Calcified necrotizing funisitis and its association with adverse neonatal outcomes: a case‒control study

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Method This retrospective study included newborns who had undergone pathological examination between July 2020 and March 2024. Twenty-one neonates who delivered at Jinan Maternal and Child Health Hospital with pathological results of calcified NF were retrospectively selected as the study subjects, and 44 neonates who were admitted during the same period without pathological results of calcified NF were selected as the control group according to a gestational age ratio of 1:2. Neonatal outcome measures were comparable between the two groups. Results Two groups were born preterm. Compared to those in the control group, the mode of delivery (cesarean vs vaginal), prolonged PROM, RDS, ROP, duration of ventilator use, white cell count, CRP, and neutrophil percentage in the observation group were significantly different from those in the control group (P<0.05). Among the 21 individuals analyzed, 14 patients (66.7%) were determined to be positive for UU infection in the observation group, and 4 patients (9.50%) were positive in the control group. The differences were statistically significant (P<0.001). Conclusion Blood cell counts, CRP levels and neutrophil proportions were markedly elevated. The rates of RDS and ROP decreased. The duration of invasive mechanical ventilation use was prolonged in neonates with calcified necrotizing funisitis. UU was a risk factor for calcified NF. Placental pathology newborn calcified necrotizing funisitis Introduction Necrotizing funisitis (NF) is a rare but severe type of umbilical inflammation. The main pathological feature is yellow‒white banding between the surface and vascular wall of the umbilical cord. The banding is formed by inflammatory cells, necrotic tissue and calcification deposits and involves two umbilical arteries or the umbilical vein [ 1 , 2 ] . The incidence of NF is 1.25% in pregnant women [ 3 ] and 1% in pregnant fetuses after 20 weeks of gestation [ 4 ] . Intrauterine infection is a common cause of NF [ 4 ] , and Ureaplasma urealyticum (UU) infection is common. Whether NF can affect the outcomes of newborns is still unknown. The purpose of this study was to explore the relationship between NF and the outcomes of newborns. The results are reported as follows. Materials and Methods 1.1 Source of sequence data . Twenty-one neonates with NF from the Neonatology Department of Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University ( Jinan , Shandong , China) from July 2020 to July 2024 were collected. According to the 1:2 ratio of gestational age, 20 neonates without NF in the same period of hospitalization were selected as the control group. There were no statistically significant differences between the two groups of mothers in terms of age, gestational age at birth, sex, or birth weight (P>0.05). Table 1 Table 1 General clinical information of mothers between the 2 groups (x± s ， N （％） ， M （ P25,P75 ） N Age of mother（years） Gestational age (weeks) Sex Birth weight(grams) Male N(%) Female N(%) NF 21 31.76±5.36 301±24 13（61.9） 8(31.8) 1350(1050,1675) non-NF 42 30.81±4.28 30 1 ±2 4 28（66.7） 14（33.3） 1340（1075，1902） t/χ 2 /F 0.764 -0.033 0.14 -0.109 P 0.448 0.974 0.709 0.913 1.2 Paraffin sections were sliced and stained with hematoxylin–eosin ( HE ). The complete placenta, including the fetal membrane, placenta and umbilical cord, was subjected to clinical testing. The placental tissue was fresh, and two rolls of fetal membranes were removed from the ruptured edge of the membranes to the edge of the placenta. Two full-thickness sections of the placenta parenchyma (including fetal and maternal surfaces), two sections of fetal membrane rolls, and two sections of the umbilical cord (proximal and distal) were collected for routine histopathological examination and diagnosis. P lacental tissues were fixed in 10 % formalin for 24 h , followed by conventional dehydration and paraffin embedding, sectioning at 4 μm, and staining with HE . 1.3 Clinical observation The data of all the enrolled mothers and newborns were analyzed. We analyzed the blood cell count, C-reactive protein (CRP) level, neutrophil proportion and procalcitonin (PCT) level of mothers within 24 hours before and after maternal delivery and of newborns within 24 hours after maternal delivery. The mode of delivery, amniotic fluid, umbilical cord, premature rupture of membrane (PROM), Apgar1, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), intracranial hemorrhage, periventricular leukomalacia (PVL), fetal distress, duration of invasive ventilator use, duration of noninvasive ventilator use and length of hospital stay were also analyzed. The diagnostic criteria for RDS, BPD, NEC, ROP, PDA intracranial hemorrhage, PVL and fetal distress were selected according to the Practice of Neonatology ( 5th Edition ) [5] . The placental tissues were diagnosed according to the criteria proposed by the Amsterdam Placental Workshop Group Consensus Statement [6] . The relationship between NF and the prognosis of neonates was further examined. 1.4 Statistical analysis SPSS 27.0 was used for the statistical analyses. Normally distributed data are expressed as X ± S , and t tests were used for comparisons between groups. Nonnormally distributed data are presented as the median (25th–75th percentile) [ M ( P25 - P75 )], and the F test was used for comparisons between groups. The percentage (%) was used to express enumeration data, and the χ 2 test was used for comparison. Univariate associations with UU infection were analyzed using logistic regression, and P 0.05) in terms of white blood cell count, neutrophil percent, PCT, amniotic fluid or antibiotic use. However, the m ode of delivery and the time of PROM were significantly different (P<0.05). The results are shown in Table 2 . Table 2 Clinical data of the two maternal groups (x± s ， N （％） ， M （ P25,P75 ） N White cell count(×10 9 /L) neutrophil percen(%) PCT（ng/ml） amniotic fluid PROM（h） mode of delivery antibiotic use Normal N（％ Abnormal N（％ Vaginal N（％） Cesarean N（%） Yes No NF 21 13.39±3.55 83.20±6.02 0.1（0.1，0.14） 15（71.4） 6（28.6） 40（5.5，144） 11（52.4） 10（47.6） 14(66.7) 7（33.3） non-NF 42 11.73±3.78 78.96±8.78 0.11（0.1，0.24） 6（14.3） 36（85.7） 0（0，24.25） 10（23.8） 32(76.2) 4(9.5) 38(90.5) t/χ 2 /F 1.684 1.989 -0.456 -3.415 5.143 2.315 P 0.093 0.051 0.152 0.719 ＜0.001 0.023 0.344 2.2 Comparison of adverse neonatal outcomes The differences in RDS, ROP, duration of invasive ventilator use, duration of noninvasive ventilator use, white cell count, CRP level, percentage of neutrophils, and percentage of positive UU infections between the two groups were statistically significant (P < 0.05). The results are shown in Table 3 . Table 3 Comparison of neonatal outcomes between the two groups (x± s ， N （％） ， M （ P25,P75 ） Groups NF N（%） non-NF N（%） t/χ 2 /F P N 21 42 RDS Yes 8（38.1） 28(66.7) 4.667 0.031 No 13（61.9） 14(33.3) BPD Yes 13（61.9） 19(45.2) 0.292 0.589 No 8（38.1） 23(54.8) NEC Yes 1(4.8) 3(7.1) 1.0 No 20(95.2) 39(92.9) ROP Yes 2(9.5) 16(38.1) 5.6 0.018 No 19(90.5) 26(61.9) PDA Yes 10(47.6) 24(57.1) 0.511 0.475 No 11(52.4) 18(42.6) SGA Yes 1(4.8) 2(4.8) 1.0 No 20(95.2) 40(95.2) intracranial hemorrhage Yes 1(4.8) 7(16.7) 0.25 No 20(95.2) 35(83.3) PVL Yes 3(14.3) 3（7.1%） 0.323 No 18(85.7) 39（92.9） fetal distress Yes 4(19.0) 7（16.7） 1.0 No 17(81.0) 35（83.3） duration of invasive ventilator use 0(0,2) 3(0,9.25) -2.149 0.032 duration of noninvasive ventilator use 18.14±20.15 23.19±20.24 -0.929 0.356 Apgar1 9(8，9) 9(8，9) -0.456 0.648 length of stay in hospital 31（24，58） 45（23，64.75） -0.839 0.402 White cell count(×10 9 /L) 20.20±7.10 10.66±6.07 5.453 ＜0.001 CRP(mg/L) 0.95（0.2，4.33） 0.2（0.2，0.21） -3.853 ＜0.001 neutrophil percen(%) 60.95±11.98 48.69±14.62 3.32 0.002 PCT(ng/ml) 0.24（0.11，0.47） 0.28（0.17，0.38） -1.065 0.287 UU Yes 14(66.7%) 4（9.5） ＜0.001 No 7(33.3%) 38（90.5） In this study, UU infection was a risk factor for NF (OR=5.846 95% CI (1 .199-28. 512)). The diagnosis of UU infection was confirmed by positive urine UU- PCR in this study. UU infection was confirmed by urine UU- PCR in 18 patients. After treatment with intravenous erythromycin , all of these patients had negative UU- PCR results. In 21 neonates with NF, placental pathology suggested fetal vascular malperfusion (FVM) in 7 patients, accounting for 33.7%. The case numbers are shown in Table 4. Table 4. Pathological findings of 21cases with NF Case number Pathological findings 1 Maternal inflammatory response (stage 2, grade 1), hemosiderin deposits are visible within the focal decidua Feta al inflammatory response (stage 3, grade 2),NF and umbilical cord bleeding, accelerated villous maturation, maternal vascular malperfusion (MVM) 2 Maternal inflammatory response (stage 3, grade 2), necrotizing c horioamnionitis. Feta al inflammatory response (stage 3, grade 2),NF,placental villous is immature, placental abruption 3 Maternal inflammatory response (stage 2, grade 2), chorionic plate inflammation Feta al inflammatory response (stage 3, grade 2),NF, placental villous is immature, few villous edema, s ubchorionic hematoma 4 Maternal inflammatory response (stage 2, grade 2) Feta al inflammatory response (stage 3, grade 2),NF, basal plate necrosis with large amount of inflammatory cells infiltration . 5 Maternal inflammatory response (stage 1, grade 1) Feta al inflammatory response (stage 3, grade 2),NF, chorioangiosis, multiple blood vessels under chorionic plate exhibit occlusive thrombus, with a large amount of avascular villi, constent with high grade "FVM" 6 Maternal inflammatory response (stage 3, grade 2), acute c horioamnionitis Feta al inflammatory response (stage 3, grade 2),NF, large amounts of immature intermediate villus , some villous edema 7 Maternal inflammatory response (stage 3, grade 2),necrotizing c horioamnionitis. Feta al inflammatory response (stage 3, grade 2),NF, multiple scattered avascular villi, constent with high grade "FVM" 8 Maternal inflammatory response (stage 1, grade 2),acute c horioamnionitis. Feta al inflammatory response(stage 3, grade 2),NF, chorionic plate inflammation (moderate), some villus vessels were dilated and congested 9 Maternal inflammatory response (stage 3, grade 2) . Feta al inflammatory response(stage 3, grade 2),NF, accelerated villous maturation, multiple blood multifocal sheets of avascular villi, constent with "overall/partial FVM" 10 Maternal inflammatory response (stage 3, grade 2) . Feta al inflammatory response(stage 3, grade 2),NF, intervillous thrombosis histologically 11 Maternal inflammatory response (stage 2 , grade 2) . acute c horioamnionitis Feta al inflammatory response(stage 2, grade 2),NF,chorionic plate vessels inflammation (moderate), chorionic plate inflammation(moderate), subchorionic inflammation(moderate), villous stunting ,the villous syncytiotrophoblast (SCT) increased. 