Subscribe to RSS
DOI: 10.1055/s-0042-1758858
Maternal Origins of Neonatal Infections: What Do Obstetrician–Gynecologist Should/Could Do?
Funding None.Abstract
Neonatal infections are responsible for 20% of neonatal deaths yearly. In this review, we focused on the origins of the commoner neonatal infections, and we define the role of obstetricians. Regarding group B Streptococcus, a key measure for the prevention of neonatal infection is the vaginal–rectal culture screening at term pregnancy. Intravenous penicillin is the first-line prophylaxis at the start of labor, with intravenous ampicillin as an alternative. First-generation cephalosporins or clindamycin are recommended in case of penicillin allergy. Concerning urinary tract infections (UTIs), guidelines recommend complete urinalysis and urine culture in the first trimester of pregnancy for the screening of asymptomatic bacteriuria. For lower UTIs, guidelines recommend nitrofurantoin as first-choice antibiotic. Amoxicillin or cefalexin are second-line antibiotics. For upper UTIs, guidelines recommend cephalexin per os as first line. Candida spp. colonization affects 20% of pregnant women; however, congenital fetal candidosis and Candida amnionitis are rare. First-line treatment in case of symptomatic vaginitis during pregnancy or asymptomatic colonization during the third trimester is vaginal clotrimazole. Fluconazole is not approved in pregnancy, especially during the first trimester. Genital mycoplasmas colonization during pregnancy is usually asymptomatic and associated with bacterial vaginosis. Colonization is related to neonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), pneumonia, chorioamnionitis, and sepsis. Macrolides are the first-line treatment along with lactobacillus supplementation. In cases of preterm premature rupture of membranes or preterm labor, ceftriaxone, clarithromycin, and metronidazole are required to prevent intra-amniotic infection. Intra-amniotic infection affects 1 to 5% of deliveries at term and one-third of preterm ones and is associated with perinatal death, early-onset neonatal sepsis, RDS, BPD, pneumonia, meningitis, and prematurity-related diseases. Guidelines recommend a combination of ampicillin and gentamicin, and in case of caesarean section, an additional dose of clindamycin or metronidazole is required. In conclusion, obstetricians should be aware that the treatment of maternal infection during pregnancy can prevent potentially lethal infections in the newborn.
Key Points
-
Part of neonatal infections starts from maternal infections that must be treated during pregnancy.
-
Streptococcus group B and asymptomatic bacteriuria should be investigated in pregnancy and treated.
-
Mycoplasma and ureaplasma vaginal colonization during pregnancy is related to negative neonatal outcomes.
Keywords
neonatal infections - maternal infections - genitourinary and gastrointestinal tracts - pregnancy - early-onset neonatal sepsis - late-onset sepsis* These authors equally contributed to this paper.
Publication History
Article published online:
19 December 2022
© 2022. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Liu L, Johnson HL, Cousens S, Perin J, Scott S. et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012; 79 (9832): 2151-2161
- 2 Schrag SJ, Farley MM, Petit S. et al. Epidemiology of invasive early-onset neonatal sepsis, 2005 to 2014. Pediatrics 2016; 138 (06) e20162013
- 3 Procianoy RS, Silveira RC. The challenges of neonatal sepsis management. J Pediatr (Rio J) 2020; 96 (suppl 1): 80-86
- 4 ACOG.. Prevention of group b streptococcal early-onset disease in newborns. ACOG Committee Opinion. Obstet Gynecol 2020;797
