Ananth, Cande V, PhD, MPH

Hanna, Nazeeh, MD

Keeler, Sean M, MD

Kiefer, Daniel, MD

Muscat, Jolene C, MD

Peltier, Morgan R, PhD

Rust, Orion, MD

Vintzileos, Anthony M, MD

English

Lehigh Valley Health Network: LVHN Scholarly Works

Lehigh Valley Health NetworkLVHN Scholarly WorksDepartment of Obstetrics & GynecologyDoes Intra-Amniotic Inflammation InfluencePregnancy Outcome After CerclageOrprogesterone (17OHP-C) Therapy ForMidtrimester Short Cervix?Orion Rust MDLehigh Valley Health Network, Orion.Rust@lvhn.orgDaniel Kiefer MDLehigh Valley Health Network, Daniel_G.Kiefer@lvhn.orgSean M. Keeler MDLehigh Valley Health NetworkMorgan R. Peltier PhDJolene C. Muscat MDSee next page for additional authorsFollow this and additional works at: https://scholarlyworks.lvhn.org/obstetrics-gynecologyPart of the Obstetrics and Gynecology Commons, and the Therapeutics CommonsThis Poster is brought to you for free and open access by LVHN Scholarly Works. It has been accepted for inclusion in LVHN Scholarly Works by anauthorized administrator. For more information, please contact LibraryServices@lvhn.org.Published In/Presented AtRust, O., Kiefer, D., Keeler, S. M., Peltier, M. R., Muscat, J. C., Hanna, N., Vintzileos, A. M., & Ananth, C. V. (2010). Does Intra-Amniotic Inflammation Influence Pregnancy Outcome After Cerclage Orprogesterone (17OHP-C) Therapy For Midtrimester ShortCervix?. LVHN Scholarly Works. Retrieved from https://scholarlyworks.lvhn.org/obstetrics-gynecology/8AuthorsOrion Rust MD; Daniel Kiefer MD; Sean M. Keeler MD; Morgan R. Peltier PhD; Jolene C. Muscat MD;Nazeeh Hanna MD; Anthony M. Vintzileos MD; and Cande V. Ananth PhD, MPHThis poster is available at LVHN Scholarly Works: https://scholarlyworks.lvhn.org/obstetrics-gynecology/8CYTOKINE INFLAMMATORY SCORE PREDICTS PREGNANCY OUTCOME IN WOMEN WITH MIDTRIMESTER SHORT CERVIXDANIEL KIEFER, MD1, SEAN KEELER, MD2, MORGAN PELTIER, PhD3, JOLENE MUSCAT, MD1, ORION RUST, MD4, NAZEEH HANNA, MD3, ANTHONY VINTZILEOS, MD3 Abstract•	 	Many,	but	not	all,	patients	with	mid-trimester	short	cervix	(≤25mm)	have	elevated	levels	of	cytokines.	However,	most	studies	have	only	examined	one	or	two	cytokines	at	a	time.	•	 	We	propose	a	novel	amniotic	fluid	(AF)	cytokine	score	based	on	a	comprehensive	cytokine	analysis	of	patients	with	midtrimester	short	cervix.OBJECTIVE: We	propose	a	novel	amniotic	fluid	(AF)	cytokine	score	based	on	a	comprehensive	cytokine	analysis	of	patients	with	mid-trimester	short	cervix.STUDY DESIGN:AF	was	collected	from	singleton	gestations	(n=44)	with	a	cervical	length	of	≤25mm	at	16-24	weeks	gestation	and	assayed	for	25	cytokines	simultaneously	using	the	Bio-Plex™	system.	Univariate	and	regression	analyses	identified	which	mediators	were	detected	in	substantial	quantities	and	predictive	of	delivery.	