Prevalence and Risk Factors of Chorioamnionitis in Dhaka, Bangladesh

ORIGINAL ARTICLE Prevalence and risk factors of chorioamnionitis in Dhaka, Bangladesh

GJ Chan1,2, M Silverman1, M Zaman3, A Murillo-Chaves4, A Mahmud3, AH Baqui5 and TK Boyd4

OBJECTIVE: To estimate the association between chorioamnionitis, maternal risk factors and birth outcomes. STUDY DESIGN: A cross-sectional study of 600 pregnant women was conducted at a maternity center in Dhaka from January to October 2011. Outcomes included histologic, microbiologic and clinical chorioamnionitis. Log-binomial models assessed the association between risk factors and histologic chorioamnionitis (HC). RESULTS: Of the 552 women with placental specimens, 70 (12.7%) were classified with HC: 46 (65.7%) with and 24 (34.3%) without fetal involvement. HC was associated with non-physician care (relative risk [RR] 2.04, 95% confidence interval [CI] 1.04 to 4.00), home slab or hanging latrine (RR 1.69, 95% CI 1.10 to 2.62), and lack of tetanus toxoid (RR 1.80, 95% CI 1.03 to 3.14). Women with fever (RR 2.30, 95% CI 1.18 to 4.50) or discolored amniotic fluid (RR 1.74, 95% CI 1.08 to 2.81) had a higher risk of HC. Microbiologic and clinical chorioamnionitis were unreliable HC measures. CONCLUSION: Prevalence of HC is high; many cases are not captured by clinical diagnosis or microbiologic cultures. Journal of Perinatology (2016) 36, 1039–1044; doi:10.1038/jp.2016.150; published online 15 September 2016

INTRODUCTION epidemiology, risk factors and diagnostic methods for Chorioamnionitis, a common complication of pregnancy, is life-threatening maternal infections. This paper describes the associated with significant maternal and perinatal adverse out- prevalence of chorioamnionitis using histologic, microbiologic and comes including puerperal and postpartum infections, stillbirth, clinical measures; the associations between maternal risk factors preterm birth and neonatal sepsis.1–6 Chorioamnionitis refers to and chorioamnionitis; and the associations between chorioamnio- acute inflammation of the membranes and chorion of the nitis and birth outcomes in Dhaka, Bangladesh. placenta, typically from an ascending polybacterial infection in the setting of membrane rupture. The definition varies according to diagnostic criteria—clinical (presence of clinical characteristics), MATERIALS AND METHODS fl microbiologic (positive culture of microbes from amniotic uid or Study design chorioamnion) or histologic (microscopic evidence of chorioam- A cross-sectional study was conducted within a larger cohort study on the fl nionic in ammation, with or without fetal vasculitis, within the maternal origins of neonatal infection at a maternity center in Dhaka, 1 placenta). Although the three diagnostic criteria overlap, women Bangladesh following 600 mother–newborn pairs from 15 January 2011 to with histologic chorioamnionitis (HC) often present asymptoma- 31 October 2011. The maternity center was operated by our partner non- tically. Women without clinical signs of intrauterine infection may governmental organization, Shimantik, and averaged 150 deliveries per still experience an underlying histologic process of inflammation month. In Bangladesh, ~ 29% of deliveries occur in facilities.12 We enrolled secondary to an infectious process. pregnant women at the maternity center during ANC visits or upon 3 ⩾ In high-income settings, chorioamnionitis is commonly diag- presentation in labor. Women who were pregnant 30 gestational weeks nosed based on histologic findings to capture both sub-clinical and planned to deliver at the maternity center were included in the study. 7,8 Women with fetal distress, obstructed labor, hemorrhage or severe pre- (clinically unapparent) as well as clinical chorioamnionitis. eclampsia were excluded to facilitate their need for urgent care. This study Microscopic examination of the placenta assesses both the origin received ethical approval from the Johns Hopkins Bloomberg School of of the inflammatory cells (maternal versus fetal) and the severity Public Health Committee on Human Research and the International Centre of the inflammation with different sites and severity scores.9 for Diarrheal Disease Research, Bangladesh Ethical Review Committee. All In low-, middle- income countries, the incidence of puerperal study participants provided written informed consent (IRB No. 00003084, sepsis (chorioamnionitis and postpartum endometritis) during approved November 2010). pregnancy is unclear but estimated to be high ranging from 0.1 Shimantik recruited four paramedics and five community health workers to 10% due to limited antenatal care (ANC) coverage and for primary data collection. Paramedics completed higher secondary school (12 years) and the national paramedic course. Community health discrepancies in diagnostic testing.10,11 The case fatality from 11 workers completed at least secondary school (10 years) education. puerperal sepsis is as high as 30 to 50%. In these settings, most Two medical officers supervised field activities and monitored quality cases of chorioamnionitis are diagnosed based on nonspecific assurance. Staff received 2 weeks of intensive training by a pediatrician clinical signs as trained pathologists and histopathology labora- and local medical officer. Sessions included presentations, exercises, tories are often unavailable. There is a great need to explore the role-plays and hospital visits to recognize clinical signs and symptoms of

