Abstract
Objective
To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis.
Methods
We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the “clinical diagnosis” of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as “suspected” or “confirmed” based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression.
Results
Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16–5.08)] and confirmed [OR 4.93 (1.65–14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70–2.61)], respiratory distress [OR 3.14 (2.16–4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01–3.60)] and 4–7 [OR 1.71 (1.43–2.04)] and 5 min Apgar score of 4–7 [OR 1.67 (1.17–2.37)] (vs. 8–10).
Conclusion
Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis.
Acknowledgments
Presented in part at the Pediatric Academic Societies’ 2015 Annual Meeting. The authors thank Richard A. Polin, MD (Columbia University College of Physicians and Surgeons) for contributions to the design of this secondary analysis and review and editing of the manuscript; Sabine Bousleiman, RNC, MSN, and Margaret Cotroneo, RN for protocol development and coordination between clinical research centers; Rebecca Clifton, PhD for protocol/data management; Vinay Bhandaru, MS for statistical analysis; and Gail D. Pearson, MD, ScD, Elizabeth Thom, PhD, James M. Roberts, MD, and Catherine Y. Spong, MD for protocol development and oversight.
Author’s statement
Conflict of interest: The authors have no conflicts of interest relevant to this article to disclose.
Material and methods: Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
Financial disclosure: The authors have no financial relationships relevant to this article to disclose.
Funding source: The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD34208, HD27869, HD40485, HD40560, HD40544, HD34116, HD40512, HD21410, HD40545, HD40500, HD27915, HD34136, HD27860, HD53118, HD53097, HD27917, and HD36801]; the National Heart, Lung, and Blood Institute; and the National Center for Research Resources [M01 RR00080, UL1 RR024153, UL1 RR024989]. Comments and views of the authors do not necessarily represent the views of the NIH.
Source of the work or study: Combined Antioxidants and Preeclampsia Prediction Studies, Clinical Trial.gov Identifier NCT00135707.
References
[1] Gilstrap LC 3rd, Leveno KJ, Cox SM, Burris JS, Mashburn M, Rosenfeld CR. Intrapartum treatment of acute chorioamnionitis: impact on neonatal sepsis. Am J Obstet Gynecol. 1988;159: 579–83.10.1016/S0002-9378(88)80012-7Search in Google Scholar
[2] Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstet Gynecol. 1988;72:823–8.10.1097/00006250-198812000-00001Search in Google Scholar PubMed
[3] Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease – revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010;59:1–36.Search in Google Scholar
[4] Polin RA, Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129:1006–15.10.1542/peds.2012-0541Search in Google Scholar PubMed
[5] Benitz WE, Wynn JL, Polin RA. Reappraisal of guidelines for management of neonates with suspected early-onset sepsis. J Pediatr. 2015;166:1070–4.10.1016/j.jpeds.2014.12.023Search in Google Scholar PubMed PubMed Central
[6] Lukacs SL, Schrag SJ. Clinical sepsis in neonates and young infants, United States, 1988–2006. J Pediatr. 2012;160: 960–5 e1.10.1016/j.jpeds.2011.12.023Search in Google Scholar PubMed
[7] Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics. 2011;127:817–26.10.1542/peds.2010-2217Search in Google Scholar PubMed PubMed Central
[8] Wortham JM, Hansen NI, Schrag SJ, Hale E, Van Meurs K, Sanchez PJ, et al. Chorioamnionitis and culture-confirmed, early-onset neonatal infections. Pediatrics. 2016;137:1–11.10.1542/peds.2015-2323Search in Google Scholar PubMed PubMed Central
[9] Gibson MK, Crofts TS, Dantas G. Antibiotics and the developing infant gut microbiota and resistome. Curr Opin Microbiol. 2015;27:51–6.10.1016/j.mib.2015.07.007Search in Google Scholar PubMed PubMed Central
[10] Thaver D, Ali SA, Zaidi AK. Antimicrobial resistance among neonatal pathogens in developing countries. Pediatr Infect Dis J. 2009;28:S19–21.10.1097/INF.0b013e3181958780Search in Google Scholar PubMed
