Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis

English version České info

Background:
Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.

Methods and Findings:
We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors.

Conclusions:
Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis.

Please see later in the article for the Editors' Summary

Vyšlo v časopise: Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis. PLoS Med 10(8): e32767. doi:10.1371/journal.pmed.1001502
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001502

Souhrn

Zdroje

1. LiuL, JohnsonHL, CousensS, PerinJ, ScottS, et al. (2012) Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 379: 2151–2161.

2. OestergaardMZ, InoueM, YoshidaS, MahananiWR, GoreFM, et al. (2011) Neonatal mortality levels for 193 countries in 2009 with trends since 1990: a systematic analysis of progress, projections, and priorities. PLoS Med 8: e1001080 doi:10.1371/journal.pmed.1001080

3. BaquiAH, DarmstadtGL, WilliamsEK, KumarV, KiranTU, et al. (2006) Rates, timing and causes of neonatal deaths in rural India: implications for neonatal health programmes. Bull World Health Organ 84: 706–713.

4. LawnJE, LeeAC, KinneyM, SibleyL, CarloWA, et al. (2009) Two million intrapartum-related stillbirths and neonatal deaths: where, why, and what can be done? Int J Gynaecol Obstet 107 Suppl 1: S5–18, S19.

5. Al-AdnaniM, SebireNJ (2007) The role of perinatal pathological examination in subclinical infection in obstetrics. Best Pract Res Clin Obstet Gynaecol 21: 505–521.

6. AyengarV, Madhulika, VaniSN (1991) Neonatal sepsis due to vertical transmission from maternal genital tract. Indian J Pediatr 58: 661–664.

7. SchragSJ, ZywickiS, FarleyMM, ReingoldAL, HarrisonLH, et al. (2000) Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 342: 15–20.

8. BangAT, BangRA, BaituleS, DeshmukhM, ReddyMH (2001) Burden of morbidities and the unmet need for health care in rural neonates–a prospective observational study in Gadchiroli, India. Indian Pediatr 38: 952–965.

9. CousensS, BlencoweH, GravettM, LawnJE (2010) Antibiotics for pre-term pre-labour rupture of membranes: prevention of neonatal deaths due to complications of pre-term birth and infection. Int J Epidemiol 39 Suppl 1: i134–143.

10. KenyonS, BoulvainM, NeilsonJP (2010) Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev CD001058.

11. OhlssonA, ShahVS (2013) Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev 1: CD007467.

12. World Bank (2012) GNI per capita, Atlas method. Available: http://data.worldbank.org/indicator/NY.GNP.PCAP.CD. Accessed 22 March 2012.

13. World Health Organization (2012) Global Burden of Disease Regions used for WHO-CHOICE Analyses. Available: http://www.who.int/choice/demography/regions/en/. Accessed 22 March 2012.

14. UNICEF (2011) The State of the World's Children. Table 1 basic indicators. Available: http://www.unicef.org/sowc2011/statistics.php. Accessed 26 March 2012.

15. DerSimonianR, LairdN (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177–188.

16. PylipowM, GaddisM, KinneyJS (1994) Selective intrapartum prophylaxis for group B streptococcus colonization: management and outcome of newborns. Pediatrics 93: 631–635.

17. KalinkaJ, KrajewskiP, SobalaW, WasielaM, Brzezinska-BlaszczykE (2006) The association between maternal cervicovaginal proinflammatory cytokines concentrations during pregnancy and subsequent early-onset neonatal infection. J Perinat Med 34: 371–377.

18. KishoreKDAK (1987) SinghM (1987) BhujwalaRA (1987) Early onset neonatal sepsis–vertical transmission from maternal genital tract. Indian Pediatr 24: 45–48.

19. KunzeM, ZublerB, MullerC, FleckenU, CladA (2006) Evaluation of placental membrane swabs in the diagnosis of intrauterine infections. Geburtshilfe und Frauenheilkunde 66: 575–578.

20. MoralesWJ, AngelJL, O'BrienWF, KnuppelRA (1989) Use of ampicillin and corticosteroids in premature rupture of membranes: a randomized study. Obstet Gynecol 73: 721–726.

21. MuthusamiA, DeviCS, KanungoR, Shashikala, Srinivasan, et al. (2007) Vaginal colonization as a risk factor for the development of neonatal sepsis. Biomedicine 27: 186–188.

22. PerssonK, BjerreB, ElfstromL, PolbergerS, ForsgrenA (1986) Group B streptococci at delivery: high count in urine increases risk for neonatal colonization. Scand J Infect Dis 18: 525–531.