1Division of Medicine Critical Care, Boston Children’s Hospital, Boston, MA, USA; 2Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 3Centre for Child and Adolescent Health, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh; 4Department of Pathology, Boston Children’s Hospital, Boston, MA, USA and 5Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Correspondence: Dr GJ Chan, Division of Medicine Critical Care, Boston Children's Hospital, 677 Huntington Ave Building 1, #1108, Boston, MA 02115, USA. E-mail: [email protected] Received 17 March 2016; revised 17 June 2016; accepted 28 June 2016; published online 15 September 2016 Prevalence and risk factors of chorioamnionitis GJ Chan et al 1040 infection.13 Written exams and standardized observations on staff skills log-binomial regression models were conducted to examine the effect were done to assess competency. between maternal risk factors on HC. Potentially significant variables in the For the primary aim of the parent cohort study, 600 mother–newborn bivariate analyses (Po0.20) were entered into a backward stepwise pairs were required to observe the estimated risk of early onset neonatal selection procedure (with a threshold at Po0.05). The final model was infection with 80% power while allowing for 5% type one error. Six adjusted for the potential confounding effects of wealth. Analyses were hundred mother–newborn pairs detected the predicted prevalence of HC repeated for HC with fetal involvement, comparing women with HC with of 10% ± 3.5% precision with 80% power. Additional details about the fetal involvement to women without HC with fetal involvement (women study design are discussed elsewhere.3 without HC and women with HC but no fetal involvement). Analyses were then repeated for secondary outcome measures—microbiologic and clinical chorioamnionitis. We assessed correlations between histologic Maternal risk factors classification, and microbiologic chorioamnionitis and clinical chorioam- Study paramedics interviewed women to collect demographic data on nionitis using kappa coefficient, which provides a measure of concordance maternal age, maternal education, ANC provider type and receipt of above that expected by chance. We conducted sensitivity and specificity tetanus toxoid as a proxy for access to health care. Wealth quintiles were tests with each of the chorioamnionitis measures with HC as the gold created using principal components analysis conducted with the following standard. Analyses were performed using STATA v13 (StataCorp, College demographic variables: housing materials of primary residence; source of Station, TX, USA). water supply; type of latrine; number of household inhabitants; number of household inhabitants under 5 years; and number of rooms where household members sleep.14 RESULTS To assess maternal risk factors and clinical signs during labor, a study – paramedic was present 24 h a day, 7 days a week in the labor and delivery We enrolled 600 mother infant pairs. Forty-eight women were room to measure duration of labor, rupture of membranes, number of missing placental samples; of these women, 19 women (39.6%) vaginal exams performed and handwashing by health workers. Paramedics delivered elsewhere, placentas were torn in two cases (4.2%), the also collected data on neonatal characteristics such as sex, birth weight to paramedic was not available at three deliveries (6.3%) and 24 the nearest 100 g and gestational age based on ultrasound report. (50%) were missing data.

