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. Author manuscript; available in PMC: 2012 Nov 13.
Published in final edited form as: J Perinat Med. 2011 Jan 26;39(2):131–136. doi: 10.1515/JPM.2010.168

CLINICAL SIGNIFICANCE OF OLIGOHYDRAMNIOS IN PATIENTS WITH PRETERM LABOR AND INTACT MEMBRANES

Byoung Jae KIM 1,2, Roberto ROMERO 3, Seung Mi LEE 1,4, Chan-Wook Park 1,4, Joong Shin PARK 1,4, Jong Kwan JUN 1,4, Bo Hyun YOON 1,4
PMCID: PMC3496379  NIHMSID: NIHMS419507  PMID: 21265728

Abstract

OBJECTIVE

To determine the frequency and clinical significance of oligohydramnios in patients with preterm labor and intact membranes.

STUDY DESIGN

An amniotic fluid index (AFI) was determined before amniocentesis (<24hrs) in 272 patients with preterm labor and intact membranes (<35 weeks of gestation). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and assayed for matrix metalloproteinase-8 (MMP-8). Nonparametric statistical techniques and survival analysis were used.

RESULTS

1) The overall prevalence of oligohydramnios (AFI of ≤5cm) in patients with preterm labor and intact membranes was 2.6% (7/272); 2) patients with oligohydramnios had a higher frequency of AF infection and/or inflammation than those without oligohydramnios (85.7% [6/7] vs. 32.8% [87/265]; p<.01); 3) Patients with oligohydramnios had a higher median AF MMP-8 concentration than those without oligohydramnios (median 664.2 [range 16.6 – 3424.7] ng/ml vs. median 2.3 [range <0.3 – 6142.6] ng/ml; p<.01); 4) women with preterm labor and oligohydramnios had a shorter interval to delivery than those without oligohydramnios (median 18 hrs [range 0-74 hrs] vs. median 311 hrs [range 0-3228 hrs]; p<.01), and this difference remained significant after adjusting for gestational age and the presence or absence of AF infection/inflammation

CONCLUSION

Patients with preterm labor and oligohydramnios are at increased risk for impending preterm delivery and intra-amniotic inflammation and, therefore, may benefit from careful surveillance.

Keywords: amniocentesis-to-delivery interval, intra-amniotic inflammation, oligohydramnios, prematurity, preterm labor

Introduction

Ultrasound examination is a part of the routine assessment of patients admitted with the diagnosis of preterm labor with intact membranes. The clinical significance of a reduced volume of amniotic fluid (AF) in this specific setting is unknown. Such a finding has prognostic significance in patients with preterm premature rupture of membranes (PROM) [1, 11, 20, 25, 30, 36, 46, 50-51]. The objective of the study was to determine the frequency and clinical significance of oligohydramnios in patients with preterm labor and intact membranes.

Material and methods

Study design

The study population consisted of consecutive patients admitted to Seoul National University Hospital between January 1993 and June 2006 with the diagnosis of preterm labor and intact membranes (<35 weeks of gestation) and singleton gestation who underwent amniocentesis and measurement of amniotic fluid index (AFI) within 24 hours before amniocentesis. Preterm labor was diagnosed as the presence of regular uterine contractions (four or more contractions in 20 minutes or eight or more in 60 minutes). Amniocentesis is routinely offered to all patients who are admitted with the diagnosis of preterm labor at our institution. Amniocentesis was perfomed after written informed consent was obtained. Intra-amniotic inflammation was defined as an elevated AF MMP-8 concentration (>23 ng/ml) as previously reported [35, 45]. The institutional review board of the participating institution approved the collection of biologic materials and data from these patients for research purposes.

AFI and amniocentesis

The AFI was determined according to the method described by Phelan et al [40]. AF was retrieved by transabdominal amniocentesis and was cultured for aerobic and anaerobic bacteria and genital mycoplasmas (ureaplasmas and Mycoplasma hominis). The results of amniotic fluid culture, white blood cell (WBC) count and lung maturity test were used for patient management. For example, in some patients with a positive lung maturity and an increased amniotic fluid WBC count, delivery was performed, and these patients had their amniocentesis-to-delivery interval treated as a censored observation and survival technique was used for the analysis. Fluid that was not used for diagnostic studies was centrifuged and stored at −70°C until assayed. MMP-8 concentrations were measured with a commercially available enzyme-linked immunosorbent assay (Amersham Pharmacia Biotech, Inc, Bucks, UK). The sensitivity of the test was 0.3 ng/mL. Intra- and interassay coefficients of variation were 3.1% and 9.5%, respectively.