23. TuppurainenN, HallmanM (1989) Prevention of neonatal group B streptococcal disease: intrapartum detection and chemoprophylaxis of heavily colonized parturients. Obstet Gynecol 73: 583–587.

24. VerganiP, PataneL, ColomboC, BorroniC, GiltriG, et al. (2002) Impact of different prevention strategies on neonatal group B streptococcal disease. Am J Perinatol 19: 341–348.

25. BhuttaZA, YusufK (1997) Early-onset neonatal sepsis in Pakistan: a case control study of risk factors in a birth cohort. Am J Perinatol 14: 577–581.

26. ChemsiM, HabziA, HarrakA, BenomarS (2012) Performance of procalcitonin diagnosis of maternofetal infection. Journal de Pediatrie et de Puericulture 25: 185–192.

27. CukrowskaB, Lodinova-ZadnikovaR, SokolD, Tlaskalova-HogenovaH (1999) In vitro immunoglobulin response of fetal B-cells is influenced by perinatal infections and antibiotic treatment: a study in preterm infants. Eur J Pediatr 158: 463–468.

28. EmamghorashiF, MahmoodiN, TagarodZ, HeydariST (2012) Maternal urinary tract infection as a risk factor for neonatal urinary tract infection. Iran J Kidney Dis 6: 178–180.

29. KovoM, SchreiberL, Ben-HaroushA, ShorS, GolanA, et al. (2012) Intrapartum fever at term: clinical characteristics and placental pathology. J Matern Fetal Neonatal Med 25: 1273–1277.

30. OddieS, EmbletonND (2002) Risk factors for early onset neonatal group B streptococcal sepsis: case-control study. BMJ 325: 308.

31. AndrewsWW, SchelonkaR, WaitesK, StammA, CliverSP, et al. (2008) Genital tract methicillin-resistant Staphylococcus aureus: risk of vertical transmission in pregnant women. Obstet Gynecol 111: 113–118.

32. BenitzWE, GouldJB, DruzinML (1999) Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review. Pediatrics 103: e77.

33. ConnellTG, ReleM, CowleyD, ButteryJP, CurtisN (2007) How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children's hospital. Pediatrics 119: 891–896.

34. EdmondKM, KortsalioudakiC, ScottS, SchragSJ, ZaidiAK, et al. (2012) Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis. Lancet 379: 547–556.

35. OhlssonA, ShahVS (2009) Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev (3): CD007467.

36. Saez-LlorensX, Ah-ChuMS, CastanoE, CortesL, TorresA, et al. (1995) Intrapartum prophylaxis with ceftriaxone decreases rates of bacterial colonization and early-onset infection in newborns. Clin Infect Dis 21: 876–880.

37. VeraniJR, McGeeL, SchragSJ (2010) Prevention of perinatal group B streptococcal disease–revised guidelines from CDC, 2010. MMWR Recomm Rep 59: 1–36.

38. BobittJR, LedgerWJ (1977) Unrecognized amnionitis and prematurity: a preliminary report. J Reprod Med 19: 8–12.

39. PassMA, GrayBM, DillonHCJr (1982) Puerperal and perinatal infections with group B streptococci. Am J Obstet Gynecol 143: 147–152.

40. BroekhuizenFF, GilmanM, HamiltonPR (1985) Amniocentesis for gram stain and culture in preterm premature rupture of the membranes. Obstet Gynecol 66: 316–321.

41. FeinsteinSJ, VintzileosAM, LodeiroJG, CampbellWA, WeinbaumPJ, et al. (1986) Amniocentesis with premature rupture of membranes. Obstet Gynecol 68: 147–152.

42. GauthierDW, MeyerWJ, BieniarzA (1994) Expectant management of premature rupture of membranes with amniotic fluid cultures positive for Ureaplasma urealyticum alone. Am J Obstet Gynecol 170: 587–590.

43. AverbuchB, MazorM, Shoham-VardiI, ChaimW, VardiH, et al. (1995) Intra-uterine infection in women with preterm premature rupture of membranes: maternal and neonatal characteristics. Eur J Obstet Gynecol Reprod Biol 62: 25–29.

44. MatsudaY, MaruyamaH, KurayaK (1995) Relationship between granulocyte elastase levels and perinatal infections. Gynecol Obstet Invest 39: 162–166.

45. YoonBH, RomeroR, ParkJS, KimM, OhSY, et al. (2000) The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis. Am J Obstet Gynecol 183: 1124–1129.

