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\begin{document}

\title{Authors' reply re: Universal screening versus risk-based protocols for
antibiotic prophylaxis during childbirth to prevent early-onset Group B
streptococcal disease: A systematic review and meta-analysis. (Response
to BJOG-20-0383)}



\author[1]{Geke Hasperhoven}%
\author[2]{Salwan Al-Nasiry}%
\author[3]{Vincent Bekker}%
\author[1]{Eduardo Villamor}%
\author[1]{Boris Kramer}%
\affil[1]{Maastricht University Medical Centre+}%
\affil[2]{Maastricht UMC}%
\affil[3]{Leiden University Medical Center}%


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  \date{May 27, 2024}


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\section*{}

{\label{letter-to-the-editor-bjog-exchange}}

Dear Editor,

We read the letter from colleagues Dr. Seedat and Dr. Marshall,
commenting on our article, with great interest (1, 2). Their
clarifications on the UK National Screening Committee (UK NSC) position
are very clear. The UK NSC decided against a general screening since
they cannot assess the benefits and harms in the patient populations of
women (3) but they could indeed in newborns. The on-going clinical trial
(GBS3 Trial; ISRCTN49639731) in the UK will compare the current
risk-based strategy to two different screening tests. A lab based
culture test at 3 to 5 weeks before anticipated delivery date will use
an established microbiological technique {[}Enriched Culture Medium
Testing{]} to reduce false-negative results and a molecular point of
care test at the onset of labour. The latter test reduces the time
period between screening and the start of labour. The predictive value
of antenatal GBS cultures decreases if the interval between culture and
delivery is longer than 5 weeks. The results of the trial will help to
determine the appropriate screening technique and the rational use of
antibiotics for the prevention of early onset GBS sepsis in newborn
babies.

Perinatal empirical therapy of newborns at risk for or with suspected
EOS represents the main contributor to the use of antibiotics in early
life (4). There is growing concern about the effects that unnecessary
exposure to antibiotics in the perinatal period may have on the future
health of these children (5, 6). Antibiotic-related alterations in the
microbiome may have downstream effects on the developing immune system
and may increase the risk of allergic, autoimmune, and metabolic
diseases (5, 6).

Seedat and Marshall state that according to another study, the use of
IAP would indeed increase if screening were implemented, and that the
portion of women receiving IAP would be `low risk women' who\ldots{}
`would not have a neonate with EOGBS in the absence of IAP' (1). In this
statement is embedded the assumption that the currently established risk
factors are indeed a good prediction of EOGBS transmission. However,
50\% of neonates with early onset sepsis with GBS did not have risk
factors. To the contrary, we confirm in our meta-analysis and systematic
review that universal screening lowered the incidence of early onset GBS
sepsis in newborn whereas risk-based approaches did not (2). This might
indicate that although screening is imperfect, risk factors might be
worse in predicting EOGBS outcomes.

Besides, we found no evidence that the rate of intrapartum antibiotic
treatment was different in risk-based screening than in universal
screening. Administration of antibiotics in risk-based policies was in
our study neither lower nor associated with a reduction in the burden of
disease in early onset GBS sepsis (2). We are looking forward to the
results of the GBS3 trial since there is a need for unbiased evidence on
the appropriate policy. A trial comparing screening with risk-factor
based intrapartum antibiotic prophylaxis is hard to conduct in areas
that currently have a screening policy. Recruitment of participants is
very challenging and a premature stop for futility is very likely. A lot
of women might not want a risk-based protocol if screening is already
the standard of care or easily available. Therefore, the UK data will be
very helpful in guiding the future way.

\par\null\par\null

\section*{References}

{\label{449877}}

1. Seedat F, Marshall J. Re: Universal screening versus risk-based
protocols for antibiotic prophylaxis during childbirth to prevent
early-onset Group B streptococcal disease: A systematic review and
meta-analysis. (First comment letter. Reference to be added). BJOG.
2020.

2. Hasperhoven GF, Al-Nasiry S, Bekker V, Villamor E, Kramer B.
Universal screening versus risk-based protocols for antibiotic
prophylaxis during childbirth to prevent early-onset Group B
streptococcal disease: a systematic review and meta-analysis. BJOG.
2020. https://doi.org/10.1111/1471-0528.16085

3. Seedat F, Geppert J, Stinton C, Patterson J, Freeman K, Johnson SA,
et al. Universal antenatal screening for group B streptococcus may cause
more harm than good. BMJ. 2019;364:l463.

4. Achten NB, Klingenberg C, Benitz WE, Stocker M, Schlapbach LJ,
Giannoni E, et al. Association of Use of the Neonatal Early-Onset Sepsis
Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic
Review and Meta-analysis. JAMA Pediatr. 2019.

5. Cotten CM. Adverse consequences of neonatal antibiotic exposure. Curr
Opin Pediatr. 2016;28(2):141-9.

6. Esaiassen E, Fjalstad JW, Juvet LK, van den Anker JN, Klingenberg C.
Antibiotic exposure in neonates and early adverse outcomes: a systematic
review and meta-analysis. J Antimicrob Chemother. 2017;72(7):1858-70.

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