Diagnosis of chorioamnionitis and small for gestational age (SGA) infant

Clinical chorioamnionitis was defined according to the criteria proposed by Gibbs et al [9]. The diagnosis required a temperature elevation to 37.8°C and two or more of the following criteria: uterine tenderness, malodorous vaginal discharge, maternal tachycardia, fetal tachycardia, and leukocytosis. Leukocytosis was defined as a white blood cell count >15,000/mm3. Histologic chorioamnionitis was defined as the presence of acute inflammatory changes in any tissue samples (amnion, choriondecidua, umbilical cord, and chorionic plate) of extraplacental membranes [55]. Small for gestational age (SGA) infants were classified as those whose weights were below the 10th percentile for their gestational age [37].

Statistical analysis

Univariate analysis was performed with the Mann-Whitney U test, the student t test, or the Fisher’s exact test. The amniocentesis-to-delivery intervals were compared by generalized Wilcoxon test for survival analysis. Patients delivered for maternal or fetal indications were treated as censored observations, with a censoring time equal to the amniocentesis-to-delivery interval. Cox proportional hazards model analysis was used to examine the relationship between AFI and amniocentesis interval after the adjustment for covariates.

Results

Amniocentesis was performed in 311 patients with preterm labor and intact membranes during the study period. Thirty seven patients with no available amniotic fluid index (AFI) within 24 hours before amniocentesis were excluded. Two patients with negative AF cultures and no available AF for MMP-8 determination were excluded from the further analysis, because they could not be evaluated with respect to the presence or absence of intra-amniotic inflammation. Two hundred seventy-two patients were eligible for study.

The prevalence of oligohydramnios (AFI of ≤5 cm) was 2.6% (7/272). The prevalence of positive AF culture was 8.1% (22/272). Three patients had polymicrobial infections with 2 species of micro-organisms and Ureaplasma urealyticum was isolated in two of them. Microorganisms isolated from the AF included Ureaplasma urealyticum (n=10), Lactobacillus species (n=2), Acinatobacter species (n=2), Streptococcus anginosus (n=2), and one isolate each of Candida species, Porphynomonas, Staphylococcus aureus, Enterococcus faecium, Enterococcus faecali, Pseudomonas aeruginosa, Burkholderia cepalia, Mycoplasma hominis, and Streptococcus viridans. The AF MMP-8 concentration of the patient with a positive AF culture for Staphylococcus aureus, which is commonly considered as a skin contaminant, was 142.6 ng/ml.

Table 1 compares the clinical characteristics and outcomes of the study population according to the AFI. The frequency of intra-amniotic inflammation was higher in patients with an AFI of ≤5 cm than those with an AFI of >5 cm (86% [6/7] vs. 30% [80/265]; p<.01). Patients with oligohydramnios had a significantly higher median AF MMP-8 (median 664.2 [range 16.6 – 3424.7] ng/ml vs. median 2.3 [range <0.3 – 6142.6] ng/ml; p<.01, Figure 1) and a lower median gestational age at birth and mean birth weight than those without oligohydramnios. There were no significant differences in the median gestational age at amniocentesis and rates of SGA, umbilical artery cord blood pH<7.15 and Apgar score <7 (1-min and 5-min) between the two groups of patients (p>.1).

Table 1.