12 Maternal inflammatory response (stage 2 , grade 2) . acute c horioamnionitis and chorionic amniotic columnar metaplasia Feta al inflammatory response(stage 2, grade 2),NF,chorionic plate vessels inflammation (moderate), chorionic plate inflammation(moderate), subchorionic inflammation(moderate), villous edema 13 Maternal inflammatory response (stage 3 , grade 2) Feta al inflammatory response(stage 2, grade 1),NF,e xcessive maturation of the placental villi the, villous syncytiotrophoblast increased. 14 Maternal inflammatory response (stage 3 , grade 2) Feta al inflammatory response(stage 3 , grade 2),NF,multiple small focal avascular villi, constent with "overall/partial FVM" 15 Maternal inflammatory response (stage 2 , grade 1),acute c horioamnionitis Feta al inflammatory response(stage 1 , grade 1 ),NF,villous immaturity 16 Maternal inflammatory response (stage 3 , grade 2) . Feta al inflammatory response(stage 3, grade 2),NF,the placental villi are excessively mature, with increased nodules of syncytiotrophoblasts，large focal avascular villi with dry villous nonocclusive thrombus，thrombosis between the villi has formed.constent with high grade "FVM" 17 Maternal inflammatory response (stage 2 , grade 1) Feta al inflammatory response(stage 3 , grade 2 ),NF,villous edema. dry chorionic thrombus was formed, along with large avascular villi. constent with "FVM" 18 Maternal inflammatory response (stage 2 , grade 2),acute c horioamnionitis Feta al inflammatory response(stage 1 , grade 1 ),NF, subchorionic inflammation (mild), a large number of mature intermediate villus, fibrinoid deposition in the intervillous space increased , partial villus edema 19 Maternal inflammatory response (stage 1 , grade 2)，acute c horioamnionitis Feta al inflammatory response(stage 2 , grade 1 ),NF, chorionic plate inflammation, subchorionic inflammation, nodules of syncytiotrophoblasts increased， placental abruption 20 Maternal inflammatory response (stage 2, grade 1), acute c horioamnionitis Feta al inflammatory response (stage 2 , grade 1),NF ,accelerated villous maturation 21 Maternal inflammatory response (stage 2, grade 2), acute c horioamnionitis Feta al inflammatory response (stage 2 , grade 2),NF , chorionic plate inflammation(moderate), subchorionic inflammation(mild), a large number of mature intermediate villus, partial villous edema, constent with "FVM" Discussion Placental inflammation includes chorioamnionitis, chorioic vasculitis and funisitis. It is possible that chorioamnionitis, which is histologically defined as the presence of inflammatory cells inside gestational membranes and is often suggestive of infection of the amniotic cavity [ 7 ] , might represent a maternal inflammatory response to intra-amniotic infection. However, chorioinic vasculitis and funisitis might predominantly represent the fetal inflammatory response. Necrotizing chorioamnionitis is the severe stage of chorioamnionitis, while calcified necrotizing funisitis is the most serious stage of necrotizing chorioamnionitis. The migration of inflammatory cells such as neutrophils from the amniotic cavity into the muscular layer of umbilical vessels is a characteristic feature of omphalitis [ 8 ] . OM typically starts at the umbilical vein, followed by the umbilical artery, because the venous walls of the umbilical cord are more prone to proinflammation than arterial walls are [ 9 ] . The initial stage involves multiple discrete foci. As inflammation progresses, these foci can eventually fuse, merge and involve the whole umbilical cord, characterized by concentric distribution of neutrophils along the blood vessel. Umbilical phlebitis represents phase 1 of fetal infection, umbilical arteritis represents phase 2, and calcified NF, as the relatively uncommon but serious omphalitis, is phase 3 and the most severe stage [ 8 ] . The calcified NFs formed distinct lesions both macroscopically and microscopically. Macroscopically, yellow‒white bands parallel to the umbilical cord and the outline are crescent or ring shaped in cross sections. Microscopy has shown nonspecific inflammatory changes, necrotic cell debris and calcium deposits [ 4 ] . Because of the lack of lymphatic capillaries, larger lymphatic vessels and fixed macrophages, it is difficult to remove necrotic cells from the umbilical cord [ 4 , 10 ] . With the accumulation and increase in mineralization of necrotic cells, zones of calcification are particularly prone to form in NF. In the present study, pathological examinations of the 21 patients revealed zones of calcification. Due to the formation of zones of calcification, there are areas of hyperechogenicity associated with calcification parallel to vascular walls on US. Because of the accumulation of necrotic debris and the deposition of calcium, the umbilical cord tends to be vulnerable, causing fetal distress and breakage [ 4 ] . If not timely recognized, fetal hypoxia, bradycardia, and even intrauterine fetal death or rupture of the umbilical cord can occur during delivery. Therefore, NF should be considered when calcification is observed on fetal ultrasound and should be addressed promptly. In the event of NF, a fetus can develop an inflammatory response, which is a high-risk factor for premature rupture of membranes and vaginal birth in premature neonates [ 11 ] . This study also revealed that the rate of vaginal birth in premature neonates was greater and that the duration of PROM was longer in the infection group than in the control group. Statistically significant differences were present. This finding also revealed that when the premature were delivered vaginally or had premature rupture of membranes, placental pathological findings of the newborns must be traveled by a NICU intensivist in our clinical work. An NF suggests a severe fetal inflammatory response, which might persist into the neonatal period. The present study revealed that the leukocyte count, CRP level and neutrophil proportion were significantly greater during the first 24 hours after delivery in the NF group than in the control group. The results were in concordance with those of a study by RALLIS D et al [ 12 ] . We also found that NF was associated with reduced RDS occurrence in preterm neonates. These findings are in agreement with previous studies by Ding R et al[13]. and BeenJ V et al [ 14 ] . When complicated with NF, severe fetal inflammatory responses can occur. The lungs are exposed to inflammatory factors due to fetal breathing movements that involve mixing amniotic fluid with fetal lung fluid. Fetal exposure to infection can accelerate the maturation of fetal lung structure and surfactant metabolism [ 15 ], which reduces the incidence of RDS in premature infants. In our study, the incidence of BPD was greater in infants with NF, but the difference was not statistically significant, which is consistent with the results of studies by the Canadian Neonatal Network [ 16 ] and Laughon et al [ 17 ] . but is contrary to those of the study by Villamor-Martinez E et al. Villamor-Martinez E et al [ 18 ] . reported that chorioamnionitis is associated with an increased risk of BPD. BPD arises from an imbalance in lung impairment, and repair during lung development is a complex and multifactorial syndrome that is influenced by antenatal and postnatal factors. Exposure to chorioamnionitis can protect infants from BPD by reducing the severity of RDS, while other types of exposure may promote BPD by triggering a progressive inflammatory response. In the present study, it was found that the use of invasive ventilation increased markedly between infants with NF and those without NF. We consider that this finding is associated with exposure to lung inflammation. However, the role of intrauterine infection in the development and progression of lung disease in neonates is uncertain. This study indicated that the incidence of ROP was lower in newborn infants with NF than in control infants, which was consistent with the findings of previous studies by Jee Yoon Park et al [ 19 ] and Leah A Owen et al [ 20 ] . The mechanisms by which placental inflammation decreases the incidence of ROP are obscure. Some studies have suggested that fetal inflammatory agents can increase the concentration of insulin-like growth factor-1 (IGF-1 )[ 19 ] and that IGF-1 stimulates the formation of retinal blood vessels and the normal retinal vascular network while maintaining the normal physiology of the retina and exerting anti-inflammatory and antioxidant effects, thus reducing the occurrence of ROP. This also explains the longer duration of invasive mechanical ventilation in newborn infants with NF, but the incidence of ROP decreased compared to that in the control group. In addition, intrauterine UU infection was detected in 14 of 21 neonates (66.7%) with NF and 4 of 42 neonates (9.5%) without NF in this study, and this difference was significant (P < 0.001). U. urealyticum is an opportunistic and common pathogen among women of reproductive age. Currently, the detection rate of UU can reach 82% in pregnant women [ 21 ] . Intrauterine UU infection indicates that the newborn tested positive for excreta or secretions according to the UU-PCR test at least once and is most frequently infected via an ascending genital tract infection [ 22 ] . The diagnosis of UU infection was confirmed by positive urine UU-PCR in this study [ 23 ] . A large number of studies have indicated that UU infection is associated with serious complications and adverse outcomes [ 22 , 24 – 28 ] . Chorioamnionitis occurred in almost half of the newborns confirmed to have intrauterine UU infection [ 29 , 30 ] . Lal et al. suggested that UU induces collagen fragmentation, PROM and neutrophil influx and can cause chorioamnionitis [ 31 ] . The results of the study indicated that intrauterine UU infection could be a risk factor for NF. However, the pathogenesis of UU infection leading to NF remains to be clarified. Future studies are needed to investigate this further. Conclusions NF is closely related to adverse outcomes. In our daily clinical work, placentas were collected by obstetricians at the time of delivery and sent to the Pathology Department for histological evaluation. However, the pathological reports were reported to the attending physicians, who are not obstetric NICU clinicians. However, there is growing evidence that pathological results are closely related to neonatal outcomes. Therefore, neonatologists should pay more attention to pathological findings. When histopathological examination shows NF, clinicians should evaluate these newborns and exclude UU infection. Early identification of NF can facilitate timely clinical interventions and adjustment of antibiotics and has the potential to improve neonatal outcomes. Abbreviations NF Necrotizing funisitis UU Ureaplasma urealyticum CRP C-reactive protein PCT procalcitonin PROM premature rupture of membrane rupture RDS respiratory distress syndrome BPD bronchopulmonary dysplasia NEC Necrotizing enterocolitis ROP retinopathy of prematurity PDA patent ductus arteriosus PVL periventricular leukomalacia FVM fetal vascular malperfusion MVM maternal vascular malperfusion IGF-1 insulin-like growth factor-1 Declarations Acknowledgments Not applicable Author Contributions X L guarantees the study. L P contributed to study management and data analysis, contributed to trial management and wrote all versions of the manuscript. M S contributed to the data analysis and critically appraised the manuscript. Q L contributed to the data analysis and critically appraised the manuscript. X F contributed to the trial management and data analysis and critically reviewed the manuscript. J L contributed to data curation. X L contributed to the study design and data analysis and critically appraised and gave final approval of the manuscript.All authors read and approved the final manuscript. Funding Statement This study was performed without any supporting funds. Data Availability Statement Data supporting the reported results can be requested from the main author.Written informed consent for publication was obtained. Ethics approval and consent to participate This study was approved by the institutional review board of the Neonatology Department of Jinan Maternity And Child Care Hospital Affiliated to Shandong First Medical University ( Jinan, Shandong , China). A statement to confirm that all methods were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards. A sentence confirming that written informed consent was obtained from all participants or if participants are under 16, from a parent and/or legal guardian. Include a statement on ethics approval and consent (even where the need for approval was waived). Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Conflicts of Interest The authors declare no conflict of interest. Consent for publication Written informed consent for publication was obtained. References KHONG T Y SA. Calcification of umbilical artery: two distinct lesions[J]. J Clin Pathol. 1989,;42(9):931–4. . JACQUES SM. Necrotizing funisitis: a study of 45 cases[J]. Hum Pathol. 1992,;23(11):1278–83. . CRAVER RD, BALDWIN VJ. Necrotizing funisitis[J]. Obstet Gynecol. 1992,;79(1):64–70. . Shao Xiaomei Y, Hongmao. Qiu Xiaoshan. Practical Neonatology [M]. People's Medical Publishing House, 2011(in Chinese). Xiaomei S, Hongmao Y, Xiaoshan. Q et al. (2011). PRACTICE OF NEONATOLOGY. People's Health. KHONG T Y I. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement[J]. Arch Pathol Lab Med. 2016,;140(7):698–713. . MITTAL N,, BYARD R W JE. A practical guide to placental examination for forensic pathologists[J]. Forensic Sci Med Pathol. 2020,;16(2):295–312. . KIM C J, ROMERO R, CHAEMSAITHONG P. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance[J]. Am J Obstet Gynecol. 2015,;213(4 Suppl):S29–52. . KIM C J M. Histo-topographic distribution of acute inflammation of the human umbilical cord[J]. Pathol Int. 2001,;51(11):861–5. . NAVARRO C, BLANC WA. Subacute necrotizing funisitis. A variant of cord inflammation with a high rate of perinatal infection[J]. J Pediatr. 1974,;85(5):689–97. . ZANARDO V, VEDOVATO S. Preterm premature rupture of membranes, chorioamnion inflammatory scores and neonatal respiratory outcome[J]. Bjog. 2010,;117(1):94–8. . RALLIS D, LITHOXOPOULOU M. Clinical chorioamnionitis and histologic placental inflammation: association with early-neonatal sepsis[J]. J Matern Fetal Neonatal Med. 2022,;35(25):8090–6. . DING R, CHEN Q, ZHANG Q W. [Association of different stages of histological chorioamnionitis with respiratory distress syndrome in preterm infants with a gestational age of < 32 weeks][J]. Zhongguo Dang Dai Er Ke Za Zhi. 2021,;23(3):248–53. . BEEN JV. Histological chorioamnionitis and respiratory outcome in preterm infants[J]. Arch Dis Child Fetal Neonatal Ed. 2009,;94(3):F218–225. . BANCALARI E.. Antenatal Infections and Respiratory Outcome in Preterm Infants[J]. Am J Perinatol. 2020,;37(S 02):S39–41. SORAISHAM A S N, MCMILLAN DD. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants[J]. Am J Obstet Gynecol. 2009,;200(4):e372371–376. . LAUGHON M, ALLRED E N C. Patterns of respiratory disease during the first 2 postnatal weeks in extremely premature infants[J]. Pediatrics. 2009,;123(4):1124–31. . VILLAMOR-MARTINEZ E, ÁLVAREZ-FUENTE M, GHAZI A M T. Association of Chorioamnionitis With Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review, Meta-analysis, and Metaregression[J]. JAMA Netw Open. 2019,;2(11):e1914611. . PARK JY, PARK C W, MOON K C. Retinopathy of prematurity in infants without fetal growth restriction is decreased with the progression of acute histologic chorioamnionitis: New observation as a protective factor against retinopathy of prematurity[J]. Placenta. 2021,;104:161–7. . OWEN L A C, SHIRER K. Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity[J]. Am J Pathol. 2023,;193(11):1776–88. . SILWEDEL C, SPEER C P. Ureaplasma-associated prenatal, perinatal, and neonatal morbidities[J]. Expert Rev Clin Immunol. 2017,;13(11):1073–87. . SUN T, FU J. Analysis of the Clinical Features of Intrauterine Ureaplasma urealyticumUreaplasma urealyticum Infection in Preterm Infants: A Case–-Control Study[J]. Front Pediatr. 2021,;9:774150. . NASSAR F A FA. Detection of Chlamydia trachomatisChlamydia trachomatis and Mycoplasma hominisMycoplasma hominis, genitalium and Ureaplasma urealyticumUreaplasma urealyticum by polymerase chain reaction in patients with sterile pyuria[J]. Adv Med Sci. 2008,;53(1):80–6. . CULTRERA R, SERACENI S, GERMANI R. Molecular evidence of Ureaplasma urealyticumUreaplasma urealyticum and Ureaplasma parvum colonization in preterm infants during respiratory distress syndrome[J]. BMC Infect Dis. 2006,;6:166. . VISCARDI RM. Ureaplasma species: role in neonatal morbidities and outcomes[J]. Arch Dis Child Fetal Neonatal Ed. 2014,;99(1):F87–92. . KWAK D W, HWANG H S, KWON J Y. CoCo-infection with vaginal Ureaplasma urealyticumUreaplasma urealyticum and Mycoplasma hominisMycoplasma hominis increases adverse pregnancy outcomes in patients with preterm labor or preterm premature rupture of membranes[J]. J Matern Fetal Neonatal Med. 2014,;27(4):333–7. . BARTKEVICIENE D, OPOLSKIENE G, BARTKEVICIUTE A. The impact of Ureaplasma infections on pregnancy complications[J]. Libyan J Med. 2020,;15(1):1812821. . KALIKKOT THEKKEVEEDU R SHIVANNAB. Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology[J]. Respir Med. 2017,;132:170–7. . TITA A T WW. Diagnosis and management of clinical chorioamnionitis[J]. Clin Perinatol. 2010,;37(2):339–54. . WAITES K B KATZB, SCHELONKA RL. Mycoplasmas and ureaplasmas as neonatal pathogens[J]. Clin Microbiol Rev. 2005,;18(4):757–89. . XU LALCV, JACKSON X. Ureaplasma infection-mediated release of matrix metalloproteinase-9 and PGP: a novel mechanism of preterm rupture of membranes and chorioamnionitis[J]. Pediatr Res. 2017,;81(1–1):75–9. . Cite Share Download PDF Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Italian Journal of Pediatrics → Version 1 posted Editorial decision: Major revision 22 Feb, 2025 Reviewers agreed at journal 02 Jul, 2024 Reviewers invited by journal 30 Jun, 2024 Editor assigned by journal 26 Jun, 2024 First submitted to journal 21 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4557511","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":320882680,"identity":"60ea8fd5-5fa0-44d3-b7c9-e26880b05a8c","order_by":0,"name":"Lei Peng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAs0lEQVRIiWNgGAWjYDACdiBmbLDh4edvIFYLM1hLmozkjAOkaTlsY9CQQKQOc2b2yx9/7jjPY8BwgPHDxxwitFg28xQYSJ65zWPO3MAsOXMbEVoMDvMkJBi23eaxbDjAxsxLrJYDiW3neAwOJBCthf1gw8G2AyRoAfqFmbGxLZlHcsbBZuL8Ys7e/vjjzzY7e37+5oMfPhLlMAZg8EIAYwMR6sFa2B8Qp3IUjIJRMApGLgAATU012nWHlMYAAAAASUVORK5CYII=","orcid":"","institution":"Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Peng","suffix":""},{"id":320882681,"identity":"2b655c5a-840f-4419-afd4-25fd9115aaab","order_by":1,"name":"Min Shi","email":"","orcid":"","institution":"Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Shi","suffix":""},{"id":320882682,"identity":"2ea17f32-9344-4c95-96a1-48329b315014","order_by":2,"name":"Qian Liu","email":"","orcid":"","institution":"Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Liu","suffix":""},{"id":320882683,"identity":"78248e94-0a23-47f4-a8b9-9aa5ba5f6a6a","order_by":3,"name":"Xiufang Fan","email":"","orcid":"","institution":"Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiufang","middleName":"","lastName":"Fan","suffix":""},{"id":320882684,"identity":"25595174-0ca7-4d91-9a4f-e06a31ffa414","order_by":4,"name":"Juan Li","email":"","orcid":"","institution":"Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Li","suffix":""},{"id":320882685,"identity":"30b963a4-8d8e-4aef-976d-0fd00d648726","order_by":5,"name":"Xia Li","email":"","orcid":"","institution":"Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xia","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-06-10 10:48:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4557511/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4557511/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13052-025-02033-4","type":"published","date":"2025-07-01T15:57:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86179732,"identity":"1b19e437-c12f-4562-9255-4da54e24e235","added_by":"auto","created_at":"2025-07-07 16:19:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":936014,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4557511/v1/212d2ddc-f409-4767-815d-87e1ac0b450c.pdf"}],"financialInterests":"","formattedTitle":"Calcified necrotizing funisitis and its association with adverse neonatal outcomes: a case‒control study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNecrotizing funisitis (NF) is a rare but severe type of umbilical inflammation. The main pathological feature is yellow‒white banding between the surface and vascular wall of the umbilical cord. The banding is formed by inflammatory cells, necrotic tissue and calcification deposits and involves two umbilical arteries or the umbilical vein\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The incidence of NF is 1.25% in pregnant women\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e and 1% in pregnant fetuses after 20 weeks of gestation\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Intrauterine infection is a common cause of NF\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e, and \u003cem\u003eUreaplasma urealyticum\u003c/em\u003e (UU) infection is common. Whether NF can affect the outcomes of newborns is still unknown. The purpose of this study was to explore the relationship between NF and the outcomes of newborns. The results are reported as follows.