Introduction

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Group B streptococcal disease is the leading cause of early onset neonatal sepsis in developed countries.¹ Despite the widespread adoption of preventive strategies in the United States and Australia in recent years,^2-4 uncertainty prevails as to whether early onset group B streptococcal sepsis is sufficiently common in the United Kingdom to justify widespread prophylaxis.⁵ There are few data on the prevalence of early onset sepsis in the United Kingdom and no population based case-control studies on risk factors.

This study aimed to evaluate risk factors for early onset group B streptococcal sepsis by using a case-control design in a geographically defined population while considering preventive strategies already employed.

	Methods

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We asked staff from 15 neonatal units throughout the former Northern region to identify neonates of 24 weeks' gestation or more in whom group B streptococcus was isolated from a normally sterile site (blood or cerebrospinal fluid) in the first week of life. We supplemented these data with information from each microbiology department and from the local perinatal mortality survey.

We selected four controls for each case in which the fetus was alive at the onset of labour. Intrapartum stillbirths were included in the case-control study but excluded from the prevalence calculations.

We reviewed obstetric, neonatal, and pathology case notes, paying particular attention to the reason for the onset of labour and the use of antibiotic prophylaxis during labour. Women were considered to have rupture of the membranes before the onset of labour if at least six hours elapsed between rupture of the membranes and the onset of regular uterine contractions.

A standardised questionnaire was sent to the clinical directors of obstetrics and senior clinical midwives at each of the region's 15 maternity units to identify written guidelines on the indications for and the use of antibiotic prophylaxis during labour, and to provide information on how often these guidelines were implemented in practice.

	Results

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Thirty six liveborn babies developed group B streptococcal sepsis in the first week of life. As 62 786 live births were registered in the study period, the prevalence is 0.57 per 1000 live births. In addition, three stillborn babies died of proved group B streptococcal infection, one during labour.

The cases presented early: 19 had symptoms by 1 hour of age and 26 by 24 hours of age. Just three babies developed symptoms after 48 hours of age. Twelve infants were admitted to neonatal units after resuscitation at birth, five had no symptoms but had blood cultures performed because of an identified risk factor, 13 developed respiratory symptoms, and four presented with seizures.

Thirty five infants had positive results on blood culture and two had positive cultures of cerebrospinal fluid. In one liveborn preterm infant infection was diagnosed at postmortem examination. Lumbar puncture was performed in 12 of 30 survivors, and meningitis was proved in three cases. Ten infants were ventilated, of whom six were less than 34 weeks' gestation. Five infants received inotropic support, and all died.

Six infants died in total. Five infants born at less than 36 weeks and presenting with symptoms of infection in the first hour died in the first 24 hours of life. One infant born at term presented with seizures on the third day and died on the 10th day.

In 17 liveborn cases (47%) a change to instrumental delivery was undertaken during labour, in contrast with 25 (17%) of the controls (P=0.001), which implies greater professional concern about the case fetuses than about the controls. Cases were more likely than controls to receive inflation by mask or intensive resuscitation at birth (20 cases, 13 controls, P0.001). Antenatal risk factors and unadjusted odds ratios are summarised in table 1.

We analysed the effect of the various risk factors on the prevalence of infection by using logistic regression (table 2). Two further models with four variables were developed to reflect the clinical situation more accurately. Each included only one variable relating to rupture of the membranes. In these analyses both prolonged rupture of the membranes (odds ratio 13.7, 95% confidence interval 4.8 to 39.5) and prelabour rupture of the membranes (10.7, 3.8 to 30.1) are shown to be independent, statistically significant risk factors for infection. Prelabour rupture of the membranes was a risk factor that was satisfied at a median 26.7 hours before delivery of the infant, compared with prolonged rupture of the membranes, which was satisfied at a median 13.5 hours before delivery.