Characteristics of patients and pregnancy outcomes according to amniotic volume

AFI
greater than 5 cm
(n=265)		 AFI
less than 5 cm
(n=7)		 P
Age (y, mean±SD) 30.2 ± 4.2 33.9 ± 6.0 NS
Nulliparous (No.) 125 (47%) 4 (57%) NS
Gestational age at amniocentesis (wk, median and range) 31.3 (16.1-34.9) 30.3 (21.3-33.9) NS
Positive AF culture results (No.) 21 (8%) 1 (14%) NS
AF MMP-8 > 23 ng/mL (No.) 80 (30%) 6 (86%) <.01
Positive AF culture and/or AF MMP-8>23 ng/ml (No.) 87 (33%) 6 (86%) <.01
Clinical chorioamnionitis (No.) 15 (6%) 1 (14%) NS
Histologic chorioamnionitis (No.) 78/182 (43%) 2/5 (40%) NS
Gestational age at delivery (wk, median and range) 34.3 (16.6-41.7) 30.4 (21.4-33.9) <.05
Birth weight (g, mean±SD) 2138 ± 940 1356 ± 690 <.05
Small for gestational age (No.) 15 (6%) 1 (14%) NS
Cord blood pH<7.15 20/207 (10%) 0/4 (0%) NS
Cord blood pH (median and range) 7.270
(6.854-7.454)		 7.295
(7.220-7.389)		 NS
1-min Apgar score<7 99 (37%) 5 (71%) NS
5-min Apgar score<7 67 (25%) 3 (43%) NS
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AFI, amniotic fluid index; AF, amniotic fluid; MMP-8, matrix metalloproteinase-8; NS, Not significant

Figure 1. Amniotic fluid matrix metalloproteinase-8 (MMP-8) concentrations according to amniotic fluid volume in patients with preterm labor and intact membranes.

Figure 1

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Patients with oligohydramnios had a significantly higher median amniotic fluid MMP-8 than those with normal amniotic volume (median 664.2 [range 16.6 – 3424.7] ng/ml vs. median 2.3 [range <0.3 – 6142.6] ng/ml; p<.01).

AFI, amniotic fluid index

Women with preterm labor and oligohydramnios had a shorter interval to delivery than those without oligohydramnios (amniocentesis-to-delivery interval: median, 18 hrs [range 0-74 hrs] vs. median, 311 hrs [range 0-3228 hrs]; p<.01, Figure 2). Thirty six patients were delivered for maternal or fetal indications [term/near term or fetal lung maturation (n=17), preeclampsia (n=3), maternal disease (n=3), suspicious fetal distress (n=5), vaginal bleeding (n=5), and others (n=3)]; these patients were treated as censored observations, with a censoring time equal to the amniocentesis-to-delivery interval. Multivariate survival analysis indicated that oligohydramnios was an independent predictor of the duration of the pregnancy after adjusting for gestational age and the presence or absence of AF infection and/or intra-amniotic inflammation (hazards ratio, 2.7; 95% confidence interval, 1.2-5.8).

Figure 2. Survival analysis of amniocentesis-to-delivery interval according to amniotic fluid volume in patients with preterm labor and intact membranes.

Figure 2

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Amniocentesis-to-delivery interval was significantly shorter in patients with oligohydramnios (solid line) than in those with normal amniotic fluid volume (open circles) (median, 18 hours; range, 0-74hours; vs. median, 311 hours; range, 0-3228 hours; P<.01).

AFI, amniotic fluid index

Table 2 shows the characteristics of the seven cases with oligohydramnios. Spontaneous or artificial ROM was subsequently confirmed after the ultrasonography/amniocentesis during hospital course in all 4 cases that were delivered vaginally.

Table 2.

Clinical information of patients with oligohydramnios

Patients
No		 GA at
amnioce
ntesis		 GA at
delivery		 Mode of
Delivery		 AF culture AF MMP-8
(ng/mL)		 Remarks
1 32.7 32.9 VD (−) 16.6 Spontaneous ROM after USG
2 33.9 33.9 VD (−) 119.6 Artificial ROM during labor
3 28.3 28.4 CS (+) 1535.9 Cesarean section due to fetal distress
4 30.3 30.4 CS (−) 75.6 Cesarean section due to placental abruption
5 33.6 33.6 CS NA 664.2 Cesarean section due to fetal distress
6 21.3 21.4 VD (−) 1773 Spontaneous ROM after USG
7 27.4 27.9 VD (−) 3424.7 Spontaneous ROM after USG
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GA, gestational age; VD, vaginal delivery; CS, Cesarean section; NA, not available; AF, amniotic fluid; MMP-8, matrix metalloproteinase-8; ROM, rupture of membranes; USG, ultrasonography

Discussion

Principal findings of this study

1) The frequency of oligohydramnios (AFI ≤5 cm) was 2.6% (7/272) among patients who had preterm labor and intact membranes; and 2) patients with a reduced volume of AF had a higher frequency of intra-amniotic inflammation and a shorter amniocentesis-to-delivery interval than those with an AFI of >5 cm.