The	distribution	of	the	inflammatory	score,	clinical	characteristics,	and	delivery	outcome	are	reported.RESULTS: Univariate	analysis	identified	13	cytokines	that	were	undetected	in	at	least	25%	of	patients.	Patients	were	assigned	1	point	for	each	of	these	cytokines	if	their	level	was	>2	times	the	level	of	detection.	Levels	of	IL-6,	IL-8,	G-CSF,	Interferon-γ,	MCP-1,	MIP-1β,	or	RANTES	in	the	upper	quartile	were	predictive	of	delivery.	Patients	were	assigned	1	point	for	each	of	these	cytokines	in	the	upper	quartile.	5	cytokines	were	detected	in	almost	all	patients,	but	were	not	predictive	of	delivery.	These	were	not	included	in	the	inflammatory	score.	The	inflammatory	score	ranged	from	0-20	and	was	bimodally	distributed	(Figure1).	Patients	with	a	score	<10	(n=18)	had	a	shorter	cervical	length	and	delivered	significantly	earlier	(Table	2,	P<0.001	for	each,	Wilcoxon).	A	score	≥10	had	a	77%	sensitivity,	100%	specificity,	100%PPV,	81%NPV	for	delivery	<32	weeks.CONCLUSION:A	cytokine	inflammatory	score	is	related	to	delivery	outcome	&	clinical	characteristics.	If	shown	to	be	predictive	in	future	studies,	this	score	may	aid	in	choosing	therapies	based	on	the	presence	or	absence	of	inflammation.Introduction•	 	Study	cohort:	 	 -	 	Singleton	pregnancies	 	 -	 Gestational	age	16-24	weeks	 	 -	 Transvaginal	cervical	length	of	<25mm	 	 -	 	Patients	who	received	no	surgical	or	hormonal	treatment	for	short	cervix	 	 -	 	No	known	fetal	chromosomal	or	structural	abnormality,	vaginal	bleeding,	or	ruptured	membranes	 	 -	 	Patients	underwent	amniocentesis	with	an	aliquot	frozen	for	cytokine	analysis.		Amniotic	fluid	(AF)	samples	were	simultaneously	analyzed	for	25	inflammatory	mediators	using	the	Bio-PlexTM	array	system	(Bio-Rad	Laboratories,	Hercules,	CA).	See	Table	1	for	a	listing	of	the	cytokines	utilized	in	our	analysis.•	 	For	each	cytokine,	univariate	analysis	was	used	to	examine	the	distribution,	define	the	upper	quartile,	and	determine	the	proportion	of	samples	which	had	cytokine	levels	below	the	level	of	detection	for	the	assay.•	 	The	ability	of	cytokine	levels	in	the	upper	quartile	to	predict	interval	to	delivery	(within	28	days	of	amniocentesis	and	before	34	weeks	gestation)	was	calculated	from	patients	who	delivered	near-term	for	each	cytokine	separately	using	odds	ratios.Statistical Analysis•	 	Forty-four	patients	met	eligibility	criteria.•	 	Univariate	analysis	showed	13	of	the	25	cytokines	were	below	the	level	of	detection	for	the	assay	in	at	least	25%	of	patients	(Table	1).	However,	in	some	patients,	levels	of	these	cytokines	were	comparatively	high.	Therefore,	patients	were	assigned	1	point	for	each	of	these	13	cytokines	if	their	level	was	≥2x	the	lower	limit	of	detection.•	 	There	were	seven	cytokines	(IL-6,	IL-8,	G-CSF,	Interferon-γ,	MCP-1,	MIP-1β,	or	RANTES)	that	were	detected	in	almost	all	patients,	and	levels	in	the	upper	quartile	were	predictive	of	delivery	(both	within	28	days	of	amniocentesis	and	prior	to	34	weeks’	gestation).	