[11] Mukhopadhyay S, Lieberman ES, Puopolo KM, Riley LE, Johnson LC. Effect of early-onset sepsis evaluations on in-hospital breastfeeding practices among asymptomatic term neonates. Hosp Pediatr. 2015;5:203–10.10.1542/hpeds.2014-0126Search in Google Scholar PubMed
[12] Higgins RD, Saade G, Polin RA, Grobman WA, Buhimschi IA, Watterberg K, et al. Evaluation and management of women and newborns with a maternal diagnosis of chorioamnionitis: summary of a workshop. Obstet Gynecol. 2016;127:426–36.10.1097/AOG.0000000000001246Search in Google Scholar PubMed PubMed Central
[13] Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, Leveno KJ, et al. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 2010;362:1282–91.10.1056/NEJMoa0908056Search in Google Scholar PubMed PubMed Central
[14] Weston EJ, Pondo T, Lewis MM, Martell-Cleary P, Morin C, Jewell B, et al. The burden of invasive early-onset neonatal sepsis in the United States, 2005–2008. Pediatr Infect Dis J. 2011;30:937–41.10.1097/INF.0b013e318223bad2Search in Google Scholar PubMed PubMed Central
[15] Braun D, Bromberger P, Ho NJ, Getahun D. Low rate of perinatal sepsis in term infants of mothers with chorioamnionitis. Am J Perinat. 2016;33:143–50.10.1055/s-0035-1560045Search in Google Scholar PubMed
[16] Jackson GL, Engle WD, Sendelbach DM, Vedro DA, Josey S, Vinson J, et al. Are complete blood cell counts useful in the evaluation of asymptomatic neonates exposed to suspected chorioamnionitis? Pediatrics. 2004;113:1173–80.10.1542/peds.113.5.1173Search in Google Scholar PubMed
[17] Jackson GL, Rawiki P, Sendelbach D, Manning MD, Engle WD. Hospital course and short-term outcomes of term and late preterm neonates following exposure to prolonged rupture of membranes and/or chorioamnionitis. Pediatr Infect Dis J. 2012;31:89–90.10.1097/INF.0b013e31822fb15dSearch in Google Scholar PubMed
[18] Kiser C, Nawab U, McKenna K, Aghai ZH. Role of guidelines on length of therapy in chorioamnionitis and neonatal sepsis. Pediatrics. 2014;133:992–8.10.1542/peds.2013-2927Search in Google Scholar PubMed
[19] Mukhopadhyay S, Puopolo KM. Clinical and microbiologic characteristics of early-onset sepsis among very low birth weight infants: opportunities for antibiotic stewardship. Pediatr Infect Dis J. 2017;36:477–81.10.1097/INF.0000000000001473Search in Google Scholar PubMed PubMed Central
[20] Wynn JL, Wong HR, Shanley TP, Bizzarro MJ, Saiman L, Polin RA. Time for a neonatal-specific consensus definition for sepsis. Pediatr Crit Care Med. 2014;15:523–8.10.1097/PCC.0000000000000157Search in Google Scholar PubMed PubMed Central
[21] Cantey JB, Baird SD. Ending the culture of culture-negative sepsis in the neonatal ICU. Pediatrics. 2017;140:e20170044.10.1542/peds.2017-0044Search in Google Scholar PubMed
[22] Pappas A, Kendrick DE, Shankaran S, Stoll BJ, Bell EF, Laptook AR, et al. Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates. JAMA Pediatr. 2014;168:137–47.10.1001/jamapediatrics.2013.4248Search in Google Scholar PubMed PubMed Central
[23] Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK, Canadian Neonatal N. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol. 2009;200:372.e1–6.10.1016/j.ajog.2008.11.034Search in Google Scholar PubMed
[24] Been JV, Lievense S, Zimmermann LJ, Kramer BW, Wolfs TG. Chorioamnionitis as a risk factor for necrotizing enterocolitis: a systematic review and meta-analysis. J Pediatr. 2013;162: 236–42.e2.10.1016/j.jpeds.2012.07.012Search in Google Scholar PubMed
[25] Watterberg KL, Demers LM, Scott SM, Murphy S. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics. 1996;97:210–5.10.1542/peds.97.2.210Search in Google Scholar
[26] Hartling L, Liang Y, Lacaze-Masmonteil T. Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2012;97:F8–17.10.1136/adc.2010.210187Search in Google Scholar PubMed
[27] Shankaran S, Lin A, Maller-Kesselman J, Zhang H, O’Shea TM, Bada HS, et al. Maternal race, demography, and health care disparities impact risk for intraventricular hemorrhage in preterm neonates. J Pediatr. 2014;164:1005–11.e3.10.1016/j.jpeds.2014.01.036Search in Google Scholar PubMed PubMed Central
