Amniotic Sludge and Prematurity: Systematic Review and Meta-analysis

To perform a systematic review and meta-analysis of studies on maternal, fetal, and neonatal outcomes of women with singleton pregnancies, after spontaneous conception, and with the diagnosis of amniotic sludge before 37 weeks of gestational age.

Data Sources

We conducted a search on the PubMed, Cochrane, Bireme, and Theses databases until June 2022.

Selection of Studies

Using the keywords intra-amniotic sludge or fluid sludge or echogenic particles, we found 263 articles, 132 of which were duplicates, and 70 were discarded because they did not meet the inclusion criteria.

Data Collection

The articles retrieved were analyzed by 2 reviewers; 61 were selected for full-text analysis, 18 were included for a qualitative analysis, and 14, for a quantitative analysis.

Data Synthesis

Among the maternal outcomes analyzed, there was an increased risk of preterm labor (95% confidence interval [95%CI]: 1.45–2.03), premature rupture of ovular membranes (95%CI: 1.99–3.79), and clinical (95%CI: 1.41–6.19) and histological chorioamnionitis (95%CI: 1.75–3.12). Regarding the fetal outcomes, there was a significant increase in the risk of morbidity (95%CI: 1.80–3.17), mortality (95%CI: 1.14–18.57), admission to the Neonatal Intensive Care Unit (NICU; 95%CI: 1.17–1.95), and neonatal sepsis (95%CI: 2.29–7.55).

Conclusion

The results of the present study indicate that the presence of amniotic sludge is a risk marker for preterm delivery. Despite the heterogeneity of the studies analyzed, even in patients with other risk factors for prematurity, such as short cervix and previous preterm delivery, the presence of amniotic sludge increases the risk of premature labor. Moreover, antibiotic therapy seems to be a treatment for amniotic sludge, and it may prolong pregnancy.

Keywords
sludge; prematurity; amniotic fluid

Author, year	N sludge	N no sludge	Short cervix	Cerclage or pessary
Adanir et al., 2018¹⁶16 Adanir I, Ozyuncu O, Gokmen Karasu AF, Onderoglu LS. Amniotic fluid “sludge”; prevalence and clinical significance of it in asymptomatic patients at high risk for spontaneous preterm delivery. J Matern Fetal Neonatal Med. 2018;31(02):135–140	18	74	UR	UR
Bujold et al., 2008¹⁷17 Bujold E, Morency AM, Rallu F, Ferland S, Tétu A, Duperron L, et al. Bacteriology of amniotic fluid in women with suspected cervical insufficiency. J Obstet Gynaecol Can. 2008;30(10):882–887	14	75	UR	UR
Espinoza et al., 2005¹⁸18 Espinoza J, Gonçalves LF, Romero R, Nien JK, Stites S, Kim YM, et al. The prevalence and clinical significance of amniotic fluid ‘sludge’ in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol. 2005;25(04):346–352	19	65	UR	4/16 and 4/65
Gorski et al., 2010¹⁹19 Gorski LA, Huang WH, Iriye BK, Hancock J. Clinical implication of intra-amniotic sludge on ultrasound in patients with cervical cerclage. Ultrasound Obstet Gynecol. 2010;36(04):482–485	60	117	Part	YES
Hatanaka et al., 2014²⁰20 Hatanaka AR, Mattar R, Kawanami T, França MS, Rolo LC, Nomura RM, et al. Clinical significance of the presence of amniotic fluid’-sludge'in asymptomatic patients at low and high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2014;44 (S1):16–6	49	146	Part	UR
Himaya et al., 2011²¹21 Himaya E, Rhalmi N, Girard M, Tétu A, Desgagné J, Abdous B, et al. Midtrimester intra-amniotic sludge and the risk of spontaneous preterm birth. Am J Perinatol. 2011;28(10):815–820	16	200	Part	UR
Huang et al., 2022²²22 Huang Y, Liang X, Liao J, Li Y, Chen Z. Relationship of Amniotic Fluid Sludge and Short Cervix With a High Rate of Preterm Birth in Women After Cervical Cerclage. J Ultrasound Med. 2022;41(11): 2687–2693. Doi: 10.1002/jum.15952 https://doi.org/10.1002/jum.15952...	45	251	Part	YES
Kovavisarach and Jongfuangprinya, 2019²³23 Kovavisarach E, Jongfuangprinya K. Prevalence of Amniotic Fluid Sludge in Low-Risk Pregnant Women of Preterm Delivery. J Med Assoc Thai. 2019;102(05):4–0	72	258	Part	NO
Kusanovic et al., 2007²⁴24 Kusanovic JP, Espinoza J, Romero R, Gonçalves LF, Nien JK, Soto E, et al. Clinical significance of the presence of amniotic fluid ‘sludge’ in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2007;30(05):706–714	66	215	Part	28/215 and 21/66
Saade et al., 2018²⁵25 Saade GR, Thom EA, Grobman WA, Iams JD, Mercer BM, Reddy UM, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30. mm. Ultrasound Obstet Gynecol. 2018;52 (06):757–762	78	579	YES	UR
Ting et al., 2012²⁶26 Ting YH, Lao TT, Law LW, Hui SYA, Chor CM, Lau TK, Leung TY. Arabin cerclage pessary in the management of cervical insufficiency. J Matern Fetal Neonatal Med. 2012;25(12): 2693–2695	5	15	YES	YES
Tsunoda et al., 2020²⁷27 Tsunoda Y, Fukami T, Yoneyama K, Kawabata I, Takeshita T. The presence of amniotic fluid sludge in pregnant women with a short cervix: an independent risk of preterm delivery. J Matern Fetal Neonatal Med. 2020;33(06):920–923	29	81	YES	6/29 and 10/81
Vaisbuch et al., 2010²⁸28 Vaisbuch E, Hassan SS, Mazaki-Tovi S, Nhan-Chang CL, Kusanovic JP, Chaiworapongsa T, et al. Patients with an asymptomatic short cervix (<or=15. mm) have a high rate of subclinical intraamniotic inflammation: implications for patient counseling. Am J Obstet Gynecol. 2010;202(05):433.e1–433.e8	64	45	YES	UR
Yasuda et al., 2020²⁹29 Yasuda S, Tanaka M, Kyozuka H, Suzuki S, Yamaguchi A, Nomura Y, Fujimori K. Association of amniotic fluid sludge with preterm labor and histologic chorioamnionitis in pregnant Japanese women with intact membranes: A retrospective study. J Obstet Gynaecol Res. 2020;46(01):87–92	11	43	UR	UR