Previous observations about the clinical significance of a reduced volume of AF in patients at risk for preterm delivery

The findings described herein are consistent with those previously reported in patients with preterm PROM in which oligohydramnios was found to be a risk factor for proven AF infection, intra-amniotic inflammation, and a short amniocentesis-to-delivery interval [11, 20, 25, 30, 36, 46, 50-51]. Moreover, patients with a reduced AF volume had a higher AF concentration of interleukin-6, tumor necrosis factor alpha and interleukin-1 beta than those with an AFI of > 5 cm [54]. In addition, the umbilical cord concentrations of interleukin-6 were higher in patients with a reduced volume of AF than in those without oligohydramnios [54].

Why is a reduced volume of AF associated with intra-amniotic inflammation and a short interval to delivery?

AF has antimicrobial properties [3, 8, 17, 44] and this may be part of the innate immune system. A reduced volume of AF may decrease the natural host defense conferred by this fluid and predispose toward intrauterine infection. Alternatively, intra-amniotic inflammation may lead to oligohydramnios. In the case of preterm PROM, we have proposed that microbial invasion of the amniotic cavity, fetal infection and the development of the fetal inflammatory response syndrome may lead to redistribution of blood flow away from the fetal kidney, decreased fetal urinary output and oligohydramnios [10, 36, 54]. This may apply to patients with preterm labor and intact membranes. However, it is noteworthy that the amniocentesis-to-delivery interval was shorter even after adjusting for the presence or absence of AF infection and/or intra-amniotic inflammation. This suggests that another mechanism may be operative. We explored whether the frequency of SGA was a potential explanation but found no difference in the rate of this complication between patients with an AFI of >5 cm and those with an AFI of ≤5 cm.

Strength and limitations of this study

The strength of our study is that it included a consecutively collected large cohort of patients with preterm labor and intact membranes delivered at the institution allowing for near complete ascertainment of outcome data. Thus, the results of this study are more applicable in this specific clinical condition. A limitation is that in contrast to studies of preterm PROM, the interval between amniocentesis and delivery of most patients was long, limiting the meaningful relationship between placental pathology, umbilical cord analysis and the findings of amniocentesis.

Clinical Implications

Patients with preterm labor and intact membranes and an AFI of ≤5 cm are at increased risk for intra-amniotic inflammation and shorter amniocentesis-to-delivery intervals. Thus, this information can be used for counseling patients about their risk for delivery and the need to assess the AF for inflammation. Previous studies have reported that intra-amniotic inflammation is associated with preterm labor[4-7, 12-13, 15, 18-19, 21-24, 27-29, 31-34, 38, 41-43, 47-49] and is a risk factor for adverse outcome [2, 14, 16, 26, 39, 45, 52-53, 56-57].

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2006-005425) and, in part, by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH.

Footnotes

This study was presented at the 27th Annual Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA (February 8, 2007).