Chorioamnionitis Prevalence of chorioamnionitis To classify HC, four sections of the placenta were collected immediately Of the 552 mother–infant pairs with placental samples, 70 (12.7%) after delivery: a section from the extraplacental membranes, a cross- were classified as having HC. Forty-six of the 70 HC cases (65.7%) section of the umbilical cord and two sections of the central placental disc were classified as having HC with fetal involvement. Of the 533 (one from the fetal surface and one from the maternal surface). Sections women with placental cultures, 57 (10.7%) women had micro- were fixed in 10% buffered formalin and then embedded in paraffin until processing. A pathologist, who was masked to patient characteristics and biologic chorioamnionitis. The most common organisms were clinical signs, reviewed the histopathology slides. An expert placental Escherichia coli (n=19, 33.3%), Pseudomonas species (n=11, pathologist reviewed a random sample (10%) of the slides for quality 19.3%) and Klebsiella pneumoniae (n=7, 12.3%) (Table 1). A small assurance. HC was defined as maternal neutrophilic inflammation in the proportion, 13 (2.4%) of the 552 with placental samples had extraplacental chorioamnionic membrane layers and/or with maternal clinical symptoms of chorioamnionitis (fever and one or more of neutrophil migration into chorionic plate. HC with fetal involvement was the following: maternal tachycardia 4120 bpm, fetal tachycardia defined as cases with maternal neutrophilic inflammation as defined above 4160 bpm, purulent or foul smelling amniotic fluid or vaginal and with concomitant migration of fetal neutrophils through the umbilical discharge, or uterine tenderness).16 vessels and/or fetal vessels of the chorionic plate. To classify microbiologic chorioamnionitis, surface cultures of placental membranes were taken with sterile swabs in the space between Maternal risk factors and clinical signs associated with histologic the chorionic and amniotic membranes immediately after delivery of the chorioamnionitis placenta. Swabs were transported daily from the maternity center to the Histologic chorioamnionitis. HC was associated with ANC by a microbiology laboratory at Dhaka Shishu Hospital using Amies transport non-physician (relative risk [RR] 2.04, 95% confidence interval [CI] medium and processed within 24 h of collection. Primary inoculation of 1.04 to 4.00), slab or hanging latrine at home (RR 1.69, 95% CI 1.10 the swabs was done on MacConkey and blood agar media with 5% sheep blood and incubated at 37 °C for 18 to 24 h. Identification of organisms to 2.62) and no receipt of tetanus toxoid during pregnancy (RR was done by gram staining and standard biochemical reactions. 1.80, 95% CI 1.03 to 3.14). Clinical chorioamnionitis was diagnosed based on the presence of HC was not associated with maternal age, maternal education, clinical signs during labor and delivery—maternal fever and one or more maternal tobacco use, source of drinking water, household wall, of the following symptoms: uterine fundal tenderness, maternal tachy- floor, roof material, medications received during ANC visits or cardia (4120 bpm), fetal tachycardia (4160 bpm), purulent, foul or handwashing by providers (Table 2). discolored amniotic fluid or vaginal discharge. Clinical signs such as fever ⩾ 99 °F (RR 2.30, 95% CI 1.18 to 4.50) The primary outcomes were as follows: (1) HC and (2) HC with fetal and discolored amniotic fluid (RR 1.74, 95% CI 1.08 to 2.81) were involvement. Secondary outcomes were microbiologic chorioamnionitis and clinical chorioamnionitis. Table 1. Distribution of organisms from placenta cultures Birth outcomes Organism Number Percent We explored associations between chorioamnionitis and potential complications such as preterm birth, small for gestational age (SGA) and Escherichia coli 19 33.3 fi o low birth weight. Preterm birth was de ned as 37 weeks gestational age Pseudomonas species 11 19.3 o and very preterm as 35 weeks of gestational age. SGA was calculated Klebsiella pneumoniae 7 12.3 using the Intergrowth-21st standards, which accounts for gestational age Cocolonized 7 12.3 fi o o and sex. We de ned SGA as 10th percentile and very SGA as 3rd Actinobacter species 5 8.8 fi o percentile. Low birth weight was de ned as 2500 g at birth and very- Group B Streptococcus 2 3.5 o low-birth weight as 2000 g at birth. Staphylococcus aureus 2 3.5 Streptococcus pneumonia 1 1.8 Statistical analysis Streptococcus species (other than Group B 1 1.8 Streptococcus) We explored each of the risk factor variables, clinical signs and potential Serratia species 2 3.5 complications using t-tests, χ2-orfisher’s exact tests. We did not make any Total 57 adjustments for multiple comparisons.15 Multivariable analyses using