Author, year	VB sludge	VB no sludge	S sludge	S no sludge	HPTD sludge	HPTD no sludge
Adanir et al., 2018¹⁶16 Adanir I, Ozyuncu O, Gokmen Karasu AF, Onderoglu LS. Amniotic fluid “sludge”; prevalence and clinical significance of it in asymptomatic patients at high risk for spontaneous preterm delivery. J Matern Fetal Neonatal Med. 2018;31(02):135–140	9\18	16/74	UR	UR	YES	YES
Bujold et al., 2008¹⁷17 Bujold E, Morency AM, Rallu F, Ferland S, Tétu A, Duperron L, et al. Bacteriology of amniotic fluid in women with suspected cervical insufficiency. J Obstet Gynaecol Can. 2008;30(10):882–887	UR	UR	UR	UR	4/14	20/75
Espinoza et al., 2005¹⁸18 Espinoza J, Gonçalves LF, Romero R, Nien JK, Stites S, Kim YM, et al. The prevalence and clinical significance of amniotic fluid ‘sludge’ in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol. 2005;25(04):346–352	6\19	3\65	UR	UR	3\19	21/65
Gorski et al., 2010¹⁹19 Gorski LA, Huang WH, Iriye BK, Hancock J. Clinical implication of intra-amniotic sludge on ultrasound in patients with cervical cerclage. Ultrasound Obstet Gynecol. 2010;36(04):482–485	10\60	19\117	5\60	8\117	18/60	34/117
Hatanaka et al., 2014²⁰20 Hatanaka AR, Mattar R, Kawanami T, França MS, Rolo LC, Nomura RM, et al. Clinical significance of the presence of amniotic fluid’-sludge'in asymptomatic patients at low and high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2014;44 (S1):16–6	UR	UR	UR	UR	UR	UR
Himaya et al., 2011²¹21 Himaya E, Rhalmi N, Girard M, Tétu A, Desgagné J, Abdous B, et al. Midtrimester intra-amniotic sludge and the risk of spontaneous preterm birth. Am J Perinatol. 2011;28(10):815–820	UR	UR	UR	UR	3\16	13/200
Huang et al., 2022²²22 Huang Y, Liang X, Liao J, Li Y, Chen Z. Relationship of Amniotic Fluid Sludge and Short Cervix With a High Rate of Preterm Birth in Women After Cervical Cerclage. J Ultrasound Med. 2022;41(11): 2687–2693. Doi: 10.1002/jum.15952 https://doi.org/10.1002/jum.15952...	UR	UR	UR	UR	7\45	40/251
Kovavisarach and Jongfuangprinya, 2019²³23 Kovavisarach E, Jongfuangprinya K. Prevalence of Amniotic Fluid Sludge in Low-Risk Pregnant Women of Preterm Delivery. J Med Assoc Thai. 2019;102(05):4–0	UR	UR	UR	UR	UR	UR
Kusanovic et al., 2007²⁴24 Kusanovic JP, Espinoza J, Romero R, Gonçalves LF, Nien JK, Soto E, et al. Clinical significance of the presence of amniotic fluid ‘sludge’ in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2007;30(05):706–714	16/66	25/215	10/57	43/192	21/66	74/215
Saade et al., 2018²⁵25 Saade GR, Thom EA, Grobman WA, Iams JD, Mercer BM, Reddy UM, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30. mm. Ultrasound Obstet Gynecol. 2018;52 (06):757–762	UR	UR	UR	UR	UR	UR
Ting et al., 2012²⁶26 Ting YH, Lao TT, Law LW, Hui SYA, Chor CM, Lau TK, Leung TY. Arabin cerclage pessary in the management of cervical insufficiency. J Matern Fetal Neonatal Med. 2012;25(12): 2693–2695	UR	UR	UR	UR	UR	UR
Tsunoda et al., 2020²⁷27 Tsunoda Y, Fukami T, Yoneyama K, Kawabata I, Takeshita T. The presence of amniotic fluid sludge in pregnant women with a short cervix: an independent risk of preterm delivery. J Matern Fetal Neonatal Med. 2020;33(06):920–923	3\29	2\81	0/29	0/81	7\29	10\81
Vaisbuch et al., 2010²⁸28 Vaisbuch E, Hassan SS, Mazaki-Tovi S, Nhan-Chang CL, Kusanovic JP, Chaiworapongsa T, et al. Patients with an asymptomatic short cervix (<or=15. mm) have a high rate of subclinical intraamniotic inflammation: implications for patient counseling. Am J Obstet Gynecol. 2010;202(05):433.e1–433.e8	UR	UR	UR	UR	UR	UR
Yasuda et al., 2020²⁹29 Yasuda S, Tanaka M, Kyozuka H, Suzuki S, Yamaguchi A, Nomura Y, Fujimori K. Association of amniotic fluid sludge with preterm labor and histologic chorioamnionitis in pregnant Japanese women with intact membranes: A retrospective study. J Obstet Gynaecol Res. 2020;46(01):87–92	UR	UR	1\11	0\43	3/11	5/43

