Association between periodontal indexes and biomarkers in gingival crevicular fluid and preterm birth in pregnancy: a nested case-control study

doi:10.7518/hxkq.2021.01.009

Abstract

Abstract: Objective

This study aimed to investigate the association between periodontal indexes and biomarkers in gingival crevicular fluid (GCF) and preterm birth (PTB) in pregnancy, as well as to assess the clinical value of these indexes as predictors of PTB.

Methods

A nested case-control study was conducted. A total of 300 systematically healthy pregnant women were selected within 36 weeks of gestation and grouped according to the enrolled weeks. Periodontal indexes, including probing depth (PD), bleeding index (BI), gingival index (GI), and five biomarkers in GCF, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured at the enrolled date. The detailed birth outcome was recorded.

Results

Only women at 24-28 weeks of gestation per PTB case (four full-term births) were selected as controls subjects, PTB displayed significantly greater GI, BI, and 8-OHdG (P<0.05). Logistic regression analysis revealed that BI and 8-OHdG were the dependent risk factors of PTB (OR=5.90, P=0.034; OR=1.18, P=0.045, respectively). The areas under the receiver operating characteristic curve (ROC) of BI and 8-OHdG were 0.80 and 0.69, and that of the combined detection was 0.82, which was larger than the individual detection, although the differences were not significant (P>0.05).

Conclusion

Increased BI and 8-OHdG at 24-28 weeks of gestation are risk factors for PTB. Their combined detection may have some value in the prediction of PTB, but further studies with a larger sample size are needed to explore it and thus provide experiment evidence for establishing an early warning system for PTB in pregnant women with periodontal disease.

Key words: preterm birth, periodontal index, gingival crevicular fliud, inflammatory mediators, prediction

CLC Number:

R 781.4

Ye Chanjuan, Wu Min, Chen Shaowu, Yang Xiuqiao, Li Huijun, Zhu Sujun, Zhou Fangming, Hao Ying. Association between periodontal indexes and biomarkers in gingival crevicular fluid and preterm birth in pregnancy: a nested case-control study[J]. West China Journal of Stomatology, 2021, 39(1): 58-63.

Figures/Tables 7

Tab 1

Tab 2

Tab 3

Tab 4

Tab 5

Tab 6

Fig 1

References 20

1	Gomes FI, Aragão MG, Barbosa FC, et al. Inflammatory cytokines interleukin-1β and tumour necrosis factor-α‒novel biomarkers for the detection of periodontal disea-ses: a literature review[J]. J Oral Maxillofac Res, 2016, 7(2): e2.
2	Wu M, Chen WS, Jiang SY. Relationship between gingival inflammation and pregnancy[J]. Mediators Inflamm, 2015, 2015: 623427.
3	Di Renzo GC, Tosto V, Giardina I. The biological basis and prevention of preterm birth[J]. Best Pract Res Clin Obstet Gynaecol, 2018, 52: 13-22.
4	Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis[J]. Mut Res, 1997, 387(3): 147-163.
5	Gil L, Mínguez I, Caffesse R, et al. Periodontal disease in pregnancy: the influence of general factors and inflammatory mediators[J]. Oral Health Prev Dent, 2019, 17(1): 69-73.
6	Wu M, Chen SW, Su WL, et al. Sex hormones enhance gingival inflammation without affecting IL-1β and TNF-α in periodontally healthy women during pregnancy[J]. Mediator Inflam, 2016, 2016: 4897890.
7	王家良. 临床流行病学: 临床科研设计、测量与评价[M]. 4版. 上海: 上海科学技术出版社, 2014: 210-211.
	Wang JL. Clinical epidemiology: design, measurement and evaluation of clinical research[M]. 4th ed. Shanghai: Shanghai Science and Technology Press, 2014: 210-211.
8	孟焕新. 临床牙周病学[M]. 2版. 北京: 北京大学医学出版社, 2014: 61.
	Meng HX. Clinical periodontology[M]. 2nd ed. Beijing: Peking University Medical Press, 2014: 61.
9	Bieri RA, Adriaens L, Spörri S, et al. Gingival fluid cytokine expression and subgingival bacterial counts du-ring pregnancy and postpartum: a case series[J]. Clin Oral lnvestig, 2013, 17(1): 19-28.
10	Tarannum F, Faizuddin M, Madaiah H. Gingival crevicular fluid prostaglandin E2 level as a predictor of preterm low birth weight: a pilot investigation[J]. J Oral Sci, 2011, 53(3): 293-300.
11	Loe H, Silness J. Periodontal disease in pregnancy. Ⅰ. Prevalence and severity[J]. Acta Odontol Scand, 1963, 21: 533-551.
12	Figuero E, Carrillo-de-Albornoz A, Martín C, et al. Effect of pregnancy on gingival inflammation in systemically healthy women: a systematic review[J]. J Clin Pe-riodontol, 2013, 40(5): 457-473.
13	吴敏, 陈少武, 王亚琛, 等. 妊娠妇女牙周组织的临床改变[J]. 临床口腔医学杂志, 2013, 29(5): 296-298.
	Wu M, Chen SW, Wang YC, et al. Clinical changes in periodontium during pregnancy[J]. J Clin Stomatol, 2013, 29(5): 296-298.
14	Haffajee AD, Socransky SS, Goodson JM. Comparison of different data analyses for detecting changes in attachment level[J]. J Clin Periodontol, 1983, 10(3): 298-310.
15	Chambrone L, Guglielmetti MR, Pannuti CM, et al. Evidence grade associating periodontitis to preterm birth and/or low birth weight: Ⅰ. A systematic review of prospective cohort studies[J]. J Clin Periodontol, 2011, 38(9): 795-808.
16	Martínez-Martínez RE, Moreno-Castillo DF, Loyola-Rodríguez JP, et al. Association between periodontitis, pe-riodontopathogens and preterm birth: is it real[J]. Arch Gynecol Obstet, 2016, 294(1): 47-54.
17	Moore S, Randhawa M, Ide M. A case-control study to investigate an association between adverse pregnancy outcome and periodontal disease[J]. J Clin Periodontol, 2005, 32(1): 1-5.
18	Abuelghar WM, Ellaithy MI, Swidan KH, et al. Prediction of spontaneous preterm birth: salivary progesterone assay and transvaginal cervical length assessment after 24 weeks of gestation, another critical window of opportunity[J]. J Matern Fetal Neonatal Med, 2019, 32(22): 3847-3858.
19	Zhou Z, Bian C, Luo Z, et al. Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells[J]. Sci Rep, 2019, 9(1): 8367.
20	Antczak DF. T-cell tolerance to the developing equine conceptus[J]. Reprod Domest Anim, 2012, 47(Suppl 4): 376-383.

