Effect of Acute Placenta Inflammatory Changes on Fetal Outcome among Paturients in Nigeria

Introduction: The placenta unit is significant for the survival of the fetus. Infections from the mother can cause histologically identifiable inflammatory changes in the placenta, which may adversely affect the fetus. Methods: Histological analysis of 189 placenta tissues of singleton birth paturients was carried out. The sociodemographic characteristics of patients and the fetal outcome was collated and analyzed. The information obtained was processed using the SPSS version 20 software and Epi info software version 7. Results were presented in tables; test of association was done using student’s t-test with P value < 0.05 set as significant. Results: The mean age of patients was 30.9±4.6 years with age range of 19-48years. Acute placental inflammatory changes of varying grades were noted in 64.6%(122) of placenta with severe inflammatory changes constituting 8.5%(16) of all examined placentae. Severely inflamed placenta was associated with birth asphyxia (P=0.0000033) and fetal demise (P=0.0352). Conclusion: Acute inflammatory changes are common among paturients in Port Harcourt Nigeria. These changes in placenta are associated with birth asphyxia and fetal demise especially when they are severe.


INTRODUCTION
The placenta is an integral part of the existance of the fetus, it serves as an interface in the transmission of requisite nutrients and other metabolic materials [1,2]. The placenta histology can be altered by intrauterine infections which is usually acquired as a result of ascending infection from the genital tract, gut or hematogenously resulting in chorioamnionitis which complicates about 10% of all pregnancies with up to 2% occurring during labour [3,4].
Several organisms have been implicated in the causation of chorioamnionitis inclusive of bacterial and viral organisms. Bacterial organisms are linked to acute inflammation while viral organisms were associated with chronic changes [3,5,6]. Polymicrobial bacterial organisms contribute to these acute inflammatory changes of which ureaplasma urealyticulum and gardnella vaginitis are the two commonest organisms [3].
The presence of infectious organisms in the chorioamnion engenders a maternal and fetal inflammatory response characterized by proinflammatory and inhibitory cytokines and chemokines in the maternal and fetal compartments; with maternal inflammatory response preceding the fetal response [7]. The placenta changes in the presence of infection can be categorized into acute, subacute or chronic with acute chorioamnionitis with or without fetal inflammatory response, villitis and decidualitis been the most common types of placenta inflammations observed [8].
Acute chorioamnionitis can be diagnosed clinically or histologically. Histological chorioamnionitis is defined by the presence of acute histological changes on examination of the amniotic membrane and chorion of the placenta [9]. Sometimes subclinical infections can be missed but captured by histological examination of placenta and histological diagnosis is the gold standard for evaluation of antenatal inflammatory process that might influence fetal development [10,11]. This modality of diagnosis of infection increases the rate of identification of chorioamnionitis than clinically diagnosed chorioamnionitis confirmed by amniotic fluid culture because of lack of detection of some organisms cultured [10].
Some series have identified that impairment of placental development as a result of infection may have a profound impact in fetal development and pregnancy outcome such as cerebral palsy and high rate of stillbirths [12,13]. It is on these basis that this study seeks to determine the prevalence of acute inflammatory placenta changes and its effect on the fetal outcome among paturients who presented for delivery at the University Teaching Hospital in Port Harcourt, Nigeria.

METHODOLOGY
A cross sectional histological study of 189 placentae of women who had singleton deliveries between 1 st September to 30 th December 2015 was conducted. The women were recruited into the study as they presented to the labour ward after due counseling on the scope of the study by the investigators. All patients who gave consent for the study were included. Exclusion criteria included: multi-order pregnancies, women who had evidence of immunosuppression like diabetes mellitus, on steroids or diagnosed with retroviral disease, patients with preeclampsia, previous antenatal infections, intrauterine growth restriction of known cause, patients with PROM and Chorioamnionitis were also excluded. All other patients who presented to the labour ward during the study period were included in the study. The sociodemographic characteristics of patients, which include: age, parity, educational status and booking status; birth weight, presence or absence of birth asphyxia and fetal outcome (dead or alive) were collated in a prestructured spread sheet and analyzed. The placenta immediately after delivery was collected and blood stain removed from it using gentle running water, preserved in 10% formaldehyde solution and transferred to the anatomical pathology laboratory of the teaching hospital for processing. Grossing of the placenta was done and representative sections were taken. Tissues were processed in the automated tissue processor and later stained using the hematoxylin and eosin methods.
Two independent pathologists reviewed processed slides and areas of disparity were resolved following a consensus decision of the two pathologists. Histologic grading of acute inflammation was assessed by the density of neutrophil infiltrates and the relative distance migrated from the vessels of origin. Placental inflammatory changes were scored and categorized as: (Nil)-no chorioamnionitis; Grade 1 (Mild): presence of polymorphonuclear leucocytes at the subchorionic plate and lower third of chorion; Grade 2(moderate): At least two separate foci of leucocytes infiltrates in the chorion and Amnion, and Grade 3 (severe)extensive leucocyte infiltrates in the chorion / amnion [14].
The information obtained was processed using the SPSS version 20 software (SPSS Inc; Chicago USA) and Epi info software version 7. Results were presented in tables, test of association was done using student's t-test with P value < 0.05 set as significant.

