereby inating the same series of events as shownin Figure 3 eo ooh ratio) | f a7 le = ek same tr Aon! UA) A Ot eeepc 2 PN Hoenn enn Ateneo honors Sneortnr atc eena epee ppencnindercne he OH oe Pass tee ‘eS ca onl al nina fasten a xin 148 52 Figure, Maternal ae ett HPA oi nd sto eed peer ge 58. = ‘infection and intlommation Preterm birth is most commonly asscited with infection, Posinfammatory ‘cytokines such as iL and THF ae central to Infection induced peters bart Other proinfammatory mediators suchas ILS were sls four to be levated in the amnotic fid of women with PTL with Intact membranes ena these levels correlated well with postive results from culture ofthe snot Rul ang fetal membranes. woul then increase the amount of erotonns such ss prostapndis and endothains, thereby inating uterine cantons 2 Inflammatory response in preterm labor may also be secondary to certain a, which produce proteases, cllogenases, ane eastases tat can cegrade membranes or produce cerca change. There is ao an addve effect he same bacteria also preduce endotoxins ang phospholipase A2, which ate uterine corrections that lea to preterm er" (Tetehie PN on fem 6 a pess]*-[ me i? Pee Wie tra ren ft sp nai Cn cts Haman: ashe In Pt kuti oproes fet ye rma tl aera poten nn nocit Me 201175. Shiu, atone oscar on ree age .ecdua! Hemontoge Yosial bleeding fom decidual hemorrhage Is assisted with a high nak of relerm labor. one study, even oul decal hemorrhage wae preentin 38% ff pttents with Pt between 22 and 32 weeks of station due to PPROM and 30% of patents experiencing PTB secondary to PTL The praence of deeldual hemorrhage releases » umber of cating factors including factor Wl, tissue factor, 2 fect Xo, alo when may contiaite othe initiation of cont etons, 5 well as produce a easeade which leads to ether cena change or rupture of membranes, 2WA tose lumnegen actotr: A Tax plngen haa PA Pine ‘cher nar i sient ct tchae mae ta toa imal Endcantyofartariton Ion enn Nib 203, "708 gue Homeroneend em sbor oge ‘Pathological Uterine Distension Pathological uterine dstentin may be secondary to palyhydramnios, mulifetal _estation, or fetal macrosomia. These conditions dstend both the uterus and the ‘amniotic membrane, which not as dstensibe asthe former Stething ofthe ‘iyometrium beyond whet Is physiologic Induces formation of gap luncions, \which increases the response of oxytocin ceceptrs, attes prostaglandin £2 {and £2, as wel as myosin ight chain kinase producing terine contractions sr cereal ripening and catation CERVICAL INSUFFICIENCY ‘The previous pathways that ead to spontaneous preter birth start with ether preterm abor or preterm prelobor rupture of membranes lacing to cervical femodeling and risening, For cervical insufleey, iis thought that ceria ‘tange occurs fist. n these casos, a peti factor may play 2 ele. One study 2 that entancng 1 alleen the an-inlammatory i406 microsstelte red more fequenty inpatients ciagnosed with cervical insufficiency "* le previous pathways tha lead to spontaneous preterm births start with ther Im labor or preterm pelabor rupture of membranes leading o cereal ling and ripening. For cena! msutfelency, i is thought that cevial ne cu est but wl stl evenly Uigger theater pathways to ou." 1. ciy Oe fetter of SsemneueFratrm Labor. cay an sale iterate! Meine: rls ane Mate. Pisphi Pk: Greate, art eer LO, Caer a thas teeta beth Ce dentin ans ine or statin snp rd presente of manent ne oon Digi! preterm abr a ever of etem bith Ueda Berta Vo} on 42019) SNe Freerton sortn (es hn ener re 20 & bol Paae Uris ur ee, ia on pfs ch igoeston Ro Heinen i trou ager Ds Masa eal Shes 3 Moo Sane ors ann era em aeecarestons ctf sewn cet patho A Prt GS 590 368, Fes Gay lot So a Cesena of parton nn enfoarel Arges Wl, Hath, Slee Mt a nid tert erelten ‘ar pst pnts tril ot nl esa! een women Sere 3 2, Sie cg pe Zoe 1A, Sherr OM, a Haag evdenc folate 10, Waren Naber it Searle Poymamhiame nth promot gn fh ler 30 (0 gene nomen th eel Pate An? Ot Gee 1, Wn eth Caves eee pananeous pete re Seri Ft eon 2sreper Clinical Diagnosis of Preterm Labor Mare Scent Vera Fopean-Benedicto, MD, MBA, FPOGS,FPSMFM, FeSUOG Spontaneous preterm bir remains the aang cause of prints morbidity and ‘monaty in many parts ofthe wel, icuaing the Philipines. The diagnose of preterm labor i based on cinieal rterlaof regular aterine contractions before 37 weeks that are associated with conical chr! Preterm lari defined 9s Uterine contractions (ot contractions per 20 minute), cervical dltation (od ere in a nulparaus and >3 cm in ¢ mutipara) ane cencal effacement (80%) or terine contractions and ceva change.” ‘question, RECOMMENDATION ‘Among patients at high risk for preterm delivery, ‘what Is the contraction rate that can idently those women who area increased is for preterm bith? A. A threshold rate of atleast four contractions er hour on 2 monitor stip should be uted to deny a patient at increased vk for preterm labor. vay of evidence: High ‘Strength of Recommendetion: Seng 1.2. Women reporting signs that thy ateibute to Dossible preterm labor oF rupture of the membranes should be taken serioush and adequately evaliated, — Sel-peesived symptoms are poor precctors of preterm ‘ith. ual of rience: Moierate Stwength of Recommendation: Strong 413. Uterine aetivty. should be essesied by palpation in al women presenting with any sien of preterm labor. The progression fom suliveal preterm to overt preterm labor is 2 RECOMMENDATION ‘often gradual, Standard criteria for the agnosis f preter labor ack peas ‘uot of Evidence: Moderate Strength of Recommendotion: Moderate IMARY OF EVIDENCE 44 randomized multi-center study by Bentley et a" an anaes was {ct to determine the association of at least four contractions er hour on {Toute strip fod by atleast four contractions per hour on a repeat tog With subsequant preter abor. Using ths tveshod, 70% of the patents (ove dassifad. This contraction ate reauted in sanity oF 57% 9 ifisty of 80%,» postive preictive value of 72%, and a negative predicive Of 69%. A threshold rate of at lest four contractions per hour on a iter strip denies a patient at incensed rik fr preterm labor (P= 003), ‘Among patients with uterine contractions, how accurate Is cervialdiattion In dlagnosing preterm labor? ‘he tradtonal criteria for labor, perstent uterine eanractons accompanied by aiattion or effacement (ofthe cervix or both, are reasonably accurate when the frequency is sk or more contsstions per hour, ‘cervical datston Is 3 am or more, effacement is 80 percent or greater, and membranes rupture or Bleeding ozeurs uot of evince: High ‘Stength of Recommendation: Stong SUMMARY OF EVIDENCE Glover etal" conducted a secondary analysis of a multicenter randomized fontro al (RCP) of women wth singleton, non-anomaous pregnancies at 34 0/7 to 36 5/7 weeks gestation at high risk for preterm bith. The analysis Showed thot carve i fon cutoff of >acm wot 60% sensitive and 68 a‘spec fr preterm bith area under the curve, AUC=0.64, 95% C10.61-0.68), A Ceti efacement cutoff of 275% was 58% sensitive and 65% specie for rete bith (AUC-0.62 95% C10.58-0.65).Fony-ane percent (4%) of women resenting with fequent uterine contractions and cervical dation ane /or effacement at 3 10 35 5/7 weeks delivered at term, ‘The ractional criteria for labor, persistent uterine contractions accompanied by dllatation or effacement ofthe cervix, ofboth ae reasonably accurate when the frequency is sit oF more contractions per hour ceria tation 3 em or ‘more, etiacement s 80 percnt cr greater, and membranes rupture cr Bleeding ‘questions ‘Among patents with terine contractions, how [RECOMMENDATION There is Ick of compeling evidence for the we of cereal messurement alone In women wth threatened preterm ber. uatty of Evidence: High Strength of Recommendtion: Strong ‘SUMMARY OF EVIDENCE ‘A 2016 systematic review and mets-analysls of RCTS using Indhidual pation level data concluded that hnowledge of cenical length in women with ‘srmptoms of acute preterm labor was assoclaed wth signican eduction In