Author, year	N sludge + ATB	N no sludge	Antibiotic scheme	Outcome
Cuff et al., 2020³⁰30 Cuff RD, Carter E, Taam R, Bruner E, Patwardhan S, Newman RB, et al. Effect of Antibiotic Treatment of Amniotic Fluid Sludge. Am J Obstet Gynecol MFM. 2020;2(01):100073–3	46	51	Azithromycin OA + moxifloxacin OA	There was no reduction in the incidence of PTD
Hatanaka et al., 2019³¹31 Hatanaka AR, Franca MS, Hamamoto TENK, Rolo LC, Mattar R, Moron AF. Antibiotic treatment for patients with amniotic fluid “sludge” to prevent spontaneous preterm birth: A historically controlled observational study. Acta Obstet Gynecol Scand. 2019; 98(09):1157–1163	64	0	Clindamycin OA + cephalexin OA, clindamycin IV + cefazolin IV	Reduction in the incidence of PTD
Hu Jin et al., 2021³²32 Jin WH, Ha Kim Y, Kim JW, Kim TY, Kim A, Yang Y. Antibiotic treatment of amniotic fluid “sludge” in patients during the second or third trimester with uterine contraction. Int J Gynaecol Obstet. 2021;153(01):119–124	58	0	Ceftriaxone IV + clarithromycin OA + metronidazole IV	Reduction in the incidence of PTD and neonatal complications
Pustotina, 2020³³33 Pustotina O. Effects of antibiotic therapy in women with the amniotic fluid “sludge” at 15-24 weeks of gestation on pregnancy outcomes. J Matern Fetal Neonatal Med. 2020;33(17):3016–3027	14	47	Clindamycin VA, butoconazole VA, cefoperazone + sulbactam IV, amoxicillin + clavulonate OA	Reduction in the incidence of PTD, intrauterine and amniotic infection

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[1] Address for correspondence Gabriel Duque Pannain, Resident physician, Federal University of Juiz de Fora, Minas Gerais, MG, Brazil (e-mail: gabrielduquep@gmail.com).