Journal of Perinatology (2016), 1039 – 1044 © 2016 Nature America, Inc., part of Springer Nature. 06Ntr mrc,Ic,pr fSrne aue ora fPrntlg 21) 1039 (2016), Perinatology of Journal Nature. Springer of part Inc., America, Nature 2016 ©

Table 2. Risk factors for chorioamnionitis (N=552)a

Total N Histologic chorioamnionitis Histologic chorioamnionitis with Microbiologic chorioamnionitis Clinical chorioamnionitis fetal involvement

n (%) RR (95% CI) n (%) RR (95% CI) n (%) RR (95% CI) n (%) RR (95% CI)

Maternal age 18–20 196 27 (13.8) Ref 16 (8.2) Ref 21 (10.1) Ref 5 (2.7) Ref 21–25 211 28 (13.3) 0.96 (0.59–1.58) 22 (10.4) 1.28 (0.69–2.36) 17 (8.1) 0.75 (0.41–1.38) 4 (2.0) 0.75 (0.20–2.74) 26–40 145 15 (10.3) 0.75 (0.42–1.36) 8 (5.5) 0.68 (0.30–1.54) 19 (13.1) 1.22 (0.68–2.19) 4 (3.0) 1.12 (0.31–4.10) No maternal schooling 109 15 (13.8) 1.11 (0.65–1.89) 9 (8.3) 0.99 (0.49–1.99) 14 (12.8) 1.32 (0.75–2.33) 2 (2.0) 0.75 (0.17–3.33) Maternal schooling 443 55 (12.4) Ref 37 (8.4) Ref 43 (9.7) Ref 11 (2.6) Ref Maternal use of tobacco 31 2 (6.5) 0.49 (0.13–1.92) 2 (6.5) 0.76 (0.19–3.01) 4 (12.9) 1.26 (0.49–3.28) 1 (3.3) 1.37 (0.18–10.18) No maternal use of tobacco 521 68 (13.1) Ref 44 (8.5) Ref 53 (10.2) Ref 12 (2.4) Ref Slab or hanging latrine at home 205 35 (17.1) 1.69 (1.10–2.62) 26 (12.7) 2.20 (1.26–3.84) 20 (9.8) 0.91 (0.55–1.53) 3 (1.5) 0.48 (0.13–1.74) Sanitary latrine at home 347 35 (10.1) Ref 20(5.8) Ref 37 (10.7) Ref 10 (3.1) Ref Tube as main source of drinking water 245 37 (15.1) 1.40 (0.91–2.18) 28 (11.4) 1.95 (1.10–3.44) 27 (11.0) 1.13 (0.69–1.84) 4 (1.7) 0.54 (0.17–1.75) Tap as main source of drinking water 307 33 (10.8) Ref 18 (5.9) Ref 30 (9.8) Ref 9 (3.1) Ref Tin or straw wall in main dwelling 208 26 (12.5) 0.98 (0.62–1.54) 15 (7.2) 0.80 (0.44–1.45) 22 (10.6) 1.04 (0.63–1.72) 5 (2.5) 1.01 (0.33–3.04) Concrete wall in main dwelling 344 44 (12.8) Ref 31 (9.0) Ref 35 (10.2) Ref 8 (2.5) Ref Tin or wood roof in main dwelling 420 54 (12.9) 1.06 (0.63–1.79) 36 (8.6) 1.13 (0.58–2.22) 40 (9.5) 0.74 (0.43–1.26) 9 (2.3) 0.72 (0.23–2.30) Concrete roof in main dwelling 132 16 (12.1) Ref 10 (7.6) Ref 17 (12.9) Ref 4 (3.2) Ref Semi-concrete floor in main dwelling 113 11 (9.7) 0.72 (0.39–1.33) 8 (7.1) 0.82 (0.39–1.70) 15 (13.3) 1.39 (0.80–2.41) 2 (1.9) 0.72 (0.16–3.17) Concrete floor in main dwelling 439 59 (13.4) Ref 38 (8.7) Ref 42 (9.6) Ref 11 (2.6) Ref ANC provided by non-physician 404 58 (14.4) 2.04 (1.04–4.00) 40 (9.9) 3.17 (1.16–8.69) 39 (9.7) 0.73 (0.43–1.24) 7 (1.8) 0.55 (0.16–1.85) ANC provided by physician 128 9 (7.0) Ref 4 (3.1) Ref 17 (13.3) Ref 4 (3.3) Ref No tetanus toxoid injection during pregnancy 57 12 (21.1) 1.80 (1.03–3.14) 7 (12.3) 1.56 (0.73–3.32) 8 (14.0) 1.42 (0.71–2.84) 2 (3.6) 1.52 (0.34–6.67) Tetanus toxoid injection during pregnancy 495 58 (11.7) Ref 39 (7.9) Ref 49 (9.9) Ref 11 (2.4) Ref chorioamnionitis Chan of GJ factors risk and Prevalence No medication during pregnancy 88 13 (14.8) 1.20 (0.69–2.10) 10 (11.4) 1.46 (0.76–2.84) 6 (6.8) 0.62 (0.27–1.40) 2 (2.6) 1.04 (0.23–4.59) Medication during pregnancy 464 57 (12.3) Ref 36 (7.8) Ref 51 (11.0) Ref 11 (2.5) Ref – – – – No handwashing during delivery 33 3 (9.1) 0.71 (0.24 2.15) 3 (9.1) 1.10 (0.36 3.34) 3 (9.1) 0.89 (0.29 2.69) 0 (0.0) 0.00 (0.00 0.00) al et Handwashing during delivery 518 66 (12.7) Ref 43 (8.3) Ref 53 (10.2) Ref 13 (2.6) Ref No handwashing during exams 138 16 (11.6) 0.91 (0.54–1.54) 9 (6.5) 0.72 (0.36–1.45) 22 (15.9) 1.91 (1.16–3.16) 5 (3.8) 1.83 (0.61–5.49) Handwashing during exams 408 52 (12.8) Ref 37 (9.1) Ref 34 (8.3) Ref 8 (2.1) Ref Rupture of membrane ⩾ 8 h before delivery 50 3 (6.0) 0.45 (0.15–1.38) 3 (6.0) 0.70 (0.23–2.18) 3 (6.0) 0.56 (0.18–1.72) 3 (6.3) 2.97 (0.85–10.42) Rupture of membrane o8 h before delivery 502 67 (13.4) Ref 43 (8.6) Ref 54 (10.8) Ref 10 (2.1) Ref Premature rupture of membrane 51 4 (7.8) 0.60 (0.23–1.57) 4 (7.8) 0.94 (0.35–2.50) 4 (7.8) 0.74 (0.28–1.96) 3 (6.4) 3.03 (0.87–10.66) No premature rupture of membrane 501 66 (13.2) Ref 42 (8.4) Ref 53 (10.6) Ref 10 (2.1) Ref Preterm premature rupture of membrane 8 1 (12.5) 1.09 (0.17–6.96) 1 (12.5) 1.57 (0.24–10.17) 2 (25.0) 2.49 (0.72–8.63) 0 (0.0) 0.00 (0.00–0.00) No preterm premature rupture of membrane 339 39 (11.5) Ref 27 (8.0) Ref 34 (10.0) Ref 6 (1.9) Ref Abbreviations: CI, confidence interval; ANC, antenatal care; RR, relative risk. aNot all covariates sum to 552 due to missing data. – 1044 1041 Prevalence and risk factors of chorioamnionitis GJ Chan et al 1042

Table 3. Clinical signs and symptoms of chorioamnionitis (N=552)a

Total N Histologic chorioamnionitis Histologic chorioamnionitis Microbiologic chorioamnionitis with fetal involvement

n (%) RR (95% CI) n (%) RR (95% CI) n (%) RR (95% CI)