因素	足月组（n=281）	早产组（n=19）	P值
年龄/岁	30.47±3.91	31.16±3.82	0.46
检测时孕周/周	18.97±7.05	19.16±7.24	0.91
分娩孕周/周	39.35±1.02	35.47±1.17	<0.01**
BMI/（kg·m^-2）	22.04±2.99	21.53±2.70	0.47
初产妇	198（70.5%）	14（73.7%）	0.80
职业（有）	239（85.1%）	8（42.1%）	<0.01**
学历（大专及以上）	231（82.2%）	16（84.2%）	0.54
民族（汉族）	260（92.5%）	19（100%）	0.51
医保	275（97.9%）	19（100%）	0.56
偶尔饮酒	15（5.3%）	1（5.3%）	1.00
刷牙次数≥2次·d^-1	246（87.5%）	16（84.2%）	0.13
刷牙时间>3 min	27（9.6%）	3（15.8%）	0.45
使用牙线	75（26.7%）	6（31.6%）	0.77
洁牙史	116（41.3%）	6（31.6%）	0.47
孕前牙周（牙龈出血）	140（49.8%）	8（42.1%）	0.36
孕期牙周（牙龈出血）	152（54.1%）	13（68.4%）	0.35

指标	巢式对照组（n=20）	早产组（n=5）	P值
PD/mm	2.69±0.60	2.22±0.66	0.14
PD≥4 mm位点/%	14.14±18.57	5.62±8.39	0.33
BI	2.01±0.76	1.70±0.73	0.42
GI	1.55±0.31	1.47±0.46	0.65
TNF-α/（pg·mL^-1）	10.35±2.47	12.49±2.86	0.11
IL-1β/（pg·mL^-1）	12.30±3.44	10.59±2.20	0.30
PGE2/（pg·mL^-1）	109.99±47.78	109.45±10.43	0.98
IL-6/（pg·mL^-1）	2.69±1.05	2.13±0.92	0.29
8-OHdG/（pg·mL^-1）	43.79±13.28	48.45±18.26	0.52

指标	巢式对照组（n=24）	早产组（n=6）	P值
PD/mm	2.41±0.66	2.36±0.66	0.89
PD≥4 mm位点/%	10.30±14.53	8.75±6.68	0.80
BI	1.95±0.92	1.75±0.50	0.61
GI	1.47±0.35	1.31±0.20	0.31
TNF-α/（pg·mL^-1）	10.76±2.81	9.84±1.48	0.45
IL-1β/（pg·mL^-1）	12.64±4.50	13.56±5.26	0.67
PGE2/（pg·mL^-1）	114.87±44.30	109.60±19.81	0.78
IL-6/（pg·mL^-1）	2.67±0.86	2.83±0.80	0.68
8-OHdG/（pg·mL^-1）	39.62±8.07	32.55±5.40	0.05

指标	巢式对照组（n=28）	早产组（n=7）	P值
PD/mm	2.51±0.56	2.78±0.38	0.23
PD≥4 mm位点/%	9.85±15.22	19.20±12.49	0.15
BI	1.66±0.64	2.35±0.69	0.02*
GI	1.41±0.30	1.68±0.19	0.04*
TNF-α/（pg·mL^-1）	10.61±2.34	11.28±1.91	0.49
IL-1β/（pg·mL^-1）	12.43±4.84	10.57±1.88	0.33
PGE2/（pg·mL^-1）	101.95±27.95	114.07±27.24	0.31
IL-6/（pg·mL^-1）	2.56±1.27	2.55±1.16	0.99
8-OHdG/（pg·mL^-1）	34.57±5.21	41.11±10.58	0.02*

指标	PD	BI	GI	TNF-α	IL-1β	PGE2	IL-6	8-OHdG
PD≥4 mm位点	0.86*	0.72*	0.67*	0.01	-0.002	-0.07	0.02	0.02
PD	—	0.67*	0.65*	-0.02	-0.01	-0.05	-0.04	0.004
BI		—	0.86*	0.05	0.07	-002	-0.03	0.06
GI			—	0.07	0.03	-0.03	0.002	0.10
TNF-α				—	0.20*	0.18*	0.15*	0.08
IL-1β					—	-0.03	-0.06	-0.08
PGE2						—	0.10	0.17*
IL-6							—	0.21*