Neonatal morbidity and placental pathology
http://www.100md.com
《美国医学杂志》
Department of Pediatrics, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA
Abstract
Objective : To investigate the association between gestational age, placental pathology and outcome among preterm births. Methods : Medical records and placental pathology results of 165 preterm infants (gestational age ￡ 34 weeks) were used to analyze the development of intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and sepsis, in association with placental findings in the gestational age categories of 22-27 (n=71) and 28-33 (n=93) weeks. Results : Significant differences were found in placental findings based on gestational age and neonatal morbidity . Lower gestational age was associated with increased infection-related lesions such as chorionic vasculitis (47.9%, P<0.001) and acute chorioamnionitis (67.6%, P<0.001). Placental lesions reflecting disturbances of fetal-placental blood flow (infarction, chorionic plate thrombi and basal perivillous fibrin) were predominantly seen in the 28-33 week gestational age category (P<0.05-0.01). Despite the high prevalence of chorioamnionitis (38.8%), no significant association was found between this lesion and the tested preterm morbidity after controlling for gestational age. Only, villous edema and chorionic vasculitis were identified as independent predictors for the development of IVH (49.2%, ORA 2.57, 95% CI 1.01, 6.58 and 39.3%, ORA1.95, 95% CI 1.01, 4.21, respectively). Conclusion : Villous edema and chorionic vasculitis are significant risk factors for the development of the IVH among neonates born at gestational age ￡ 34 weeks.
Keywords: Preterm infants; Placental pathology; Neonatal morbidity
Placental pathology has been implicated in the pathogenesis of preterm neonatal morbidity. [1],[2],[3],[4],[5]However, the role of placental infection in the occurrence of neurological, lung and infection morbidity among prematurely born infants remains controversial.[1], [6] It has been reported that fetal thrombotic vasculopathy[7], chorionic plate thrombi[8],[9] villous edema[10] and maternal floor infarction[11] are responsible for the increased risk of neurological complications in preterm neonates. Some studies show an association between placental infection and the occurrence of brain damage in neonates,[2], [12],[13],[14],[15],[16],[17],[18],[19] while others do not support these findings.[20],[21],[22] Furthe0.rmore, there is disagreement regarding the association between chronic lung disease and sepsis in preterm neonates and in utero exposure to placental infection.[3],[23],[24],[25],[26] A strong association between the degree of prematurity with preterm morbidity as well as with the types of placental pathology would influence the interpretation of the results.
None of the studies have assessed the risk for the development of common preterm morbidity such as retinopathy of prematurity (ROP) and patent ductus arteriosus (PDA) in connection with placental lesions related to infection and/or pathological events reflecting abnormalities of placental-fetal blood flow.
This study was designed to investigate the association between gestational age, placental pathology and outcome among preterm births.
Materials and methods
The Neonatal Intensive Care Unit (NICU) discharge files and placental pathology reports of 165 preterm neonates with gestational age less than 34 weeks and without congenital malformation, admitted to the Tertiary Care NICU at Saint Peter's University Hospital from January 1999 to December 2001, were utilized for the analysis. The discharge data from the neonatal chart and discharge record is entered by the NICU physician and includes information about the pregnancy, delivery, and neonatal morbidity and mortality.
All placentas were examined by the same senior pathologist who was unaware of the clinical outcome of the infant. The reports were reviewed for evidence of placental abnormalities using standard definitions of commonly described placental pathological lesions.[27] Pathological placental findings were linked to the discharge data using maternal and neonatal charts numbers as the identifiers. Placental reports were available for all neonates included in the present study. The authors acknowledge the possibility of inter-observer variance and lack of consensus on the diagnosis of placental lesions. However, because the same pathologist evaluated all the placentas, it is assumed that all possible classification errors were equally distributed.
The cause-specific morbidity such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and neonatal sepsis was analyzed. IVH and PVL were diagnosed by cranial ultrasound; BPD was defined as a requirement for oxygen supplementation at 36 weeks postmenstrual age; ROP was diagnosed by the standard eye examination at four to six weeks of age; PDA was diagnosed using clinical, X-ray and echocardiography findings; and sepsis was confirmed by bacteriological positive blood or spinal fluid culture.