- 5 Vornhagen J, Adams Waldorf KM, Rajagopal L. Perinatal group B Streptococcal Infections: virulence factors, immunity, and prevention strategies. Trends Microbiol 2017; 25 (11) 919-931
- 6 Brown AP, Denison FC. Selective or universal screening for GBS in pregnancy (review). (review) Early Hum Dev 2018; 126: 18-22
- 7 Turrentine MA, Greisinger AJ, Brown KS, Wehmanen OA, Mouzoon ME. Duration of intrapartum antibiotics for group B Streptococcus on the diagnosis of clinical neonatal sepsis. Infect Dis Obstet Gynecol 2013; 2013: 525878
- 8 Fairlie T, Zell ER, Schrag S. Effectiveness of intrapartum antibiotic prophylaxis for prevention of early-onset group B streptococcal disease. Obstet Gynecol 2013; 121 (03) 570-577
- 9 Schrag SJ, Zywicki S, Farley MM. et al. Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 2000; 342 (01) 15-20
- 10 Matuszkiewicz-Rowińska J, Małyszko J, Wieliczko M. Urinary tract infections in pregnancy: old and new unresolved diagnostic and therapeutic problems. Arch Med Sci 2015; 11 (01) 67-77
- 11 Cheung KL, Lafayette RA. Renal physiology of pregnancy. Adv Chronic Kidney Dis 2013; 20 (03) 209-214
- 12 Sharami SH, Afrakhteh M, Shakiba M. Urinary tract infections in pregnant women with bacterial vaginosis. J Obstet Gynaecol 2007; 27 (03) 252-254
- 13 Hillebrand L, Harmanli OH, Whiteman V, Khandelwal M. Urinary tract infections in pregnant women with bacterial vaginosis. Am J Obstet Gynecol 2002; 186 (05) 916-917
- 14 Sheiner E, Mazor-Drey E, Levy A. Asymptomatic bacteriuria during pregnancy. J Matern Fetal Neonatal Med 2009; 22 (05) 423-427
- 15 Szweda H, Jóźwik M. Urinary tract infections during pregnancy—an updated overview. Dev Period Med 2016; 4: 263-272
- 16 Antenatal Care for Uncomplicated Pregnancies. London, United Kingdom: National Institute for Health and Care Excellence (NICE); 2019
- 17 Widmer M, Lopez I, Gülmezoglu AM, Mignini L, Roganti A. Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev 2015; (11) CD000491
- 18 Vazquez JC, Abalos E. Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev 2011; (01) CD002256
- 19 National Institute for Health and Care Excellence (NICE) Urinary tract infection (lower): Antimicrobial prescribing. Clinical guideline [NG109] 2018. Accessed December 1, 2022 at: https://www.nice.org.uk/guidance/ng109
- 20 Park JC, Buono D, Smith DK. et al; HIV Epidemiology Research Study (HERS) group. Urinary tract infections in women with or at risk for human immunodeficiency virus infection. Am J Obstet Gynecol 2002; 187 (03) 581-588
- 21 Glaser AP, Schaeffer AJ. Urinary tract infection and bacteriuria in pregnancy. Urol Clin North Am 2015; 42 (04) 547-560
- 22 Thomas AA, Thomas AZ, Campbell SC, Palmer JS. Urologic emergencies in pregnancy. Urology 2010; 76 (02) 453-460
- 23 Wing DA, Fassett MJ, Getahun D. Acute pyelonephritis in pregnancy: an 18-year retrospective analysis. Am J Obstet Gynecol 2014; 210 (03) 219.e1-219.e6
- 24 National Institute for Health and Care Excellence (NICE). Pyelonephritis (acute): antimicrobial prescribing. Guidance and guidelines. [NG111] 2018. Accessed December 1, 2022 at: https://www.nice.org.uk/guidance/ng111
- 25 Schneeberger C, Geerlings SE, Middleton P, Crowther CA. Interventions for preventing recurrent urinary tract infection during pregnancy. Cochrane Database Syst Rev 2015; (07) CD009279
- 26 Warzecha D, Pietrzak B, Urban A, Wielgoś M. How to avoid drug resistance during treatment and prevention of urinary tract infections. Prz Menopauzalny 2021; 20 (04) 217-221
- 27 Farr A, Effendy I, Frey Tirri B. et al. Guideline: vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses 2021; 64 (06) 583-602