References

  • [1].Ananth CV, Oyelese Y, Srinivas N, Yeo L, Vintzileos AM. Preterm premature rupture of membranes, intrauterine infection, and oligohydramnios: risk factors for placental abruption. Obstet Gynecol. 2004;104:71–7. doi: 10.1097/01.AOG.0000128172.71408.a0. [DOI] [PubMed] [Google Scholar]
  • [2].Baud O, Emilie D, Pelletier E, Lacaze-Masmonteil T, Zupan V, Fernandez H, et al. Amniotic fluid concentrations of interleukin-1beta, interleukin-6 and TNF-alpha in chorioamnionitis before 32 weeks of gestation: histological associations and neonatal outcome. Br J Obstet Gynaecol. 1999;106:72–7. doi: 10.1111/j.1471-0528.1999.tb08088.x. [DOI] [PubMed] [Google Scholar]
  • [3].Bergman N, Bercovici B, Sacks T. Antibacterial activity of human amniotic fluid. Am J Obstet Gynecol. 1972;114:520–3. doi: 10.1016/0002-9378(72)90214-1. [DOI] [PubMed] [Google Scholar]
  • [4].Bujold E, Romero R, Kusanovic JP, Erez O, Gotsch F, Chaiworapongsa T, et al. Proteomic profiling of amniotic fluid in preterm labor using two-dimensional liquid separation and mass spectrometry. J Matern Fetal Neonatal Med. 2008;21:697–713. doi: 10.1080/14767050802053289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [5].Chaiworapongsa T, Erez O, Kusanovic JP, Vaisbuch E, Mazaki-Tovi S, Gotsch F, et al. Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition. J Matern Fetal Neonatal Med. 2008;21:449–61. doi: 10.1080/14767050802054550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Cruciani L, Romero R, Vaisbuch E, Kusanovic JP, Chaiworapongsa T, Mazaki-Tovi S, et al. Pentraxin 3 in amniotic fluid: a novel association with intra-amniotic infection and inflammation. J Perinat Med. 2009 doi: 10.1515/JPM.2009.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Erez O, Romero R, Tarca AL, Chaiworapongsa T, Kim YM, Than NG, et al. Differential expression pattern of genes encoding for anti-microbial peptides in the fetal membranes of patients with spontaneous preterm labor and intact membranes and those with preterm prelabor rupture of the membranes. J Matern Fetal Neonatal Med. 2009;22:1103–15. doi: 10.3109/14767050902994796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Galask RP, Snyder IS. Antimicrobial factors in amniotic fluid. Am J Obstet Gynecol. 1970;106:59–65. doi: 10.1016/0002-9378(70)90126-2. [DOI] [PubMed] [Google Scholar]
  • [9].Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis. 1982;145:1–8. doi: 10.1093/infdis/145.1.1. [DOI] [PubMed] [Google Scholar]
  • [10].Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol. 1998;179:194–202. doi: 10.1016/s0002-9378(98)70272-8. [DOI] [PubMed] [Google Scholar]
  • [11].Gonik B, Bottoms SF, Cotton DB. Amniotic fluid volume as a risk factor in preterm premature rupture of the membranes. Obstet Gynecol. 1985;65:456–9. [PubMed] [Google Scholar]
  • [12].Gotsch F, Romero R, Chaiworapongsa T, Erez O, Vaisbuch E, Espinoza J, et al. Evidence of the involvement of caspase-1 under physiologic and pathologic cellular stress during human pregnancy: a link between the inflammasome and parturition. J Matern Fetal Neonatal Med. 2008;21:605–16. doi: 10.1080/14767050802212109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13].Gotsch F, Romero R, Kusanovic JP, Erez O, Espinoza J, Kim CJ, et al. The anti-inflammatory limb of the immune response in preterm labor, intra-amniotic infection/inflammation, and spontaneous parturition at term: a role for interleukin-10. J Matern Fetal Neonatal Med. 2008;21:529–47. doi: 10.1080/14767050802127349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Greci LS, Gilson GJ, Nevils B, Izquierdo LA, Qualls CR, Curet LB. Is amniotic fluid analysis the key to preterm labor? A model using interleukin-6 for predicting rapid delivery. Am J Obstet Gynecol. 1998;179:172–8. doi: 10.1016/s0002-9378(98)70269-8. [DOI] [PubMed] [Google Scholar]
