Antibiotics and Gut Microbiota Among Newborn Infants

NCT02072798 | Completed Phase 4 DMC

• 2 other identifiers: s-201301172012-002068-29
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Background Women undergoing Caesarean Section (CS) have an increased risk of postpartum infections compared to women undergoing vaginal delivery. In Denmark the incidence of post-CS infections is 7-10%. The most common infections are endometritis, Urinary tract infections (UTI) and wound infections (WI). Prophylactic antibiotics are effective in preventing postoperative infections and national guidelines recommend that antibiotics should be administered as a single dose immediately before surgical incision. CS is an exception to this pre-incision administration approach. National guidelines recommend administration of antibiotics after umbilical cord clamping to avoid exposure of the child to antibiotics before birth. Recent studies of antibiotic prophylaxis for CS suggest that prophylactic antibiotics administered before incision compared to after umbilical cord clamping may reduce post-CS infections by up to 50%. Two Cochrane reviews from 2012 criticize these types of studies for lack of data for outcomes on the baby and on late infection in the mother. At birth, all mammals must rapidly adapt to intake of complex milk nutrients via the gut and simultaneously tolerate the invasion of billions of microbes. This requires rapid maturation of the digestive and immune functions to avoid gut disorders and infections. Full-term, breast-fed infants normally adapt well, but factors such as caesarean birth, high hygiene levels, antibiotics treatment and formula feeding may inhibit immune development both short and long term. Birth by caesarean section in high-hygiene hospital environments, and widespread use of antibiotics, are factors that reduce gut microbiota density and diversity in the newborn for some time after birth. On the other hand, high-hygiene environments and antibiotics are essential tools to combat infections, especially for the weakest newborn infants. This pilot study will be a feasibility study to the original study, which examines the effect of change in timing of prophylactic antibiotics on the rate of post-CS infections (endometritis, UTI and WI). The pilot study focus on antibiotic and changes in the gut microbiota of newborn infants. The feasibility study will only include pregnant women in Odense with a body mass index below 30, and planned cesarean section.

Conditions

Surgical Wound Infection; Infection; Cesarean Section; Complications; Cesarean Section

Keywords

Randomized Controlled Trial; Caesarean Section; Surgical Site Infections; Wound Infections; Infectious Morbidity

Outcome Measures

Primary Outcomes (2)

• Maternal: incidence of post-CS infection (endometritis, urinary tract infections and wound infection) in each study group

  Within the first 30 days after surgery

• Infant: fecal microbiota at the tenth day of life

  on the tenth day of life

Secondary Outcomes (5)

• Maternal: Length of hospitalization

  Within the first 30 days after Caesarean Section

• Maternal: readmissions to hospital on suspicion of postpartum infection following cesarean section

  Within the first 30 days after Caesarean Section

• Antibiotic treatment

  within the first 30 days after Caesarean Section

• Infant: concentration of cefuroxime in blood samples

  during the first 24 hours of life

• Infant: immunological analyses in blood samples on day 3

  On the third day of life

Study Arms (2)

preoperative antibiotic

ACTIVE COMPARATOR

iv Cefuroxime 1,5g administered 15-60 minutes before incision

Drug: Cefuroxime

postoperative antibiotic

ACTIVE COMPARATOR

iv Cefuroxime 1,5g administered after umbilical cord clamping

Drug: Cefuroxime

Interventions

Cefuroxime DRUG

iv Cefuroxime 1,5g administered 15-60 minutes before incision versus iv Cefuroxime 1,5g administered after umbilical cord clamping

Also known as: Cefuroxime "Fresenius Kabi"

postoperative antibiotic; preoperative antibiotic

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 year
• Women, who can read and understand Danish
• A gestational age ≥ completed 28 weeks of gestation
• Rupture of membranes and active labour (uterine contractions) is allowed.
• BMI \< 30

You may not qualify if:

• Hypersensitivity to cefuroxime or to any other cephalosporin antibiotics
• Previous immediate and/or severe hypersensitivity reaction to penicillin or any other beta-lactam antibiotic.
• Systemic exposure to any antibiotic agent within 1 week before delivery Antibiotic indicated due to PROM, fever, group B Streptococcus or other indications at the time of caesarean section.
• Women being immunologically incompetent (e.g. HIV positive)
• Very sick newborn infants transferred to a neonatal intensive care unit and treated with antibiotics will be excluded from the study

Sponsors & Collaborators

• Odense University Hospital: lead
• University of Copenhagen: collaborator
• Aase and Ejnar Danielsens Foundation: collaborator
• Region of Southern Denmark: collaborator
• University of Southern Denmark: collaborator

Study Sites (1)

Odense University Hospital

Odense, Fyn, 5000, Denmark

Location

Related Publications (1)

• Kamal SS, Hyldig N, Krych L, Greisen G, Krogfelt KA, Zachariassen G, Nielsen DS. Impact of Early Exposure to Cefuroxime on the Composition of the Gut Microbiota in Infants Following Cesarean Delivery. J Pediatr. 2019 Jul;210:99-105.e2. doi: 10.1016/j.jpeds.2019.03.001. Epub 2019 Apr 30.

  PMID: 31053348 DERIVED

Related Links

• "The NEOMUNE centre" is a research platform aiming to improve clinical care of newborn infants, particular those born with developmental problems

MeSH Terms

Conditions

Surgical Wound Infection; Infections; Wound Infection

Interventions

Cefuroxime

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Nana Hyldig, PhD student

  Odense University Hospital, department of Plastic Surgery, University of Southern Denmark, Faculty of Health Sciences, institute of Clinical Research, research unit, department of Gynaecology and Obstetrics

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD Student

Study Record Dates

• First Submitted: February 25, 2014
• First Posted: February 27, 2014
• Study Start: February 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: August 12, 2014

Record last verified: 2014-02

Locations

DK (1)