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003e1.1 Source of sequence \u003cem\u003edata\u003c/em\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwenty-one neonates with NF \u003cem\u003efrom\u003c/em\u003e \u003cem\u003ethe\u003c/em\u003e Neonatology\u0026nbsp;Department of Jinan Maternity \u003cem\u003eand\u0026nbsp;\u003c/em\u003eChild Care Hospital \u003cem\u003eAffiliated to Shandong First Medical University\u0026nbsp;\u003c/em\u003e(\u003cem\u003eJinan\u003c/em\u003e, \u003cem\u003eShandong\u003c/em\u003e, China) \u003cem\u003efrom\u003c/em\u003e \u003cem\u003eJuly\u003c/em\u003e 2020 \u003cem\u003eto\u003c/em\u003e \u003cem\u003eJuly\u003c/em\u003e 2024 were collected. According to the 1:2 ratio of gestational age, 20 \u003cem\u003eneonates\u0026nbsp;\u003c/em\u003ewithout NF\u0026nbsp;in the same period of hospitalization were selected as the control group. There were no statistically significant differences between the two groups of mothers in terms of age, gestational age at birth, sex, or birth weight (P\u0026gt;0.05). Table 1\u003c/p\u003e\n\u003cp\u003eTable 1 \u003cem\u003eGeneral\u003c/em\u003e clinical information of mothers between the 2 \u003cem\u003egroups\u003c/em\u003e(x\u0026plusmn;\u003cem\u003es\u003c/em\u003e\u003cem\u003e，\u003c/em\u003e\u003cem\u003eN\u003c/em\u003e（％）\u003cem\u003e，\u003c/em\u003e\u003cem\u003eM\u003c/em\u003e\u003cem\u003e（\u003c/em\u003e\u003cem\u003eP25,P75\u003c/em\u003e\u003cem\u003e）\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.318840579710145%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.072463768115942%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.942028985507246%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAge of mother（years）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.855072463768115%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGestational age (weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.702898550724637%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.108695652173914%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eBirth weight(grams)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eMale N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003eFemale N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.318840579710145%\" valign=\"top\"\u003e\n \u003cp\u003eNF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.072463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.942028985507246%\" valign=\"top\"\u003e\n \u003cp\u003e31.76\u0026plusmn;5.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.855072463768115%\" valign=\"top\"\u003e\n \u003cp\u003e301\u0026plusmn;24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003e13（61.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.942028985507246%\" valign=\"top\"\u003e\n \u003cp\u003e8(31.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.108695652173914%\" valign=\"top\"\u003e\n \u003cp\u003e1350(1050,1675)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.318840579710145%\" valign=\"top\"\u003e\n \u003cp\u003enon-NF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.072463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.942028985507246%\" valign=\"top\"\u003e\n \u003cp\u003e30.81\u0026plusmn;4.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.855072463768115%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003csup\u003e1\u003c/sup\u003e\u0026plusmn;2\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003e28（66.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.942028985507246%\" valign=\"top\"\u003e\n \u003cp\u003e14（33.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.108695652173914%\" valign=\"top\"\u003e\n \u003cp\u003e1340（1075，1902）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.318840579710145%\" valign=\"top\"\u003e\n \u003cp\u003et/\u0026chi;\u003csup\u003e2\u003c/sup\u003e/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.072463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.942028985507246%\" valign=\"top\"\u003e\n \u003cp\u003e0.764\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.855072463768115%\" valign=\"top\"\u003e\n \u003cp\u003e-0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.702898550724637%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.108695652173914%\" valign=\"top\"\u003e\n \u003cp\u003e-0.109\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.318840579710145%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.072463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.942028985507246%\" valign=\"top\"\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.855072463768115%\" valign=\"top\"\u003e\n \u003cp\u003e0.974\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.702898550724637%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.709\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.108695652173914%\" valign=\"top\"\u003e\n \u003cp\u003e0.913\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e1.2 Paraffin sections were sliced and stained with hematoxylin\u0026ndash;eosin (\u003cem\u003eHE\u003c/em\u003e).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe complete placenta, including the fetal membrane, placenta and umbilical cord, was subjected to clinical testing. The placental tissue was fresh, and two rolls \u003cem\u003eof\u003c/em\u003e fetal \u003cem\u003emembranes\u003c/em\u003e were removed \u003cem\u003efrom the\u0026nbsp;\u003c/em\u003eruptured \u003cem\u003eedge of the membranes to the edge of\u003c/em\u003e \u003cem\u003ethe\u003c/em\u003e placenta. Two full-thickness sections of the \u003cem\u003eplacenta\u003c/em\u003e parenchyma (including \u003cem\u003efetal\u003c/em\u003e \u003cem\u003eand\u003c/em\u003e \u003cem\u003ematernal\u003c/em\u003e surfaces), two sections of fetal \u003cem\u003emembrane\u003c/em\u003e rolls, \u003cem\u003eand\u003c/em\u003e two sections of \u003cem\u003ethe\u003c/em\u003e \u003cem\u003eumbilical\u003c/em\u003e \u003cem\u003ecord\u003c/em\u003e (proximal \u003cem\u003eand\u003c/em\u003e distal) were collected for routine histopathological examination \u003cem\u003eand\u003c/em\u003e diagnosis.\u003c/p\u003e\n\u003cp\u003eP\u003cem\u003elacental\u003c/em\u003e tissues were fixed in \u003cem\u003e10\u003c/em\u003e% formalin for \u003cem\u003e24\u003c/em\u003e \u003cem\u003eh\u003c/em\u003e, followed by conventional dehydration and paraffin embedding, sectioning at 4\u0026thinsp;\u0026mu;m, and staining with \u003cem\u003eHE\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.3 Clinical observation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data of all the \u003cem\u003eenrolled\u003c/em\u003e \u003cem\u003emothers and newborns\u003c/em\u003e \u003cem\u003ewere\u003c/em\u003e analyzed. We analyzed\u0026nbsp;the blood cell count,\u0026nbsp;C-reactive protein (CRP) level, neutrophil proportion and\u0026nbsp;procalcitonin\u0026nbsp;(PCT)\u0026nbsp;level of mothers within 24 hours before and after maternal delivery and\u0026nbsp;of newborns within 24 hours after maternal delivery.\u003cstrong\u003e\u0026nbsp;The mode\u0026nbsp;of delivery,\u0026nbsp;\u003c/strong\u003eamniotic fluid, umbilical\u0026nbsp;cord, premature rupture of membrane (PROM), Apgar1, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus\u0026nbsp;arteriosus (PDA), intracranial\u0026nbsp;hemorrhage,\u0026nbsp;periventricular\u0026nbsp;leukomalacia (PVL), fetal\u0026nbsp;distress, duration of invasive ventilator use, duration of noninvasive ventilator use and length of hospital\u0026nbsp;stay were also\u0026nbsp;analyzed.\u0026nbsp;The diagnostic criteria for RDS, BPD, NEC, ROP, PDA\u0026nbsp;intracranial hemorrhage, PVL and fetal distress\u0026nbsp;were selected according to \u003cem\u003ethe\u003c/em\u003e Practice of \u003cem\u003eNeonatology\u003c/em\u003e (\u003cem\u003e5th\u003c/em\u003e \u003cem\u003eEdition\u003c/em\u003e)\u003csup\u003e[5]\u003c/sup\u003e. The placental tissues were diagnosed according to the criteria proposed by the Amsterdam Placental Workshop Group Consensus Statement\u003csup\u003e[6]\u003c/sup\u003e. \u003cem\u003eThe\u003c/em\u003e \u003cem\u003erelationship\u003c/em\u003e between NF and the prognosis of neonates was further examined.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.4 Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSPSS\u003c/em\u003e \u003cem\u003e27.0\u003c/em\u003e was used for the statistical analyses. Normally distributed data are expressed as \u003cem\u003eX\u003c/em\u003e \u0026plusmn; \u003cem\u003eS\u003c/em\u003e, and \u003cem\u003et\u003c/em\u003e tests were used for comparisons between groups. Nonnormally distributed data are presented as the median (25th\u0026ndash;75th percentile) [\u003cem\u003eM\u003c/em\u003e (\u003cem\u003eP25\u003c/em\u003e-\u003cem\u003eP75\u003c/em\u003e)], and the \u003cem\u003eF\u003c/em\u003e test was used for comparisons between groups.\u003cem\u003e\u0026nbsp;The percentage\u003c/em\u003e (%) was used to express enumeration data, and the \u0026chi;\u003cem\u003e2\u003c/em\u003e \u003cem\u003etest\u003c/em\u003e was used for comparison. Univariate associations with UU infection were analyzed using logistic regression, and \u003cem\u003eP\u003c/em\u003e \u0026lt; \u003cem\u003e0.05\u003c/em\u003e was regarded as a statistically significant difference.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e2.1 \u003cem\u003eComparison\u003c/em\u003e \u003cem\u003eof\u003c/em\u003e \u003cem\u003eclinical\u003c/em\u003e \u003cem\u003edata\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThere\u003c/em\u003e was \u003cem\u003eno\u003c/em\u003e significant difference between \u003cem\u003ethe two\u003c/em\u003e \u003cem\u003egroups\u003c/em\u003e (P\u0026gt;0.05) in terms of \u003cem\u003ewhite\u003c/em\u003e \u003cem\u003eblood\u003c/em\u003e \u003cem\u003ecell\u003c/em\u003e \u003cem\u003ecount, neutrophil\u003c/em\u003e percent, \u003cem\u003ePCT,\u003c/em\u003e\u003cem\u003e\u0026nbsp;amniotic\u003c/em\u003e \u003cem\u003efluid\u0026nbsp;\u003c/em\u003eor \u003cem\u003eantibiotic\u003c/em\u003e \u003cem\u003euse. However, the m\u003c/em\u003e\u003cstrong\u003eode of delivery\u003c/strong\u003e\u003cem\u003e\u0026nbsp;and the time of PROM were significantly different (P\u0026lt;0.05).\u0026nbsp;\u003c/em\u003eThe results are shown in \u003cem\u003eTable\u003c/em\u003e \u003cem\u003e2\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eTable 2 \u003cem\u003eClinical\u003c/em\u003e \u003cem\u003edata\u003c/em\u003e of the two \u003cem\u003ematernal\u003c/em\u003e \u003cem\u003egroups\u003c/em\u003e(x\u0026plusmn;\u003cem\u003es\u003c/em\u003e\u003cem\u003e，\u003c/em\u003e\u003cem\u003eN\u003c/em\u003e（％）\u003cem\u003e，\u003c/em\u003e\u003cem\u003eM\u003c/em\u003e\u003cem\u003e（\u003c/em\u003e\u003cem\u003eP25,P75\u003c/em\u003e\u003cem\u003e）\u003c/em\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"554\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\" rowspan=\"2\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" rowspan=\"2\"\u003e\n \u003cp\u003eWhite cell count(\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eneutrophil\u003c/em\u003e percen(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\" rowspan=\"2\"\u003e\n \u003cp\u003ePCT（ng/ml）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cem\u003eamniotic\u003c/em\u003e \u003cem\u003efluid\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\" rowspan=\"2\"\u003e\n \u003cp\u003ePROM（h）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.789473684210526%\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003emode of delivery\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.68421052631579%\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eantibiotic\u003c/em\u003e \u003cem\u003euse\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.454545454545453%\"\u003e\n \u003cp\u003e\u003cem\u003eNormal\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN（％\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u003cem\u003eAbnormal\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN（％\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.181818181818183%\"\u003e\n \u003cp\u003eVaginal\u003c/p\u003e\n \u003cp\u003eN（％）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.909090909090908%\"\u003e\n \u003cp\u003eCesarean\u0026nbsp;N（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.636363636363637%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.636363636363637%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eNF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\"\u003e\n \u003cp\u003e13.39\u0026plusmn;3.