RESULTS
The mean age of patients was 30.9±4.6 years with an age range of 19-48 years. 69.8% (132) were in the age group 25-34 years and 74.6% (141) were nulliparous patients, 74.6% (141) had tertiary education and 93.7% (177) of examined placenta belonged to booked patients while 6.3% (12) were unbooked. Other sociodemographic variables are as shown in Table 1. Table 2 showed the relationship of booking status to placenta inflammatory changes. Acute placenta inflammatory changes were observed in 122(64.6%) of all patients studied with 16(8.5%) having severe inflammatory changes. Among the patients, 177(93.7%) were booked while 6.3% were unbooked. In patients with severe inflammatory changes 14 (87.5%) were booked while 2 (12.5%) were unbooked. Booking status was not significantly associated with placenta inflammatory changes (P=0.08541). Among babies delivered 11 (5.8%) had low birth weight while 94.2% (178) were not low birth weight. Among all babies born to mothers with severe placenta inflammatory changes, 2 (12.5%) were low birth weight while 14 (87.5%) were not low birth weight. Other distributions are as shown in Table 2. Patients with severe placenta inflammatory changes were not significantly associated with low birth weight babies (P=0.15).  Table 3 showed the relationship between fetal outcome and placenta inflammatory changes: 140 (74.1%) had no birth asphyxia while 49 (25.9%) had some form of birth asphyxia. Among those with severe placenta inflammatory changes 12 (75%) had some form of asphyxia while 4 (25%) had no birth asphyxia. Placenta inflammatory changes are significantly associated with birth asphyxia (P =0.00367). Severe inflammatory changes are significantly associated with severe birth asphyxia (P= 0.0000033).
Fetal demise was not significantly associated with general placenta inflammatory changes (P= 0.2666), however severe placenta changes was significantly associated with fetal demise (P=0.0352).

DISCUSSION
The average age of paturients was similar to what was observed in other areas in Nigeria [15,16], which was the peak of the sexual and reproductive ages of the patients studied. This study also noted that a large proportion of women with inflammatory placenta changes were nulliparous which was in conformity with what was observed by Baker et al, who identified that acute placenta infections decrease with increasing parity [17]. The reason as postulated by Lagadari et al. [18] is the development of protective layer of macrophages between decidua and trophoblastic layers as parity increased as demonstrated in rat models.
Acute placenta inflammatory changes of varying degree were observed in more than half of all patients' placentae examined, with similar distribution of placenta changes observed by Rhone et al. [19], where about 50% of placenta studied by his group identified changes consistent with inflammatory changes. Variations in the prevalence rate of acute inflammatory changes are related to the differences in tissue sampling techniques and diagnostic criteria.
Acute placenta inflammatory changes have a direct correlation to clinical chorioamnionitis, which is linked to poor fetal outcome [20]. These observations brings to the front burner the need to screen paturients for possible organisms that are linked to acute infections such as bacterial vaginosis which is a known etiological factor for chorioamnionitis and preterm membrane rupture.
The unskilled supervised deliveries (unbooked) have been associated with increased risk of chorioamnionitis and puerperal sepsis due to some unhygienic birth practices [21]. In this group of patients, placenta inflammatory changes was not associated with the booking status of the paturients; thus there may be some other confounding factors which are not related to the booking status of the patient that need to be unearthed.  It was observed that, as in this study, severe placenta inflammatory changes are associated with poor fetal outcome such as asphyxia and even stillbirths [23,24]. The mechanism by which this is made possible is via placenta damage with loss of function, preterm labour, release of inflammatory mediators, which result in fetal organ damage and transplacental infection [5]. The fetal inflammatory response syndrome which is related to placenta infections had also be linked with the development of cerebral palsy and the development of neurological deficits in the babies that survive the infectious onslaught [25].

CONCLUSION
Based on the above it is pertinent to know that placental inflammatory changes being the hallmark of fetal infection is associated with poor fetal outcome in Port Harcourt Nigeria. Hence it is imperative that steps be instituted to reduce the risk of placenta infection among paturients by creating protocols for screening of bacterial pathogens, reduce the factors that increase risk and possibly prophylaxis therapy of all at risk patients. Also a protocol of histological examination of placentae of stillborns and babies with severe birth asphyxia is also recommended to eliminate the long-term complications of infections related morbidities.

ETHICAL APPROVAL
Ethical approval was obtained from the Internal Ethics Board of the University of Port Harcourt Teaching hospital before the commencement of the study.