Babies who survive GBS disease more likely to require special educational support

Largest study of its kind shows infected babies face greater risk of neurodevelopmental impairments and underlines need for follow-up care for survivors and maternal GBS vaccines.

Invasive Group B Streptococcus (GBS) disease, notably meningitis, during the first days and months of a baby’s life can have persistent effects for children and hence their families, according to new research. Published in The Lancet Child & Adolescent Health, the study is the first evidence of long-term effects including after GBS sepsis (infection in the bloodstream).

This large study analysed outcomes for nearly 25,000 children born in Denmark and The Netherlands, between 1997 and 2017. Results show that children who had invasive GBS infection are twice as likely to have neurodevelopmental impairments (NDI) and to require special educational support than children who did not have GBS disease. 

Effects later in life are significant - about one in 20 survivors will experience some form of neurodevelopmental disability. The authors note that the majority of GBS infection survivors will not have long-term effects.

An estimated 20 –30% of pregnant women carry the GBS bacteria but 99% of babies born to mothers who carry the bacteria are perfectly healthy.

This study was conducted through a partnership of the London School of Hygiene & Tropical Medicine (LSHTM), Aarhus University (Denmark), Amsterdam UMC (Netherlands) and the Dutch National Institute for Public Health and the Environment.

Invasive GBS infection is increasingly recognised as a leading cause of newborn illness worldwide, with ~300,000 cases estimated annually. Important knowledge gaps have been highlighted especially regarding the long-term outcomes of patients who survive the acute disease during this critical period of life. Previous small studies have followed babies after GBS meningitis to a median age of about two years.  No study has examined outcomes after GBS sepsis.

Children in the study were identified using national administrative, medical, and laboratory databases.  2,258 babies were diagnosed as having had GBS infection, including meningitis and sepsis, within the first three months of life.  For every GBS case, ten children who did not have the infection were matched on age, sex and other characteristics influencing long-term outcomes.

Children were followed up for an average of fourteen years in Denmark and nine years in the Netherlands, to analyse risks of death and of NDI (eg motor, cognitive, and socio- behavioural, and special educational needs). The findings are striking and reinforce the severity of this condition with a 5% mortality risk for babies dying from invasive GBS disease in high-income settings, although the risk is much higher in low and middle income countries. Compellingly, there are also serious consequences for some of the children who survive. 

In Denmark, history of GBS infection in the first three months of life was associated with 1.8-fold increase in risk of NDI: 45 of the 969 children who survived the acute phase of the disease had moderate or severe NDI, such as motor impairment, by the age of 10. The risk was even higher in the Netherlands, where 36 of the 252 children with a history of invasive GBS disease needed special educational support by age 10, a more than two-fold risk.

Currently, the only available GBS disease prevention strategy is to provide antibiotic prophylaxis to women in labour whose baby is at increased risk of developing GBS disease. However, this strategy is not sufficient even in these two European countries and currently not adopted in settings with limited resources. 

Professor Merijn Bijlsma, a paediatrician at Amsterdam University and a lead author said:

"Even with the best medical care, such as available for Dutch and Danish babies, survivors of GBS meningitis and also sepsis may be affected for life. The best way to protect these children is prevention of invasive GBS disease. We need better ways to identify at birth who is at risk, so prevention including with intrapartum antibiotics becomes more effective.”

Vinny Smith, Chief Executive of Meningitis Research Foundation, said:

“This very welcome paper provides new evidence on the poor outcomes for people with invasive GBS infection and especially GBS meningitis. As well as killing people, GBS can cause damage that seriously affects development and education for many of those who survive, with those affected being more likely than others to need extra school support long after infection. This is further evidence of the need to prioritise prevention, such as a vaccine for GBS, and better support for families, as identified by the new WHO Global Roadmap to Defeat Meningitis by 2030."
 

Unlike other leading causes of meningitis, there is currently no vaccine available to prevent GBS disease.
 

Professor Joy Lawn, of the London School of Hygiene & Tropical Medicine, senior author and PI said: 

“Every year hundreds of thousands of babies have GBS sepsis or meningitis, with a high mortality risk. Families in all continents are affected. Our study shows that GBS also affects educational potential for survivors. The global burden of disease is more than has previously been estimated, underlining the urgent need for prevention. Despite 30 years of research, maternal GBS vaccines currently are not yet available - a contrast to more than 100 COVID-19 vaccines in process within one year. We can and must deliver more for families affected by GBS all over the world.” 

Charlotte Cleary's daughter Aimee developed early-onset group B Strep meningitis and sepsis shortly after birth in July 2011. She spent three weeks very sick in hospital. and has recovered with brain damage and physical disabilities. Aimee was diagnosed with quadriplegic spastic cerebral palsy and pseudobulbar palsy, along with learning difficulties and sensory issues. Put simply, she can't sit, stand, walk, talk and is mostly tube-fed.

The authors acknowledge study limitations including differences in the identification of children with GBS infection cases selection between the two countries. Importantly, these results from Denmark and the Netherlands reflect two high income European countries, and results in low and middle income countries may differ, hence data are needed from these contexts. Further research is needed as to why different children are affected differently. We know preterm birth is an important linked risk factor and more studies are needed to explore this association. 

This study was funded by the Bill & Melinda Gates Foundation to address a key global data gap regarding GBS, and contribute vital information for the World Health Organization’s Report on GBS prevention, linked to the new Global Roadmap to Defeat Meningitis. The Dutch team was also supported by the Stichting Remmert Adriaan Laan Fonds. 

Publication

Erzsébet Horváth-Puhó*, Merel N van Kassel*, Bronner P Gonçalves*, Brechje de Gier, Simon R Procter, Proma Paul, Arie van der Ende, Kirstine K Søgaard, Susan J M Hahné, Jaya Chandna, Stephanie J Schrag, Diederik van de Beek, Mark Jit†, Henrik T Sørensen†, Merijn W Bijlsma†, Joy E Lawn†.  Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study. Lancet Child and Adolescent Health. DOI:10.1016/S2352-4642(21)00022-5