Discolored amniotic fluid 97 19 (19.6) 1.74 (1.08–2.81) 14 (14.4) 2.04 (1.13–3.68) 5 (5.2) 0.46 (0.19–1.12) Clear amniotic fluid 453 51 (11.3) Ref 32 (7.1) Ref 51 (11.3) Ref Maternal temperature ⩾ 99 °F 25 7 (28.0) 2.30 (1.18–4.50) 4 (16.0) 1.99 (0.78–5.12) 0 (0.0) 0.00 (0.00–0.00) Maternal temperature o99 °F 510 62 (12.2) Ref 41 (8.0) Ref 56 (11.0) Ref Experienced uterine tenderness 168 16 (9.5) 0.69 (0.31–1.53) 10 (6.0) 0.58 (0.22–1.51) 13 (7.7) 0.41 (0.19–0.86) Did not experience uterine tenderness 58 8 (13.8) Ref 6 (10.3) Ref 11 (19.0) Ref Foul smelling discharge 7 0 (0.0) 0.00 (0.00–0.00) 0 (0.0) 0.00 (0.00–0.00) 1 (14.3) 1.39 (0.22–8.67) No foul smelling discharge 545 70 (12.8) Ref 46 (8.4) Ref 56 (10.3) Ref Purulent discharge 5 1 (20.0) 1.58 (0.27–9.26) 1 (20.0) 2.43 (0.41–14.32) 1 (20.0) 1.98 (0.34–11.67) No purulent discharge 546 69 (12.6) Ref 45 (8.2) Ref 55 (10.1) Ref Maternal tachycardia 4120 bpm 24 2 (8.3) 0.63 (0.16–2.43) 1 (4.2) 0.48 (0.07–3.35) 1 (4.2) 0.39 (0.06–2.67) No maternal tachycardia 509 67 (13.2) Ref 44 (8.6) Ref 55 (10.8) Ref Fetal tachycardia 4160 bpm 5 1 (20.0) 1.56 (0.27–9.14) 1 (20.0) 2.41 (0.41–14.25) 1 (20.0) 1.93 (0.33–11.35) No fetal tachycardia 531 68 (12.8) Ref 44 (8.3) Ref 55 (10.4) Ref Abbreviations: CI, confidence interval; RR, relative risk. aNot all covariates sum to 552 due to missing data.

household wall, floor, roof material, no receipt of tetanus toxoid Table 4. Log-binomial multivariable models on the risk factors and during pregnancy, medications received during ANC visits or clinical signs for histologic chorioamnionitis, histologic handwashing by providers (Table 2). chorioamnionitis with fetal involvement and microbiologic HC with fetal involvement was associated with one clinical chorioamnionitis adjusting for wealth sign—discolored amniotic fluid (RR 2.04, 95% CI 1.13 to 3.68) (Table 3). After adjusting for wealth, ANC by a non-physician RR 95% CI P-value health worker (RR 2.95, 95% CI 1.07 to 8.11) and discolored fl fi Histologic chorioamnionitis amniotic uid (RR 2.01, 95% CI 1.11 to 3.64) was signi cantly Antenatal care by non-physician 2.13 1.08–4.21 0.029 associated with a higher risk of HC with fetal involvement No tetanus toxoid injection 1.95 1.09–3.47 0.024 (Table 4). Discolored amniotic fluid 1.88 1.18–3.00 0.008 Maternal temperature ⩾ 99 °F 2.88 1.56–5.32 0.001 Poorest quintile 0.89 0.49–1.60 0.690 Maternal risk factors and clinical signs associated with microbiologic chorioamnionitis Histologic chorioamnionitis with fetal Microbiologic chorioamnionitis was associated with handwashing involvement by providers (RR 1.91, 95% CI 1.16 to 3.16) (Table 2). Uterine Antenatal care by non-physician 2.95 1.07–8.11 0.036 tenderness was associated with microbiologic chorioamnionitis fl – Discolored amniotic uid 2.01 1.11 3.64 0.021 (RR 0.41, 95% CI 0.19 to 0.86) (Table 3). When adjusting for wealth, Poorest quintile 0.94 0.47–1.88 0.853 microbiologic chorioamnionitis remained significantly associated Microbiologic chorioamnionitis with uterine tenderness (RR 0.42, 95% CI 0.20 to 0.91) (Table 4). Experienced uterine tenderness 0.42 0.20–0.91 0.027 Microbiologic data were not a reliable measure of HC (k = − 0.004). Poorest quintile 1.26 0.53–2.98 0.598 Using HC as the gold standard, microbiologic chorioamnionitis had a sensitivity of 10.9% and positive predictive value of 12.3%. Abbreviations: CI, confidence interval; RR, relative risk.