- 28 Denning DW, Kneale M, Sobel JD, Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect Dis 2018; 18 (11) e339-e347
- 29 Yano J, Peters BM, Noverr MC, Fidel Jr PL. Novel mechanism behind the immunopathogenesis of vulvovaginal candidiasis: “neutrophil anergy”. Infect Immun 2018; 86 (03) e00684-e17
- 30 Marschalek J, Farr A, Kiss H. et al. Risk of vaginal infections at early gestation in patients with diabetic conditions during pregnancy: a retrospective cohort study. PLoS One 2016; 11 (05) e0155182
- 31 Yano J, Sobel JD, Nyirjesy P. et al. Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes. BMC Womens Health 2019; 19 (01) 48
- 32 Zhang X, Liao Q, Wang F, Li D. Association of gestational diabetes mellitus and abnormal vaginal flora with adverse pregnancy outcomes. Medicine (Baltimore) 2018; 97 (34) e11891
- 33 Aagaard K, Riehle K, Ma J. et al. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS One 2012; 7 (06) e36466
- 34 Santos CMA, Pires MCV, Leão TL. et al. Selection of Lactobacillus strains as potential probiotics for vaginitis treatment. Microbiology 2016;162(07): Doi: org/10.1099/mic.0.000302
- 35 Gupta P, Faridi MM, Rawat S, Sharma P. Clinical profile and risk factors for oral candidosis in sick newborns. Indian Pediatr 1996; 33 (04) 299-303
- 36 Roberts CL, Rickard K, Kotsiou G, Morris JM. Treatment of asymptomatic vaginal candidiasis in pregnancy to prevent preterm birth: an open-label pilot randomized controlled trial. BMC Pregnancy Childbirth 2011; 11: 18
- 37 Farr A, Kiss H, Holzer I, Husslein P, Hagmann M, Petricevic L. Effect of asymptomatic vaginal colonization with Candida albicans on pregnancy outcome. Acta Obstet Gynecol Scand 2015; 94 (09) 989-996
- 38 Mølgaard-Nielsen D, Svanström H, Melbye M, Hviid A, Pasternak B. Association between use of oral fluconazole during pregnancy and risk of spontaneous abortion and stillbirth. JAMA 2016; 315 (01) 58-67
- 39 Howley MM, Carter TC, Browne ML, Romitti PA, Cunniff CM, Druschel CM. National Birth Defects Prevention Study. Fluconazole use and birth defects in the national birth defects prevention study. Am J Obstet Gynecol 2016; 214 (05) 657.e1-657.e9
- 40 Mølgaard-Nielsen D, Pasternak B, Hviid A. Use of oral fluconazole during pregnancy and the risk of birth defects. N Engl J Med 2013; 369 (09) 830-839
- 41 Ma C, Du J, Dou Y. et al. The associations of genital mycoplasmas with female infertility and adverse pregnancy outcomes: a systematic review and meta-analysis. Reprod Sci 2021; 28 (11) 3013-3031
- 42 Dallo SF, Baseman JB. Intracellular DNA replication and long-term survival of pathogenic mycoplasmas. Microb Pathog 2000; 29 (05) 301-309
- 43 Waites KB, Katz B, Schelonka RL. Mycoplasmas and ureaplasmas as neonatal pathogens. Clin Microbiol Rev 2005; 18 (04) 757-789
- 44 Donders GGG, Ruban K, Bellen G, Petricevic L. Mycoplasma/Ureaplasma infection in pregnancy: to screen or not to screen. J Perinat Med 2017; 45 (05) 505-515
- 45 Ruzman N, Miskulin M, Rudan S, Bosnjak Z. The prevalence and the risk factors of the cervical colonization by the genital mycoplasmas among pregnant women from Eastern Croatia. Coll Antropol 2013; 37 (01) 135-140
- 46 Motomura K, Romero R, Xu Y. et al. Intra-amniotic infection with Ureaplasma parvum causes preterm birth and neonatal mortality that are prevented by treatment with clarithromycin. MBio 2020; 11 (03) e00797-e20
- 47 Peuchant O, Le Roy C, Desveaux C. et al. Screening for Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium should it be integrated into routine pregnancy care in French young pregnant women?. Diagn Microbiol Infect Dis 2015; 82 (01) 14-19