preterm bith « 37 weets gestation [RR 0.64,95% 048-084). However, the ‘other outcomes, wthich included preterm birth <36, <3, <32, <30, and <2 ‘weeks gestation, tie from randomization to delivery, time from evaluation to ‘scharge, and other neonatal outcomes were not statistical cferen between ‘hove who nad krowlecge of ceria length an thote Who del not Ths, the clinical impact of cervical measurement in this poptistion remains unter. JDRTION Routine use of cewieal length scsening in lowes population snot recommended ual of uldence: High ‘Swength of Recommendation: Strong IMMARY OF EVIDENCE bean shown in two RCTs that vtilzd universal screening in large 1/80 that treatment with vaginal progesterone is associated with an oximately 40% reduction inthe risk of preterm birth in women with short (beth ncuson erterion of cereal length <2Smm' or 10-20mn) fit notable thatthe lrequerces of a CL <1Smm or CL 10-20rm in tse mesty “Tewrsk” population about 80% of enclled women had no oror eter ith] were 1.7% and 238)!" respective, Furthermere, in fquentstuies of the implementation of universal ceria ent screening the frequency ofa short cervkn women witout a history ofa toe birth has ranged from 1% to 2% depending on the cervical length Meshold used ™"™! re remains a sgrfieant bate about the ust of universal cervical length ng of woren with sagletongestations but without pie ereterm birth “eric length in this population sil 3 large observational stay showed thet “Iroducton ofan ination uriveral cervical length erening program was "tehoiated witha significant decrease in Ue frequency of preterm bith <37 "Weeks [5.7%ys. 50% acjusted OF 082 (95% Cl 076-08), routine {tansvaginal ceria length sresring ‘Quay of sence: High ‘Swenath of Recommendetion: Strong JMMARY OF EVIDENCE Seca eta!" in 3 European tial screened 24,540 women between 20 1025, us of gestation. Only 1.7% of the women were found to have a cervical nth less than or equal ts 15 eum and were elie forthe trial. Those who Ti 8 ver shore cervical length (25 mm oF less| demonstrated 2 lower risk of Bich when treated wit vaginal progesterone suppostory, 200 m@ nly compares with those who were treeted with a placebo. Hassan eta! in a rancorized tril of wemen with singleton gestation, Fount ‘vaginal progesterone gel, 30 mg dal, was associated with 2 decrease a © spontaneous preterm bith at lss than 33 weehs of gestation (9% v5. 16% mR "085; 8% .0.33-0.92) and a decease n composite neonatal morbisty and mortaity (3% vs. 14%; AR 0.7; 95% cL 0.33-0.99) among asymptomatic women With a ceria length of 10-20 mm at 19-23 6/7 weeks of gestation. E RECOMMENDATION. Functional cervical length appears to be the best Single cereal parameter to predict spontaneous rote birth, What is the best sonographic cervial parameter to detect spontaneous preterm birth? Quai of uence: High ‘Strength of Pecormendtion: Strong 38SUMMARY OF EVIDENCE. In a prospective cohort study by Guzman, eta!" twas shown that ceria! length was best in the prediction of preterm birth in women with 3 prior mid ‘nmester loss An optimal cua of 15 emhad sani force ot 28 +30, <3 and 34 weeks gestation of 100%, 100% 92% and 81% respectively. ‘To eto, in their study of ceva! length and funneling inthe prediction of spontaneous early preterm devery, concluded tat funneing didnot prove ® Signcnt addlonal contribution to cereal length in the predition of spontaneous delivery before 33 weeks (odds cai for short cervix = 26.5, 2 = 4443, 0.0001; odds eto for funneing=1.8,2=0.84, P= 0.0). ‘question What is the best ultrasonographic approach in _measuting cervical ength? [RECOMMENDATION The wansvaginal route Is the preferred route in the assessment of eral length and moreholoy. It is highly reproducible with relatively low inter= observer variation rate of S-10% Measurements are ot affected by maternal body-mass index, cervial poston, and shadowing tor maternal structures ot fetal pars unity of vience: High ‘Strength of Recommendation tong SUMMARY OF EVIDENCE Herzberg, et all® concuded that both transpeinasl and. endovagnal Litrasonography can provide sausfocory images of the ceri, but endovarval lmeges re frequeily superior to tansperneal images. Transabominal of ‘ransperines! ltrasoncgraphy can abso be used, but if the cenix is nat adequately depicted from these perspectives, endovaginal utrasoncgraphy Is Indicated. Transperineal measurements of cervical length can be senficanty shorter than endovaginl measurements before 20 weoks Hence shor cervical 6 pts documented at transperineal ultrasonography belore 20 weeks should onfrmed by endovaginautrasonography. the study of Hemander-Andrade ot al" traneabdominal measuremert stimated ceria length on average by 8mm among women with a short and resulted inthe undardiagnsi of S7kof exes. Trarsveinal US was ‘move reprocucble ntaiasscotelston coefcent (IC 095; 95% CL 97) based on cornparsans batwesn 20 mages ad medina amie volume carats reitive to ansabdominal US (ICC 71; 95% (1057-038, jr tudy published in 2001, lero eta. !found that a 22 to 24 weeks age Geitation (AOS) the cervix can be visualized adequately by varslobia- perineal sonography in about 80% of patients and the measurements of eal length obtained by ths appeosch ae very similar to thse obtained by sonography universal screening for proterm birth recommended? Implementation of ths serening svategy may be viewed 25 reasonable and may be considered by Inciviual practitioners, {COMMENDATION uot of Evidence: Moderate Strength of Recommendation: Strong IMARY OF EVIDENCE fa meta-analysis dane by Romero et a! universal transvaginal cen ength screening at 18 to 24 wets of gestation la women with 2 singleton fettaion ane the acmioisvation of vaginal progesterone for those with 3 | fonographic sor cerax were recommended ‘A study by Son et al! introduced seeening from 18 to 24 weeks in women fthout history of preterm bith (PTB) and recommended vaginal [progesterone i the cerdcal length was <20 mm. There was 2 significant {edition in the frequencies of spontaneous PTB following the introduction oF “sereoning at <7, <36, <32 weaks. This despite the prevalence of cervical Tenath £25 ram of 0.8956 at screening and the rate of spontaneous PTB <37 ‘Weeks AOG of 143 and <2 weeks of SOD aIn the study of Newnham et a," the implementation of a multtscetes ‘rogram in 2014 tha inched universal eral length creeing ad treatment ‘th vagina progesterone to women with a cereal lang <5 nn wat followed bya stay signin’ 7.6% resucton nthe et of preter birth in 2015. The effect extended from the 28-21 week gastalonal age group Cnward. I both ofthese stusles, surveillance ofthe projets wae adaableand ‘motvation ofboth taf and atin was gh QUESTIONS What 1 the optimum cut-oft for cerca Length | _-mescurementin predicting preterm ith? RECOMMENDATION For asymptomatic singleton pregnancies, cercl length at 24 weet of gestation for preterm birth risk tos defined as 25 mm. For symptomatic singleton prograncies beyond 30 wees gastato, shor CL was ‘etined a below 15 mm, ality of evidence: High ‘Srength of Recarmmendotion: Strong SUMMARY OF EVIDENCE toms et a pushed a seminal work that established noxms for cervical length et 24 weeks’ gestation centiying cercl length <25 re [the 10th cant) 5 2 cinally important theshod in predicting spontaneous preterm birth ae cervical length at 26 weeks as the mast predictive value. Short CLs cansiered one ofthe stonges ik factor fora spontaneous preterm Birth th 437.3% senctvty and 92.2% spe. The postve predictive value (PPV) of = short cereal ler i poor when assessed ina normal antenatl population Incuding low- and hig women; only 38% of women inthe Stuy wth ‘av length <25 mm (et 22-25 weeks) delvered por to 35 wreck estan, oe IMENDATION The cervix should be assessed betweon 16-26 weeks gestation. itis when iniaton of therapies or Interventions such a cerclageané progesterone may bbe done. Cera length sereening beyond 24 weak £406 In asymptomatic women sovidesinted cnc “alu an'there fe absence of data to sumgest that i