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\"\u003e\n \u003cp\u003e83.20\u0026plusmn;6.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\"\u003e\n \u003cp\u003e0.1（0.1，0.14）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e15（71.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003e6（28.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e40（5.5，144）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003e11（52.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003e10（47.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003e14(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003e7（33.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003enon-NF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\"\u003e\n \u003cp\u003e11.73\u0026plusmn;3.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\"\u003e\n \u003cp\u003e78.96\u0026plusmn;8.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.702127659574469%\"\u003e\n \u003cp\u003e0.11（0.1，0.24）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e6（14.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003e36（85.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e0（0，24.25）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003e10（23.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003e32(76.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003e4(9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003e38(90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003et/\u0026chi;\u003csup\u003e2\u003c/sup\u003e/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003e1.684\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003e1.989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003e-0.456\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" colspan=\"3\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003e-3.415\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.789473684210526%\" colspan=\"2\"\u003e\n \u003cp\u003e5.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.68421052631579%\" colspan=\"2\"\u003e\n \u003cp\u003e2.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.1052631578947367%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.526315789473685%\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.578947368421053%\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.894736842105264%\" colspan=\"3\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.789473684210526%\" colspan=\"2\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.68421052631579%\" colspan=\"2\"\u003e\n \u003cp\u003e0.344\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Comparison of adverse neonatal outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe \u003cem\u003edifferences in RDS, ROP, duration of invasive ventilator use, duration of noninvasive ventilator use, white cell count, CRP level, percentage of neutrophils, and percentage of positive UU infections\u0026nbsp;\u003c/em\u003ebetween the two groups were \u003cem\u003estatistically\u003c/em\u003e \u003cem\u003esignificant\u003c/em\u003e (P \u0026lt; 0.05). The results are shown in \u003cem\u003eTable\u003c/em\u003e \u003cem\u003e3\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eTable 3 \u003cem\u003eComparison\u003c/em\u003e \u003cem\u003eof\u003c/em\u003e \u003cem\u003eneonatal\u003c/em\u003e \u003cem\u003eoutcomes\u003c/em\u003e between \u003cem\u003ethe\u003c/em\u003e two groups (x\u0026plusmn;\u003cem\u003es\u003c/em\u003e\u003cem\u003e，\u003c/em\u003e\u003cem\u003eN\u003c/em\u003e（％）\u003cem\u003e，\u003c/em\u003e\u003cem\u003eM\u003c/em\u003e\u003cem\u003e（\u003c/em\u003e\u003cem\u003eP25,P75\u003c/em\u003e\u003cem\u003e）\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003eNF N（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003enon-NF\u0026nbsp;N（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003et/\u0026chi;\u003csup\u003e2\u003c/sup\u003e/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003eRDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e8（38.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e28(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e4.667\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e13（61.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e14(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003eBPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e13（61.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e19(45.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.292\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.589\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e8（38.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e23(54.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003eNEC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e1(4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e3(7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e20(95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e39(92.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003eROP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e2(9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e16(38.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e19(90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e26(61.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003ePDA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e10(47.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e24(57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.511\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.475\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e11(52.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e18(42.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003eSGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e1(4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e2(4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e20(95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e40(95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003eintracranial\u003c/p\u003e\n \u003cp\u003ehemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e1(4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e7(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e20(95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e35(83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003ePVL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e3(14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e3（7.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.323\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e18(85.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e39（92.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003efetal\u0026nbsp;distress\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e4(19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e7（16.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e17(81.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e35（83.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003eduration\u0026nbsp;of\u0026nbsp;invasive ventilator\u0026nbsp;use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e0(0,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e3(0,9.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e-2.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003eduration of noninvasive ventilator use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e18.14\u0026plusmn;20.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e23.19\u0026plusmn;20.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e-0.929\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e0.356\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003eApgar1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e9(8，9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e9(8，9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e-0.456\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e0.648\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003elength of stay in hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e31（24，58）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e45（23，64.75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e-0.839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e0.402\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003eWhite cell count(\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e20.20\u0026plusmn;7.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e10.66\u0026plusmn;6.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e5.453\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003eCRP(mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e0.95（0.2，4.33）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e0.2（0.2，0.21）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e-3.853\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003eneutrophil\u0026nbsp;percen(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e60.95\u0026plusmn;11.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e48.69\u0026plusmn;14.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e3.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.483304042179263%\" colspan=\"2\"\u003e\n \u003cp\u003ePCT(ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e0.24（0.11，0.47）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e0.28（0.17，0.38）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e-1.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.586994727592268%\" rowspan=\"2\"\u003e\n \u003cp\u003eUU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.896309314586995%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e14(66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\"\u003e\n \u003cp\u003e4（9.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.599297012302285%\" rowspan=\"2\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.51412429378531%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e7(33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.24293785310734%\"\u003e\n \u003cp\u003e38（90.