- 48 Martius J, Eschenbach DA. The role of bacterial vaginosis as a cause of amniotic fluid infection, chorioamnionitis and prematurity—a review. Arch Gynecol Obstet 1990; 247 (01) 1-13
- 49 Taylor-Robinson D, McCormack WM. The genital mycoplasmas (second of two parts). N Engl J Med 1980; 302 (19) 1063-1067
- 50 Gravett MG, Eschenbach DA. Possible role of Ureaplasma urealyticum in preterm premature rupture of the fetal membranes. Pediatr Infect Dis 1986; 5 (6, suppl): S253-S257
- 51 Harada K, Tanaka H, Komori S. et al. Vaginal infection with Ureaplasma urealyticum accounts for preterm delivery via induction of inflammatory responses. Microbiol Immunol 2008; 52 (06) 297-304
- 52 Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK, Eschenbach DA. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med 1988; 319 (15) 972-978
- 53 Xu YP, Hu JM, Huang YQ, Shi LP. Maternal Ureaplasma exposure during pregnancy and the risk of preterm birth and BPD: a meta-analysis. Arch Gynecol Obstet 2022; 306 (06) 1863-1872
- 54 Gray DJ, Robinson HB, Malone J, Thomson Jr RB. Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum . Prenat Diagn 1992; 12 (02) 111-117
- 55 Waites KB, Crouse DT, Cassell GH. Systemic neonatal infection due to Ureaplasma urealyticum . Clin Infect Dis 1993; 17 (suppl 1): S131-S135
- 56 Sprong KE, Mabenge M, Wright CA, Govender S. Ureaplasma species and preterm birth: current perspectives. Crit Rev Microbiol 2020; 46 (02) 169-181
- 57 Chu A, de St Maurice A, Sim MS, Kallapur SG. Neonatal mycoplasma and ureaplasma infections. Pediatr Ann 2020; 49 (07) e305-e312
- 58 Cassell GH, Waites KB, Crouse DT. et al. Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birth-weight infants. Lancet 1988; 2 (8605): 240-245
- 59 Bartkeviciene D, Opolskiene G, Bartkeviciute A. et al. The impact of Ureaplasma infections on pregnancy complications. Libyan J Med 2020; 15 (01) 1812821
- 60 Lyon A. Chronic lung disease of prematurity. The role of intra-uterine infection. Eur J Pediatr 2000; 159 (11) 798-802
- 61 Viscardi RM, Hashmi N, Gross GW, Sun CC, Rodriguez A, Fairchild KD. Incidence of invasive ureaplasma in VLBW infants: relationship to severe intraventricular hemorrhage. J Perinatol 2008; 28 (11) 759-765
- 62 Brus F, van Waarde WM, Schoots C, Oetomo SB. Fatal ureaplasmal pneumonia and sepsis in a newborn infant. Eur J Pediatr 1991; 150 (11) 782-783
- 63 Sethi S, Sharma M, Narang A, Aggrawal PB. Isolation pattern and clinical outcome of genital mycoplasma in neonates from a tertiary care neonatal unit. J Trop Pediatr 1999; 45 (03) 143-145
- 64 Rao RP, Ghanayem NS, Kaufman BA, Kehl KS, Gregg DC, Chusid MJ. Mycoplasma hominis and Ureaplasma species brain abscess in a neonate. Pediatr Infect Dis J 2002; 21 (11) 1083-1085
- 65 Kasper DC, Mechtler TP, Böhm J. et al. In utero exposure to Ureaplasma spp. is associated with increased rate of bronchopulmonary dysplasia and intraventricular hemorrhage in preterm infants. J Perinat Med 2011; 39 (03) 331-336
- 66 Carey JC, Blackwelder WC, Nugent RP. et al; The Vaginal Infections and Prematurity Study Group. Antepartum cultures for Ureaplasma urealyticum are not useful in predicting pregnancy outcome. Am J Obstet Gynecol 1991; 164 (03) 728-733
- 67 Donders GG, Van Bulck B, Caudron J, Londers L, Vereecken A, Spitz B. Relationship of bacterial vaginosis and mycoplasmas to the risk of spontaneous abortion. Am J Obstet Gynecol 2000; 183 (02) 431-437
- 68 De Francesco MA, Caracciolo S, Bonfanti C, Manca N. Incidence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum isolated in Brescia, Italy, over 7 years. J Infect Chemother 2013; 19 (04) 621-627