Patients	were	assigned	1	point	for	each	of	these	cytokines	in	the	upper	quartile.•	 	There	were	five	cytokines	(IL-1ra,	IL-7,	IL-9,	IP-10,	PDGF-bb)	that	were	detected	in	almost	all	patients,	but	were	not	predictive	of	delivery.	No	points	were	assigned	for	these	cytokines.•	 	Therefore,	the	AF	cytokine	score	could	range	from	0-20.	The	Inflammatory	Score	was	bimodally	distributed	as	shown	in	Figure	1.	Sixteen	patients	had	a	score	<10	and	18	had	a	score	≥10.•	 	An	Inflammatory	score	≥10	had:	 	 -	 	77%	sensitivity,	100%	specificity,	100%	PPV,	81%	NPV	for	delivery	<32	weeks.	 	 -	 81%	sensitivity,	96%	specificity,	94%	PPV,	85%	NPV	for	delivery	<28	weeks•	 	The	Inflammatory	score	was	inversely	related	to	cervical	length	(Figure	2)	(-0.590,	P<0.0001,	Spearman)•	 	All	patients	with	Inflammatory	Score	≥10	delivered	prior	to	30	weeks’	gestation	(Figure	3).Results•	 	An	amniotic	fluid	cytokine	inflammatory	score	is	related	to	clinical	characteristics	&	delivery	outcome.	•	 	If	shown	to	be	predictive	in	future	studies,	this	score	may	aid	in	choosing	therapies	based	on	the	degree	of	inflammation.ConclusionsMaterials and MethodsTable 2. Comparison of Clinical Characteristics by ScoreVariableLowInflammatory Score (<10) N=16HighInflammatory Score (>10) N=18P Value*Demographic Characteristics**Maternal Age (yrs) 30 (16-41) 24 (16-35) 0.11Parity 1 (0-3) 0.5 (0-2) 0.03Gestational Age at Admission (weeks)20 (17-24) 21.5 (18-24) 0.08Clinical Characteristics**Cervical Length (mm)16 (0-25) 0 (0-55) <0.0001AF Glucose 41 (22-63) 25.8 (1-40) 0.003AF WBC Count 22 (0-400) 80 (5-1400) 0.06Pregnancy Outcome***Delivery Interval(days)116 (92-129) 4 (2-14) <0.0001pPROMn (%) 4 (15.4%) 10 (55.6%) 0.007Gestational Age at Delivery (weeks) 38 (34-39) 23 (21-25) <0.0001*    Wilcoxon Rank-Sum for continuous data; Fisher’s Exact for proportions**  Data are presented as median (range)***Data are presented as median (interquartile range) or n(%)Figure 1. Distribution of AF Cytokine Inflammatory ScoreTable 1. Univariate AnalysisOdds (99.8% CI) Ratio to PredictCytokineMedian(pg/ml)Lower limit of detection (pg/ml)% of samples below level of detectionDelivery within 28 daysDelivery before 34 weeksCytokines with >25% undetected; 1 point given for each cytokine if level was >2 times the lower limit of detectionIL-1β 0.9 0.8 47.7 21.60 (1.81 - 258.13) 40.00 (2.65 - 604.53)IL-2 1.4 1.1 47.7 5.67 (0.73 - 43.99) 6.00 (0.75 - 48.15)IL-4 0.5 0.5 52.3 6.33 (0.72 - 55.96) 7.80 (0.76 - 79.72)IL-5 0.8 0.8 93.2 NE NEIL-10 1.1 0.9 45.5 17.00 (1.51 - 191.60) 15.20 (1.49 - 155.14)IL-12 1.1 0.5 27.3 17.00 (1.51 - 191.60) 15.20 (1.49 - 155.14)IL-13 2.1 2.1 86.4 6.87 (0.20 - 235.51) 5.56 (0.16 - 189.69)IL-15 6.6 4.2 27.3 12.04 (1.26 - 115.26) 11.52 (1.25 - 106.52)IL-17 