46. GoldenbergRL, AndrewsWW, GoepfertAR, Faye-PetersenO, CliverSP, et al. (2008) The Alabama Preterm Birth Study: Umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol 198: 43.e41–43.e45.

47. LeeSY, CheungCW (2012) Histological chorioamnionitis - implication for bacterial colonization, laboratory markers of infection, and early onset sepsis in very-low-birth-weight neonates. J Matern Fetal Neonatal Med 25: 364–368.

48. KasperDC, MechtlerTP, ReischerGH, WittA, LanggartnerM, et al. (2010) The bacterial load of Ureaplasma parvum in amniotic fluid is correlated with an increased intrauterine inflammatory response. Diagn Microbiol Infect Dis 67: 117–121.

49. ElderHA, SantamarinaBA, SmithS, KassEH (1971) The natural history of asymptomatic bacteriuria during pregnancy: the effect of tetracycline on the clinical course and the outcome of pregnancy. Am J Obstet Gynecol 441–462.

50. McGradyGA, DalingJR, PetersonDR (1985) Maternal urinary tract infection and adverse fetal outcomes. Am J Epidemiol 121: 377–381.

51. DudleyJ, MalcolmG, EllwoodD (1991) Amniocentesis in the management of preterm premature rupture of the membranes. Aust N Z J Obstet Gynaecol 31: 331–336.

52. PuchnerT, EgarterC, WimmerC, LederhilgerF, WeichselbraunI (1993) Amniotic-Fluid Interleukin-8 as a Marker for Intraamniotic Infection. Arch Gynecol Obstet 253: 9–14.

53. de AraujoMC, SchultzR, VazFA, MassadE, FeferbaumR, et al. (1994) A case-control study of histological chorioamnionitis and neonatal infection. Early Hum Dev 40: 51–58.

54. PapantoniouNE, AntsaklisAJ, ProtopapasAG, VogiatziAI, AravantinosDI (1997) Predictive value of amniotic fluid and fetal blood cultures in pregnancy outcome in preterm prelabour rupture of membranes. J Obstet Gynaecol 17: 18–22.

55. RonnestadA, AbrahamsenTG, MedboS, ReigstadH, LossiusK, et al. (2005) Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants. Pediatrics 115: e262–268.

56. DuttaS, ReddyR, SheikhS, KalraJ, RayP, et al. (2010) Intrapartum antibiotics and risk factors for early onset sepsis. Arch Dis Child Fetal Neonatal Ed 95: F99–103.

57. PuopoloKM, DraperD, WiS, NewmanTB, ZupancicJ, et al. (2011) Estimating the probability of neonatal early-onset infection on the basis of maternal risk factors. Pediatrics 128: e1155–1163.

58. WilsonJC, LevyDL, WildsPL (1982) Premature rupture of membranes prior to term: consequences of nonintervention. Obstet Gynecol 60: 601–606.

59. NewtonER, PrihodaTJ, GibbsRS (1989) Logistic regression analysis of risk factors for intra-amniotic infection. Obstet Gynecol 73: 571–575.

60. RosemondRL, GlassCA, WingoCE (1995) Daily fetal movement and breathing assessments in the management of preterm membrane rupture. J Matern-Fetal Investigation 5: 236–239.

61. MercerBM, CarrTL, BeazleyDD, CrouseDT, SibaiBM (1999) Antibiotic use in pregnancy and drug-resistant infant sepsis. Am J Obstet Gynecol 181: 816–821.

62. TudelaCM, StewartRD, RobertsSW, WendelGDJr, StaffordIA, et al. (2012) Intrapartum evidence of early-onset group B streptococcus. Obstet Gynecol 119: 626–629.

63. DollnerH, VattenL, HalgunsetJ, RahimipoorS, AustgulenR (2002) Histologic chorioamnionitis and umbilical serum levels of pro-inflammatory cytokines and cytokine inhibitors. BJOG 109: 534–539.

64. Wójkowska-MachJ, Borszewska-KornackaM, DomańskaJ, GadzinowskiJ, GulczyńskaE, et al. (2012) Early-onset infections of very-low-birth-weight infants in Polish neonatal intensive care units. Pediatr Infect Dis J 31: 691–695.

65. KordekA, TorbeA, CzajkaR (2006) Maternal venous procalcitonin levels do not correlate with umbilical cord blood and venous blood concentrations in the neonate. J Perinat Med 34: 462–465.