Maternal risk factors and clinical signs associated with clinical associated with HC (Table 3). Clinical signs such as uterine chorioamnionitis tenderness, foul smelling vaginal discharge and purulent vaginal Clinical chorioamnionitis was not associated with any risk factors discharge were not associated with HC with or without fetal (Table 2). After adjusting for wealth, there was still no association involvement (Table 3). with any risk factors. Clinical chorioamnionitis was not a reliable After adjusting for wealth, ANC by a non-physician (RR 2.13, measure of HC (k = 0.037). Using HC as the gold standard, clinical 95% CI 1.08 to 4.21), no receipt of tetanus toxoid during signs of chorioamnionitis had a sensitivity of 4.3% and positive pregnancy (RR 1.95, 95% CI 1.09 to 3.47), discolored amniotic predictive value of 23.1%. Among 65 women with HC and data on fluid (RR 1.88, 95% CI 1.18 to 3.00) and fever ⩾ 99 °F (RR 2.88, 95% clinical signs of chorioamnionitis, 62 (95.3%) were clinically CI 1.56 to 5.32) were significantly associated with a higher risk of asymptomatic. HC (Table 4). Chorioamnionitis and birth outcomes Histologic chorioamnionitis with fetal involvement. HC with fetal HC with fetal involvement and clinical chorioamnionitis were both involvement was associated with risk factors such as maternal significantly associated with a higher risk of preterm birth receipt of ANC by a non-physician health worker (RR 3.17, 95% CI o35 weeks (RR 5.70, 95% CI 1.09 to 29.75 and RR 10.9, 95% CI 1.16 to 8.69), tube water source rather than tap water (RR 1.95, 1.49 to 79.69, respectively). There were no classifications of 95% CI 1.10 to 3.44) and slab or hanging latrine at home (RR 2.20, chorioamnionitis associated with a higher risk of SGAo10th 95% CI 1.26 to 3.84). Fetal involvement was not associated with percentile, SGAo3rd percentile, low birth weight, very-low-birth maternal age, maternal education, maternal tobacco use, weight or preterm birth o37 weeks (Table 5).

Journal of Perinatology (2016), 1039 – 1044 © 2016 Nature America, Inc., part of Springer Nature. Prevalence and risk factors of chorioamnionitis GJ Chan et al 1043 DISCUSSION 1.85) 2.35) 3.07) 1.64) In the sample of 552 placentas, the prevalence of HC was – – – – estimated to be 13% and HC with fetal involvement to be 8%. In

2500 g prior studies, the prevalence of chorioamnionitis, based on

o placental pathology, varied widely from 7 to 85% depending on gestational age, race and ethnicity, and the threshold of polymorphonuclear leukocytes per high power ﬁeld.17 Most studies have been done in high-income settings in relation to stillbirths and preterm births.18 In a study of 7505 placentas (%) RR (95% CI) delivered after 20 weeks gestation, the prevalence of HC was 40% N /

n between 25 and 28 weeks gestation, 35, 10 and 4% at gestational weeks 29 to 32, 33 to 36 and 37 weeks or greater, respectively.19 In a case–case-control study in Sweden, HC was diagnosed in 82% of stillbirths and 68% of ‘healthy’ deliveries.20 Results were similar in a case-control study in Mozambique; chorioamnionitis was 21 20.29) 13/68 (19.1) 1.09 (0.65 29.75) 10/44 (22.7) 1.32 (0.74 79.69) 2/13 (15.3) 0.85 (0.23 14.38) 9/57 (15.8) 0.88 (0.47 diagnosed in 96% of stillbirths and in 67% of term deliveries. In – – – – our study in Dhaka, HC with fetal involvement was signiﬁcantly associated with preterm birth o35 weeks. The large difference in 35 weeks Low birth weight the prevalence of HC can be explained by methodological o differences in deﬁnitions and histologic methods, and differences in the populations and contexts where the study took place. The etiology of HC is not clear, however it is believed to be associated with a microbial cause, based on the high correlation (%) RR (95% CI)