  • [15].Hamill N, Romero R, Gotsch F, Kusanovic JP, Edwin S, Erez O, et al. Exodus-1 (CCL20): evidence for the participation of this chemokine in spontaneous labor at term, preterm labor, and intrauterine infection. J Perinat Med. 2008;36:217–27. doi: 10.1515/JPM.2008.034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16].Hitti J, Krohn MA, Patton DL, Tarczy-Hornoch P, Hillier SL, Cassen EM, et al. Amniotic fluid tumor necrosis factor-alpha and the risk of respiratory distress syndrome among preterm infants. Am J Obstet Gynecol. 1997;177:50–6. doi: 10.1016/s0002-9378(97)70437-x. [DOI] [PubMed] [Google Scholar]
  • [17].Ismail MA, Salti GI, Block BS, Moawad AH. The effect of filtration of amniotic fluid on the growth of Chlamydia trachomatis and Escherichia coli. Am J Perinatol. 1991;8:50–2. doi: 10.1055/s-2007-999341. [DOI] [PubMed] [Google Scholar]
  • [18].Kim SK, Romero R, Chaiworapongsa T, Pedro Kusanovic J, Mazaki-Tovi S, Mittal P, et al. Evidence of changes in the immunophenotype and metabolic characteristics (intracellular reactive oxygen radicals) of fetal, but not maternal, monocytes and granulocytes in the fetal inflammatory response syndrome. J Perinat Med. 2009;37:543–52. doi: 10.1515/JPM.2009.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Kusanovic JP, Romero R, Mazaki-Tovi S, Chaiworapongsa T, Mittal P, Gotsch F, et al. Resistin in amniotic fluid and its association with intra-amniotic infection and inflammation. J Matern Fetal Neonatal Med. 2008;21:902–16. doi: 10.1080/14767050802320357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Lao TT, Cheung VY. Expectant management of preterm prelabour rupture of membranes--the significance of oligohydramnios at presentation. Eur J Obstet Gynecol Reprod Biol. 1993;48:87–91. doi: 10.1016/0028-2243(93)90245-8. [DOI] [PubMed] [Google Scholar]
  • [21].Lee J, Seong HS, Kim BJ, Jun JK, Romero R, Yoon BH. Evidence to support that spontaneous preterm labor is adaptive in nature: neonatal RDS is more common in “indicated” than in “spontaneous” preterm birth. J Perinat Med. 2009;37:53–8. doi: 10.1515/JPM.2009.036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Lee SE, Han BD, Park IS, Romero R, Yoon BH. Evidence supporting proteolytic cleavage of insulin-like growth factor binding protein-1 (IGFBP-1) protein in amniotic fluid. J Perinat Med. 2008;36:316–23. doi: 10.1515/JPM.2008.067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Lee SE, Park IS, Romero R, Yoon BH. Amniotic fluid prostaglandin F2 increases even in sterile amniotic fluid and is an independent predictor of impending delivery in preterm premature rupture of membranes. J Matern Fetal Neonatal Med. 2009;22:880–6. doi: 10.1080/14767050902994648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [24].Lee SE, Romero R, Kim EC, Yoon BH. A high Nugent score but not a positive culture for genital mycoplasmas is a risk factor for spontaneous preterm birth. J Matern Fetal Neonatal Med. 2009;22:212–7. doi: 10.1080/14767050802616994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25].MacMillan WE, Mann SE, Shmoys SM, Saltzman DH. Amniotic fluid index as a predictor of latency after preterm premature rupture of the membranes. Am J Perinatol. 1994;11:249–52. doi: 10.1055/s-2007-994584. [DOI] [PubMed] [Google Scholar]
  • [26].Martinez E, Figueroa R, Garry D, Visintainer P, Patel K, Verma U, et al. Elevated Amniotic Fluid Interleukin-6 as a Predictor of Neonatal Periventricular Leukomalacia and Intraventricular Hemorrhage. Journal of Maternal-Fetal Investigation. 1998;8:101–107. [PubMed] [Google Scholar]
  • [27].Mazaki-Tovi S, Romero R, Kusanovic JP, Erez O, Gotsch F, Mittal P, et al. Visfatin/Pre-B cell colony-enhancing factor in amniotic fluid in normal pregnancy, spontaneous labor at term, preterm labor and prelabor rupture of membranes: an association with subclinical intrauterine infection in preterm parturition. J Perinat Med. 2008;36:485–96. doi: 10.1515/JPM.2008.084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28].Mazaki-Tovi S, Romero R, Vaisbuch E, Erez O, Mittal P, Chaiworapongsa T, et al. Dysregulation of maternal serum adiponectin in preterm labor. J Matern Fetal Neonatal Med. 2009;22:887–904. doi: 