66. KordekA, TorbeA, PodrazaW, LoniewskaB, Jursa-KuleszaJ, et al. (2011) Does prenatal antibiotic therapy compromise the diagnosis of early-onset infection and management of the neonate? J Perinat Med 39: 337–342.

67. BoyerKM, GadzalaCA, KellyPC (1981) Rapid identification of maternal colonization with group B streptococci by use of fluorescent antibody. J Clin Microbiol 14: 550–556.

68. ChristensenKK, SvenningsenN, DahlanderK, IngemarssonE, LindenV, et al. (1982) Relation between neonatal pneumonia and maternal carriage of group B streptococci. Scand J Infect Dis 14: 261–266.

69. TowersCV, GariteTJ, FriedmanWW, PirconRA, NageotteMP (1990) Comparison of a rapid enzyme-linked immunosorbent assay test and the Gram stain for detection of group B streptococcus in high-risk antepartum patients. Am J Obstet Gynecol 163: 965–967.

70. BurmanLG, ChristensenP, ChristensenK, FryklundB, HelgessonAM, et al. (1992) Prevention of excess neonatal morbidity associated with group B streptococci by vaginal chlorhexidine disinfection during labour. The Swedish Chlorhexidine Study Group. Lancet 340: 65–69.

71. ReganJA, KlebanoffMA, NugentRP, EschenbachDA, BlackwelderWC, et al. (1996) Colonization with group B streptococci in pregnancy and adverse outcome. VIP Study Group. Am J Obstet Gynecol 174: 1354–1360.

72. PiperJM, GeorgiouS, XenakisEM, LangerO (1999) Group B streptococcus infection rate unchanged by gestational diabetes. Obstet Gynecol 93: 292–296.

73. Namavar JahromiB, PoorarianS, PoorbarfeheeS (2008) The prevalence and adverse effects of group B streptococcal colonization during pregnancy. Arch Iran Med 11: 654–657.

74. FaroS, BrehmB, SmithF, MouzoonM, GreisingerA, et al. (2010) Screening for group B streptococcus: a private hospital's experience. Infect Dis Obstet Gynecol 2010.

75. KunzeM, ZieglerA, FlueggeK, HentschelR, ProempelerH, et al. (2011) Colonization, serotypes and transmission rates of group B streptococci in pregnant women and their infants born at a single University Center in Germany. J Perinat Med 39: 417–422.

76. BobittJR, DamatoJD, SakakiniJJr (1985) Perinatal complications in group B streptococcal carriers: a longitudinal study of prenatal patients. Am J Obstet Gynecol 151: 711–717.

77. ItakuraA, KurauchiO, MorikawaS, MatsuzawaK, MizutaniS, et al. (1996) A prospective study on the relationship between intrapartum maternal group-B streptococcal concentration and signs of infection in neonates. J Obstet Gynaecol Res 22: 101–105.

78. MaY, WuL, HuangX (2000) [Study on perinatal group B Streptococcus carriers and the maternal and neonatal outcome]. Zhonghua Fu Chan Ke Za Zhi 35: 32–35.

79. MercerBM, MiodovnikM, ThurnauGR, GoldenbergRL, DasAF, et al. (1997) Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA 278: 989–995.

80. VolumenieJL, FernandezH, VialM, LebrunL, FrydmanR (2001) Neonatal group B streptococcal infection. Results of 33 months of universal maternal screening and antibioprophylaxis. Eur J Obstet Gynecol Reprod Biol 94: 79–85.

81. MerensteinGB, ToddWA, BrownG, YostCC, LuzierT (1980) Group B beta-hemolytic streptococcus: randomized controlled treatment study at term. Obstet Gynecol 55: 315–318.

82. WeintraubZ, RegevR, IancuTC, FerneM, RabinowitzBS (1983) Perinatal group B streptococcal infections in Israel. Isr J Med Sci 19: 900–902.

83. ViscontiA, OreficiG, NotarnicolaAM (1985) Colonization and infection of mothers and neonates with group B streptococci in three Italian hospitals. J Hosp Infect 6: 265–276.

84. LiangST, LauSP, ChanSH, FokTF, MuraiT, et al. (1986) Perinatal colonization of group B streptococcus–an epidemiological study in a Chinese population. Aust N Z J Obstet Gynaecol 26: 138–141.

85. KolleeLA, SpeyerI, van KuijckMA, KoopmanR, DonyJM, et al. (1989) Prevention of group B streptococci transmission during delivery by vaginal application of chlorhexidine gel. Eur J Obstet Gynecol Reprod Biol 31: 47–51.