N with preterm births. Prior studies found that HC with colonization / 3 n was strongly associated with neonatal sepsis. Several clinical signs of chorioamnionitis were associated with HC, including amniotic ﬂuid color and maternal temperature ⩾ 99 °F. Hygiene and sanitation as measured by the type of latrine at home was a 3.13) 2/40 (5.0) 3.84 (0.73 3.03) 2/28 (7.1) 5.70 (1.09 8.57) 1/6 (16.7) 10.9 (1.49 2.70) 1/36 (2.8) 1.73 (0.21 risk factor associated with chorioamnionitis. Some studies have – – – – found term HC to be from a non-infectious cause.22 Overall, clinical signs of chorioamnionitis had a low positive predictive value for HC. The poor association between clinical

37 weeks Very Preterm chorioamnionitis and HC suggests that women with chorioamnio-

o nitis may be asymptomatic or may indicate non-infectious causes of inﬂammation.22 Microbial chorioamnionitis diagnosed by placental cultures also had a low positive predictive value for (%) RR (95% CI) HC. The swab sample between the chorion and amnion provides a N / ﬁ

n sterile site, however it is a dif cult site to collect and detect bacteria leading to an underestimation of chorioamnionitis. Misclassification of the microbial chorioamnionitis outcome may bias our results towards the null. This is the first study in Bangladesh to estimate the prevalence 1.82) 7/40 (17.5) 1.49 (0.71 2.21) 4/28 (14.3) 1.17 (0.45 3.93) 1/6 (16.7) 1.40 (0.23 1.50) 5/36 (13.9) 1.14 (0.48 – – – – of chorioamnionitis with fetal involvement as defined by histologic classifications. In addition to histologic examinations, chorioamnionitis was defined using microbiological cultures and clinical signs, which allowed us to compare the results across the different definitions of chorioamnionitis. The study had several

10th percentile Preterm limitations. This was a facility-based study and results may not be 552) o generalizable to all pregnancy outcomes that occur at home. As N=

(%) RR (95% CI) the majority of women deliver at home in Dhaka, women who SGA N

/ delivered in the facility may differ in their socioeconomic status, n education or clinical acuity. We excluded women who presented in fetal distress or obstructed labor to avoid interfering with medical care. However, as fetal distress and prolonged labor may be strongly associated with chorioamnionitis, excluding this sample may bias our results. Women who were missing placental samples may be different from women with samples. The sample size was calculated to study the risk factors of early onset neonatal

dence interval; HC, histologic chorioamnionitis; RR, relative risk; SGA, small for gestational age. infection and was not powered to detect predictors of HC. Given ﬁ the small sample size, there was a limited number of parameters to test. A larger study is needed to assess the variables associated with chorioamnionitis-related adverse outcomes and to better identify women who would beneﬁt from interventions such as Chorioamnionitis and birth outcomes ( intrapartum antibiotic prophylaxis. The prevalence of HC is high in Dhaka, Bangladesh and well within the range of other reported studies. Diagnosis of histologic HC 12/34 (35.3) 1.12 (0.69 No HCHC with fetal involvement 10/24 (41.7) 1.34 (0.81 88/279 (31.5) Ref 36/307 (11.7) Ref 4/307 (1.3) Ref 83/475 (17.5) Ref No HC with fetalClinical involvement chorioamnionitis 90/289 (31.1) 3/5 (60.0) Ref 1.88 (0.90 39/319 (12.2) Ref 4/319 (1.3) Ref 86/499 (17.2) Ref No clinical chorioamnionitisMicrobiologic chorioamnionitis 94/295 (31.9) 9/33 (27.3) 0.84 (0.47 Ref 39/327 (11.9) Ref 5/327 (1.5) Ref 91/502 (18.1) Ref No microbiologic chorioamnionitis 91/280 (32.5) Ref 38/311 (12.2) Ref 5/311 (1.6) Ref 87/486 (17.9) Ref Table 5. Abbreviations: CI, con chorioamnionitis is only possible after examination of the placenta

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