10.1080/14767050902994655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [29].Mazaki-Tovi S, Romero R, Vaisbuch E, Kusanovic JP, Erez O, Mittal P, et al. Adiponectin in amniotic fluid in normal pregnancy, spontaneous labor at term, and preterm labor: A novel association with intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2009:1–11. doi: 10.3109/14767050903026481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Mercer BM, Rabello YA, Thurnau GR, Miodovnik M, Goldenberg RL, Das AF, et al. The NICHD-MFMU antibiotic treatment of preterm PROM study: impact of initial amniotic fluid volume on pregnancy outcome. Am J Obstet Gynecol. 2006;194:438–45. doi: 10.1016/j.ajog.2005.07.097. [DOI] [PubMed] [Google Scholar]
  • [31].Murphy SP, Hanna NN, Fast LD, Shaw SK, Berg G, Padbury JF, et al. Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery. Am J Obstet Gynecol. 2009;200:308, e1–9. doi: 10.1016/j.ajog.2008.10.043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [32].Nhan-Chang CL, Romero R, Kusanovic JP, Gotsch F, Edwin SS, Erez O, et al. A role for CXCL13 (BCA-1) in pregnancy and intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2008;21:763–75. doi: 10.1080/14767050802244946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [33].Pacora P, Romero R, Chaiworapongsa T, Kusanovic JP, Erez O, Vaisbuch E, et al. Amniotic fluid angiopoietin-2 in term and preterm parturition, and intra-amniotic infection/inflammation. J Perinat Med. 2009;37:503–11. doi: 10.1515/JPM.2009.093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [34].Park CW, Lee SM, Park JS, Jun JK, Romero R, Yoon BH. The antenatal identification of funisitis with a rapid MMP-8 bedside test. J Perinat Med. 2008;36:497–502. doi: 10.1515/JPM.2008.079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].Park JS, Romero R, Yoon BH, Moon JB, Oh SY, Han SY, et al. The relationship between amniotic fluid matrix metalloproteinase-8 and funisitis. Am J Obstet Gynecol. 2001;185:1156–61. doi: 10.1067/mob.2001.117679. [DOI] [PubMed] [Google Scholar]
  • [36].Park JS, Yoon BH, Romero R, Moon JB, Oh SY, Kim JC, et al. The relationship between oligohydramnios and the onset of preterm labor in preterm premature rupture of membranes. Am J Obstet Gynecol. 2001;184:459–62. doi: 10.1067/mob.2001.109398. [DOI] [PubMed] [Google Scholar]
  • [37].Park NH, Yoon BH, Syn HC, Kim SW. Growth pattern of the newborn infants by gestational age. Korean journal of obstetrics and gynecology. 1991;34:322–30. [Google Scholar]
  • [38].Pedro Kusanovic J, Romero R, Jodicke C, Mazaki-Tovi S, Vaisbuch E, Erez O, et al. Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition, and intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2009;22:1151–66. doi: 10.3109/14767050903019684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Perni SC, Vardhana S, Korneeva I, Tuttle SL, Paraskevas LR, Chasen ST, et al. Mycoplasma hominis and Ureaplasma urealyticum in midtrimester amniotic fluid: association with amniotic fluid cytokine levels and pregnancy outcome. Am J Obstet Gynecol. 2004;191:1382–6. doi: 10.1016/j.ajog.2004.05.070. [DOI] [PubMed] [Google Scholar]
  • [40].Phelan JP, Ahn MO, Smith CV, Rutherford SE, Anderson E. Amniotic fluid index measurements during pregnancy. J Reprod Med. 1987;32:601–4. [PubMed] [Google Scholar]
  • [41].Romero R, Espinoza J, Hassan S, Gotsch F, Kusanovic JP, Avila C, et al. Soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) in amniotic fluid: modulation by infection and inflammation. J Perinat Med. 2008;36:388–98. doi: 10.1515/JPM.2008.076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [42].Romero R, Espinoza J, Rogers WT, Moser A, Nien JK, Kusanovic JP, et al. Proteomic analysis of amniotic fluid to identify women with preterm labor and intra-amniotic inflammation/infection: the use of a novel computational method to analyze mass spectrometric profiling. J Matern Fetal Neonatal Med. 2008;21:367–88. doi: 10.1080/14767050802045848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [43].Romero R, Kusanovic JP, Gotsch F, Erez O, Vaisbuch E, Mazaki-Tovi S, et al. Isobaric labeling and tandem mass spectrometry: A novel approach for profiling and quantifying proteins differentially expressed in amniotic fluid in preterm labor with and without intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2009:1–20. doi: 10.3109/14767050903067386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [44].Schlievert P, Johnson W, Galask RP. Bacterial growth inhibition by amniotic fluid. VII. The effect of zinc supplementation on bacterial inhibitory activity of amniotic fluids from gestation of 20 weeks. Am J Obstet Gynecol. 