Improunsoteomes ‘dusty of Evidence: high Seengthef Recammendaton Strong IMARY OF EVIDENCE et 21 In is publication on cerca! sonography published in 2008, snd tat cervical length (Cl shold not be route measures peor t2 wecks of gestation since the lowor uterine segment is underdeveloped, itchallenret cstingush this ara from the endocerel cr cal length, rening for risk for spantaneou preterm ith maybe done 8 fist timeser, The Investgators estimated that the detection rate of elvery wes only 54.8% (95% €144.7-646), with alalespostve rate cf Furthermore, the mesian cervical lngth mulls of the median (MOM, ced for matemal characters, wes sipaicntly lower In te preterm 2 Mo, 25% Cl 0.829045 tran inthe ter delivery group (0.998 MM, (10.919-1.082; p< 0.000) Derpeto ct 1 showed that before 1¢ wosts gestation, the sent, ey ond postive nd negate preditie vals ots shot Cann were 57%, SOM and 2%, repeal (AR 28; oH Cl 146) The mean “vapol sonora cere gt before 14 weet of gestation wos 387 “Y.68 nmin pregronces which delvered preterm (36 end 38.0%/-68 rm Inshore devering at wr na] 0.2). Folow-p tare! used "aration oe certo 24 week reese hatte average gestational spe Mich e short ceric as detected wes 187-29 weeks The investastors fopcived tat corsa length <25 mm” on transvginal sonographic tnsessmentrerely ocus elo 14 weeks age of gestation arin gms Fypatients destined to cele pceterm, cereal changes predictive of preterm ‘th develop most ater tis gevtatona age RECOMMENDATION Women with a Nitory of spontaneous preterm bith should undergo candeal gin seeening with transvaginal ukratound, Their senal assessment of Cerca length is snualy performed every 1-2 weeks ftom 15 un 24 weeks of gestation For patents at highest sk for preterm delivery (rir to 24 weeks delvery in a previous pregnancy, second Inworen found to have» short ces [25 im] eng routine screening, have a hstoryef por preterm birth or have previously recvived surgical Interventions (earage (EP, cold kif excision there is nseiclent ‘ata showing crcl Benet of serial messurement and surveilane, Although there may be a peychologcal benefit to both patient nd provider to sera wualze land messure the cervix outside routine evlustion in these women, the ination of proper “ecical Intervention (rogerterona is more effective vay of Evidence: Moderate Suength of Recommendation: Strong twimesterlesses), an Intl examination at 15 to 18 \wente shuld be consdere. For paints at alower isk [cone iopy, uterine malformations), a lest exam could be obesined ching the IBto 20 weeks anatomy sta, IMARY OF EVIDENCE ho et a" concluded that thas is 2 spontaneous cherterng inthe tert from the frst to the second trimester of pregnancy. The ing is more rapid i ptegnant women who delve prematurely and who jes hitory of previous preterm delivery. voy ofEidence: Hib Srengthof Recommendation Strong “SUMMARY OF EVIDENCE grant a showed the rate of endocersal canal length shortening of pstent cores dagnosed between 15 and 29 weeks gestation was 0.82 jek (P 0.05). The median interval rom the detection of cervical changes at san to delivery Wat 13 (4-19) week. See transvaginal ultrasonography after caval erlog dente a group of women who ate more likely to deliver preterm, and provides an eopartuniy Tor Intervention (repeat corclage) which apaare ta delay dover by an average of Teoh. Dita wt a showed that an increase in cervical length afte cerclag snot edith of term delivery eral CL measurement n the late second or eaty Ahird timesterpredictpreterm ith but could provide eater warning it ‘alent with a pronbyatc cercage than in patent with urgent cercage ‘These were sted! in the evaluation of 89 women whose primary physician 5 em and TWCL>2 em greaty improved the potential to remain undelivered at 7 days fllowing cervical length assessment. Caran et at! tuted 92 singleton presrancies complicated by PROM at 24-34 weeks gestation and aisigned them randemiy to groups having no ‘agial sonography (ne47] or having endoveginal ultrasound (n=48) Tis Study showed incidence of chrioamrionis among thse in the norabe and probe groups (28% vs. 20%). The inedance af endometrts (6% vs. $9) and neonatal infection (17% vs. 208) were also similar between groups, studies used a cervical length cutoff of 30mm to define the cervix as short” rd reported that those with a short cervical length wer rore likey 10 Nave smorthage and emergent delivery. These three stuces demonstrate that (2) fe may be an sssocation Between shortened cerca length and preterm th in the setting of placenta prela, 2) there are no prospective studes ng 8 management sretegy bared on cereal length, and (3) there Is uflent data to suggest a proven clinical benefit of routine cervical lenght surement or survellancs. Stafford etal! noted that fn pregnancies with placenta previa, a thir ‘mest cervical length of 30 im or less associated with increased sk forhemortage, uterine activity, and preterm birth Women wth gree and ‘short cervix were mare likely to require delivery for hemorchage, 79% Compared with 28%, and to deliver preterm, 6% compared wth 20% (oth PPcoot}, Tacadynamometerevideace of regular uterine contractions was more common with» short crv than witha longer crv 68% compared vith 21% (2<00)) Conversay, 64% wi 2 cervial ength greater than 30 tm had ne bleeding epsodes and progressed to term. {Gh et al! showed that transvaginal sonographic cervical length preets the ssk of emergency. The mean v/- £0 gestational age atulrasound was 1307 +/- 2.7 weeks and the cervical length was 369 ¢/- 88 mm. Cesarean Gelvery was performed inal cases, a a mean gestational age of 34.7 2.3 weeks. Twentyrine (49.1%) of the women preserted with prepartum blsesing and 12 (203%) required an emergency cesarean section pi to 34 completed weeks due to massive hemorrhage. Cervical length didnot difler Sieiearty between cases wh and those without prepartum Bieesing [95.3+/-9. mm ve. 38.44/82 mm; P=0.18), but was slgiicantly shorter ‘mone patients who underwent emergency cesarean section « 34 weeks the to massive hemorthage compared whin patients who underwent fective cesarean section (29-4 +/-5.7 rm vs. 38.8 4/-8. mm; P= 10006), Zitoun eta in a study of cates with confred diagnosis of complete Placenta preva, showed antepartum bleeding was observed io 51.4% 8) of 35 patients with cervical length measurements <30 mm, of whom ‘889% (U6 out of 18) hod showed severe attack that necessitated emergency cesarean delivery belore 36 weaks, versus 212% (n=4) of 19 patients with cerca length 230 mm. By combining cervical length with Tower placental eage thickness measurement sensitivity, specialty, posiive predictive value (PPV] negative predictve value (NPV) anc ecuraey Ineeased 0 833,784, $3.4, 788 and 89.7%, respectively forthe “9‘rection of antepartum bleeding and emergency cesarean section “36 weeks using recehuer operating characteris curve wth ora under the curve 0882, ‘8, OTHER SONOGRAPHIC MARKERS RECOMMENDATION The development of new uraxound tecniaues was shown tobe elective inthe prediction of preterm rth ‘but funsonal cerca length remain. to be the superior predictive tecl among them. These new techniques include arma ll stage (APS), cereal consistancy index, assessment of eaves elstoganhy (Grain elategraphy and shear wave elartography, \terocerval angle (UCA), uterine artery pusaity Index (during peak uterine contraction, placental Stain ratio, and measurement ofthe central zone of fetal adrenal land SUMMARY OF EVIDENCE Amniotic Bid Stadae ‘Adare ina study of pales at high tk for spontaneous preterm delvery, evalusted for the. presence of omiatc Tid sludge. with transvaginal ultrasonography, The study showed tht the provalenca of amniotic ful sludge in the study population was 29.5%, The rates of spontaneous preterm delvery <37 weeks of gestation were 6.7% for the patients with ‘sludge and 27.0% forthe patente without sludge, Patents with shige had = higher rate of spontaneous preter debvery {(p*0.002).The amniotic fd sludge 1 an Independant rk factor for ‘spontaneous pretar