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIn this study, UU infection was a risk factor for NF (OR=5.846\u0026nbsp;\u003cu\u003e95% CI (1\u003c/u\u003e\u003cu\u003e.199-28.\u003c/u\u003e\u003cu\u003e512)).\u003c/u\u003e The diagnosis of UU\u0026nbsp;\u003cem\u003einfection\u0026nbsp;\u003c/em\u003ewas confirmed by positive urine\u0026nbsp;UU-\u003cem\u003ePCR\u0026nbsp;\u003c/em\u003ein this study.\u0026nbsp;UU\u0026nbsp;infection\u0026nbsp;was confirmed by urine UU-\u003cem\u003ePCR in 18\u003c/em\u003e patients. After treatment \u003cem\u003ewith\u003c/em\u003e intravenous \u003cem\u003eerythromycin\u003c/em\u003e, all of these patients had negative UU-\u003cem\u003ePCR\u003c/em\u003e results.\u003c/p\u003e\n\u003cp\u003eIn 21 neonates with NF, placental pathology suggested fetal vascular malperfusion\u0026nbsp;(FVM) in 7\u0026nbsp;patients, accounting for 33.7%.\u003cem\u003e\u0026nbsp;The case\u003c/em\u003e numbers are shown in Table 4.\u003c/p\u003e\n\u003cp\u003eTable 4. \u003cem\u003ePathological\u003c/em\u003e findings of 21cases with NF\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003eCase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ePathological\u003c/em\u003e findings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e2,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 1),\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003ehemosiderin\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003edeposits\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eare visible within \u0026nbsp;\u003cem\u003ethe focal\u003c/em\u003e \u003cem\u003edecidua\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e2),NF and \u003cem\u003eumbilical cord bleeding,\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eaccelerated\u003c/em\u003e villous maturation, maternal vascular malperfusion (MVM)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory response\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2), necrotizing \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e2),NF,placental villous is immature, \u003cem\u003eplacental\u003c/em\u003e \u003cem\u003eabruption\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e2,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2),\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003echorionic\u003c/em\u003e \u003cem\u003eplate\u003c/em\u003e inflammation\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF, placental villous is immature, few \u003cem\u003evillous\u003c/em\u003e edema, s\u003cem\u003eubchorionic\u003c/em\u003e \u003cem\u003ehematoma\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e2,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF, basal \u003cem\u003eplate\u003c/em\u003e \u003cem\u003enecrosis with\u0026nbsp;\u003c/em\u003elarge amount \u003cem\u003eof\u003c/em\u003e \u003cem\u003einflammatory\u003c/em\u003e \u003cem\u003ecells\u003c/em\u003e \u003cem\u003einfiltration\u003c/em\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e1,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 1)\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF, chorioangiosis, multiple blood vessels under \u003cem\u003echorionic\u003c/em\u003e \u003cem\u003eplate\u0026nbsp;\u003c/em\u003eexhibit occlusive thrombus, with a large amount of avascular villi,\u003c/p\u003e\n \u003cp\u003econstent with high grade \u0026quot;FVM\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2), acute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF, large amounts of immature intermediate villus , some villous edema\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2),necrotizing \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF,\u0026nbsp;multiple scattered avascular villi, constent with high grade \u0026quot;FVM\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e1,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2),acute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF, chorionic plate inflammation (moderate), some villus vessels were dilated and \u003cem\u003econgested\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF, \u003cem\u003eaccelerated\u003c/em\u003e villous maturation, multiple blood multifocal sheets of avascular villi, constent with \u0026quot;overall/partial FVM\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF, \u003cem\u003eintervillous thrombosis\u0026nbsp;\u003c/em\u003ehistologically\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 2\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)\u003cem\u003e.\u003c/em\u003eacute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e \u003cem\u003e2,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF,chorionic plate vessels inflammation (moderate), chorionic plate inflammation(moderate), subchorionic inflammation(moderate), villous stunting ,the \u003cem\u003evillous\u003c/em\u003e syncytiotrophoblast (SCT) increased.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 2\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)\u003cem\u003e.\u003c/em\u003eacute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis and\u0026nbsp;\u003c/em\u003echorionic \u003cem\u003eamniotic\u0026nbsp;\u003c/em\u003ecolumnar \u003cem\u003emetaplasia\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e \u003cem\u003e2,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF,chorionic plate vessels inflammation (moderate), chorionic plate inflammation(moderate), subchorionic inflammation(moderate), villous \u003cem\u003eedema\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 3\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e \u003cem\u003e2,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e1),NF,e\u003cem\u003excessive maturation of the placental villi\u003c/em\u003ethe, \u003cem\u003evillous\u003c/em\u003e syncytiotrophoblast increased.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 3\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e 3\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF,multiple small focal avascular villi, constent with \u0026quot;overall/partial FVM\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 2\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 1),acute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e 1\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade 1\u003c/em\u003e),NF,villous immaturity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 3\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e \u003cem\u003e3,\u003c/em\u003e \u003cem\u003egrade\u0026nbsp;\u003c/em\u003e2),NF,the placental villi are excessively mature, with increased nodules of syncytiotrophoblasts，large focal avascular villi with dry villous nonocclusive thrombus，thrombosis between the villi has formed.constent with high grade \u0026quot;FVM\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 2\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 1)\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e 3\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade 2\u003c/em\u003e),NF,villous \u003cem\u003eedema. dry chorionic thrombus was formed, along with large avascular villi.\u003c/em\u003econstent with \u0026quot;FVM\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 2\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2),acute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e 1\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade 1\u003c/em\u003e),NF, subchorionic inflammation \u0026nbsp;(mild),\u003cem\u003ea large number of mature\u003c/em\u003e \u003cem\u003eintermediate\u003c/em\u003e \u003cem\u003evillus,\u0026nbsp;\u003c/em\u003efibrinoid \u003cem\u003edeposition in the\u0026nbsp;\u003c/em\u003eintervillous \u003cem\u003espace increased ,\u003c/em\u003e partial villus edema\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e 1\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2)，acute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal inflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse(stage\u003c/em\u003e 2\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade 1\u003c/em\u003e),NF, chorionic plate inflammation, subchorionic inflammation,\u0026nbsp;nodules of syncytiotrophoblasts\u0026nbsp;increased，\u003cem\u003eplacental\u003c/em\u003e \u003cem\u003eabruption\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e2,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 1),\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eacute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e 2\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e1),NF\u003cem\u003e,accelerated\u003c/em\u003e villous maturation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.981949458483754%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85.01805054151625%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse\u003c/em\u003e \u003cem\u003e(stage\u003c/em\u003e \u003cem\u003e2,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e 2),\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eacute \u003cstrong\u003ec\u003c/strong\u003e\u003cem\u003ehorioamnionitis\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFeta\u003cem\u003eal\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003einflammatory\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cem\u003eresponse (stage\u003c/em\u003e 2\u003cem\u003e,\u003c/em\u003e \u003cem\u003egrade\u003c/em\u003e2),NF\u003cem\u003e,\u003c/em\u003echorionic plate inflammation(moderate), subchorionic inflammation(mild),\u003cem\u003ea large number of mature\u003c/em\u003e \u003cem\u003eintermediate\u003c/em\u003e \u003cem\u003evillus,\u0026nbsp;\u003c/em\u003epartial villous \u003cem\u003eedema,\u0026nbsp;\u003c/em\u003econstent with \u0026quot;FVM\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003ePlacental inflammation includes chorioamnionitis, chorioic vasculitis and funisitis. It is possible that chorioamnionitis, which is histologically defined as the presence of inflammatory cells inside gestational membranes and is often suggestive of infection of the amniotic cavity\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e, might represent a maternal inflammatory response to intra-amniotic infection. However, chorioinic vasculitis and funisitis might predominantly represent the fetal inflammatory response. Necrotizing chorioamnionitis is the severe stage of chorioamnionitis, while calcified necrotizing funisitis is the most serious stage of necrotizing chorioamnionitis. The migration of inflammatory cells such as neutrophils from the amniotic cavity into the muscular layer of umbilical vessels is a characteristic feature of omphalitis\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. OM typically starts at the umbilical vein, followed by the umbilical artery, because the venous walls of the umbilical cord are more prone to proinflammation than arterial walls are\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The initial stage involves multiple discrete foci. As inflammation progresses, these foci can eventually fuse, merge and involve the whole