1977;127:603–8. [PubMed] [Google Scholar]
  • [45].Shim SS, Romero R, Hong JS, Park CW, Jun JK, Kim BI, et al. Clinical significance of intra-amniotic inflammation in patients with preterm premature rupture of membranes. Am J Obstet Gynecol. 2004;191:1339–45. doi: 10.1016/j.ajog.2004.06.085. [DOI] [PubMed] [Google Scholar]
  • [46].Silver RK, MacGregor SN, Hobart ED. Impact of residual amniotic fluid volume in patients receiving parenteral tocolysis after premature rupture of the membranes. Am J Obstet Gynecol. 1989;161:784–7. doi: 10.1016/0002-9378(89)90402-x. [DOI] [PubMed] [Google Scholar]
  • [47].Soto E, Romero R, Richani K, Yoon BH, Chaiworapongsa T, Vaisbuch E, et al. Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection. J Matern Fetal Neonatal Med. 2009;22:983–92. doi: 10.3109/14767050902994747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [48].Vaisbuch E, Mazaki-Tovi S, Pedro Kusanovic J, Erez O, Gabor Than N, Kwon Kim S, et al. Retinol binding protein 4: An adipokine associated with intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2009 doi: 10.3109/14767050902994739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [49].Vaisbuch E, Romero R, Erez O, Mazaki-Tovi S, Pedro KJ, Soto E, et al. Fragment Bb in amniotic fluid: evidence for complement activation by the alternative pathway in women with intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2009;22:905–16. doi: 10.1080/14767050902994663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [50].Vermillion ST, Kooba AM, Soper DE. Amniotic fluid index values after preterm premature rupture of the membranes and subsequent perinatal infection. Am J Obstet Gynecol. 2000;183:271–6. doi: 10.1067/mob.2000.107653. [DOI] [PubMed] [Google Scholar]
  • [51].Vintzileos AM, Campbell WA, Nochimson DJ, Weinbaum PJ. Degree of oligohydramnios and pregnancy outcome in patients with premature rupture of the membranes. Obstet Gynecol. 1985;66:162–7. [PubMed] [Google Scholar]
  • [52].Wenstrom KD, Andrews WW, Hauth JC, Goldenberg RL, DuBard MB, Cliver SP. Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery. Am J Obstet Gynecol. 1998;178:546–50. doi: 10.1016/s0002-9378(98)70436-3. [DOI] [PubMed] [Google Scholar]
  • [53].Yoon BH, Jun JK, Romero R, Park KH, Gomez R, Choi JH, et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol. 1997;177:19–26. doi: 10.1016/s0002-9378(97)70432-0. [DOI] [PubMed] [Google Scholar]
  • [54].Yoon BH, Kim YA, Romero R, Kim JC, Park KH, Kim MH, et al. Association of oligohydramnios in women with preterm premature rupture of membranes with an inflammatory response in fetal, amniotic, and maternal compartments. Am J Obstet Gynecol. 1999;181:784–8. doi: 10.1016/s0002-9378(99)70301-7. [DOI] [PubMed] [Google Scholar]
  • [55].Yoon BH, Romero R, Kim CJ, Jun JK, Gomez R, Choi JH, et al. Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity. Am J Obstet Gynecol. 1995;172:960–70. doi: 10.1016/0002-9378(95)90028-4. [DOI] [PubMed] [Google Scholar]
  • [56].Yoon BH, Romero R, Moon JB, Shim SS, Kim M, Kim G, et al. Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 2001;185:1130–6. doi: 10.1067/mob.2001.117680. [DOI] [PubMed] [Google Scholar]
  • [57].Yoon BH, Romero R, Park JS, Kim CJ, Kim SH, Choi JH, et al. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol. 2000;182:675–81. doi: 10.1067/mob.2000.104207. [DOI] [PubMed] [Google Scholar]

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