delivery among asymptomti patents thigh ik for spontaneous preter delivery. Fuchs et a. ® noted that amnlote hid sige was observed in 74% of patients na case-contrel sud Including singleton pregnancies between 15- 232 weeks of gestatlon. It was associated with shorter cervical length, pester 50 ody mass inden, cers eerelage and preterm bth before 28 weeks, but ater adjustment, it wns no longer associated with preterm delivery before ‘orsswee's Qual of Evidence: tow “Strength of Recommendation: Weak ‘The cern consetoncy ndeie computed using the formal: Corvical consistency inden =(APL/AP) «300 iets AP = anteroposterior canical diameter before (AP) {49 1- anteroposterior coal diameter after Bator otal showed that earvical consistency index, determined using nterosporterr cmeter measrements of the cori wth and without Cervical pressure, has been snown tobe a peices 2 least comparable to evel length for preterm bie, slough eternal validation an larger ample size nod tobe carsdered to futher assess lial sty uot of Evidence: tow Srength of Recommendation: Weok cena ‘nin elastgraphy and shear wave eastography, when combined with Cenzl length, are promising predictive measurements aithough there are ft limitations inte techn implementation. ‘urna et al, n 30 cases resting in preterm bth and 30 gestational ‘age-matched contro, snowed that when vaginal ulvasound examination ith cervical length and elastography messurement were performed, 30 ‘Sezociaton betwean the value ofthe strain rato that was calelated from the ROS paced side by sce in the migdla of the anerr lip (SRA), ‘and preterm delivery (Pc.001) was observed. The predictive values of anil length and SRE ware comparable (RUC 07394; ALC 08322), respectively stWing ot 31! showed In a mete-analis and systematic review that ‘cervical elastography s 2 promising ard lable method to predict preterm eluery. i this study, cereal eastgraphy showed etter agnostic performance to preset preterm deliver than ceria length measurement, ‘This meta-analysis showed that corcal elastography had a ensitvity of (0.84 (95% C0.68-083, a speciy oF 0.82 (88% C10.53-03), a dagrastic ‘ds ratio of 25 (38% €1 7-83), and an area uncer the curve (AUC) of SROC ‘f 090 (853 61087-0393). Cereal length measurement showed tht the AUC of SROC was 0.50 (88K 0 056-06). auoy of Eden: tow Stengthof Recommendation: Weak terocenice Angle Dastalais eta showed that terocerval ange Ie measured between lower uterina segment and ceria! canal. nthe syrteratc vevew thet Included 3018 women, the eising data supports that second tester terocervical angle measurement might be useful 3s a preceie factor of preterm bith <4 weeks, asa least two studies 'n unselected singleton Pregnancies and two studles In pregnancies with an ulraronographically shortened cerax supported the hypothesis. The mast commonly reported ataff vols were 105° and 95°. vay of idencestow Strength of Recemmendotion: Weak Uerine Artery Paso Index igen at al studied the use of uterine artery doppler velocimetry uring peak uterine conraevon for patients exhibiting symptoms of preterm labor forthe dentifction of pregnant women a sk of preterm ‘alvery, In 172 patients adrattd wth preterm [24-35 weeks gestation) Uterine cantractons, uterine artery PI dating the peak of contractions was ‘ipnfiantly higher in patiens who delvere within 7 daye than in those who dé not (® 0003). ‘vat ofEvdence:tow ‘Stength of Recommendetion: Weak 52 _Navra eta!ncute!70 pregnant woren wherein placental real tne onotlsteeraphy measurement vee plored. Two afeant realtime “onoelstegraphy measurements were performed by tng two diferent tts as references, The rea me soncetastography value measured when ‘aking the rectus abdominis muscle 0 a reference was termed the muscle ‘eplocenta sain rato (MSR, while the realtime sonosastogapy value treasured when tating subeutaneous tissue a reference was termed the fatto pacenta strain ratio (FSR. Women whose gestational ege at bith Ines es thon 37 weeks @ days ware accaped as spontaneots preterm bith ‘There was 2 low level negative correlation between MPSR and gestational age 2 bith 0300, P.012) and there was # moderate! negate fartclation between FPSR and gestational age a bth (-=0.813, 003), “he mulvarste nes regression ans showed thatthe FPSR (3-0: roa] was the slgnfcan preictor fer the spontaneous preterm birth ‘Quai of Evidence: tow ‘Sength of Recommendation: Weak Conta Lemos a! conducted 2 prospective cross-sectional study of pregnant women between 24 an 36 weeks of gestation. An ultrasound exam Was Derformes fer each portcpant ra obain the eri length measurement [tensvognal route] and fetal adrenal gind biometry. The provaleace of dalvery within 7 cays was 35.8%, whlch showed a statistically sinicat ference for te dept ofthe cent! 2002 of the fetal adreral gen (p = 12036), The cute for the dept ofthe central zore ofthe fetal adrenal Gand was 7.2 mm fensitisty 66.7%, specify 61.8% and accuracy 63.5%) hese values were not signee ferent than the cutoffs for ceria fereth measurement. 20mm [p = 03267) and Sram (p = O18). The biometry fr the central 2one ofthe fetal adrenal gland predicted delivery ‘wthin 7 ¢ays in pregnant women with spontaneous preterm birt 3nd had 2 preditve accuracy sir t that of cervical length measurement Quoty of Evidence: iow Strength of Racomendoion: Weaky A. CERVICAL FLUID [RECOMMENDATION Tho folowing ceria id biomarkers may be useful in ‘he prediction of preterm birt. 1 Fetal flronectin (FX) 2. eS.nd bd leelsin coveoveginal fis 3. Placental alpha macroglbuli- (PAMG-1) 4 Insulin arowth factor binding. proteins (ioFae-y) SUMMARY OF EVIDENCE etal Fibronectin The quaitative fetal Mlronecin tect has traiionaly been used a 3 test for etectng imminent delvery In women with threatened preterm labor The {greatest value ofthis qualtative test les in high negate predictive values, Bfsoitcan be ausoful et in reassuring wemen wth 2 negative result neta. n 8 prospective study includ 85 women with syatomatle ‘reterm labor of a singleton pregnancy, showed thet thir approach using the fetal Abronectn (FF) test could not impave the abt to predct reer birth (18), but ico sentity women a or dover before 34 0 37 weeks of gastation. Thity-sic a-ha percent showed 8 positive FFM and 51.8% had ashore CL PTB occured within 7 and 14 Gay f testing ‘and before 34 and 37 weeks of gstavon In 17-5, 200,22 and 494% of the ‘women, respectively. The FN and CL resus showed low predictive tfectneness forthe staied outcomes wih UR (FN, 15-19; CL, 10-15) ‘and LR FN, 0.7; CL, 0.7-08). The combined use of FN and CL could not ‘improve these results (UR, 14-2.; LX, 07-09). Hower, te risk of PIB before 37 weeks war Inseased in wornen with pasive IFN tut ot Ce Shortening compare tothe reference group (OR 38; 95% C1 1-23). The ‘ik of PTB before 3¢ weeks was ieresea in both sestve TFN and CL ‘compere te the reference group (8, 8.3; 95% C1 15-285), a ‘Abbott et aL in a prospective cohort study of women in threatened preterm labor showed that fetal flyonectin (FN) concentration correlated ‘nth risk of preterm delivery, Fr FN levels <10 ng/ml, there was anegtive preclcive value of 98.2% for delivery before 34 weeks, whereas evls 2200 ‘g/ml were astocated witha positive preitive vale of 37% for eliery “before 24 weeks, The adakionl tsk svaiicaton of quantitative fF may help to gue cnicons on identthing women requiing intervention 2nd misior ‘Watson eta recommended the QUIPP app a clinica prediction tol for spontaneous preterm bith, which finer 2 poreantage ak of=retrm ih based on gestation, obstetric history and quanttatie feta fibronectin. The app has been shown to accurately guide management at certain risk Thresholds to avoid unnecsesary intervention in low tse women, The " sévantage ofthe app that it combines cine history and intarrogates sk e085 he hale rarge of branetn anid cereal eng | Belin et 21°, na systematic review, reported that although the accuracy feta oronectin a predleting spontaneous preterm birth varied itis most sccurate in preicing