- 69 Lee SJ, Ahn JW, Lee JY, Lee SH, Roh HJ, Kwon YS. Maternal azithromycin administration eradicates intra-amniotic Ureaplasma infection: the first human case report. J Obstet Gynaecol 2016; 36 (02) 259-260
- 70 Manhart LE, Broad JM, Golden MR. Mycoplasma genitalium: should we treat and how?. Clin Infect Dis 2011; 53 (suppl 3): S129-S142
- 71 Jensen JS, Cusini M, Gomberg M, Moi H. 2016 European guideline on Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol 2016; 30 (10) 1650-1656
- 72 Oh KJ, Romero R, Park JY. et al. Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency. Am J Obstet Gynecol 2019; 221 (02) 140.e1-140.e18
- 73 Yoon BH, Romero R, Park JY. et al. Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. Am J Obstet Gynecol 2019; 221 (02) 142.e1-142.e22
- 74 Lee J, Romero R, Kim SM. et al. A new anti-microbial combination prolongs the latency period, reduces acute histologic chorioamnionitis as well as funisitis, and improves neonatal outcomes in preterm PROM. J Matern Fetal Neonatal Med 2016; 29 (05) 707-720
- 75 Stafford GP, Parker JL, Amabebe E. et al. Spontaneous preterm birth is associated with differential expression of vaginal metabolites by lactobacilli-dominated microflora. Front Physiol 2017; 8: 615
- 76 Daniele M, Ruiz F, Pascual L, Barberis L. Ureaplasma urealyticum and Mycoplasma hominis sensitivity to bacteriocins produced by two Lactobacilli strains. Curr Microbiol 2011; 63 (04) 360-365
- 77 Higgins RD, Saade G, Polin RA. et al; Chorioamnionitis Workshop Participants. Evaluation and management of women and newborns with a maternal diagnosis of chorioamnionitis: summary of a workshop. Obstet Gynecol 2016; 127 (03) 426-436
- 78 Yoon BH, Romero R, Moon JB. et al. Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol 2001; 185 (05) 1130-1136
- 79 Kachikis A, Eckert LO, Walker C. et al; Brighton Collaboration Chorioamnionitis Working Group. Chorioamnionitis: case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2019; 37 (52) 7610-7622
- 80 Romero R, Schaudinn C, Kusanovic JP. et al. Detection of a microbial biofilm in intraamniotic infection. Am J Obstet Gynecol 2008; 198 (01) 135.e1-135.e5
- 81 Romero R, Miranda J, Chaiworapongsa T. et al. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol 2014; 72 (05) 458-474
- 82 Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol 2015; 213 (4, suppl) S29-S52
- 83 Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998; 179 (01) 194-202
- 84 Jain VG, Kong F, Kallapur SG. et al. IRAK1 is a critical mediator of inflammation-induced preterm birth. J Immunol 2020; 204 (10) 2651-2660
- 85 Venkatesh KK, Jackson W, Hughes BL, Laughon MM, Thorp JM, Stamilio DM. Association of chorioamnionitis and its duration with neonatal morbidity and mortality. J Perinatol 2019; 39 (05) 673-682 [ Erratum in: J Perinatol. 2019 Mar 7]
- 86 Beck C, Gallagher K, Taylor LA, Goldstein JA, Mithal LB, Gernand AD. Chorioamnionitis and risk for maternal and neonatal sepsis: a systematic review and meta-analysis. Obstet Gynecol 2021; 137 (06) 1007-1022
- 87 Pappas A, Kendrick DE, Shankaran S. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates. JAMA Pediatr 2014; 168 (02) 137-147
- 88 Al-Haddad BJS, Oler E, Armistead B. et al. The fetal origins of mental illness. Am J Obstet Gynecol 2019; 221 (06) 549-562
- 89 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 (02) 236-42.e2
- 90 Committee Opinion No. Committee Opinion No. 712: intrapartum management of intraamniotic infection. Obstet Gynecol 2017; 130 (02) e95-e101
- 91 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 (06) 823-828