For the statistical analysis, all the grades of chorioamnionitis, IVH and ROP were deemed as either absent or present since insufficient data existed to individually analyze the results for each grade. Because PVL was diagnosed in only three of the infants, no separate analysis of its association with placenta pathology was done. All the infants with PVL had been diagnosed with severe IVH and were therefore analyzed as morbidity due to IVH. The study infants were divided into two gestational age categories: 22-27 weeks and 28-33 weeks.
Statistical analysis was performed using "STATISTICA" (Statistica for Windows, 1984-1994, StatSoft, Inc., Tulsa, OK) and Win Episcope 2.0 software. The Chi-square test was used to determine the difference in proportion of neonatal morbidity and placental lesions in the different gestational age categories. Multiple regression analysis was used to define the likelihood of single placental lesions being contributory to the development of preterm neonatal morbidity. Homogeneity of the effect of placental pathology on preterm neonatal mortality across gestational age was tested using the Mantel-Haenszel odds ratios (ORA) and calculating 95 percent confidence interval (95%CI). Two-sided P value <0.05 was considered statistically significant.
Results
Placental pathological lesions with respect to the gestational age at birth were analysed table1. A higher rate of chorionic vasculitis (47.9%) and chorioamnionitis (67.7%) was found among the preterm deliveries in the gestational age category of 22-27 weeks as compared to deliveries at 28-33 weeks (P<0.001). Acute chorioamnionitis was diagnosed in 63 out of the total 64 cases of chorioamnionitis in the two gestational age categories, and the majority had severe chorioamnionitis (71.1% and 68.8%, respectively). Villous edema was diagnosed in a small number of cases (11.7-14.1%) with the same frequency in both the gestational age categories, and 57.2% (12/21) of the placentas with villous edema concomitantly demonstrated acute chorioamnionitis. Placentas at 28-33 week of gestation predominantly showed lesions such as infarction (40.7%, P<0.001), chorionic plate thrombi (21.3%, P<0.05), and basal perivillous fibrin (94.7%, P<0.02) table1.
There was a strong association between gestational age and preterm neonatal morbidity Figure1. As compared to preterm neonates without IVH, the placental exam of preterm neonates with IVH more frequently exhibited pathological lesions such as villous edema (19.7% vs 8.7%, P<0.04), chorionic vasculitis (39.3% vs 20.2%, P<0.01) and chorioamnionitis (49.2 vs 32.7%, P<0.04) table2. In the cases diagnosed with chorioamnionitis, villous edema was present in 8/64 (12.5%) and chorionic vasculitis in 5/64 (7.8%) of the placentas. Chorionic vasculitis and chorioamnionitis were found with a higher frequency among preterm neonates with BPD, ROP and sepsis as compared to neonates without these conditions . No difference in the placental pathology of preterm neonates with and without PDA was found. Placental infarction was less commonly seen in preterm neonates with IVH, BPD, and ROP.
After controlling for the gestational age, a significant association between in utero exposure to villous edema or chorionic vasculitis and the risk for the development of IVH was noticed. However, there was no association between the placental pathological lesions and any other tested preterm morbidity. The 'adjusted to gestational age' odds ratio (ORA) suggests that villous edema and chorionic vasculitis were significant predictors for the development of IVH (ORA 2.57, 95% CI 1.01, 6.58 and ORA 1.95, 95% CI 1.01, 4.21, respectively).
Discussion
The present study shows that preterm delivery at 22-27 weeks of gestation is associated with a high incidence of chorioamnionitis and chorionic vasculitis that represents infection-related placental pathological lesions. [28],[29],[30] As compared to the lower gestational age category, the placentas at 28-33 week of gestation predominantly showed lesions such as infarction, chorionic plate thrombi and basal perivillous fibrin, which may compromise the fetal-placental blood flow.[8], [27], [31] These observations are consistent with the findings of others.[3], [4], [32], [33]
Acute chorioamnionitis is the main predisposing factor for preterm delivery at less than 28 weeks and does not influence the occurrence of neonatal morbidity after controlling for gestational age. These findings are in accord with other publications. [20],[21],[22], [26] An approximate two-fold increase in the odds of developing IVH was observed in preterm infants who had in utero exposure to placental villous edema or chorionic vasculitis. Therefore, villous edema and chorionic vasculitis were identified as independent predictors for the occurrence of IVH. Chorionic vasculitis is described as the histologic counterpart of the fetal inflammatory response syndrome[34] and villous edema may either represent the placental feature of fetal infection[10] or be a marker of antenatal hypoxia.[35], [36] Hence, chorionic vasculitis that reflects placental infection of fetal origin and villous edema that may be related to placental infection are significant independent predictors of brain damage among preterm neonates born at ￡ 34 weeks. The involvement of placental villous edema and chorionic vasculitis in the development of neurological impairments in very low birth weight children has been previously reported.[17], [36] Pro-inflammatory cytokines that are released into the fetal circulation in response to in utero infection have the ability to cross the blood-brain barrier and cause brain damage. [36],[37],[38]
Thus, placental pathological features such as villous edema and chorionic vasculitis can help predict the development of brain pathology among preterm born infants by providing clues regarding the pathogenesis of the preterm delivery and neonatal morbidity.