preterm birth in women with theatened preterm Tabor without sdvenced sors distation within 7-10 days ater tsting, Berghellaet al, ina meta-znaly, eporied tha etal bronetin testing In singleton gestatons wa not aaocated wit pevertion of preterm birth improved perinatal outcomes, reprtng that preterm birt incidences before 28 weeks, 32 wees, 34 wecs, anc 37 wesks dd not change despite Is higher costs. While testing fetal isronoctin,bloed-tained swabs were Stl effective in predicting preterm bit; however, they had higher fle postive rate. ral cbeervtinal tudes have nated that the combination of envi ength td feta foronecan fF] assessment may improve preticion ef preterm bith mong women wit smpioms of sate preterm abo. Gomer et a™ showed the prevalence of spontaneous preterm delivery within 48 hours, 7 dys, and 14 days of admission, and delivery or = 30 mm and in inedence of spontaneous preterm bith in all women wth preterm abot ‘Van Baaren et al showed that a combination of ceva ent serening and fetal fbonectin tering in “symptomatic” patients shows that feta) ‘ibonectia does otal to praerm Binh prediction in women with 2 very short {20 mm) cereal length In these station, fetal bronectin may be lscarded because the NPV of cerca length 30 mm alone i Neh (96 100%). When wed in combination with CL screnivg, FEN may be most Useful in women wih ceria length of 2-29 mm eth "grey zone") in ‘his tution a “negative test” (80% of eases) may alow fr no treatment hie a postive test would suggest the need Tor intervention antenatal ovcosteroas, transfer to tertiary contr, tc} ueity of Evidence: Mogerte Strength of Recommendation: Strong Interteukin 8) Levels Jung et lS! showed 16 and 1 levee In cerveovaginal uid were ‘associated with preterm Birth within 7 days and successful when especialy ‘combined with cerveallergth. Combination ofl levels and ceva length had a speccyof £2.85 fr predicting pretarm birth in 7 ys; however ts relatively ow sensi (56.08) was a miation fr ts cial we. ue of fidence: tow Strength of Recommendation: Strong ‘stow! et aL showed placental alpha macroglobulin-1 {PAMG-I) was ‘comared with fetal flronectn and cervical length measurement andi was Fesorted that PAM was more accurate in predicting preterm Bh within 7 ays wth 80% sensitty ar 55% speciicty and It was reported It had ‘he preter uty ptierts whe cereal ent was 15-350. uot of evidence: Hie Strength af commendation Strong lke Growth je etal! reported that ati biomarker of nstve and total IGFBP-t nd 6 was ono succesful tat with 87.96 sertiy, 92.4% speci, ‘5.0% PPV, 100% NPV, and 958 accuracy in predicting preterm bith in 7 As, Bran et all, in this study 350 women were testod, of whom 20% ‘elves within seven days. Egy four woman hed a positive IGFEP1 test Sand 162 women a postve fetal laronecin (FN) test of whom 64% and 39% delivered within seven days, respectively. Ninety-seven women hed 9 ‘area length below 15 rim, of whom 52% delivered within seven dys. Sensitey, spect, postive and negative prescive values of combining ervcllerath withthe IGF! testo the FN test wore 91%, 75%, 47% and 97%, and 96%, 58% 36% and 98%, respectively Fuchs et a! noted that, among 180 women, 11.7% had 2 positive DNIGFBP- tect. Spontaneous preterm birth occurred within 7 cay 1a days Gf testing and before 34 weeks and 37 weeks in 7.8%, 106%, 12.9% and 2ABK, respectively. The phIGFBO-1 test alone oF in combination with arc length has alow predictive accuracy to pret preterm bth In symptomatic women, Melchor en a meta- analyst wharea Bharat mixed model pooled sanstigy of PAMG-1, fetal Flrenectin, and phosphorylated {GFBP-1) In simptomatc women was Used, PAMG- wa Feported to have the highest poste preicive valve and postive tcticod rata (UR while negative predicive value and LR. romsined similary high uthin whe tree biomarkers. The areas under te receiveroperatingcharatersts (ROC) srcurves for PAMG:2, fF and pHGFBP+ for sPTB <7 days wove 0961, 0874 snd 0801, rexpoctivay uit of Evidence: Hh Stength of Recommendation: Song [RECOMMENDATION Fetal ronectin Is of no benefit inthe management of symptomatic women with «pir preterm bith of or ‘the tisk populations, such as twin gesttons vay of idence: Moderate ‘Sswength of Recommendation Strong SUMMARY OF EVIDENCE Berghe etal, ina systematic review and meta-analysis of randomized convo trials, ‘concilded that fetal Mbronectin testing In singleton fesstions with thestened preterm lor Is not assodted with the revention of preterm bith or improvement in perinatal outcome but i ssoaited wih higher cost. os Santos ea stated ina systematic review that curently o evidence supporting the use of fetal Abronectn (FN) testing in asymtomatie women. Tis review suggest that in women with singleton pregnancies without rk factors fo preterm birth, 2 postive FFM may be predetive of preterm birth but should be sed with caution, Further good qualy research is needed to determine the usefulness of FN testing In the pathway of cate for women without Fisk factors who ae asymptomatic fr preterm birth, showed signieat rests in their respecive studs, butt enough lial stuies a recommend her use 1 Lewannioti fd glucose 2. inte (16) 3. Vascular Endothelial Groweh Factor (VEGH, Pacertal Growth Facts (PGF) ne Slubie VEGF Receptor (ee) Inearieukin-38 (1-19) Neutrophil elastase Bane Annexin (gu et 2: conclae hat amniotic Hud glucose levels wre sinfcanty lower in patients with preterm éelvery than term celiveries (P (002) although this reat is signfcant and notable, there fs not enough Civica eidence to recommend thor us 362 rreeing tet for pretrr ‘elvery and intrauterine growth retardation (USR] in routine race. ‘Quality of dence: tow ‘Strength of Recommendation: Weak (0 etal concluded 6 levels in the armlale Fid were sigicaniy higerin the preterm deliver group, are there was asttstalysigicat negative corelation between IL-6 concentration in he alot id and gestational age at delivery (correlation coffer (CC) 18.5%, p 42 weeks. The sacondry outcomes studied whch are relovant to [FG were length of gestion, maternal adverse ete, serous moro, mortality, and hemorrhage forthe mother, sillths, lw bit weight “or gestational age, and several compiations of prematurity for the one mores forte fans and se of heath sevice ‘observational studies inthe 19605 have reported longer pregnancy duration in {ish-enting communis Subsequent randomizee contol tial upported ‘his observation’ though tne get mechaism of action i stl unknown, resus of studs have stpported the suggestions that omega LOPUFAS ‘modulate prosalendn syhere and init plmitat-induceeinfamstory ‘cade, both of whien atin prolonging gestation RECOMMENDATION Supplementation with omoga-3 LCOUFAS significantly decrease te risk of preterm delvary at < 37 weeks and <34 weeks age of gestation (ACG) uot of uidence: Hoh ‘Strength of Recommendation: Strong 88 0‘The results were a shown blow: 3 Figure 2 Forest of riko preterm delivery 34 weeks with EShornefianet suolomentation with LCPUFA in efeent doses s20n in Figure 2, omega LCPUFAS aso significantly decreased the risk of rm delivery at fess than 3¢ weeks age of gastation (AOG) (RR 0.58, 955 C1 (0.77), Thebes results ware seen a doze: between SOO mg and 1/6 IRR, 1, 95% 1030, 0-75)" Figure 1. Forest pot of risk of preterm delivery <34 weeks wth supplementation with LCPUFAS in diferent dares ‘As seen in Figure 1, Omega-3 LCPUFAS significantly deceased the risk of prota dalvory st ess than 37 weeks (RRO 83, 95% C0. 80-097), ith tbat rests fr doses oF $00 mg to e/day (RR O.73, 985 C.6E-098)."" * omy Figure 3. Forest plot of rskof prolonged gestation with ‘supplementation with LCPUFAS diferent doses As Figure 3 shows, the Cochrane systematic review further conduded that supalomertation with omega-3 LCPUFAs didnot significantly proton gestation to> 2 weeks AG" Figure 4 Risk of perinatal death with supplementation with ‘omego3 CPUFAsin diferent dorer re shows that perinatal death wae aso not sgnifcanl affected by the omertaton with omega-3LCPUFAS.