[28] Lee Y, Kim HJ, Choi SJ, Oh SY, Kim JS, Roh CR, et al. Is there a stepwise increase in neonatal morbidities according to histological stage (or grade) of acute chorioamnionitis and funisitis?: effect of gestational age at delivery. J Perinat Med. 2015;43:259–67.10.1515/jpm-2014-0035Search in Google Scholar PubMed
[29] Park CW, Moon KC, Park JS, Jun JK, Romero R, Yoon BH. The involvement of human amnion in histologic chorioamnionitis is an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe: clinical implications. Placenta. 2009;30:56–61.10.1016/j.placenta.2008.09.017Search in Google Scholar PubMed PubMed Central
[30] Thomas W, Speer CP. Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome? Neonatology. 2011;99:177–87.10.1159/000320170Search in Google Scholar PubMed
[31] Greenberg MB, Anderson BL, Schulkin J, Norton ME, Aziz N. A first look at chorioamnionitis management practice variation among US obstetricians. Infect Dis Obstet Gynecol. 2012;2012:628362.10.1155/2012/628362Search in Google Scholar PubMed PubMed Central
[32] Blanc WA. Pathways of fetal and early neonatal infection. Viral placentitis, bacterial and fungal chorioamnionitis. J Pediatr. 1961;59:473–96.10.1016/S0022-3476(61)80232-1Search in Google Scholar
[33] Romero R, Chaemsaithong P, Korzeniewski SJ, Kusanovic JP, Docheva N, Martinez-Varea A, et al. Clinical chorioamnionitis at term III: how well do clinical criteria perform in the identification of proven intra-amniotic infection? J Perinat Med. 2016;44:23–32.10.1515/jpm-2015-0044Search in Google Scholar
[34] Martinez-Varea A, Romero R, Xu Y, Miller D, Ahmed AI, Chaemsaithong P, et al. Clinical chorioamnionitis at term VII: the amniotic fluid cellular immune response. J Perinat Med. 2017;45:523–38.10.1515/jpm-2016-0225Search in Google Scholar
[35] Romero R, Chaemsaithong P, Docheva N, Korzeniewski SJ, Tarca AL, Bhatti G, et al. Clinical chorioamnionitis at term IV: the maternal plasma cytokine profile. J Perinat Med. 2016;44:77–98.10.1515/jpm-2015-0103Search in Google Scholar
[36] Chaiyasit N, Romero R, Chaemsaithong P, Docheva N, Bhatti G, Kusanovic JP, et al. Clinical chorioamnionitis at term VIII: a rapid MMP-8 test for the identification of intra-amniotic inflammation. J Perinat Med. 2017;45:539–50.10.1515/jpm-2016-0344Search in Google Scholar
[37] Romero R, Chaemsaithong P, Korzeniewski SJ, Tarca AL, Bhatti G, Xu Z, et al. Clinical chorioamnionitis at term II: the intra-amniotic inflammatory response. J Perinat Med. 2016;44:5–22.10.1515/jpm-2015-0045Search in Google Scholar
[38] Gibbs RS, Castillo MS, Rodgers PJ. Management of acute chorioamnionitis. Am J Obstet Gynecol. 1980;136:709–13.10.1016/0002-9378(80)90445-7Search in Google Scholar
[39] Berardi A, Fornaciari S, Rossi C, Patianna V, Bacchi Reggiani ML, Ferrari F, et al. Safety of physical examination alone for managing well-appearing neonates >/= 35 weeks’ gestation at risk for early-onset sepsis. J Mat Fetal Med. 2015;28:1123–7.10.3109/14767058.2014.946499Search in Google Scholar PubMed
[40] Cantoni L, Ronfani L, Da Riol R, Demarini S, Perinatal Study Group of the Region Friuli-Venezia G. Physical examination instead of laboratory tests for most infants born to mothers colonized with group B Streptococcus: support for the Centers for Disease Control and Prevention’s 2010 recommendations. J Pediatr. 2013;163:568–73.10.1016/j.jpeds.2013.01.034Search in Google Scholar PubMed
[41] Flidel-Rimon O, Galstyan S, Juster-Reicher A, Rozin I, Shinwell ES. Limitations of the risk factor based approach in early neonatal sepsis evaluations. Acta Paediatr. 2012;101:e540–4.10.1111/apa.12013Search in Google Scholar PubMed
[42] Escobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, et al. Stratification of risk of early-onset sepsis in newborns >/= 34 weeks’ gestation. Pediatrics. 2014;133:30–6.10.1542/peds.2013-1689Search in Google Scholar PubMed PubMed Central
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2017-0192).
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