References
1. Langston C, Kaplan C, Macpherson T, Manci E, Peevy K, Clark B, Murtagh C, Cox S, Glenn G. Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists. Arch Pathol Lab Med 1997; 121 : 449-476.
2. Grafe MR. The correlation of prenatal brain damage with placental pathology. J Neuropath Exp Neurol 1994; 53 : 407-415.
3. Russell P. Inflammatory lesions of the human placenta. 1. Clinical significance of acute chorioamnionitis. Am J Diagn Gynecol Obstet 1979; 1 : 127-137
4. Watts DH, Krohn MA, Hillier SL, Eschenbach DA. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol 1992; 79 : 351-357.
5. Als H. Neurobehavioral development of preterm infant. Sixth Edition. In Fanaroff A.A, Martin RJ, eds. Neonatal-Prenatal Medicine. Diseases of the Fetus and Infant . 6th edn. St. Louis; Mosby 1997; 964-990.
6. Salafia CM, Vintzileos AM. Why all placentas should be examined by a pathologist in 1990. Am J Obst Gynecol 1990; 163 : 1282-1293.
7. Kraus FT, Acheen VI. Fetal thrombotic vasculopathy in the placenta: cerebral thrombi and infarcts, coagulopathies, and cerebral palsy. Hum Pathol 1999; 30 : 759-769.
8. Redline RW, Wilson-Costello D, Borawski E, Fanaroff AA, Hack M. Placental lesions associated with neurologic impairment and cerebral palsy in very low-birth-weight infants. Arch Pathol Lab Med 1998; 122 : 1091-1098.
9. Redline RW, Willson-Costello D, Borawski E, Faranoff AA, Hack M. The relationship between placental and other perinatal risk factors for neurologic impairment in very low birth weight children. Ped Res 2000; 47 : 721-726.
10. Kliman HJ, Jones DC, Morotti RA. The rise and fall of villous edema as a function of time from initiation of intrauterine infection. Am J Obstet Gynecol 1995; 172 : 312.
11. Adams-Chapman I, Vaucher YE, Bejar RF, Benirschke K, Baergen RN, Moore TR. Maternal floor infarction of the placenta: association with central nervous system injury and adverse neurodevelopmental outcome. J Perinatol 2002; 22 : 236-241.
12. Tauscher MK, Berg D, Brockmann M, Seidenspinner S, Speer CP, Groneck P. Association of histologic chorioamnionitis, increased levels of cord blood cytokines, and intracerebral hemorrhage in preterm neonates. Biol Neon 2003; 83 : 166-170.
13. Alexander JM, Gilstrap LC, Cox SM, Mcintire DM, Leveno KJ. Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obst Gynecol 1998; 91 : 725-729.
14. Murphy DJ, Sellers S, MacKenzie IZ, Yudkin PL, Johnson AM. Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies. Lancet 1995; 346 : 1449-1454.
15. Yoon BH, Jun JK, Romero R, Park KH, Gomes R, Choi JH, Kim IO. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol 1996; 174 : 1433-1440.
16. Arias F, Victoria A, Cho K, Kraus F. Placental histology and clinical characteristics of patients with preterm premature rupture of membranes. Obstet Gynecol 1997; 89 : 265-271.
17. Dexter SC, Pinar H, Malee M, Hogan J, Carpenter MW, Vohr BR. Outcome of very low birth weight infants with histopathologic chorioamnionitis. Obstet Gynecol 2000; 96 : 172-177
18. De Felice C, Toni P, Laurini RN, Stumpo M, Enrico P, Todtos T, Tanganelli P, Buonocore G, Bracci R. Early neonatal brain injury in histologic chorioamnionitis. J Pediatr 2001; 138 : 101-104.