86. AyataA, GuvencH, FelekS, AygunAD, KocabayK, et al. (1994) Maternal carriage and neonatal colonization of group-B streptococci in labor are uncommon in Turkey. Paediatr Perinat Ep 8: 188–192.

87. SuaraRO, AdegbolaRA, BakerCJ, SeckaO, MulhollandEK, et al. (1994) Carriage of group-B streptococci in pregnant Gambian mothers and their infants. J Infect Dis 170: 1316–1319.

88. SensiniA, TissiL, VerducciN, OrofinoM, Von HunolsteinC, et al. (1997) Carriage of group B streptococcus in pregnant women and newborns: A 2-year study at Perugia General Hospital. Clinl Microbiol Infec 3: 324–328.

89. HickmanME, RenchMA, FerrieriP, BakerCJ (1999) Changing epidemiology of group B streptococcal colonization. Pediatrics 104: 203–209.

90. El-KershTA, Al-NuaimLA, KharfyTA, Al-ShammaryFJ, Al-SalehSS, et al. (2002) Detection of genital colonization of group B streptococci during late pregnancy. Saudi Med J 23: 56–61.

91. TsoliaM, PsomaM, GavriliS, PetrochilouV, MichalasS, et al. (2003) Group B streptococcus colonization of Greek pregnant women and neonates: prevalence, risk factors and serotypes. Clin Microbiol Infect 9: 832–838.

92. ErenA, KucukercanM, OguzogluN, UnalN, KaratekeA (2005) The carriage of group B streptococci in Turkish pregnant women and its transmission rate in newborns and serotype distribution. Turk J Pediatr 47: 28–33.

93. LijoiD, Di CapuaE, FerreroS, MistrangeloE, GiannattasioA, et al. (2007) The efficacy of 2002 CDC guidelines in preventing perinatal group B Streptococcal vertical transmission: a prospective study. Arch Gynecol Obstet 275: 373–379.

94. ElzbietaK, JoannaSM, JanuszW, EdytaB, TomaszK, et al. (2009) The incidence of Streptococcus Group B in 100 parturient women and the transmission of pathogens to the newborn. Ginekologia Polska 80: 285–289.

95. SeoudM, NassarAH, ZallouaP, BoghossianN, EzeddineJ, et al. (2010) Prenatal and neonatal Group B Streptococcus screening and serotyping in Lebanon: incidence and implications. Acta Obstet Gynecol Scand 89: 399–403.

96. BarcaiteE, BartuseviciusA, TamelieneR, MaleckieneL, VitkauskieneA, et al. (2012) Group B streptococcus and Escherichia coli colonization in pregnant women and neonates in Lithuania. Int J Gynaecol Obstet 117: 69–73.

97. MitsudaT, AraiK, FujitaS, YokotaS (1996) Demonstration of mother-to-infant transmission of Staphylococcus aureus by pulsed-field gel electrophoresis. Eur J Pediatr 155: 194–199.

98. PinterDM, MandelJ, HultenKG, MinkoffH, TosiMF (2009) Maternal-infant perinatal transmission of methicillin-resistant and methicillin-sensitive Staphylococcus aureus. Am J Perinatol 26: 145–151.

99. Bourgeois-NicolaosN, LucetJC, DaubieC, BenchabaF, RajguruM, et al. (2010) Maternal vaginal colonisation by Staphylococcus aureus and newborn acquisition at delivery. Paediatr Perinat Epidemiol 24: 488–491.

100. HuangYC, ChaoAS, SuLH, ChangSD (2012) A cluster of methicillin-sensitive Staphylococcus aureus colonization in a nursery. J Perinat Med 40: 307–310.

101. TamelieneR, BarcaiteE, NadisauskieneRJ, VitkauskieneA, JomantieneD, et al. (2010) Impact of maternal and neonatal risk factors on neonatal Escherichia coli colonization. Early Hum Dev 86: S75.

102. KafetzisDA, SkevakiCL, SkouteriV, GavriliS, PeppaK, et al. (2004) Maternal genital colonization with Ureaplasma urealyticum promotes preterm delivery: association of the respiratory colonization of premature infants with chronic lung disease and increased mortality. Clin Infect Dis 39: 1113–1122.

103. TafariN, Ljungh-WadstromA (1979) Consequences of amniotic fluid infections: early neonatal septicaemia. Ciba Found Symp 55–67.