We applied the criteria from the Public Health Laboratory Service's recommendations for best practice sequentially to the cases and controls (table 3).⁶ Of the 29 cases to which the criteria would have applied, review of medical notes showed that 23 were in hospital long enough before delivery to have received antibiotic prophylaxis for at least four hours before delivery. Application of these criteria might have resulted in treatment of 23 (16%, 10% to 22%) control mothers. Intrapartum temperature was not clearly documented in 16 controls.

	Discussion

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This study shows that 78% of cases of early onset group B streptococcal sepsis occurring in the Northern region had the opportunity to receive prophylaxis during labour had the guidelines for best practice been applied rigorously. Such rigorous application of the guidelines would, however, have resulted in antibiotics being given to 16% of all women in labour.

	Risk factors

Top Abstract Introduction Methods Results Discussion Risk factors Conclusion References

Delivery at less than 34 weeks was a significant risk factor among cases (odds ratio 33.6), and in addition five of the six infants who died were preterm. Although this study is too small to define mortality accurately, at 0.94 deaths per 10 000 live births the rate is similar to that previously quoted for the United States, Europe, and Australasia.⁷

The frequency of change to instrumental delivery and resuscitation at birth illustrates that many of the cases were probably infected in utero. For this reason antibiotic prophylaxis during labour should be started as soon as possible after risk factors have been identified.² Published data show that giving intrapartum antibiotic prophylaxis for four hours significantly reduces the chances of early onset group B streptococcal sepsis in neonates after high risk labour. ^{8 9} This study implies that most (78%) case women giving birth who were at high risk according to the criteria of the Public Health Laboratory Service could have been identified in time to give at least four hours of antibiotic prophylaxis before delivery.

	Conclusion

Top Abstract Introduction Methods Results Discussion Risk factors Conclusion References

This study confirms the importance of well established antenatal risk factors for early onset group B streptococcal sepsis and shows that rupture of the membranes before the onset of labour is an important risk factor. Although prelabour rupture is strongly associated with prolonged rupture of the membranes and is not an independent risk factor, its use in guidelines for prophylaxis may make it possible for antibiotics to be prescribed at an earlier stage. Its occurrence is usually known well before delivery, unlike prolonged rupture of the membranes, which can often be determined with certainty only after delivery.¹⁰ Combinations of these risk factors will "predict" risk in more cases.

Any risk factor based strategy of antibiotic prophylaxis during labour should concentrate on risk factors most prevalent in the infected population while minimising the number of women overall who are exposed to antibiotics. The Public Health Laboratory Service's recommendations for best practice can be applied in different ways depending on the definitions used for prolonged rupture of the membranes and intrapartum fever.⁶ Had the criteria been applied as aggressively as here (for example, counting 19 hours of rupture of the membranes as a risk factor), intrapartum antibiotic prophylaxis would have been offered to 16% of women in labour and might have prevented or ameliorated infection in almost three quarters of the cases.

Realistically, however, the criteria might well be variably or incompletely applied, not all eligible women might accept antibiotics during labour, and prophylaxis might be ineffective.¹¹ This interpretation of our data might therefore overestimate the potential effect of implementing the current recommendations rigorously. In addition, universal use of antibiotics is not without problems. Prophylactic strategies do not seem to have increased the prevalence of resistant organisms on the neonatal intensive care unit,⁴ but occasional reports have found that resistant coliforms may now be more common because of such an approach.¹² Recent data also show that the use of broad spectrum intrapartum antibiotics might increase the incidence of necrotising enterocolitis.¹³ Guidelines should therefore seek to minimise the overall number of women exposed. This study provides data that will aid the development of such guidelines in the United Kingdom.

	Acknowledgments

We thank everyone who contributed to this survey and in particular members of the Northern Neonatal Network, the medical records staff and Alice Downes, Jim Dodd, Roshan Adappa, Diane Snowden, and Dominic Sailor for retrieving the notes; and Edmund Hey, Louise Parker, and Unni Wariyar for support with the study design and the writing of this paper.

Contributors: See bmj.com

	Footnotes

Funding: Northern Neonatal Network.

Competing interests: None declared.

The full version of this article appears on bmj.com

	References

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(Accepted 12 February 2002)