19. Kumazaki K, Nakayama M, Sumida Y, Ozono K, Mushiake S, Suehara N, Wada Y, Fujimura M. Placental features in preterm infants with periventricular leukomalacia. Pediatrics 2002; 109 : 650-655.
20. Ambalavanan N, Nelson KG. Alexander G, Johnson SE. Biasini F. Carlo WA. Prediction of neurologic Morbidity in Extremely low birth weight infants. J Perinatol 2000; 20 : 496-503.
21. Dexter SC, Malee MP, Pinar H, Hogan JW, Carpenter MW, Vohr BR. Influence of chorioamnionitis on developmental outcome in very low birth weight infants. Obstet Gynecol 1999; 94 : 267-273.
22. Verma U, Trjani N, Reale MR, Beneck D, Figueroa R, Visintainer I. Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate. Am J Obstet Genecol 1997; 176 : 275-281.
23. Lyon A. Chronic lung disease of prematurity. The role of intra-uterine infection. Eur J Pediatr 200; 159 : 798-802.
24. Hallman M. Cytokines, pulmonary surfactant and consequences of intrauterine infection. Biol Neonate 1999; 76(suppl 1):2-9
25. Vigneswaran R. Infection and preterm birth: Evidence of a common causal relationship with bronchopulmonary dysplasia and cerebral palsy. J Paediatr Child Health 2000; 36 : 293-296.
26. Redline RW, Wilson-Costello D, Hack M. Placental and other perinatal risk factors for chronic lung disease in very low birth weigh infants. Ped Res 2002; 52 : 713-719.
27. Jacques SM, Qureshi F. Chronic chorioamnionitis: a clinicopathologic and immunohistochemical study: Hum Pathol 1998; 29 : 1457-1461.
28. Khong TY, Bendon RW, Qureshi F, Redline RW, Gould S, Stallmach T, Lipsett J, Staples A. Chronic deciduitis in the placental basal plate: definition and interobserver reliability. Hum Pathol 2000; 31 : 292-295.
29. Kim CJ, Yoon BH, Park SS, Kim MH, Chi JG. Acute funisitis of preterm but not term placentas is associated with severe fetal inflammatory response. Hum Pathol 2001; 32 : 623-629.
30. Benirschke K, Kaufmann P. The pathology of the human placenta. 3rd edn. New York; Springer-Verlag, 1995: 484-500.
31. Naeye RL, Maisels MJ, Lorenz RP, Botti JJ. The clinical significance of placental villous edema. Pediatrics 1988; 71 : 588-594.
32. Arias F, Victoria A, Cho K, Kraus F. Placental histology and clinical characteristics of patients with preterm premature rupture of membranes. Obstet Gynecol 1997; 89 : 265-271.
33. Redline RW, Patterson P. Patterns of placental injury. Correlations with gestational age, placental weight and clinical diagnoses. Arch Pathol Lab Med 1994; 118 : 698-701.
34. Rosen T, Schatz F, Kuczynski H, Lam H, Koo AB, Lockwood CJ. Funisitis and chorionic vasculitis: the histologic counterpart of the inflammatory response syndrome. J Mat-Fetal Neon Med 2002; 11 : 18-26.
35. Naeye RL, Maisels MJ, Lorenz RP, Botti JJ. The clinical significance of placental villous edema. Pediatrics 1983; 71 : 588-594.
36. Leviton A, Paneth N, Reuss ML, ML, Susser M, Allred EN, Dammann O, Kuban K, Van Marter LJ, Pagano M, Hegyi T, Hiatt M, Sanocka U, Shahrival F, Abiri M, Disalvo D, Doubilet P, Kairam R, Kazam E, Kirpekar M, Rosenfeld D, Schonfeld S, Share J, Collins M, Genest D, Shen-Schwarz et al. Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators. Pediatr Res 1999; 46 : 566-575.
37. Adinolfi M. Infectious diseases in pregnancy, cytokines and neurological impairment: a hypothesis. Dev Med Child Neurol 1993; 35 : 549-553.
38. Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Ped Res 1997; 42 : 1-8.(Mehta Rajeev, Nanjundaswa)
Abstract
Objective : To investigate the association between gestational age, placental pathology and outcome among preterm births. Methods : Medical records and placental pathology results of 165 preterm infants (gestational age ￡ 34 weeks) were used to analyze the development of intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and sepsis, in association with placental findings in the gestational age categories of 22-27 (n=71) and 28-33 (n=93) weeks. Results : Significant differences were found in placental findings based on gestational age and neonatal morbidity . Lower gestational age was associated with increased infection-related lesions such as chorionic vasculitis (47.9%, P<0.001) and acute chorioamnionitis (67.6%, P<0.001). Placental lesions reflecting disturbances of fetal-placental blood flow (infarction, chorionic plate thrombi and basal perivillous fibrin) were predominantly seen in the 28-33 week gestational age category (P<0.05-0.01). Despite the high prevalence of chorioamnionitis (38.8%), no significant association was found between this lesion and the tested preterm morbidity after controlling for gestational age. Only, villous edema and chorionic vasculitis were identified as independent predictors for the development of IVH (49.2%, ORA 2.57, 95% CI 1.01, 6.58 and 39.3%, ORA1.95, 95% CI 1.01, 4.21, respectively). Conclusion : Villous edema and chorionic vasculitis are significant risk factors for the development of the IVH among neonates born at gestational age ￡ 34 weeks.
Keywords: Preterm infants; Placental pathology; Neonatal morbidity
Placental pathology has been implicated in the pathogenesis of preterm neonatal morbidity. [1],[2],[3],[4],[5]However, the role of placental infection in the occurrence of neurological, lung and infection morbidity among prematurely born infants remains controversial.[1], [6] It has been reported that fetal thrombotic vasculopathy[7], chorionic plate thrombi[8],[9] villous edema[10] and maternal floor infarction[11] are responsible for the increased risk of neurological complications in preterm neonates. Some studies show an association between placental infection and the occurrence of brain damage in neonates,[2], [12],[13],[14],[15],[16],[17],[18],[19] while others do not support these findings.[20],[21],[22] Furthe0.rmore, there is disagreement regarding the association between chronic lung disease and sepsis in preterm neonates and in utero exposure to placental infection.[3],[23],[24],[25],[26] A strong association between the degree of prematurity with preterm morbidity as well as with the types of placental pathology would influence the interpretation of the results.
None of the studies have assessed the risk for the development of common preterm morbidity such as retinopathy of prematurity (ROP) and patent ductus arteriosus (PDA) in connection with placental lesions related to infection and/or pathological events reflecting abnormalities of placental-fetal blood flow.
This study was designed to investigate the association between gestational age, placental pathology and outcome among preterm births.
Materials and methods
The Neonatal Intensive Care Unit (NICU) discharge files and placental pathology reports of 165 preterm neonates with gestational age less than 34 weeks and without congenital malformation, admitted to the Tertiary Care NICU at Saint Peter's University Hospital from January 1999 to December 2001, were utilized for the analysis. The discharge data from the neonatal chart and discharge record is entered by the NICU physician and includes information about the pregnancy, delivery, and neonatal morbidity and mortality.
All placentas were examined by the same senior pathologist who was unaware of the clinical outcome of the infant. The reports were reviewed for evidence of placental abnormalities using standard definitions of commonly described placental pathological lesions.[27] Pathological placental findings were linked to the discharge data using maternal and neonatal charts numbers as the identifiers. Placental reports were available for all neonates included in the present study. The authors acknowledge the possibility of inter-observer variance and lack of consensus on the diagnosis of placental lesions. However, because the same pathologist evaluated all the placentas, it is assumed that all possible classification errors were equally distributed.
The cause-specific morbidity such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and neonatal sepsis was analyzed. IVH and PVL were diagnosed by cranial ultrasound; BPD was defined as a requirement for oxygen supplementation at 36 weeks postmenstrual age; ROP was diagnosed by the standard eye examination at four to six weeks of age; PDA was diagnosed using clinical, X-ray and echocardiography findings; and sepsis was confirmed by bacteriological positive blood or spinal fluid culture.
For the statistical analysis, all the grades of chorioamnionitis, IVH and ROP were deemed as either absent or present since insufficient data existed to individually analyze the results for each grade. Because PVL was diagnosed in only three of the infants, no separate analysis of its association with placenta pathology was done. All the infants with PVL had been diagnosed with severe IVH and were therefore analyzed as morbidity due to IVH. The study infants were divided into two gestational age categories: 22-27 weeks and 28-33 weeks.