*sBaiiateadk Fivesstitanete Figure 5 Rsk of preterm delivery according to time fintation ‘of omega-3 LCPUFAS supplementation ‘QUESTION 2 tn preventing preterm bith, omega 3 LCPUFAS work best gen ¢ 20 weeks age of gestation uty of Evidence: High ‘Strength of Recommendation: Strong o JMMARY OF EVIDENCE 5 shsvates that in preverting preterm birt, omega-3 LCPUFAS work Ifthe are even < 20 weeks age of gestation (RRBs, 95% 10.76.95)" 2 ae Ea Se Figure 6 Forest pot of rik of prterm delivery <34 weeks according {time of tation of supplomentation af omega-3 LCPUFAE js, in preventing eary preterm delivery (¢ 24 weeks), they are best at 20 west (RRO, 95% Cl 0.43-0.75)™ a5 Figure shows,r] aak seas sent ssa sean Figure. Forest plot of isk of adverse maternal events wth ‘Supplementation of omege-3 LPUFAS Figure 7 states that omega'3 LCPUFAE were easly tolerated, Qerl there "Was Significant increase in postpartum hemorrhage (AR. .03, 95% C1 0.82 £130), severe matemal adverse events (RE 1.08, 95% Cl 042.72) or in events ‘severe enough to cause cessation ofthe medication (RR L.01. 95% C1052 1.93) sithough there were increased complains of voriting,beching or burp.” ‘From this meteanayss, t_may be concluded thot omega LCPUFA supplementation, started eatin pregnancy, at dose of S00 mgt 28/y, ‘etve in proventing preterm Isbor ana delivery wth Mle or no sigifeart rivers oferts and with late low cost tthe mother. 98 uh he Cochrane reviewers di not recommen further studies comparing 13-3 LCPUFAS supplementation and plaabo in reverting preter sbor ‘elvery, they propores that further tudes be conducted onthe effect of 4-3 LCPUFA supplementation on growth ana development and longer outcomes forthe mother ae child” Lip ct utnr 857h t of3 PUFA plone on oe ater Iolanesten nt gacrn ana mater Some sng reemrey Foner a en ny aes 26 13859 nin €7 Gon Phew A Mie Mh fog in ahead ten Somat 1 da ret a Ong oy acl bin Ao ene, ean oat 20 3:02chon 10 Sgt (13% ma 1h 075, 95% 1058-098 hte thre was no Sant iferece between the two reps In te wos nanber of Cervical Cerclage riage, stilbene and deaths following live births, suberoup analyses for Prevention of Preterm Birth yealed that women with a history of 3 more pregnancies. ending before 37 Gs ncttad rom ora tts delvery bere 23 west Geese by ate Catelen Senge, MO, FPOG,FSUDG, Far iin the erclge soup (55.32% P eS) let was sen nose DEFINITION oF TERMS ‘+ PRETERM BIRTH ith between 20and 36 6/7 weeks” SHORT CERVIX ~coricsllorgth of es than 25 mm, messured at the mid ‘master, a tansvaginal or vanslbalubrasouna! 1+ CERCLAGE ~ a procurein neh sutures are uted te dose the crv dune pregnancy to prover pregnancy loss or preter bith, The approach may be ‘eansagial,ransabdorinal or laparoscope ‘+ MsTORYANDICATED CERCLAGE ~cercace performed because of woman's increased rik for preterm delivery secondary ta her obstetric oc eynecloek isang ‘+ ULTRASOUND INDICATED CERCLAGE—cerage performed in asymptomatic women, where the ceric is seen te Be shortaned Ia. tanwagial Strasouna™ 4 RESCUE CERCLAGE ~cercago performed as an emergency measure in cases ‘of ceri latation with exposed fetal membranes ater dbeovery through uitrasound of pelvic examination” Cerlage ry be offered to pregnant women oth history of spontaneous second trimester losses or preterm bir, wo, on transvaginal ultrasound Survellanee were found to have erica length oF 2S mm oles before 24 wee of gestation. Ie ismot recommended in women: 1. Without 2 history of spontaneous preterm delvory or mid-rimester loss who Rave an Incidental fining of a short carviz on uraiound 2 With uneling of the cowie where the cervical lengths 25 mm or longer ue of Evidence: Hoh ‘Swenat of Recommendotion: Strong RECOMMENDATION Histoyindeated corte may be offered to women JMRAARY OF EVIDENCE ‘th history of 3 or more preveus preterm deliveries and or second vimeste losses, net al, in randomized controle ral and Berghe al "ina mets rll, both found that these with history of preterm bits and wid-rimester plus acerca length atc less than 25 mon sonographic survellance st before 24 weeks, benefited trom carlage compared to those Weated wit ectant management (RR 0.57; 95% C1 033-099 and AR 0.62; 95% CO. ‘unity of Evidence: Hi Srength of Recommendation: Song SUMMARY OF EVIDENCE Three randomized contol trials (ACT) compared the outcome of history: J To. a! measured the caval length of 47,123 woren with rik actos for Indicated cercage against expectant management. Thro wers fewer deliveries ri birth at 22-24 weeks AOG. Fourhunded seventy (470) women wa before 33 weeks inthe ceriage group matched up agsinst those with no eto have a cervix measuring 1.5 cm or less, Fy four percent (55) of 00 101‘those women agreed tobe randomized to ether the performance of a earcage ‘of expectant management. There was no signfiant ference the ieidense preterm bith In the cerdage versus expectant management group (22% vers 268). There sno ovealeidence of benef for crlage in worn with a shartened eric with no ether rFactor: RECOMMENDATION The choice to place a rescue cerdaze should be Indlualed since the risks of preterm delivery and ‘neonatal mortal are high. Advarces distton ofthe ‘cervix of 4 cm or move cr prolapse ofthe membrane beyond the eternal ceria os fe associated ith 2 igh incidence of cercage allure Quo of Evidence: oderate Stergth of Recommendoion: Weak SUMMARY OF EVIDENCE ‘Theres only one RCT comparing rescue crclage and bed ret sone. Althusis tal. stated 23 women who were seen to have ollatedeavics and prolapsed Imambranes. at 3 mean gestation of 22-23 weeks All of them were hospital and on ad rest uni 30 wees of gertalon Those allocated to the ‘cetage group were ven preoperative indomethacin, Those inthe cerdlage sroupdelveres on average 4 weeks later tan thos inthe bed ext group an» Elgitican eduction in delivery before 34 weeks (59% vs, 100%, PeD93). There was no deta provided on the incidence of chorlumniontis or neonatal ‘more. 102 ]ONd When iscercageconaindetest IENDATION The performance of 3 cenical cerdage is not rezommended inthe following cumstances + Actve preterm labor Evidence of ovtoarriontis Continuous vaginal bleeding Preterm prelabor ruptureof membranes {Evidence of etal cmpromize Lethal fetal congenital defect Fetal demise" uot of Evidence: tow ‘Stengthof Recommendetion Weak /GPP ethan vot a veal seamen by uaa for pig Peter din {Rene The Ccronecolaarton 2082 ance agua er opi proven cel ec the prerion of eee arn wre wh ong hoe ere, prev pres th an pet "fst sytenseetaanas dine cemanean meena te ra ‘fobsmasandGyeany, 201 iy 28k ca vee, 2 Ciel te etl fr peeing pret ln regan, Gxraneosoestnste ia 20288 oo reen Ton encine ocr ay 208 tan Gepon 5 Deo eal Muicered cnt i of xe coins Eta 5 tal Avena rte kt eral cogs woman 298 rsp tem deny Oot perl ne 79880 Fl vpo of the Model fseah cau? ol Clkgr of Obeies and Gnaogss tara arco lf eta ee, MMIDG Harn ary ncevealsdage Oh Oya 199 056-9 ‘ven Hale erp Wet eid fea ar presi rn revo fh wien mi stares i net es ag mdb Gee 288 20375028 Berea, Ode 80, To Sst OA, Ae SM Cerne fo sho ce on [Mbeeearone: metre fel ng tba pene en, Oras el40. To mS AME 2 Hen NE Cet Ft Meena Sc Teer Scene Gn, aul arcs o mevern ot pete day wah eh sero anamzed coal ne 2008 389553 ‘tha 2 altar ual en lH, Cade compan prevanon Yanda crag st ery cre th nd tet vrs bd os lor rete 20 180730, 104 afore |. Sates, MD, FPOGS, FPSUOG, FPSM>M Use of pessaries near reports was for the prevention of spontaneous tern birth that useé modal thet were ocgeally intended to treat genital p50 Closet a. descibes hie experianee sing 3 rng pear in 13 patios lier 2 story of crea lacerations, eval ineomaetence of uterus phys, as ted by Oheran and dei 3968, Vrsky described the use of a Hodge pesaryin sven patients and in 8 patients from colleagues. He postulated that the redution of peste on = Internal os prevented the protresion of membranes.2® He sso suggested the pessary might change the inesnation of the cereal canal to id In cessing the ceri but ths was never proven, and considoing the lrge ngs of he Hodge snd ng pesraries, this