0.2 0.2 61.4 70.40 (2.05 ->999.99) NEEotaxin 18.2 14.6 36.4 7.08 (0.87 - 57.45) 7.31 (0.88 - 60.56)MIP-1α 2.4 2.1 59.1 93.50 (2.56 - >999.99) NETNF-α 3.0 3.0 68.2 35.74 (1.13 - >999.99) NEVEGF 4.7 0.5 27.3 2.13 (0.29 - 15.74) 2.46 (0.32 - 19.09)Cytokines levels in upper quartaile were predictive of delivery; 1 point given for each cytokinein upper quartileIL-6 515.9 1.1 4.6 26.92 (1.76 - 411.03) 21.33 (1.78 - 255.52)IL-8 576.7 0.5 6.8 17.00 (1.51 - 191.60) 15.20 (1.49  155.14-)G-CSF 308.4 1.1 4.6 26.92 (1.76 - 411.03) 21.33 (1.78 - 255.52)INF-γ 86.6 19.3 2.3 9.00 (1.04 - 78.10) 9.71 (1.06 - 89.07)MCP-1 539.1 6.7 2.3 45.71 (1.43 - >999.99) 70.40 (2.05 - >999.99)MIP-1β 60.2 1.1 4.6 13.71 (1.27 - 48.45) 21.33 (1.78 - 255.52)RANTES 20.2 1.2 2.3 17.00 (1.51 - 191.60) .20 (1.49 - 155.14)Cytokines detected in most patients, but were not predictive of delivery; No points were given for these cytokinesIL-1ra 5414.3 1.4 4.6 3.71 (0.517 - 26.69) 6.00 (0.75 - 48.15)IL-7 3.9 0.5 13.6 2.92 ( 0.325 - 26.25) 2.27 (0.26 - 20.17)IL-9 17.1 0.7 4.6 3.71 (0.52 - 26.69) 6.00 (0.748 - 48.15)IL-10 26147.2 6.5 4.6 0.89 (0.10 - 7.670) 1.129 (0.130 - 9.78)PDGF-bb 327.9 1.0 2.3 3.05 (0.43 - 21.50) 4.98 (0.63 - 39.12)•	 	Data	from	the	above	analysis	was	used	to	determine	which	cytokines	should	be	included	in	the	AF	cytokine	score.•	 The	AF	cytokine	score	was	determined	for	each	patient.•	 	The	distribution	of	the	score,	its	relationship	to	other	clinical	characteristics,	and	its	ability	to	predict	perinatal	outcome	were	then	examined.•	 	A	P	value	<0.05	was	required	for	statistical	significance,	with	utilization	of	the	Bonferroni	correction	where	appropriate	to	control	for	simultaneous	examination	of	25	cytokines.1Stony Brook-Winthrop University Hospitals, Long Island, New York; 2Naval Medical Center Portsmouth, Portsmouth, Virginia; 3Winthrop University Hospital, Miineola, New York; 4Lehigh Valley Health Network, Allentown, PennsylvaniaFigure 2. Correlation of AF Cytokine Score with Cervical LengthFigure 3. Kaplan-Meier Pregnancy Survival Curve by Inflammatory ScoreInflammatory ScoreFrequency1 2 3 4 5 6 7 8 9 10 1211 13 14 15 16 17 18 19 20 21012345678Cervical Length (cm)InflammatoryScore000.5 1 1.5 2 2.52468101214161820Gestational Age (weeks)ProportionUndelivered15020 25 30 35 400.250.500.751.00 High Inflammatory ScoreLow Inflammatory ScoreP<0.0001

Does Intra-Amniotic Inflammation Influence Pregnancy Outcome After Cerclage Orprogesterone (17OHP-C) Therapy For Midtrimester Short Cervix?

https://scholarlyworks.lvhn.org/cgi/viewcontent.cgi?article=1007&context=obstetrics-gynecology

Does Intra-Amniotic Inflammation Influence Pregnancy Outcome After Cerclage Orprogesterone (17OHP-C) Therapy For Midtrimester Short Cervix?

Abstract

Similar works

Full text

Available Versions

Lehigh Valley Health Network: LVHN Scholarly Works