In the UK, about a quarter of women give birth by Caesarean Section (CS). Before 2011, national guidance recommended offering antibiotics to women undergoing CS after the umbilical cord was cut, to reduce the risk of the mother developing an infection. However, evidence showed that the earlier antibiotics were given, the less likely mothers were to develop an infection. Therefore, in 2011 the guidance changed to recommend giving antibiotics before the operation.
Antibiotics given to the mother before CS also reach the baby via the placenta. We do not know whether these antibiotics have any long-term impact on children's health. During and after birth, the newborn gut is colonised by bacteria which are believed to be important in development of the child's immune system. The bacteria differ between babies who do and do not receive antibiotics during a CS, which may affect their chances of developing health conditions such as asthma, eczema and food allergies.
This study will investigate whether there is any long-term impact of antibiotics given at the time of CS on children's health. Findings will help women and their families make informed decisions before CS regarding whether or not, and how, they wish to receive antibiotics before their baby is born.
Aim:
To investigate whether the change in NICE guidance in 2011 from recommending prophylactic antibiotics after cord clamping to pre-incision antibiotics has had any effect on incidence of allergic and other related health conditions in children born by Caesarean Section (CS).
Design:
A controlled interrupted time-series study using mother-baby linked data from UK primary care (CPRD).
Target population:
Children born in the UK during 2006-2018 delivered by CS, compared to a control cohort delivered vaginally.
Intervention and comparator:
In utero exposure to prophylactic antibiotics immediately prior to delivery by CS will be compared to no exposure when given after the cord was clamped at CS. Exposure to intra-partum antibiotics is not routinely recorded in the UK, but nearly all (98%) women undergoing CS receive prophylactic antibiotics. We will use findings from a national survey of hospitals regarding change in timing of antibiotic administration as an indicator of the probability of exposure. We will account for the cumulative increase of hospitals giving pre-incision antibiotics in our analysis.
Outcomes:
Primary: Asthma and eczema.
Secondary: Other allergic and allergy related diseases, autoimmune diseases, infections and inflammation, other immune system related conditions, healthcare utilisation; maternal postpartum infectious morbidity, to assess whether the effects of pre-incision antibiotics demonstrated in randomised trials can be replicated using routine data.
Primary Outcomes: Examine whether in-utero exposure to antibiotics immediately prior to birth (Intervention) compared to no pre-incisional antibiotic exposure (Comparator) in children born by caesarean section increases
- Risk of asthma
- Risk of eczema
Secondary outcomes - children: We will investigate the effect of pre-incision prophylactic antibiotics in children born by CS on
- Other allergic and allergy related diseases (food allergies and intolerance, allergic rhinitis
- Autoimmune diseases (type 1 diabetes, juvenile idiopathic arthritis, other systemic connective tissue disorders)
- Infections and inflammation (e.g. neonatal sepsis, wheeze, respiratory tract infections, respiratory conditions, gastroenteritis)
- Other immune system related conditions (leukaemia, immune deficiencies, necrotising enterocolitis)
- Healthcare utilisation (overall consultation frequency in primary care, hospital admissions)
- Less specific measures of child health (colic, failure to thrive)
- Other outcomes suggested by clinicians and parents may be added, for instance neurodevelopmental conditions (e.g. autism spectrum disorder, ADHD)
Secondary outcomes - mothers: We will investigate if the effects of a reduction in post-partum maternal infectious morbidity shown in randomised controlled trials outside the UK can be replicated in the UK using routine healthcare data
- Maternal postpartum infectious morbidity (e.g. all maternal infection, endometritis, caesarean wound infection, UTI/cystitis/pyelonephritis, pelvic abscesses, respiratory infections (e.g. pneumonia), febrile illness, length of hospital stay)
Dana Sumilo - Chief Investigator - University of Birmingham
Dana Sumilo - Corresponding Applicant - University of Birmingham
Brian Willis - Collaborator - University of Birmingham
Gavin Rudge - Collaborator - University of Birmingham
James Martin - Collaborator - University of Birmingham
Jon Deeks - Collaborator - University of Birmingham
Krishna Gokhale - Collaborator - University of Birmingham
Krishnarajah Nirantharakumar - Collaborator - University of Birmingham
Magdalena Skrybant - Collaborator - University of Birmingham
Nicola Adderley - Collaborator - University of Birmingham
Peter Brocklehurst - Collaborator - University of Birmingham
Rasiah Thayakaran - Collaborator - University of Birmingham
Ruth Hewston - Collaborator - University of Birmingham
CPRD Mother-Baby Link;HES Admitted Patient Care;Patient Level Townsend Score;Pregnancy Register