oe Not seen tobe hey. Ones ver! aso used Hooge essary in 29 patients with “crveal srpetence, guns that treatment with 8 pessary would be supener 0 jl erage since reduces the kof leedng or maternal sepsis, Inter pessaies that were designed soeiclly for pregnant women ated mainly from East European counties. ato eta desea + faye ring passa” which ic made of organic aes” Jerde and Hamann ‘Germany developed s pessory that was supposed to sutound the ning cervix witha a butterli-shiped design that had lager eameter rs te saetum and asmaler diameter towards the symm the ate 19705, Hans rain of West Germany devised a round cone-shaped ry that Is made of fenblesilone. Its dome: tke design resembled the nal omic that eed to surround the car a8 close ae posible to the al 05! The design had the intention of not only supporting. an pressing, But se Icing the cervix ane pony rotating i mre towards 105RECOMMENDATION ‘The use of caval pessary for the prevention of preterm br in women with 2 sonogeaphicaly shor. fcevie maybe benefidal in certain populations. Further studies are needed to validate Is potential benefits as curentstudles show inconsstent resus, uot of Evidence: iow ‘Stengthaf Recommendation: Weak SUMMARY OF EVIDENCE “he fist mulieenter randomized contclled wal (RCXY" on the use of the peseacy included 385 unselected wornen who were screened by transvaginal ‘resound (TWUS) The sty showed tatin woman wth short cerca ength (25 mm between 18 and 22 weoks age of gestation (AOG), the pessary brolonged she pregrancy and edaced the rte of poor outcome compared with font. The women wore randomized to receive petty (S192) of expectant management (913) Inthe pessary group, there were fewer bts before 3¢ weeks (3 versus 27% RA. 024; $55 C10.13-043, before 37 wees (27% vers 59%; RR 0.36; 95% C1 0.27-0.49) and before 28 west (2% vereut 3% RR 98% Cl 0.09-0.73), showing a signifi ference inthe occurence ot composite poor neonatal outcome 2 smaller RCT that involved 108 Asian wornen with snleton pregnancy an» ‘cerca lerath 25 mmr routine second trimester transvaginal san showed 2 Sima trend favoring the Use af cecal pessary. The mean gestatonal age st alvery wat 38.1 wees inthe pessry group compared wih 37.8 wets inthe fexoecant group, wth ne significant aferences inte rates of delivery afore 28, 34037 ach | single-center parallel group RCT by Saecon tal" included 300 women wth ‘zymptomatie pregnancies and without prior spontaneous preterm Hh but ‘th shore card! length [-20 mm) on ansvaghalulvascund. The subjects ‘were randomized to Yeceve 2 cereal pessary (intervention group} or no Desrary (contol group). Women In both groups were prescribed vagina ‘progesterone 200 g supposes daly ntl 36 weeks and dys of gestation. No recommendation ia rade about ted es, att) or vagina inereoures 106 7 primary outcome was spontaneous preterm bith at ss than 34 weeks of on. The results showed that spontaneous preterm birth 2t<34 weeks red in 11 women 7 3 nthe pssay group and 23 women (15.3%) nthe rl group (between-group eillerece, 8.0%: SSK C157 to 0.4%). The therefore concluded that smong women without pror spontaneous feterm bith who hod. ssymetomatic singleton pregnancies end. short vaginal cereal length, cricalpassary use rested In a lower rate of neque preterm bin at < 34 weece of gesabOn, sacondary outcome measure in Saccone's study also favor the ute of eal essary a was asodated with lower rate af spontaneous preterm ‘at <37 weeks gestation, a longer gestational age at delivery and latency ancomizationt delivery, higher bith weight, ower rates of admision to ‘neonatal intensive care unit (NICU) and a lower Incidence of adverse natal outcome compared to group thathad no pessary. ny nthe systematic review and mets-anayss conduc by Seccone alin 20179 aire 3 RCT (= 1420) wore included, cervalpessary use dd duce the rate of spontaneous preterm delivery or Improve perineta 3c. However, Incvcual patient date mets analy may nate whether | pesary could be Benfl in cartaln subgroups of women angeton nes without prior Nstory of spontanzous peter birth but have short rvces on transvaginal ultesound), rulicanter RCT conducted in 2026 by Nicelide a a, ako supported Aine thatthe use of ceva pssary showed no sigliieant ference In rate of spontaneous delvery before 34 weeks, perinatal death, adverse outcome or neonstl speci care compared withthe contre group “The use of cervical pessary in twin pregnancies with shor cereal length on transvaginal Ustasound at 126-24 weeks i not recommends because It does not prevent spontaneous preterm birth or improve perinatal outcome. uct of Evidence: High Suength of Recommendetion: Strong 107‘SUMMARY OF EVIDENCE In 2017, « meta-analysis evaluated the effectveness of conical penser for preventing spontansoue preterm beth (SPTB) vn twin pregnancies with an symptomatic transvaginal ultrasound earvl length (TVU CL) in the second ‘eimester. Three RCTs that included 482 twin pregnaeles with sonogrephiclly ‘hor cervixin th second waster 26-22 weeks) camped the use of ervet ‘estar with expectant management. Two RCTs used VU CLs 25 mm andone ‘see TWU CL 38 mm 35 cutoff. the meta-analysis concluded that dhe use ef ‘ceric pesary was nt sssecated with preverton of spontaneous preter bith, ane tha mesn gestational age at delivery an the mead latency wer sirlar in the pessary group compared to the contol group. Simi, no benefits were noticen the neonatal outcomesin the pessry group. ‘Thangtorai etal” conducted arather systematic review and mete analysis in 2018 to ases the electvenes of cerscalpessary inthe prevention of preter births They were ikewisa unable to show benefit of uring erie! peteary i twin eegrances with short cons ‘questions: ‘Should women receive supplemental vaginal progesterone afer cerclpessry insertion? RECOMMENDATION Vesna progesterone may be given to woman after cervical pessar insertion to lower the rate of preterm deivery ‘elt of Evidence: Weok ‘Svengt of Recommendation: Strong SUMMARY OF EVIDENCE In a retrorpective cohort study af 202 women with slogeton pragnancc: managed in to tertiary medical centers, one canter used 2 combination ct ‘ere pessory ang supplemental vagal progesterone (study group) and the Second ed oniywebnal rogesterene. in worn who had 9 short can 07 ‘TWUs done between 18 ad 29 weeks gestation (corto grup). Ninety fur (34 ‘F465 women were incuded in the study group and 108 (S3%} waren were indus inthe conte group. he study showal that the cmblned treatment of cervical pesary and vagina peserone had a lower rte of preterm delivery <34 weeks of gestation and abl to prolonged gestation when compired to those women who were ted wth only vaginal progesterone; Nowover, mare randomized control fs ee ned to validate these resulta Prato 3933838, (ny mes etme of te nett candle. at Gye 19631732 {hy N.The compet ena sand the pe A Ca yal SG P44 (= ve rnin fh nampa cov wih the Hobe psy. Obet Epc ss 205308 Int un ats fuse enmert ef reccous ery. Contin ft {needy eg: tone pay Cskaal TULA “Sra chown cron ng spre peste Peon an eae ot rath sol atl oP 09386635. Eien rrerooc (ent wh pvr gegen ih Tiss ‘Serean oY 81208278, cr ra a ce pn pat one o 2 ast or CM, Lau Tao TT Lung ¥-Ceelage psa fr prevent peer thin ivr astain Sarna ee ot 8 m3 mand Sine ttn © Shake & Min ec of Cn en on xSomeac em rin Warn aha Mewes rd Shr Covel eg aoe sr iss ae ‘Scare crs cota Caren psy et prvering pret rn pen Seip tetaaeies s amenae cw sanco ssn) Oe fea irae 2880. free were aston th MEnl Mad 936 943010052 Src crt ew ap clon erga ith Inimitle ep win nr cr SPA composted mea Sat Maeno Necea es 04,382) Ia owe en etal Sonal ey whine Jouce/irensa seaasT08 109Chapa 12 Calcium Channel Blockers (Gumesnda Cuz-Jver, MD, FPOGS,FPSWFM, FPSUOG ‘aa Konsuelo , Cha, MD, FPOGS lium channel blocker sone ofthe most commonly uted tools tacts by reducing smooth muscle contacity by decreasing the ff of ealeur into ‘els. iene, which hasbeen widely use in the treatment of hypertension, has been exensvely died in the management and contol of preterm