Prospective multicentre observational cohort study on perinatal bacterial infections ;Part 1 of the Netherlands observational study on group B streptococcal disease, bacterial virulence and protective serology (NO GBS)

Streptococcus agalactiae (Group B Streptococcus, GBS) and Escherichia coli are
the leading cause of neonatal sepsis and meningitis. One out of five pregnant
women is asymptomatically colonized by GBS. Transmission of GBS bacteria to the
neonate can result in invasive disease, which has been associated with a case
fatality rate of 7%.

Dutch GBS prevention guidelines recommend intrapartum antibiotic prophylaxis
for pregnant women with risk factors for GBS disease. We have shown that the
incidence of neonatal GBS disease is increasing, despite guideline
implementation in 1999. In addition, current guidelines recommend bacterial
prophylaxis and treatment for mothers and their children based on a
risk-calculation. With this strategy a relatively large group of children is
exposed to antibiotics. Another shortcoming of these guidelines is the focus on
early onset disease. Late onset disease occurring after 7 days of age is an
important problem. The incidence of late onset disease has not changed in the
western world over the past decades. Improved risk assessment, a better
understanding of GBS pathophysiology and new prevention strategies are needed.

An important future option to reduce invasive disease in neonates is GBS
vaccination of mothers during pregnancy. GBS vaccines were shown to be safe and
immunogenic in pregnant woman. However, further evaluation of these vaccines is
hampered because of the high costs of a phase 3 RCT with clinical endpoints.
Therefore, immune correlates of protection are needed to evaluate potential
effectiveness of these vaccines.

In this observational cohort study we will determine the sensitivity of Dutch
risk-based prevention guidelines to identify cases of invasive disease caused
by GBS or E. coli in 0-3 months old patients. Furthermore, we will collect
invasive bacterial isolates and blood from patients and their mothers to
perform whole genome sequencing of invasive GBS isolates and determine
empirical reverse cumulative distributions of specific IgG concentrations
against vaccine targets in GBS patients and their mothers. These results will
be combined with results from the other parts of the *Netherlands observational
study on group b streptococcal disease, bacterial virulence and protective
serology (NO GBS)* to discover GBS bacterial virulence genes and determine
specific antibody concentrations that protect neonates against invasive GBS
disease.

The primary objectives of the NO GBS study part 1 are to:
- determine the clinical characteristics and outcome, and the prevalence of
risk factors used by Dutch guidelines for risk assessment in GBS and E. coli
meningitis and sepsis cases aged 0-3 months in the Netherlands.
- determine the genetic profile of invasive GBS isolates by whole genome
sequencing

The secondary objectives are to:
- develop a methodology to measure antibody concentrations against bacterial
antigens in dried blood spots;
- determine antibody concentrations against GBS vaccine targets that are
correlated with protection against invasive GBS disease.
To accomplish these secondary objectives, the results will be combined with the
findings from the other parts of the NO GBS study.

Prospective observational cohort study

The burden on and risk for the baby is limited is negligible. The burden for
the mother is minor and the risk minimal