Statistical analysis was performed using "STATISTICA" (Statistica for Windows, 1984-1994, StatSoft, Inc., Tulsa, OK) and Win Episcope 2.0 software. The Chi-square test was used to determine the difference in proportion of neonatal morbidity and placental lesions in the different gestational age categories. Multiple regression analysis was used to define the likelihood of single placental lesions being contributory to the development of preterm neonatal morbidity. Homogeneity of the effect of placental pathology on preterm neonatal mortality across gestational age was tested using the Mantel-Haenszel odds ratios (ORA) and calculating 95 percent confidence interval (95%CI). Two-sided P value <0.05 was considered statistically significant.
Results
Placental pathological lesions with respect to the gestational age at birth were analysed table1. A higher rate of chorionic vasculitis (47.9%) and chorioamnionitis (67.7%) was found among the preterm deliveries in the gestational age category of 22-27 weeks as compared to deliveries at 28-33 weeks (P<0.001). Acute chorioamnionitis was diagnosed in 63 out of the total 64 cases of chorioamnionitis in the two gestational age categories, and the majority had severe chorioamnionitis (71.1% and 68.8%, respectively). Villous edema was diagnosed in a small number of cases (11.7-14.1%) with the same frequency in both the gestational age categories, and 57.2% (12/21) of the placentas with villous edema concomitantly demonstrated acute chorioamnionitis. Placentas at 28-33 week of gestation predominantly showed lesions such as infarction (40.7%, P<0.001), chorionic plate thrombi (21.3%, P<0.05), and basal perivillous fibrin (94.7%, P<0.02) table1.
There was a strong association between gestational age and preterm neonatal morbidity Figure1. As compared to preterm neonates without IVH, the placental exam of preterm neonates with IVH more frequently exhibited pathological lesions such as villous edema (19.7% vs 8.7%, P<0.04), chorionic vasculitis (39.3% vs 20.2%, P<0.01) and chorioamnionitis (49.2 vs 32.7%, P<0.04) table2. In the cases diagnosed with chorioamnionitis, villous edema was present in 8/64 (12.5%) and chorionic vasculitis in 5/64 (7.8%) of the placentas. Chorionic vasculitis and chorioamnionitis were found with a higher frequency among preterm neonates with BPD, ROP and sepsis as compared to neonates without these conditions . No difference in the placental pathology of preterm neonates with and without PDA was found. Placental infarction was less commonly seen in preterm neonates with IVH, BPD, and ROP.
After controlling for the gestational age, a significant association between in utero exposure to villous edema or chorionic vasculitis and the risk for the development of IVH was noticed. However, there was no association between the placental pathological lesions and any other tested preterm morbidity. The 'adjusted to gestational age' odds ratio (ORA) suggests that villous edema and chorionic vasculitis were significant predictors for the development of IVH (ORA 2.57, 95% CI 1.01, 6.58 and ORA 1.95, 95% CI 1.01, 4.21, respectively).
Discussion
The present study shows that preterm delivery at 22-27 weeks of gestation is associated with a high incidence of chorioamnionitis and chorionic vasculitis that represents infection-related placental pathological lesions. [28],[29],[30] As compared to the lower gestational age category, the placentas at 28-33 week of gestation predominantly showed lesions such as infarction, chorionic plate thrombi and basal perivillous fibrin, which may compromise the fetal-placental blood flow.[8], [27], [31] These observations are consistent with the findings of others.[3], [4], [32], [33]
Acute chorioamnionitis is the main predisposing factor for preterm delivery at less than 28 weeks and does not influence the occurrence of neonatal morbidity after controlling for gestational age. These findings are in accord with other publications. [20],[21],[22], [26] An approximate two-fold increase in the odds of developing IVH was observed in preterm infants who had in utero exposure to placental villous edema or chorionic vasculitis. Therefore, villous edema and chorionic vasculitis were identified as independent predictors for the occurrence of IVH. Chorionic vasculitis is described as the histologic counterpart of the fetal inflammatory response syndrome[34] and villous edema may either represent the placental feature of fetal infection[10] or be a marker of antenatal hypoxia.[35], [36] Hence, chorionic vasculitis that reflects placental infection of fetal origin and villous edema that may be related to placental infection are significant independent predictors of brain damage among preterm neonates born at ￡ 34 weeks. The involvement of placental villous edema and chorionic vasculitis in the development of neurological impairments in very low birth weight children has been previously reported.[17], [36] Pro-inflammatory cytokines that are released into the fetal circulation in response to in utero infection have the ability to cross the blood-brain barrier and cause brain damage. [36],[37],[38]
Thus, placental pathological features such as villous edema and chorionic vasculitis can help predict the development of brain pathology among preterm born infants by providing clues regarding the pathogenesis of the preterm delivery and neonatal morbidity.