ler ‘Talimprove neonatal oucomor, it ic racommended that women with imminent preterm lator receive tocol therapy and antenatal cortinsterads and ‘elverina tert come. The goal of iil tools iso delay dalery For at leost 48 hour, allowing completion of couree of crtiostrois fr feta uns ‘maturation and maternal trarfer to a tertiary center with capale neonatal fntesive are unt (NICU) fies * ‘QUESTION 1 ‘Which tocovtic agent is mast eflacive at delaying ‘elvery for 48 hours to allow the adehnsration of antenatal corcosterolds? RECOMMENDATIONS fedpine hod the highest probability of delaying doivery by 48 hours, Improving neonatal outcomes nd with relathely tow materal side effects and therefore ti racommended for proce uty of Evidence: High Seng of Recommendation: Song SUMMARY OF EVIDENCE “ne work of Hass and clsgus utes network meta-analysis methodslogy forthe steeemont of different tocol therapies. This is the fst of sein coiteres because It alws dest and indirect comparisons ot toolyte {Testes among ifaent trials, ft was concluded tha provtaplandin inhibitors land calcu chanel bicckrs had tho highest probably of delaying deliver by ‘42 houre and improving neonatal outcomes and with vlativey low eacern’ ‘Sdeeffecs. 10 Fostananain inhibitors, magnesium sulfate, calduen channel blockers. B matics and atoslan were the toclvies included nthe analysis. When pared with olsesa, prostaglandin inhibitors had the Nghastprobeblity oF fbjing deiery by 48 hous (OR 5.39, 5% 1 214-1224), There was no syde that was signfeanty superior to placebo In reducing neonatal pratorydstess syrome er neonatal morality. Compared with ploebe, Tocolyics that has the hehest maternal adverse elects were mimetics 2.68 95% 0 7.51-73.67) and magnesium suifate (OR 8.15, 958 cl 247 70), Prostgandin inhibitors and calcium channel bleckers were ranked In top tree medestion clases for maternal and fetal outcomes and side Ee iON ‘Among pregnant women with preterm labor how ‘effective nifedipine In improving perinatal. ‘outcomes compare to other tools? IMENDATIONS Nifedipine is superior to. Pr2-adrenestreceptor agonists and magnesiur sullate for tocol in women with preterm labor and can be ued 35 the gent first cole for toch uit of idence gh Strength of Recommendation: Strong IARY OF EVIDENCE systematic review and metaanalsls conducted by Conde-Agudeo et a. in 21 evaluated the resuts of twenty-sx randomized conlled trai that yded 2179 women. The rasuts showed thet rHesipine was associated witha enficant reduction In the risk of delvery within 7 cays of the onset of nent and belore 34 weeks! gestation compared with B-2-adrenergc- 10 agonists. It aso has sigaicanty fewar maternal adverse events onatal averse cutcomes such 35 respiratory distress syndrome, necotin ercoli, nraventiular hemerthage, neonatal janice, and admission tO NICU were ato reduced Comparing magnesium su'steon nifesiping, bot ‘shown to ve the some toalyticeffcay. As a maatenance 2a, pine was not effete In prolonging gestation or improving neonetl cs when compored with ne tress mTable 1 shows that sfeipine was asocated wth a sgnfeant increase in pregnancy prolongation compared with magnesium sulfate, atasban, ad nivic ‘ne donors. “ABLE. ACUTE 1OCOLYSS:NFEDIPNE COMPARED WITH MAGNESIUM SULFATE, ATOSIAN, AND METRIC ONDE DONORS ww a7 Ee ams Saami 2 Ram ‘sarcnarepnt re SoscER tenant a raeemnpceapc 2 IMENDATION The effect of nifedipine in prolonging pregnancy is sual to the oflec of ther treatments (placebo, ‘Progesterone o atosban) and its use for one-term tocolsis isnot assodated wth improved perinatal ‘euteome; therefore I should not be recommondd ‘or routine practice fr this purpose uct of Evidence: gh “Serength of Recommendation: Strong JMMARY OF EVIDENCE als for Pregnancy Prolongation Below are the resus of 2 metaanaisis of ten journal ates that usted the effect of rfedipne on pregnancy prolongation As observed from "study of Pir, the longest pregnaney prolongntion among thor teates rifeipine estiated at 468 days with an estimated mean diference equ 0 dave, Half of te stuces Favor riesipine in rotonging pregnaney mean ce, MD>O], Among these 10 stuces, the highest contribution to pacled ‘iernea came from the study of valet in 2015! while te lowest luton came from the study of Pany ublsted in 2014. high percertage ) of the total valation among estimates can be attibuted to the nety of the suciee rather than chanes, On the average, the mean ‘estimates vary rom the true effect siz by as muchas 36.68 (Tu), measures imply tat ties included nthe alysis Yay in pasty many ete uch ae sampling vartion and elillrencs of the targat population. ely, hevarozenity test found that vation in mean ference was (toe signa, leading the conclusion cat he stdles included wore a, the mean premnancy prolongation amorg sifcipine weated women 26.01 days (Table 2, This wn lower than the mean pregnancy prlorgaion 2754 days obcerved ariang women wha were aven other veatman's. The Jed mean sliference was estimated to be “153, indicating tat the fancy prolongation in women tweated with awas lower than the pregnancy ration In control women. Howave, this poled men difernco wes not 3stately sgnifant f-alue-0.485),impyng thatthe effect of epi to long pregnancy was equal to the eet of ther treatments such placebo, broverteroneoratosban Table 3). “ASLE2: AVERAGE PREGHANCY PROLONGATION AB1£ 3 PooUrD MEAN DFFERENCE “The forest plot in Figur 1 istretes the affect sine of nifedhine compared to coer treatrents. teary shows thar stele ae dided in suggest Which trestment arm worked better. can be seen from the plot thatthe estimat= from the study of Roos sth closes othe etinatd tras fect sie (poste) 'Mo) and te estimate is aso precise, Hence, high weight was assigned to this study (22.42%). Pregnancy Prolongation FIGURE FOREST PLOT OF PREGNANCY PROLONGATION. the study of van Vit eta entitled “Mediine Maintenance Tocohsis ane tal Outcome: An Individual Paripent. Data Meta-Analysis si rized controlled tals (RCT) encompassing 787 patients (n=390 for pine; n=397 fr plaebo(no treatment were evaluated. The meta-analysis uses (at maintenance tocolysis Is not associated with Improved natal outcome and is therefor nt recommended for outing practice. 2 sud further notes that there was no ference between the groups in i ofthe incidence of pernatl death (sk rato, @R 1.38, 95% confidence |, 95% C1 035-533}, traventiclar haemorrhage (WH) 2 grade HR 5 95% C1 0.16-2.67), necting enterocolts (NEC [AR 1.13; 95% C1 0.80 infant respiratory distress syndrome (ROS) (RR 036; 85% Cl .1-1.85), i prolongation of prepnancy (hazard ratio, MR O74; 85% C1 0.55-1.01)") all the affect of nifedipine on the rsk of neonatal deeth (Table 4), ratory dstress syndrome Table 5) itraventriular hemorhage (Table 6) necrotizing ontrocolt (Table 7) equol othe effect of other treatment hae placebo progesterone or atosiban based on the peced cds atc (03) ‘the meta analysis of RCTs by Cand, vant" Tan" Songthmwat eisai 5ABLE 8. META.AUALYSS FOR NEONATAL DEATH "TABLES. META. NALS FOR INFANT RESPHATORY DISTRESS SNOROME Seyeaenie | To 16 {COMMENDATION The comrinaton of 1} sional cate with rifeipine and 2) Indomethacin. with ifecpine oper to be superior in the management of ‘Greatened preterm labor compared either ofthe Imedietont especialy nfedpine aloe. The ‘ombination may rerefore ba used in practice. uolty of idence: Moderate Svength of Recommendetion: Strong OF EVIDENCE the 2014 Cochrane Database Syetematc Review done by Vogtle ented bination of Tocclytc. Agents for inhbing Preterm Labour" was fomed tha" remain unclear whether using 2 combination of tocolte for inhibiting peste nbour is more advantageous for women and/or orm gen the lack of tis" Therocos use nthe various stules were evaluated ints teview were Betaimais oF magnesium slate nation with indomethacin, vaginal progesterone, hexoprenaine suet, lol and penton One study even used fenoterel plus oral rose. Nove ofthe stiles ures the mote popular toate agents such 25, lam chanel Blockers fesipine) nd indomethacin, 7