umbilical cord, characterized by concentric distribution of neutrophils along the blood vessel. Umbilical phlebitis represents phase 1 of fetal infection, umbilical arteritis represents phase 2, and calcified NF, as the relatively uncommon but serious omphalitis, is phase 3 and the most severe stage\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. The calcified NFs formed distinct lesions both macroscopically and microscopically. Macroscopically, yellow‒white bands parallel to the umbilical cord and the outline are crescent or ring shaped in cross sections. Microscopy has shown nonspecific inflammatory changes, necrotic cell debris and calcium deposits\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Because of the lack of lymphatic capillaries, larger lymphatic vessels and fixed macrophages, it is difficult to remove necrotic cells from the umbilical cord\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. With the accumulation and increase in mineralization of necrotic cells, zones of calcification are particularly prone to form in NF. In the present study, pathological examinations of the 21 patients revealed zones of calcification. Due to the formation of zones of calcification, there are areas of hyperechogenicity associated with calcification parallel to vascular walls on US. Because of the accumulation of necrotic debris and the deposition of calcium, the umbilical cord tends to be vulnerable, causing fetal distress and breakage\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. If not timely recognized, fetal hypoxia, bradycardia, and even intrauterine fetal death or rupture of the umbilical cord can occur during delivery. Therefore, NF should be considered when calcification is observed on fetal ultrasound and should be addressed promptly.\u003c/p\u003e\n\u003cp\u003eIn the event of NF, a fetus can develop an inflammatory response, which is a high-risk factor for premature rupture of membranes and vaginal birth in premature neonates\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. This study also revealed that the rate of vaginal birth in premature neonates was greater and that the duration of PROM was longer in the infection group than in the control group. Statistically significant differences were present. This finding also revealed that when the premature were delivered vaginally or had premature rupture of membranes, placental pathological findings of the newborns must be traveled by a NICU intensivist in our clinical work.\u003c/p\u003e\n\u003cp\u003eAn NF suggests a severe fetal inflammatory response, which might persist into the neonatal period. The present study revealed that the leukocyte count, CRP level and neutrophil proportion were significantly greater during the first 24 hours after delivery in the NF group than in the control group. The results were in concordance with those of a study by RALLIS D et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eWe also found that NF was associated with reduced RDS occurrence in preterm neonates. These findings are in agreement with previous studies by Ding R et al[13]. and BeenJ V et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. When complicated with NF, severe fetal inflammatory responses can occur. The lungs are exposed to inflammatory factors due to fetal breathing movements that involve mixing amniotic fluid with fetal lung fluid. Fetal exposure to infection can accelerate the maturation of fetal lung structure and surfactant metabolism\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e],\u003c/sup\u003e which reduces the incidence of RDS in premature infants. In our study, the incidence of BPD was greater in infants with NF, but the difference was not statistically significant, which is consistent with the results of studies by the Canadian Neonatal Network\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e and Laughon et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. but is contrary to those of the study by Villamor-Martinez E et al.\u003c/p\u003e\n\u003cp\u003eVillamor-Martinez E et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. reported that chorioamnionitis is associated with an increased risk of BPD. BPD arises from an imbalance in lung impairment, and repair during lung development is a complex and multifactorial syndrome that is influenced by antenatal and postnatal factors. Exposure to chorioamnionitis can protect infants from BPD by reducing the severity of RDS, while other types of exposure may promote BPD by triggering a progressive inflammatory response. In the present study, it was found that the use of invasive ventilation increased markedly between infants with NF and those without NF. We consider that this finding is associated with exposure to lung inflammation. However, the role of intrauterine infection in the development and progression of lung disease in neonates is uncertain.\u003c/p\u003e\n\u003cp\u003eThis study indicated that the incidence of ROP was lower in newborn infants with NF than in control infants, which was consistent with the findings of previous studies by Jee Yoon Park et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e and Leah A Owen et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. The mechanisms by which placental inflammation decreases the incidence of ROP are obscure. Some studies have suggested that fetal inflammatory agents can increase the concentration of insulin-like growth factor-1 (IGF-1\u003csup\u003e)[\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e and that IGF-1 stimulates the formation of retinal blood vessels and the normal retinal vascular network while maintaining the normal physiology of the retina and exerting anti-inflammatory and antioxidant effects, thus reducing the occurrence of ROP. This also explains the longer duration of invasive mechanical ventilation in newborn infants with NF, but the incidence of ROP decreased compared to that in the control group.\u003c/p\u003e\n\u003cp\u003eIn addition, intrauterine UU infection was \u003cem\u003edetected\u003c/em\u003e in 14 of 21 \u003cem\u003eneonates (66.7%)\u003c/em\u003e with NF and 4 of 42 \u003cem\u003eneonates (9.5%) without\u003c/em\u003e NF in this study, \u003cem\u003eand\u003c/em\u003e this difference was \u003cem\u003esignificant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eU. urealyticum is an opportunistic and common pathogen among women of reproductive age. Currently, the detection rate of UU can reach 82% in pregnant women\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Intrauterine UU infection \u003cem\u003eindicates\u003c/em\u003e that the newborn tested positive for excreta or secretions according to the UU-PCR test at least once and is most frequently infected via an ascending genital tract infection\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. The diagnosis of UU infection was confirmed by positive urine UU-PCR in this study\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. A large number of studies have indicated that UU infection is associated with serious complications and adverse outcomes\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Chorioamnionitis occurred in almost half of the \u003cem\u003enewborns\u003c/em\u003e confirmed to have intrauterine UU infection\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Lal et al. suggested that UU induces collagen fragmentation, PROM and neutrophil influx and can cause chorioamnionitis\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. The results of the study indicated that intrauterine UU infection could be a risk factor for NF. However, the pathogenesis of UU infection leading to NF remains to be clarified. Future studies are needed to investigate this further.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eNF is closely related to adverse outcomes. In our daily clinical work, placentas were collected by obstetricians at the time of delivery and sent to the Pathology Department for histological evaluation. However, the pathological reports were reported to the attending physicians, who are not obstetric NICU clinicians. However, there is growing evidence that pathological results are closely related to neonatal outcomes. Therefore, neonatologists should pay more attention to pathological findings. When histopathological examination shows NF, clinicians should evaluate these newborns and exclude\u003c/p\u003e \u003cp\u003eUU infection. Early identification of NF can facilitate timely clinical interventions and adjustment of antibiotics and has the potential to improve neonatal outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNF Necrotizing funisitis\u003c/p\u003e\n\u003cp\u003eUU \u003cem\u003eUreaplasma urealyticum\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCRP\u0026nbsp;\u0026nbsp;C-reactive protein\u003c/p\u003e\n\u003cp\u003ePCT \u0026nbsp;procalcitonin\u003c/p\u003e\n\u003cp\u003ePROM \u0026nbsp;premature rupture of membrane\u0026nbsp;rupture\u003c/p\u003e\n\u003cp\u003eRDS \u0026nbsp;respiratory distress syndrome\u003c/p\u003e\n\u003cp\u003eBPD \u0026nbsp;bronchopulmonary dysplasia\u003c/p\u003e\n\u003cp\u003eNEC\u0026nbsp;Necrotizing enterocolitis\u003c/p\u003e\n\u003cp\u003eROP\u0026nbsp;retinopathy of prematurity\u003c/p\u003e\n\u003cp\u003ePDA \u0026nbsp;patent ductus arteriosus\u003c/p\u003e\n\u003cp\u003ePVL\u0026nbsp;periventricular\u0026nbsp;leukomalacia\u003c/p\u003e\n\u003cp\u003eFVM \u0026nbsp;fetal vascular malperfusion\u003c/p\u003e\n\u003cp\u003eMVM \u0026nbsp;maternal\u0026nbsp;vascular malperfusion\u003c/p\u003e\n\u003cp\u003eIGF-1 insulin-like growth factor-1\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eX L guarantees the study. L P contributed to study management and data analysis, contributed to trial management and wrote all versions of the manuscript. M S contributed to the data analysis and critically appraised the manuscript. Q L contributed to the data analysis and critically appraised the manuscript. X F contributed to the trial management and data analysis and critically reviewed the manuscript. J L contributed to data curation. X L contributed to the study design and data analysis and critically appraised and gave final approval of the manuscript.All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study\u0026nbsp;was\u0026nbsp;performed without any supporting\u0026nbsp;funds.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData supporting the reported results can be requested from the main author.Written informed consent for publication was obtained.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThis\u003c/em\u003e \u003cem\u003estudy\u003c/em\u003e was approved \u003cem\u003eby\u003c/em\u003e \u003cem\u003ethe\u003c/em\u003e \u003cem\u003einstitutional\u003c/em\u003e \u003cem\u003ereview\u003c/em\u003e \u003cem\u003eboard\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eof\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003ethe\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eNeonatology\u0026nbsp;\u003c/em\u003e\u003cem\u003eDepartment\u0026nbsp;of Jinan Maternity\u0026nbsp;\u003c/em\u003e\u003cem\u003eAnd\u0026nbsp;Child Care Hospital\u0026nbsp;\u003c/em\u003e\u003cem\u003eAffiliated\u0026nbsp;\u003c/em\u003e\u003cem\u003eto\u0026nbsp;\u003c/em\u003e\u003cem\u003eShandong First Medical University \u0026nbsp;(\u003c/em\u003e\u003cem\u003eJinan,\u0026nbsp;\u003c/em\u003e\u003cem\u003eShandong\u003c/em\u003e, China).