References
1. Langston C, Kaplan C, Macpherson T, Manci E, Peevy K, Clark B, Murtagh C, Cox S, Glenn G. Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists. Arch Pathol Lab Med 1997; 121 : 449-476.
2. Grafe MR. The correlation of prenatal brain damage with placental pathology. J Neuropath Exp Neurol 1994; 53 : 407-415.
3. Russell P. Inflammatory lesions of the human placenta. 1. Clinical significance of acute chorioamnionitis. Am J Diagn Gynecol Obstet 1979; 1 : 127-137
4. Watts DH, Krohn MA, Hillier SL, Eschenbach DA. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol 1992; 79 : 351-357.
5. Als H. Neurobehavioral development of preterm infant. Sixth Edition. In Fanaroff A.A, Martin RJ, eds. Neonatal-Prenatal Medicine. Diseases of the Fetus and Infant . 6th edn. St. Louis; Mosby 1997; 964-990.
6. Salafia CM, Vintzileos AM. Why all placentas should be examined by a pathologist in 1990. Am J Obst Gynecol 1990; 163 : 1282-1293.
7. Kraus FT, Acheen VI. Fetal thrombotic vasculopathy in the placenta: cerebral thrombi and infarcts, coagulopathies, and cerebral palsy. Hum Pathol 1999; 30 : 759-769.
8. Redline RW, Wilson-Costello D, Borawski E, Fanaroff AA, Hack M. Placental lesions associated with neurologic impairment and cerebral palsy in very low-birth-weight infants. Arch Pathol Lab Med 1998; 122 : 1091-1098.
9. Redline RW, Willson-Costello D, Borawski E, Faranoff AA, Hack M. The relationship between placental and other perinatal risk factors for neurologic impairment in very low birth weight children. Ped Res 2000; 47 : 721-726.
10. Kliman HJ, Jones DC, Morotti RA. The rise and fall of villous edema as a function of time from initiation of intrauterine infection. Am J Obstet Gynecol 1995; 172 : 312.
11. Adams-Chapman I, Vaucher YE, Bejar RF, Benirschke K, Baergen RN, Moore TR. Maternal floor infarction of the placenta: association with central nervous system injury and adverse neurodevelopmental outcome. J Perinatol 2002; 22 : 236-241.
12. Tauscher MK, Berg D, Brockmann M, Seidenspinner S, Speer CP, Groneck P. Association of histologic chorioamnionitis, increased levels of cord blood cytokines, and intracerebral hemorrhage in preterm neonates. Biol Neon 2003; 83 : 166-170.
13. Alexander JM, Gilstrap LC, Cox SM, Mcintire DM, Leveno KJ. Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obst Gynecol 1998; 91 : 725-729.
14. Murphy DJ, Sellers S, MacKenzie IZ, Yudkin PL, Johnson AM. Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies. Lancet 1995; 346 : 1449-1454.
15. Yoon BH, Jun JK, Romero R, Park KH, Gomes R, Choi JH, Kim IO. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol 1996; 174 : 1433-1440.
16. Arias F, Victoria A, Cho K, Kraus F. Placental histology and clinical characteristics of patients with preterm premature rupture of membranes. Obstet Gynecol 1997; 89 : 265-271.
17. Dexter SC, Pinar H, Malee M, Hogan J, Carpenter MW, Vohr BR. Outcome of very low birth weight infants with histopathologic chorioamnionitis. Obstet Gynecol 2000; 96 : 172-177
18. De Felice C, Toni P, Laurini RN, Stumpo M, Enrico P, Todtos T, Tanganelli P, Buonocore G, Bracci R. Early neonatal brain injury in histologic chorioamnionitis. J Pediatr 2001; 138 : 101-104.
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