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA statement to confirm that all methods were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards.\u003cbr\u003e\u0026nbsp;A sentence confirming that written informed consent was obtained from all participants or if participants are under 16, from a parent and/or legal guardian. Include a statement on ethics approval and consent (even where the need for approval was waived).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all subjects involved in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKHONG T Y SA. Calcification of umbilical artery: two distinct lesions[J]. J Clin Pathol. 1989,;42(9):931\u0026ndash;4. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJACQUES SM. Necrotizing funisitis: a study of 45 cases[J]. Hum Pathol. 1992,;23(11):1278\u0026ndash;83. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCRAVER RD, BALDWIN VJ. Necrotizing funisitis[J]. Obstet Gynecol. 1992,;79(1):64\u0026ndash;70. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShao Xiaomei Y, Hongmao. Qiu Xiaoshan. Practical Neonatology [M]. People's Medical Publishing House, 2011(in Chinese).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiaomei S, Hongmao Y, Xiaoshan. Q et al. (2011). PRACTICE OF NEONATOLOGY. People's Health.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKHONG T Y I. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement[J]. Arch Pathol Lab Med. 2016,;140(7):698\u0026ndash;713. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMITTAL N,, BYARD R W JE. A practical guide to placental examination for forensic pathologists[J]. Forensic Sci Med Pathol. 2020,;16(2):295\u0026ndash;312. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKIM C J, ROMERO R, CHAEMSAITHONG P. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance[J]. Am J Obstet Gynecol. 2015,;213(4 Suppl):S29\u0026ndash;52. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKIM C J M. Histo-topographic distribution of acute inflammation of the human umbilical cord[J]. Pathol Int. 2001,;51(11):861\u0026ndash;5. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNAVARRO C, BLANC WA. Subacute necrotizing funisitis. A variant of cord inflammation with a high rate of perinatal infection[J]. J Pediatr. 1974,;85(5):689\u0026ndash;97. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZANARDO V, VEDOVATO S. Preterm premature rupture of membranes, chorioamnion inflammatory scores and neonatal respiratory outcome[J]. Bjog. 2010,;117(1):94\u0026ndash;8. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRALLIS D, LITHOXOPOULOU M. Clinical chorioamnionitis and histologic placental inflammation: association with early-neonatal sepsis[J]. J Matern Fetal Neonatal Med. 2022,;35(25):8090\u0026ndash;6. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDING R, CHEN Q, ZHANG Q W. [Association of different stages of histological chorioamnionitis with respiratory distress syndrome in preterm infants with a gestational age of \u0026lt;\u0026thinsp;32 weeks][J]. Zhongguo Dang Dai Er Ke Za Zhi. 2021,;23(3):248\u0026ndash;53. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBEEN JV. Histological chorioamnionitis and respiratory outcome in preterm infants[J]. Arch Dis Child Fetal Neonatal Ed. 2009,;94(3):F218\u0026ndash;225. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBANCALARI E.. Antenatal Infections and Respiratory Outcome in Preterm Infants[J]. Am J Perinatol. 2020,;37(S 02):S39\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSORAISHAM A S N, MCMILLAN DD. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants[J]. Am J Obstet Gynecol. 2009,;200(4):e372371\u0026ndash;376. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLAUGHON M, ALLRED E N C. Patterns of respiratory disease during the first 2 postnatal weeks in extremely premature infants[J]. Pediatrics. 2009,;123(4):1124\u0026ndash;31. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVILLAMOR-MARTINEZ E, \u0026Aacute;LVAREZ-FUENTE M, GHAZI A M T. Association of Chorioamnionitis With Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review, Meta-analysis, and Metaregression[J]. JAMA Netw Open. 2019,;2(11):e1914611. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePARK JY, PARK C W, MOON K C. Retinopathy of prematurity in infants without fetal growth restriction is decreased with the progression of acute histologic chorioamnionitis: New observation as a protective factor against retinopathy of prematurity[J]. Placenta. 2021,;104:161\u0026ndash;7. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOWEN L A C, SHIRER K. Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity[J]. Am J Pathol. 2023,;193(11):1776\u0026ndash;88. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSILWEDEL C, SPEER C P. Ureaplasma-associated prenatal, perinatal, and neonatal morbidities[J]. Expert Rev Clin Immunol. 2017,;13(11):1073\u0026ndash;87. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSUN T, FU J. Analysis of the Clinical Features of Intrauterine Ureaplasma urealyticumUreaplasma urealyticum Infection in Preterm Infants: A Case\u0026ndash;-Control Study[J]. Front Pediatr. 2021,;9:774150. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNASSAR F A FA. Detection of Chlamydia trachomatisChlamydia trachomatis and Mycoplasma hominisMycoplasma hominis, genitalium and Ureaplasma urealyticumUreaplasma urealyticum by polymerase chain reaction in patients with sterile pyuria[J]. Adv Med Sci. 2008,;53(1):80\u0026ndash;6. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCULTRERA R, SERACENI S, GERMANI R. Molecular evidence of Ureaplasma urealyticumUreaplasma urealyticum and Ureaplasma parvum colonization in preterm infants during respiratory distress syndrome[J]. BMC Infect Dis. 2006,;6:166. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVISCARDI RM. Ureaplasma species: role in neonatal morbidities and outcomes[J]. Arch Dis Child Fetal Neonatal Ed. 2014,;99(1):F87\u0026ndash;92. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKWAK D W, HWANG H S, KWON J Y. CoCo-infection with vaginal Ureaplasma urealyticumUreaplasma urealyticum and Mycoplasma hominisMycoplasma hominis increases adverse pregnancy outcomes in patients with preterm labor or preterm premature rupture of membranes[J]. J Matern Fetal Neonatal Med. 2014,;27(4):333\u0026ndash;7. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBARTKEVICIENE D, OPOLSKIENE G, BARTKEVICIUTE A. The impact of Ureaplasma infections on pregnancy complications[J]. Libyan J Med. 2020,;15(1):1812821. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKALIKKOT THEKKEVEEDU R SHIVANNAB. Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology[J]. Respir Med. 2017,;132:170\u0026ndash;7. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTITA A T WW. Diagnosis and management of clinical chorioamnionitis[J]. Clin Perinatol. 2010,;37(2):339\u0026ndash;54. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWAITES K B KATZB, SCHELONKA RL. Mycoplasmas and ureaplasmas as neonatal pathogens[J]. Clin Microbiol Rev. 2005,;18(4):757\u0026ndash;89. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXU LALCV, JACKSON X. Ureaplasma infection-mediated release of matrix metalloproteinase-9 and PGP: a novel mechanism of preterm rupture of membranes and chorioamnionitis[J]. Pediatr Res. 2017,;81(1\u0026ndash;1):75\u0026ndash;9. .\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Placental pathology, newborn, calcified necrotizing funisitis","lastPublishedDoi":"10.21203/rs.3.rs-4557511/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4557511/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eTo determine the association of calcified necrotizing funisitis with adverse neonatal outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod \u003c/strong\u003eThis retrospective study included newborns who had undergone pathological examination between July 2020 and March 2024. Twenty-one neonates who delivered at Jinan Maternal and Child Health Hospital with pathological results of calcified NF were retrospectively selected as the study subjects, and 44 neonates who were admitted during the same period without pathological results of calcified NF were selected as the control group according to a gestational age ratio of 1:2. Neonatal outcome measures were comparable between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eTwo groups were born preterm. Compared to those in the control group, the mode of delivery (cesarean vs vaginal), prolonged PROM, RDS, ROP, duration of ventilator use, white cell count, CRP, and neutrophil percentage in the observation group were significantly different from those in the control group (P\u0026lt;0.05). Among the 21 individuals analyzed, 14 patients (66.7%) were determined to be positive for UU infection in the observation group, and 4 patients (9.50%) were positive in the control group. The differences were statistically significant (P\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003e\u0026nbsp;Blood cell counts, CRP levels and neutrophil proportions were markedly elevated. The rates of RDS and ROP decreased. The duration of invasive mechanical ventilation use was prolonged in neonates with calcified necrotizing funisitis. UU was a risk factor for calcified NF.\u003c/p\u003e","manuscriptTitle":"Calcified necrotizing funisitis and its association with adverse neonatal outcomes: a case‒control study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-23 04:29:38","doi":"10.21203/rs.3.rs-4557511/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-02-22T12:15:52+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-07-02T05:38:47+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-30T21:28:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-26T13:52:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2024-06-21T11:38:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fc02e4cc-40cc-471d-ad16-d2972dcaa24e","owner":[],"postedDate":"July 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:10:46+00:00","versionOfRecord":{"articleIdentity":"rs-4557511","link":"https://doi.org/10.1186/s13052-025-02033-4","journal":{"identity":"italian-journal-of-pediatrics","isVorOnly":false,"title":"Italian Journal of Pediatrics"},"publishedOn":"2025-07-01 15:57:47","publishedOnDateReadable":"July 1st, 2025"},"versionCreatedAt":"2024-07-23 04:29:38","video":"","vorDoi":"10.1186/s13052-025-02033-4","vorDoiUrl":"https://doi.org/10.1186/s13052-025-02033-4","workflowStages":[]},"version":"v1","identity":"rs-4557511","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4557511","identity":"rs-4557511","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}